Lessons in Lifespan Health

Wayne Lehrer is an author, coach and teacher who leads a yoga class at the USC Leonard Davis School. He joined us to talk about his book, The Art of Conscious Aging and how to redefine yourself and find fulfillment as you age.  Transcript I hear all the time, I used to do yoga, but now my body doesn't like it. Well, find a new yoga class. If you remember how it made you feel, then doing it in a new way, maybe a gentler class, maybe a hot yoga class that's in the dark, that's slow, where you hold the poses and no one's looking at you because you may be self-conscious, maybe that's the answer to it. But not doing it is only going to make your life collapse. And I believe that one of the biggest problems with aging is people's worlds get smaller and smaller. Orli Belman (00:00): From the USC Leonard Davis School of Gerontology, this is Lessons in Lifespan Health, a podcast about the science and scientists improving how we live and age. I'm Orli Belman, Chief Communications Officer. On today's episode, how teacher and coach Wayne Lehrer found purpose in aging and is working to help others do the same. Lehrer is the author of The Art of Conscious Aging, the Operating Manual for an Extraordinary Third Act. He also leads a weekly yoga class here at the USC Leonard Davis School. Welcome to our podcast, Wayne, and thank you for being here today. Wayne Lehrer (00:39): Oh, thank you for the opportunity. Orli Belman (00:41): I think it would be helpful to start with some definitions. Let's begin with the terms in your book title. What is conscious aging? Wayne Lehrer (00:48): Well, conscious aging is accepting the fact that it happens for everybody. That's the conscious part of it. You know, most of us live most of our lives under the assumption that we're never going to age, certainly, that we're never going to be old or get older. So conscious aging is how we approach the process and the practice of aging. It's just basically becoming mindful of all of the elements that go into the process of aging, whether it's exercise and diet, sleep, or the subtler things like stress, poor relationships, you know, creating value in the world. So conscious aging is showing up for your life in a way that your life creates value for you and others. Orli Belman (01:32): That's a wonderful idea. And what is the third act? Wayne Lehrer (01:36): So historically, you know, what people normally now refer to as the third act is retirement. Historically, you know, the average lifespan in 1900 was 47 years. So, there wasn't really a third act. You know, people were children, they went to work and then they passed away, basically. And around 1950, with the onset of Social Security and Medicare and all of the other elements that increased life expectancy: the fitness revolution, psychological help, retirement funds, a little bit more disposable income available and a less stressful life, people began to live long enough to have a third act. So basically, life in three acts is the first act of childhood–which I say basically goes from zero to 20–is a time of exploring, discovering who you are, gathering information, finding how you fit into your world and the world. And that's also a period of dependency, could be categorized. Wayne Lehrer (02:42): The second act, starting in your twenties, and for most of, us going to our mid-fifties or 60 years, so about 35 or 40 years, the second act is a time of independence. We develop the ego, the separate self, we explore the world as an individual. We acquire, achieve, build, collect, succeed, compete. And during that time we, you know, sort of begin to build the separate self and what is mine, which could be, you know, my profession, my identity, my family, my place in my community. And then what's historically happened is that 55 or 60 people began to retire. They began to get phased out of their jobs. Empty nest happened and all of a sudden, they're left alone. And historically what happened is people went into a period referred to as retirement, which was really a period of on the highest-level seeking comfort and serenity. Wayne Lehrer (03:41): But on the lower levels what it happened to be was security, being less engaged in life, withdrawing, you know, that just started changing. Now that people have a period of time of 30 or 40 years from the time of retirement–if you retire at 55 or 60 with the average life expectancy rising above 90–there's a good chance you're going to have 30, 40, maybe even 50 more years of life. And so it's as long as the period of the second act. And historically that was seen as a time where you just withdrew and you know, kind of went on this long slow decline towards oblivion, you know. And now for the first time, you know, their health is better, they have some money in the bank, some sense of ways of creating new value and transforming themselves, so it's what I call the new third act. And the new third act is a period of time where you look at how you're going to create value, become an elder, give back, build community and collaboration. Also, if you think about it in the theater or in the film historically, you know, the second act is where all the drama happens. The third act is where the hero rises from the ashes, pulls all the diverse parts of themselves together, finds a new level of who they are, and really makes a difference and redeems themself. At least in the better stories. Orli Belman (05:02): And you've advocated for a different word for retirement. What do you call this new third act instead of retirement and how would you describe it? Wayne Lehrer (05:12): Well, the woman who created AARP called it refirement, but I really think it's a time of reinventing ourselves. You know, where we're looking at all of the gifts we have, all of the professions we've participated in, what we're passionate about and what talks to us in the world, what speaks to us that we feel like we may be the answer to, or we may be able to make a contribution in regard to. And so we have to basically, you know, reimagine, recreate, redesign and reinvent who we are and then reboot as that person. So, you know, I think it's a time of reinvention and reimagining. Orli Belman (05:54): These ideas, are they based on your own personal experience? Wayne Lehrer (05:58): Both my own, those of a lot of my friends. Obviously, I'm in a number of communities right now of people that are, you know, my age or entering into their third act or deep into their third act. And when I look around at the people that are happy and that are actually where they feel that they're in the sweetest point in their life, they're actually in the sweet spot, all of those people are people that have made this transition. And I think the transition is the hardest thing because historically also there's been no role models for a healthy third act. So part of it is observation. A lot of reading. There's a lot of good new research out there. You know, that longtime Harvard study that talks about people that have been, you know, where they followed people for I think 75 years and they found that the people that had long-term relationships, the people that found ways to continue to create value in later life. So yeah, and I also think it's indicative of our time period. So it's really an observation of both our time period and those people that are around me and then my own process of moving through this transition. Orli Belman (07:06): And can you talk a little bit about your own process? I know you've had several careers and maybe you could give some advice to people who finished their first career. Is there anything to take away from your example about restarting, investing yourself and even becoming an entrepreneur? Wayne Lehrer (07:22): It's challenging, especially challenging to do something maybe you've never done before. I put myself in a position or feel called to be in a position where I'm having to use skills I never developed before but based upon all of these other things that I'm very passionate about. So, you know, when I was younger, I studied Oriental medicine, I invented medical machinery, I had a whole life as a designer. I designed theme parks, museums, and world's fairs. I was an IMAX and computer graphics filmmaker, have taught yoga and meditation now for 25 years. So, I've had this full life and, and multiple different experiences and what was in common to all of them. And I believe that this is a case for everybody when they start to approach their third act, is that each of us sort of has a core way we meet the world. Wayne Lehrer (08:12): So, for me, my gift was creating immersive, transformative, spiritually uplifting experiences. So whether it's a yoga class or meditation or it's a ride in a theme park. If you take my ride in the theme park, you're going to be swept away. You know, it's not just going to be a thrill ride; you're going to be pulled into another world. So I think one of the things that a lot of people are maybe terrified or feel really challenged about making a transition out of the career they've had is first assessing and acknowledging the skills that they've actually developed and not seeing a single job as they had, as something that wasn't something that brought them a skillset, brought them a new way to know themselves and have something to offer. And then also, and this I think is particularly indicative of the third act, it's very important at this age to look into the world and see what the things are that you respond to. Wayne Lehrer (09:07): So you know, the most obvious examples would be Mother Teresa said, Oh, somebody needs to take care of the lepers in Calcutta. And Jimmy Carter, who may be one of the better examples of somebody who has a way more profound third act than his first or second act went and started Habitat for Humanity or what Clinton did. And these are skill sets that yes, they had all of the diverse pieces for, you know, they could talk to world leaders, they could get in the door, they'd work with health people and that kind of stuff. But it was also them each being entrepreneurial, you know, actually being the spearhead of those things. And I know for me personally, you know, I've written this book and I feel that it's a message that I've been given to share and that really no one is talking about in the way that I am. As a result of that, I have to learn technology, the most dreaded thing that anybody in their seventies can have to do, you know. And I have to practice social media; you know, I'm a really warm and friendly person. I talk to everybody on the street and at Starbucks, but have me post on Facebook and you know, I shiver. You know, so I'm having to learn all these things and, and the thing that's allowing me to do it is my passion for the thing that I'm doing. Orli Belman (10:21): And you've spent some time around our school over the years, and you know that we are focused on healthy aging and there are a number of scientific studies that show measurable benefits of practices like yoga, meditation, gratitude. We have a course on the mind-body connection, and I'm sure none of these positive findings are a surprise to you. How did you come to these practices and what do you see people getting out of them, particularly as they age? Wayne Lehrer (10:49): That's a great question, and I think it's important to say that even in my book, anybody can start conscious aging at the age of 20. So I started doing yoga and meditation in my twenties. Now that, you know, gave me a bit of a head start, but that was my natural inclination. I was not so drawn to a professional career as I was to the life of a seeker, let's say. So as people age though, they need ways to disengage from their story. You know, if you notice a lot of older people, their stories, you know, the story you tell is the life you're living. And if you're telling a story that's 30 or 40 years old and may not even be true anymore and might not have even been true when you started telling it, may have only been from your trauma point of view, then you need all the help you can get to get free of that, if you want to reinvent yourself in your third act. Wayne Lehrer (11:43): So meditation is one of the ways of doing that. As we get older, if we look metaphorically at aging, part of what happens for people as they age is they become rigid in their thinking emotionally. You know, they limit their emotional life. They don't read new things; they don't go to new places as much. If they go to a new place, it's in the safe confines of a luxury cruise or whatever it is. And same thing happens in the physical body. So any kind of exercise like yoga or tai chi or qigong that's fluid and flowing is going to exercise and lubricate the joints. They actually have, you know, done research and they found out that the synovial fluid, it just needs movement and regular and it'll actually come back. So these are really simple and obvious things, and part of that has to do with the fact that you're only going to notice that if you're paying attention to your experience in the body that you have and in the mind that you have when you're in your sixties or seventies. If you're not paying attention to it, and you still think, oh I can play basketball, I can stay up till one o'clock at night and not pay for it the next day or the next two days. Wayne Lehrer (12:54): You know, so if you're paying attention and you actually have valuing that feedback system, then there's a great chance that you're going to start making the quality of choices that are going to lead you to things like yoga. And you're going to listen to those podcasts and those scientists and the people at the Davis School of Gerontology that are telling you about intermittent fasting. You know, all of these things that are all incredibly valuable that may not have been at all a part of your world while you were striving to earn a living and you know, build your home and your family and your business. Orli Belman (13:29): Can you tell me a little bit more about this feedback system that develops as we age? Wayne Lehrer (13:34): Yeah. When we're younger, we can get away with everything and anything. You know, when you're in your twenties, you want to stay up all night, no problem. You want to stay up two nights and then do a presentation for work? No problem. You want to eat french fries? No problem. Exercise until you drop? No problem. But when you get older, those things are not negotiable anymore; there's a very narrow window. Most people look at that in a negative way. They think, oh I can't do this and I can't do that anymore. But the truth is that you finally have a feedback system that scientists have always had. And the only way that science moves ahead is by having a ground zero or placebo study to go against. All of a sudden you recognize that if I do this, for example, if I say I want to write a book and yet I have an allergy to wheat and I eat wheat and I'm foggy the next day, then I can't write that book. Wayne Lehrer (14:27): And if I'm committed to that thing I'm passionate about, then I'll take a look at what it's going to take for me to accomplish that. Same thing with any dietary thing or exercise element. All of a sudden I have a feedback system because my body will let me know right away and my mind will let me know and I'll know emotionally this person is somebody I'm not comfortable about. I feel toxic after I hang out with them. This is how much time I can do that for. And the value of that is it really makes us more conscious beings, so we have finally have something to measure against that allows us to grow and actually become aware and cognizant of that fine-tuned area called quality of life or wellbeing. Orli Belman (15:12): So you're saying there's a real benefit that we get to be more in tune with ourselves and know what works for us and what doesn't. Wayne Lehrer (15:19): Absolutely. Orli Belman (15:20): And you mentioned earlier this idea of contributing or doing something of value as being important as people enter their third act. And this is also a big concept in the field of gerontology: this idea that there is a benefit to living with purpose. And that's something you're obviously doing. And what do you think about the importance of purpose and the role it plays in your life? Wayne Lehrer (15:45): Well, one of the things that you see really common in people as they age is they begin to feel devalued. If you've been at a job for 20 or 30 years and all of a sudden that job's over and you derived your value from showing up at the job and that's gone, that takes a toll. Now none of these things may individually take you down, but all of a sudden there are five or 200 people every day that you're not seeing either. And so the value that they have for you and that you have for them, that's gone. Your children have moved out and you're not a parent anymore. So the value you got from parenting, from making a contribution to somebody, that's gone. So it's not so much that we need it more in later life, it's that a lot of the sources of value we've had have inadvertently–and not so necessarily obviously–disappeared. Wayne Lehrer (16:38): That said, there's also, I believe, a natural thing that happens in India. They talk about three stages of life and the third stage. And you know, you go from being a householder to somebody who gives back, also sometimes known as a forest dweller. But somebody who becomes a seeker and moves into a more spiritual stage of life where they're making a contribution. So I believe it's a natural thing that actually elevates, if we're getting our value from what we do in the world and all of a sudden we're not doing as much in the world and we need to find a new way to get our value. And it may not be as much from what we do in the world as from actually going inside. Because those jobs that we got in the world, a lot of the jobs that people have for 30 or 40 years weren't jobs that they really chose. Wayne Lehrer (17:25): They were jobs that they were shuttled into by school, by parents, by opportunities that were purely monetary. So all of a sudden, when that's taken away and you become the person that makes the choice over what you want to do with the rest of your life, you have to look inside. And that is where the real value comes. Not just the looking inside, but looking inside and coming up and saying, wait a second, this in the world really matters to me. Like it became obvious to me that I had a contribution to make because those things I started at 20 that had to do with healthy aging, I kept doing them. And so all of a sudden all my friends were saying, oh my God, you're the youngest 73-year-old, we know. You should write a book. And I thought, yeah, that'd be nice. Wayne Lehrer (18:07): And then all of a sudden it, you know, just kept occurring to me. And next thing you know, I felt a calling because I saw a lot of people struggling, making a transition from their second to their third act. So I think a lot of people, it's almost a necessity that they find value because lack of value could result in what most people term depression, isolation, loneliness. These are all the natural things that happen for a lot of people as they age. And a lot of that has to do with that. They haven't found a place to be in the world. And our value comes from multiple places. So our communities have disappeared when we get older because we're not at work, we're not at school, you know, our kids aren't there. So we're not in the family as much. Our communities have disappeared. That's a place we get value. Wayne Lehrer (18:49): A lot of our relationships change. People move away or die. All of a sudden a place that we get value in, intimate relationships is gone. We're not doing our work. So the value we're creating as a worker or as somebody making a contribution that's been taken away, I believe, it's essential on multiple levels. Not the least of which has to do with, I believe, it's the period in our life when it's our job to give back. You know, historically, in other cultures there's a tradition called the elder, you know? And the elder was valued for the lifetime's worth of wisdom and experiences that they'd had, that they could relate to others, to help others avoid the pitfalls and the pain and the struggling and the suffering. That's not a common part of our society at this time. Orli Belman (19:38): Yeah, I think what you're talking about is something that many of our faculty talk about, which is this concept of generativity. A concern for guiding and giving back to the next generation, and that certainly comes across in what you're talking about and in your book. And why do you think that is something that plays such an important role in aging? Wayne Lehrer (19:59): Well, we're tribal. You know, we're part of a society now that's all filled with individuality and ego and a separate self. And a lot of us have benefited from being masterful, in going after things on our own and achieving things. But what has taken us to is the brink in a lot of different places. And that idea of generating value for society and for others is really essential to the very nature of who we are as people, which is we are not individuals. We're part of the human family, we're part of a planet and we're at a stage now that all of those things breaking down has become cumulatively painful to us if we don't stay in denial of it. And a lot of people do stay in denial of it because they don't want to face that pain, and they don't want to face the responsibility. But as you wake up to what your value is and what value you want to create in the world, I think that whatever value that most of the people are orienting their third acts around see as their contribution actually becomes something that contributes to the momentum of future generations. And turning things around for the collectivity. Orli Belman (21:15): And we've been talking about the third act, and which is the focus of your book and your work. But at our school, we're educating so many students of all ages and some of them as young as 18. And are there any lessons that they can apply to their own lives? Wayne Lehrer (21:31): Well, first of all, I have to say that I lived my whole life bulletproof. I had no physical problems. I didn't go to a doctor for like, 30 years, so I wasn't aware. And almost everyone I know, I talk to 57-year-olds who think that I'm exaggerating certain things because they haven't actually hit the transition from their second to third act. The reality of mortality, the reality of a body that doesn't always get fixed, the reality of being able to go out and get a new job, those things haven't really hit them yet. So they haven't been – I talk about in the book ­­— as being shattered. So for younger people, since that's not part of the reality, and most of us put off this idea that it's ever going to come, the best thing you can do is live well. Now, you know, the greatest contribution you can make to your own wellbeing as a 60, 70, or 80-year-old is to pay attention to these things that now surround us. Wayne Lehrer (22:27): You know, I mean, fitness didn't exist until the ‘50s. Psychology is only 50 or 100 years old, really. You know, or at least in the common parlance. It also kind of came in in the ‘50s. Retirement wasn't ever a possibility. So all of these things are new things. So, you know, to prepare yourself for a life that's going to go beyond just what you're doing now and just what you're attempting to achieve. Because you talk about an 18-year-old, they're at the beginning of their second act and all they see is, you know, the people that they admire, the role models in the second act. They see few role models in their third act. You know, the few people like, let's say, Jimmy Carter may be people that are sparking on one or two cylinders. But what about the people that are still healthy? Still can run a marathon? That have found ways to, you know, generate whole new fields of study. Wayne Lehrer (23:22): As I said, I think the most important thing that a young person can do, whether they're in the field of gerontology or not, is to really pay attention to what is required to live a healthy, well-balanced life, that's going to lead to a quality of living that's going to last you into your eighties or nineties or a hundred years old. Because a lot of the stuff that you lose, you can't get back. Now, a lot of it you can. I mean, I teach yoga to people that are incredibly inflexible, that start at 60 or 70. And if I watch a 50% turnaround in their flexibility, that means that the next 10 or 20 years of their life are going to be a lot better. Not just minimally better, but they're going to be a lot better. They're going to wake up in the morning and not immediately have to take some sort of medicine that's going to numb them out a little bit because they're in pain all day. And we know that a lot of people that age are doing that. Yeah, so the best medicine is doing it in advance. Orli Belman (24:21): And on the flip side, are there any lessons you think that people in their third act can draw from young people today? Any things that they're doing in their own lives that could be beneficial as we age? Wayne Lehrer (24:33): That's a really great question. And I know it's been really challenging for me and a lot of the people I know, one of the greatest qualities of young people, in fact, when we talk about old people, a lot of times what we say is they're stuck. They're rigid, they're not interested in new things. And if we talk about somebody that's young, curious to become curious again, that's an amazing quality that you can get from hanging around kids. And I think it's a lot of the thing that so many people in their third act love about being with their grandchildren. You know, you hang out with your grandchild for a couple hours and it's like, why? What? How come, you know? So I think curiosity is one of those things. Doing new things, you know, it's a chapter in my book. It's really important because what happens is you find a lot of older people and they say, oh, I've been there, I've done that. Wayne Lehrer (25:26): I don't like that anymore. Rather than look at maybe there's a new way to do that thing that you don't like, that could be incredibly joyful at this stage of your life. The other thing that young people I think can teach to older people is to really be willing to just live with your fears. Like I know at 30 I went back to school to become a filmmaker. My first job out of film school was directing the top newscaster in the world. That was my first job. I didn't think anything about it. And here I am, starting this whole new thing and I've got to learn all of these new things. It's no different than I did 40 years ago. And yet I want to admit, I feel terror often now, you know. Feel the fear and do it anyway is what you do when you're younger. Wayne Lehrer (26:12): Even if you're feeling the fear, most young people are in denial of it. But most of the time it's just like, okay, well, you know, what's the worst that can happen? When an old person says, what's the worst that can happen? They come up with a litany of worst-case scenarios, maybe only one or two of which actually were horrible and even happened. So I think that's another great thing, you know, to do new things, remain curious, investigate. Oh, finally be playful. You know, I have a group of guys that are between 30 and I'm the oldest and we go to the beach, and we meet at the beach in the morning. We meditate on the sand, and then we body surf. You want to turn into an 8-year-old boy? Go to the beach with a bunch of guys and at 6:30 in the morning, jump in the ocean and body surf. That just changes the quality and tenor of the rest of my day. A little bit of playfulness, a little bit of curiosity, a little bit of willingness to do things that I'm terrified of, all are reinvigorating me. And I believe that when you hear a lot of people say, this is the best time of their life, they're all probably have those qualities happening. Orli Belman (27:18): That's really wonderful advice. What would you say to people on this idea of trying new things? Who say, I can't do yoga, I'm not able to do that, I don't want, I'm not interested in meditation. How do you convince people to try something new? Wayne Lehrer (27:34): Well, I think it's really valuable to look around. You know, there's a saying, if you want to stop doing heroin, stop hanging out with heroin addicts. [laughs] You know, if you want to do these things, start hanging out with people that are living that new third act. So what happens to a lot of older people is they stay in the same circles. You know, I know that almost everybody that's in my life right now, of any age or people that inspire me, I don't really hang out with anybody that doesn't inspire me anymore. And so now obviously some people say, well, family, okay, so put family aside if they don't inspire you. But I think that it's essential to look around and see the people that you admire the most, that have aged the best, who you think have a real quality of life and do what they do. Wayne Lehrer (28:19): You know? And the other thing is, again, if you're doing new things and you're curious. You know, I hear all the time, I used to do yoga, but now my body doesn't like it. Well find a new yoga class. If you remember how it made you feel, then doing it in a new way, maybe a gentler class, maybe a, a hot yoga class that's in the dark, that's slow, where you hold the poses and no one's looking at you because you may be self-conscious. Maybe that's the answer to it. But not doing it is only going to make your life collapse. And I believe that one of the biggest problems with aging is people's worlds get smaller and smaller. Orli Belman (28:58): And just on an actual like, practical level, if you know someone in your life who says, I'm not going to try yoga. What's a way to convince them to give it a try? Wayne Lehrer (29:07): Like anything, tell them how it makes you feel. You know, share your enthusiasm, share your joy. Share the difference it's made for you. Whether it's meditation–I mean, so many people I know that are older, because I teach meditation and yoga, you know, they'll say to me, I say, well try this class or go there. And once I get a taste of it, there's a song by a friend of mine and he's got a line in it. He says, I've just had a taste of something fine. I think if you can get somebody to just try something, you know, so that may be part of your negotiating with them is like, just try it. If you don't like it, you never need to do it again. But what do you have to lose? Because the downside is, I joke in my yoga class all the time, I said, okay, so you're 40 years old and you can't do the splits. What if it takes you 40 years to be able to do the splits? That means at 80 years old, you're going to be doing the splits. You're going to be the hottest person in your senior housing place. People are going to be knocking on your door at 11 o'clock at night. Orli Belman (30:04): [laughs] Well, being curious and playful and active and flexible. That is all really wonderful advice. And is there anything you want to add that we haven't talked about? Wayne Lehrer (30:16): Yeah, I think one of the things that I didn't know when I started writing my book and what caused me to write it, what inspired it was that I got moderately depressed. Which is, you know, I got depressed, you know, and I didn't know what it was about. So I went to a psychotherapist who specialized in gerontology, and while I was working with him, he kept working on my depression. And after a couple months there, I realized that depression wasn't my problem. My problem was that I was stuck in this, what I call second act operating system of achieving and acquiring and accumulating and building and competing when in fact, that's not what I was doing anymore. So I was defining myself. I was in a losing proposition. And I think a lot of people when they get into their fifties, sixties, and seventies, keep defining themselves by their second act, body, minds, jobs. Wayne Lehrer (31:08): And so making that transition is one of the most challenging things. So historically we had the, you know, what's called an identity crisis. Which was between 20 and 21, you know, somewhere, you know, between your first and your second act. Tons of role models, easy transition. You went to college, you got a job, you know, decided on a profession, you got married. These are all natural things that, what do you do? What does someone do? Going from not working, from working every day, having kids at home, and all of a sudden all of that's gone? There are no role models for it. So it's a very challenging proposition. You need to find healthy communities, you need the help of, whether it's a therapist who specializes in this or somebody who coaches you through this transition process. I believe it's the biggest challenge that anyone's going to face as they enter into old age, which is learning to redefine themselves by a new operating system. Orli Belman (32:05): Well, thank you so much for being that role model. Our podcast is called Lessons in Lifespan Health, and you've certainly given us so many lessons to learn from today. So thank you so much for joining us. Wayne Lehrer (32:17): Oh, it was such a pleasure. Thank you, Orli. Orli Belman (32:19): That wraps up this Lesson in Lifespan Health. Thank you to Wayne Lehrer for his time and expertise, and to all of you for choosing to listen. Join us next time for another Lesson in Lifespan Health and please subscribe to our podcast at lifespanhealth.usc.edu. Lessons in Lifespan Health is supported by the Ney Center for Healthspan Science.

Dan Nation is a professor of gerontology and medicine at USC. His research focuses on vascular factors in the brain and how they affect memory decline and dementia in older adults. He joined us to talk about studying blood vessels in the brain to identify early signs of dementia and potential therapies to treat it. Transcript Speaker 1 (00:01): The variability in your blood pressure day to day, month to month, year to year, and sometimes even beat to beat–the variability in your blood pressure is predictive of dementia risk. So higher levels of blood pressure variability are bad, even if you have very well controlled blood pressure levels. And this is important because currently we only treat average blood pressure. There is no treatment for variability in blood pressure. So it's a new area that we should try to look into controlling to see if we can prevent dementia in people who have high variation, even if they're already treated for hypertension. Speaker 2 (00:45): From the USC Leonard Davis School of Gerontology, this is Lessons in Lifespan Health, a podcast about the science and scientists improving how we live and age. I'm Orli Belman, Chief Communications Officer. On today's episode: how Professor Dan Nation is studying blood vessels in the brain to identify early signs of dementia and potential therapies to treat it. Dan Nation is a professor of gerontology and medicine at USC. His research focuses on vascular factors in the brain and how they affect memory decline and dementia in older adults. Welcome to our podcast Dan, and thank you for being here today. Speaker 1 (01:26): Thanks for having me. Speaker 2 (01:28): I wanna start by asking you about blood vessels in our brain. Is there anything unique about the brain's vasculature system, and how did it become the focus of your research? Speaker 1 (01:39): Yeah, it's a great question. So there's actually several things that are unique about the brain vasculature. For one thing, just the number of blood vessels. So you might think about the larger vessels that you can see with the naked eye, but most of the vessels are microscopic. And we have so many blood vessels in the brain that there's actually one blood vessel for every neuron. So every brain cell basically has its own microscopic blood vessel. So it's billions and billions of blood vessels, and this is likely the case because the brain has an incredible need for blood flow to support its very high metabolic rate. And the brain cannot store energy unlike other tissues in the body, and so any energy that the neurons need, they have to get on the fly from blood. So there's a torrential amount of blood flow that's disproportionate to the size of the brain. Speaker 1 (02:34): In addition to that, blood is actually toxic to brain tissue. And so the neurons need a special environment to operate, and so that milieu has to be well controlled. So the blood contains proteins, cells, infectious agents, metals, ions–all of which, if it were to get into the actual brain compartment, would be very toxic and would cause degeneration of the brain cells, cell death. And so their brain has a special structure that divides the blood off from the brain. This doesn't exist in other parts of our body; it's called the blood brain barrier. So that has to have integrity in order for the brain to survive and function properly. In addition, because of that, the way waste products of regular cellular metabolism and so forth, any other toxins that are in the brain, the way that gets moved out of the brain is different than other parts of the body because the lymphatic system in the brain is really different because we have to have this blood-brain barrier. So for a number of different reasons, the vessels are special. A lot of it has to do with the blood-brain barrier because the separation of the blood from the brain means that all of the nutrients have to be pumped actively into the brain. And all of these, again, waste products have to be pumped actively out somehow. And so any dysfunction there could lead to the buildup of toxins in the brain, which would cause degeneration. Speaker 2 (04:11): So your PhD is in psychology, correct? Speaker 1 (04:14): Yeah, neuropsychology. Speaker 2 (04:15): Neuropsychology. So how did you get interested in the vascular system? Speaker 1 (04:19): Yeah, I actually have always studied the vascular system because I was in a neuroscience lab that was focused on relationship between behavior and cardiovascular disease and basically neurovascular function and in particular as a clinical neuropsychologist we're involved in treating patients with neurocognitive disorders of aging, like dementia of Alzheimer's disease. And so I became interested in how these neurovascular factors may contribute to those diseases and to cognitive decline from those experiences. Speaker 2 (04:54): This sounds like a very complex system. What happens to it as we age? Speaker 1 (04:58): So as we get older, most people will develop a number of different vascular changes or will be at risk for different age-related vascular diseases. The most common is hypertension or high blood pressure. As we get older, the odds of developing high blood pressure just go up and up, and ultimately if you live long enough, most people will develop hypertension at some point. The majority of people over the age 65 have high blood pressure. And so that has to do with changes in your overall vascular system that can lead to a hardening or stiffening of the arteries and development of specific changes in the way the blood vessels of the brain work, which can damage the blood-brain barrier, lead to leakage of blood into the brain, decreased blood flow to the brain. And also what we've found is that older adults, their micro blood vessels don't dilate as well, and so they need to be able to dilate in order to provide more blood flow as needed to support brain health. Speaker 2 (06:11): It sounds like you know a lot about what's happening and the inner workings of our brain. Have updated imaging technologies improved our understanding of the role of these small blood vessels, and what can you tell us about your research in this area? Speaker 1 (06:24): Yes, so brain MRI has been very useful because it's usually relatively non-invasive, and we can use MRI to actually study the functioning of these microscopic blood vessels that would be otherwise very difficult to study. And we can actually visualize some microscopic changes such as small bleeds in the brain because they have this blooming artifact on brain MR. So we can see things that are microscopic, and we can study how the blood vessels can dilate or constrict using brain MRI. And we can study whether anything is leaking from the blood into the brain using brain MRI. So there's a lot more that is happening in MRI science that we're constantly monitoring and trying to incorporate into our studies. So I think there will be further advances, and we'll be able to study brain blood vessels even better in the future. Speaker 2 (07:19): And when you look at brain blood vessels, are you looking , particularly, at these microscopic ones? Speaker 1 (07:24): Yeah, we study the blood flow through these microscopic vessels and also whether or not they're leaking the leakiness of these vessels. Speaker 2 (07:32): I listened to a talk you gave, and you mentioned something called a neurovascular unit. What role does that play in brain health or brain dysfunction? Speaker 1 (07:41): It's a relatively newer concept that sort of springs off of the fact that again, there's a blood vessel for every neuron in your brain. It becomes clear when you understand how dense the micro vasculature is in the brain, that really it can't be totally separated from the functioning of the neurons themselves. When an area of your brain becomes active and neurons increase their activity, they need more blood flow, more nutrients, more clearance of waste, more oxygenation. And so they actually send a signal to other cells that control how much blood flow is happening, how much blood flow is coming to the vessels. So the blood vessels and the neurons are connected and communicating with each other. And so it's become clear that there's really this micro organ that we call the neurovascular unit, which is comprised of the blood vessel cells themselves, the neurons and other support cells, astrocytes, pericytes. And so all these different cells work together as a unit to make sure that blood flow meets the neurons’ metabolic demand. Speaker 2 (08:50): And when this isn't working correctly, why is early detection of dysfunction in this area so important? Speaker 1 (08:56): Yeah, it's extremely important because if you think about it, when you have a problem with the blood vessel that could predate the actual injury to the brain, you can have dysfunctional blood vessels, but that doesn't mean you have any brain damage yet. You just have vascular disease. The blood vessels have a disease happening within them, but that can ultimately lead to death of the brain tissue. And in the brain, once tissue is dead, those neurons died. They're not replaced, and the brain can kind of rewire itself, but it can't really regrow that brain tissue. So the idea is if you cannot detect the blood vessel problem before the brain injury has happened, then you could intervene and prevent irreversible brain damage. Speaker 2 (09:47): That sounds important. How would somebody know? How do you test for blood vessel function? Speaker 1 (09:52): So, as I mentioned, we're using brain MRI technology. We're also working on blood tests. There's different markers people are interested in. It's still, you know, at the research phase, but we have the ability to quantify how well your blood vessels are responding to stimuli, how much blood flow you have into sensitive areas of your brain that are very important for memory and other mental functions and whether those vessels are leaking, which could lead to, again, irreversible brain damage. Speaker 2 (10:27): What can we do to improve our vascular health? Speaker 1 (10:30): So the number one thing is, well first of all to monitor your vascular health through going to see your physician so that you can catch cardiovascular risk factors early. If your blood pressure is elevated, if you have a problem with your cholesterol levels, if you're pre-diabetic or diabetic, it's extremely important that those cardiovascular risk factors are caught early and are well controlled and treated right away. If they are, they're not likely to lead to brain damage, but if they're left untreated, then you have a very high risk of this ultimately damaging your brain. The other thing is basic stuff that you would do for heart health is also good for brain health. So things like a good healthy diet, exercise. Physical activity doesn't have to be running marathons. Moderate levels of physical activity are helpful for the blood vessels in your brain. Speaker 2 (11:31): That's certainly a message we've heard on this podcast before: what's good for the heart is good for the brain. I think most people are familiar with the idea of high or low blood pressure, but you're looking at something called blood pressure variability. What is that, and what do we know about its connection to dementia risk? Speaker 1 (11:48): Yeah, so as I mentioned, many people over the age of 65 are going to have high blood pressure, and those rates just go up and up. But the research has shown that once you're over 65, if you have high blood pressure, develop high blood pressure, and as long as it's being treated, your actual blood pressure level doesn't really correlate with dementia risk very much. I mean, it needs to be treated; that's important. We know that. But beyond that, where you're at with your blood pressure as an older adult hasn't been very predictive of things like brain degeneration, dementia. But what we've observed is that, even if you are treated and even if you are treated pretty aggressively, have have very low blood pressure with treatment, the variability in your blood pressure day to day, month to month, year to year, and sometimes even beat to beat the variability in your blood pressure is predictive of dementia risk. So higher levels of blood pressure variability are bad, even if you have very well controlled blood pressure levels. And this is important because currently we only treat average blood pressure. There is no treatment for variability in blood pressure. So it's a new area that we should try to look into controlling to see if we can prevent dementia in people who have high variation, even if they're already treated for hypertension. Speaker 2 (13:18): And are the traditional treatments effective? Has your research revealed anything about blood pressure medications and whether they can affect variability? Speaker 1 (13:27): Yeah, we're just now starting to do this work. It's complicated because there's many different things that affect blood pressure variability, and we need to do a lot more research. But it's already known that medications that are longer lasting, drugs that have a longer half-life or have longer term effects, for example, those tend to be better at keeping variability low in addition to keeping your blood pressure levels low. And that makes sense, right? If the drug is wearing off, you know, after a short period of time or by the end of the day, then you would expect to have more variation between doses. And so we plan to do more research on the different types of blood pressure medicines, the classes, specific agents, and we'll call their pharmacokinetic properties, how long they last in your blood, the half-life and so forth. But also adherence to blood pressure medication if people skip a dose or they're taking it at the wrong time of day–that kind of thing can also affect blood pressure variability. Speaker 2 (14:28): And is this research that's still in the lab stage, or is this informing clinical practice yet? Speaker 1 (14:36): Well it's clinical research,  so we're studying human beings, older adults from the community who are taking blood pressure medications and that kind of thing. So it should, you know, our findings will be of value to clinicians, I think. And they're very interested in anything as it relates to blood pressure medicines because they're dispensing these drugs all the time in such a common condition. Speaker 2 (14:58): We have talked to Mara Mather about heart rate variability in this podcast, and I know that's a big area of research for her. Is there a connection between heart rate variability and blood pressure variability? Speaker 1 (15:11): Yeah, they're different things, but they are connected in the sense that your body tries to maintain steady blood pressure. It's not necessarily a good thing to have your blood pressure fluctuating all the time. And one of the ways that that happens, just homeostatically with normal functioning of your physiology, is changes in heart rate can help to modulate blood pressure. So they are related in terms of your cardiovascular system, but they're distinct. High heart rate variability is probably a good thing in relation to better health, whereas high blood pressure variability is a bad thing. Speaker 2 (15:48): This is a little bit of a subject change, but can damage blood vessels repair or regenerate themselves? And what might this mean for cognitive decline? Speaker 1 (15:58): Yeah, so anytime you receive any kind of injury, including a brain injury, the blood vessels and the tissue goes through a regeneration, healing restoration process. And in this case, usually it's the branching of additional vessels off of the existing vasculature. This is a process called angiogenesis, generating new branch points off of the blood vessel. So, if somebody has a stroke for example, you're gonna have a large piece of brain tissue that has been destroyed by not getting any blood flow. There's going to be a healing process that's gonna happen there, and there's gonna be some regrowth of branches of neurons as the brain kind of rewires itself and people healing from a stroke. And that has to be supported by branching off of blood vessels. So I said the neurons are very dependent on blood flow. So they work together during wound healing. And so yes, we certainly have an interest in this process since it's likely ongoing if you have some kind of microvascular damage happening, and we wanna understand more about whether it could be of benefit or it could go wrong and potentially cause harm and so forth. So we're studying this angiogenesis process in people with cognitive impairment. Speaker 2 (17:18): And can you tell me a little bit about how you're studying it? Speaker 1 (17:21): Yes. So we have lots of different projects happening. We are studying these cells that are in your blood circulation and come from different parts of your body, and they're very important in this angiogenesis process. They can actually form new blood vessels to replace damaged or dysfunctional ones. And so we can take blood from, again, older adults in the community who may or may not have different levels of vascular damage in their brains. And we can grow these cells in a dish and try to better understand whether they're functioning well, whether they're able to form blood vessels the way they're supposed to or if there's something wrong with that process. Speaker 2 (18:06): Is this what you're talking about when you say growing a brain in the lab? Speaker 1 (18:09): Yeah, so I've partnered with a bioengineering team that grows these micro brains, little brains in a dish. And what we can do now, and this is our new initiative we just started, is we can take blood from our participants and actually grow their brain vasculature in a dish. So these brain micro vessels that we're studying with brain MRI, we can actually grow them in the dish from these blood samples because we can grow these specialized cells that I'm referring to. They'll grow blood vessels in a dish, and we can see how they function. Are they forming blood vessels that are leaking? Are they forming blood vessels that are not branching properly or have other kinds of dysfunctional properties that don't support blood flow and so forth? And then we can tie that back to what's happening with that person's brain MRI. Do they have leaky blood vessels in their brains? Do they have proper blood flow on brain MRI or not? And so by doing this process, we can actually, the goal is to develop this sort of personalized medicine approach to try and better diagnose and treat brain blood vessel problems. Speaker 2 (19:19): So everybody's brain grows differently in a dish depending on what you're putting in? Speaker 1 (19:25): Yeah, this is what we're testing. So just let me give you a concrete example. If somebody has cognitive impairment and we do a brain MRI and we see that, sure enough, they have leaky blood vessels, might it be the case that this regeneration process isn't working in that person? So we could take their blood and grow a little mini brain that has their brain blood vessels in it and see whether they're leaking or not. If they are leaking, then it suggests that perhaps there's something wrong with this regeneration process, and we can actually try out different drugs in the dish and treat that person's micro brain with different potential therapies and see if any of them work. And then that might give us a clue as to how to fix the problem. Speaker 2 (20:07): Wow, that's really exciting. Is there anything you wanna add or any of your other research studies that you wanna give us an overview of?  Speaker 1 (20:14): Yeah, I think the only other thing I would wanna highlight, something that I'm really excited about that we've made a number of discoveries on and are continuing to, and we actually have some papers just now coming out, is this connection between memory decline and dementia and the functioning of these tiny blood vessels, these micro vessels. We've continued to find that the memory centers in the brain, which are the same areas that are affected by Alzheimer's disease and that degenerate in neurodegenerative disease that causes a really bad memory problem and dementia in older adults, the microvessels in those areas are dysfunctional in people who are at genetic risk for Alzheimer's. And in people who have memory problems, we found that they're leaking. We found that they don't dilate properly when we give them a stimulus that's supposed to dilate the blood vessels. And in some cases they have decreased blood flow. And so it's important because it demonstrates that there is this connection between the micro vessel function and neuro degeneration, which has, I think, eluded the research committee for a long time. We've known that there's a connection between vascular disease and neurodegeneration, but that's something I'm very interested in unpacking. Speaker 2 (21:33): Just to follow up on that, I know we hear a lot about the plaques and the tangles that are associated with Alzheimer's disease. Where does the vascular system come into play with this? Is there a connection? Speaker 1 (21:44): Yeah, so the way we normally think about Alzheimer's disease is that it has, as you mentioned, these two proteins that build up. You could form the plaques and the tangles, but also ever since Alois Alzheimer first described the disease, he noticed that there were problems with the blood vessels, a condition called cerebral amyloid angiopathy, where there's also a buildup of toxic proteins in the blood vessels. And it's been noticed again over the decades that a lot of cardiovascular risk factors are also risk factors for Alzheimer's, but no one was able to quite figure out how the blood vessel changes relate to Alzheimer's disease. And I think it's only just now that we're able to study these micro vessels with newer technology, that we're understanding that the micro vasculature is probably where this link is occurring. And what we’ve found is that there's a connection to the tangles, the tangles that are happening inside the neurons that lead to degeneration of those neurons. When you have microvascular dysfunction, you tend to see that kind of degeneration happening. Speaker 2 (22:52): Wow. This is a really interesting window into a whole new research direction that we haven't learned about before. So thank you very much for joining us today and explaining it all to us. Speaker 1 (23:01): Thank you. Speaker 2 (23:03): That wraps up this Lesson in Lifespan Health. Thanks to Professor Dan Nation for his time and expertise and to all of you for choosing to listen. Join us next time for another Lesson in Lifespan Health, and please subscribe to our podcast at lifespan health.usc.edu. Lessons in Lifespan Health is supported by the Nay Center for Healthspan Science.

Michelle Keller is an assistant professor of gerontology and the Leonard and Sophie Davis Early Career Chair in Minority Aging at the USC Leonard Davis School. She spoke to us about her research focused on improving patient-clinician communication, medication management, and the identification of dementia in minority older adults. Here are highlights from our conversation. On polypharmacy “When it comes to older adults and medications, it's important to understand that while medications can be incredibly beneficial for treating various conditions, they can also present really unique risks in this population. Older adults often take multiple medications at the same time. This is what we call polypharmacy.” “Older adults can be more sensitive to certain medications, they might experience side effects more intensely or even at lower doses than younger individuals. … This is particularly true for medications that affect our central nervous system, our brain, right? So, thinking about medications that are sedating or that have some sort of psychoactive effect. These medications, especially when they're combined together, can lead to things like confusion, dizziness and an increased risk of falls.” On her study of interventions to address polypharmacy “What we found in this study was that interventions to address polypharmacy can do a great job of reducing medications which are potentially harmful, identifying which medications people should be taking, improving the appropriateness of the medications people are taking, and reducing the total number of medications. So thinking about outcomes related to medications, what we have found is that it is really hard to change more downstream clinical outcomes, things like mortality, falls, hospitalizations, and emergency department visits. We did find that interventions that had multiple components; in other words, where a clinician is meeting face to face with a patient, reviewing their medications, reviewing all the chronic diseases that they have, along with their full patient history of what has happened to them in the past, those interventions tend to have a greater effect on mortality. So in other words, those types of interventions are reducing the risk of that someone actually dies.” “We also found that falls decrease when patients fully stop potentially harmful medications. These may be medications where somebody is feeling very dizzy or that make people feel very dizzy or drowsy, medications that may control somebody's blood sugar a little bit too much… So, their blood pressure's a little too low and they may actually fall as a result of these medications. But what we found was that stopping medications such as benzodiazepines, which are often taken for sleep or anxiety, can take months. These types of medications can have withdrawal effects. And so it's really, really important for somebody to work very closely with a healthcare provider to slowly taper these medications down to try to reduce those withdrawal effects.” “What we have found in working with other researchers and clinicians is that when patients team up with a healthcare provider, such as their primary care physician or clinical pharmacist who's embedded in the healthcare system, they really are able to stop taking some of these medications, and they feel a lot better. They feel much more energy, they're able to do the things that they really enjoy. They have a greater quality of life. But it's something that just takes time.” On the Empower Intervention for benzodiazepines “The typical recommendation for benzodiazepines is that they really should be taken short-term. These are medications that physicians typically recommend somebody take for a maximum of four weeks. What we have found in some of our research is that people are actually taking these for years, if not decades. And so stopping these medications can be quite challenging, and sometimes patients aren't fully convinced about why they should be stopping these medications. So, we took an intervention that started in Canada. It was developed by researchers in Quebec, and this is called the Empower Intervention. And what we did is we tailored it to a health system here in the US. The Empower Intervention is a really great brochure that contains some pretty striking facts about benzodiazepines.” “To give you some examples of benzodiazepine, these are like your Xanax, your Ativan, your Klonopin; these are the medications that we're talking about here. These brochures highlighted some really interesting facts, such as the fact that they can be harmful or linked to hip fractures and car accidents, and they can make people feel very tired and weak. What we did for this intervention is we sent these brochures to about 300 people along with a letter from their primary care physician, emphasizing that these medications can be harmful if taken for too long and especially among older adults. So what we did for this study is we compared patients who had received these brochures to patients who did not receive them. So they're going on usual care. Their physicians may have mentioned something to them, this was our control group, right? We didn't send anything to this particular group.” “We reviewed the medical records for both groups, and we looked at what kinds of medications they had been prescribed. And what we found is that patients who received the brochures were really activated. You know, when they received this messaging they would send messages in the patient portal to their physicians saying, ‘I didn't know that there were these risks of these medications. I would really like to come in and talk to you about them.’ They made appointments to start tapering down these medications. What we found was for every 10 brochures that we sent, one person completely stopped taking these medications, which is a really good return on investment. This is a simple intervention. It has now been done in some other health systems in the US, particularly the Veterans Affairs health system.” On challenges in de-prescribing “I think some of the challenges that physicians face in de-prescribing is that de-prescribing takes a lot of time. As we all know, our primary care visits are very short; physicians, particularly in the primary care setting, are really rushed through their visits. And so I think having some of these conversations can just be something that's challenging. I also think they're quite complex conversations to have. They may not have received the training, for example, on how to taper a medication in a safe way so that a patient does not feel withdrawal effects. And I do think that there is something about getting physician buy-in … they are concerned [that] if they bring it up, the patient may be angry with them; they may be upset. And so I think really showing physicians ways in which this can be brought up that are really framed around ‘how do we center the patient's health and quality of life’ – I think those are still questions that we as researchers are working on.” On the role of caregivers “It's really important for caregivers to be aware of the medications their loved ones are taking for many reasons. I think they can be amazing advocates in helping bring up potential side effects during doctor's visits. So, for example, if a caregiver is noticing that someone is feeling drowsy or doesn't have that much energy or is feeling dizzy, any sort of cognitive impairments such as those that may be seen in dementia, [they] may actually be a result of medication side effects. So, I think really becoming an advocate for somebody when seeing the doctor is one really important thing that caregivers can do.”  “Another area where caregivers can play a really important role is among people with dementia. People with dementia can have really some challenges in managing their medications. They may miss doses, they may take several medications twice, so they may have an overdose, or they may take the wrong medication altogether. So, caregivers can play really pivotal roles in helping somebody manage medication changes. There have been some early interventions looking at how to engage caregivers and persons with dementia. And some of the challenges that those researchers have seen is that there [is] often more than one person actually caring for somebody with dementia. And so, engaging that whole group of people who may be working with that person has been a real challenge.” On challenges facing patients with language barriers  “There is research showing that patients with language barriers have a greater risk of being hospitalized or re-hospitalized because of some of the communication challenges that come with medication management. So, you can imagine that, for example, older adults and their caregivers with language barriers may have a difficult time understanding medication instructions, which can lead to improper use. So when and how to take medications, recognizing potential side effects, understanding the purpose of each medication. And on top of that, you can layer on things, like if somebody doesn't have a great understanding of the condition. We call that disease literacy, or they may have health literacy issues.” “Right now, a mentee and I are working on this review of interventions that have been done specifically for patients with language barriers focused on improving medication management. And what we found was that interventions that really engaged people from communities with language barriers have been some of the most effective ways to really help people learn about which medications are working really well for them, how to improve medication adherence and other important outcomes. So, for example, an intervention that we found was researchers engaged folks in the community, co-created videos about medications in the community and why it was important to take them. And then when they actually distributed these interventions, they made sure that both in terms of the videos and some of the other educational materials that were handed out to folks that these really were very tailored both language-wise, literacy-wise, and culturally tailored to the communities that they were serving.” On new dementia medications and disparities in the diagnosis of dementia  “We are learning that older Black and Latino adults tend to get diagnosed with dementia once the disease has progressed more. And what that means is that they may not have received some of the kind of services that may help them or their families. So, for example, they may not have received enough support to be able to plan for the rest of their lives, or their families may not necessarily have received caregiving support early on in disease progress.” “I think in regard to these particular dementia medications, for example, if older adults are diagnosed with dementia at a place where they're no longer eligible to receive these medications, I think that'll be a really pretty serious health equity issue. So, I am really interested in how we make sure that people are getting diagnosed in time to make them eligible for really potentially beneficial treatments that may help them down the road.” On effective strategies for de-prescribing  “The most effective strategies that we see de-prescribing these medications is offering something else. So, for example, some of the most evidence for insomnia really exists around the use of using cognitive behavioral therapy. There's also been well-done systematic reviews that have found evidence that music or acupuncture may help people with insomnia. … I think one thing that's very important to think about when we de-prescribe medications is what else can we offer people? We're not just leaving people in the lurch and saying, ‘We're taking this away and we're leaving you with nothing.’ We're actually able to offer them some non-pharmacological options as well.” Transcript Speaker 1 (00:02): One thing that's very important to think about when we de-prescribe medications is: what else can we offer people? We're not just leaving people in the lurch and saying, we're taking this away and we're leaving you with nothing. We're actually able to offer them some non-pharmacological options as well Speaker 2 (00:17): From the USC Leonard Davis School of Gerontology, this is Lessons in Lifespan Health, a podcast about the science and scientists improving how we live and age. I'm Orli Belman, Chief Communications Officer. On today's episode: how Professor Michelle Keller is working with older adults, caregivers and clinicians to manage the use and potential overuse of high risk medications. Michelle Keller is an Assistant Professor of Gerontology and the Leonard and Sophie Davis Early Career Chair in Minority Aging at the USC Leonard Davis School. Her research is focused on improving patient-clinician communication, medication management, and the identification of dementia in minority older adults. Hi, Michelle. Welcome and thank you for joining us today. Speaker 1 (01:06): Thank you so much for having me. Speaker 2 (01:08): I wanna start by asking you to talk about older adults and medications. We can all understand why medications are beneficial, but when it comes to older adults, what are some of the ways they can be problematic? Speaker 1 (01:19): Absolutely. So when it comes to older adults and medications, it's important to understand that while medications can be incredibly beneficial for treating various conditions, they can also present really unique risks in this population. So older adults often take multiple medications at the same time. This is what we call polypharmacy. Polypharmacy can increase the risk of drug interactions, right? So I like to think of the example of a suitcase, right? So imagine that you are packing up, getting ready to go to a trip. You start putting one thing into the suitcase, gets a little heavy, but you can manage it, right? You're suddenly adding more and more things and the suitcase is getting heavier and heavier to the point where you actually throw out your back at the airport, right? This is really what I think of when our bodies are kind of processing multiple medications at once with the additional challenge that some of these drugs may actually interact with one another. Speaker 1 (02:15): This is why it's so important for patients to talk to their doctors about the medications they're taking and the potential risks of each medication as people get older. I think one thing that people don't often think about is that when clinical trials are being done, often many clinical trials have excluded older adults. So we don't always have a great sense of how these medications work in older adult populations. And on top of that, they may exclude people with chronic conditions who are already taking a variety of other medications. And so as a result, what is happening now is that we have many people who are taking these medications, and it hasn't been well tested in these populations. It hasn't really been, you know, we don't have a clear sense of what is happening when all of these medications are being taken together. So polypharmacy can really increase the risk of drug interactions. Speaker 1 (03:09): As I was saying, when one medication affects another, and this can lead to a variety of adverse effects. So for example, if someone is taking multiple medications that make you feel drowsy or sleepy when you stack them on top of each other–thinking again about that suitcase, that can lead someone to have an increased risk of falls, potentially a fracture resulting from those falls, car accidents if they're feeling very drowsy or dizzy and other medications can increase our risk of internal bleeding. Another thing that's really important to think about for older adults is that as we get older, our bodies undergo various changes that can alter how our medications are absorbed, distributed, and actually excreted from the body. So for example, kidney and liver function can really decline with age. And so that can actually affect how well we process the drugs through our body. Speaker 1 (04:05): What that means is that drugs may stay in our bodies for longer periods of time leading to more side effects or adverse effects. The last thing I really wanted to bring up is this idea of how things change as we get older. So we maybe have been taking a medication for many years, but as we get older because of the changes that are happening within our body, some medications, which were fine for us when we were younger, are now gonna lead to more serious adverse effects now that we're older. So older adults can be more sensitive to certain medications, so they might experience side effects more intensely or even at lower doses than younger individuals. They might feel the effects. So this is particularly true for medications that affect our central nervous system, our brain, right? So thinking about medications that are sedating or that have some sort of psychoactive effect. Speaker 1 (05:04): These medications, especially when they're combined together, can lead to things like confusion, dizziness, and an increased risk of falls. One medication which people often take to help them sleep is Benadryl or Tylenol PM. This medication is actually a drug that's really recommended to avoid in older adults because it can be very sedating, making people feel very drowsy throughout the day. And it actually also has the effects on the brain and has been associated with a higher increased risk of dementia. So these are medications that again, we don't think of as generally harmful, but again, in an older person might really be an issue. Speaker 2 (05:46): That's a really helpful example 'cause that's just an over the counter medication that anyone can get, even without a doctor. You recently published two papers looking at interventions for addressing polypharmacy. The first one was a review of several studies. What did you learn in that review about the effectiveness or not of programs that are designed to reduce harmful polypharmacy? Speaker 1 (06:08): So we reviewed several systematic reviews. These are collections, as you mentioned, of numerous studies to understand how well interventions to address polypharmacy are working. Many of these interventions include a process called de-prescribing, which is the process of systematically reducing or stopping medications that may no longer be beneficial or might be causing harm, particularly in older adults. The goal of deprescribing is to optimize an individual's medication regimen to improve their overall health and quality of life. What we found in this study was that interventions to address polypharmacy can do a great job of reducing medications which are potentially harmful, identifying which medications people should be taking, improving the appropriateness of the medications people are taking, and reducing the total number of medications. So thinking about outcomes related to medications, what we have found is that it is really hard to change more downstream clinical outcomes. Speaker 1 (07:11): Things like mortality falls, hospitalizations, and emergency department visits. We did find that interventions that had multiple components, in other words where a clinician is meeting face-to-face with a patient, reviewing their medications, reviewing all the chronic diseases that they have along with their full patient history of what has happened to them in the past, those interventions tend to have a greater effect on mortality. So in other words, those types of interventions are reducing the risk that someone actually dies. We also found that falls decrease when patients fully stop potentially harmful medications. So these may be medications that make people feel very dizzy or drowsy medications that may control somebody's blood sugar a little bit too much and so they're actually feeling very low blood sugar or medications where their blood pressure is overly controlled. So their blood pressure's a little too low, and they may actually fall as a result of these medications. Speaker 1 (08:12): But what we found was that stopping medications such as benzodiazepines, which are often taken for sleep or anxiety, can take months. These types of medications can have withdrawal effects. And so it's really, really important for somebody to work very closely with a healthcare provider to slowly taper these medications down, to try to reduce those withdrawal effects. And because it takes so long to fully stop these medications, it's hard for studies to really find an effect unless they're following that person for a long period of time, which studies often don't. And so that's one of the challenges that we've seen in the research is that studies haven't followed people for enough time. Or at the time that they're measuring some of these clinical outcomes, not enough time has gone by to really see the full effects. So what we have found in working with other researchers and clinicians is that when patients team up with a healthcare provider such as their primary care physician or clinical pharmacist who's embedded in the healthcare system, they really are able to stop taking some of these medications and they feel a lot better. They feel much more energy, they're able to do the things that they really enjoy. They have a greater quality of life, but it's something that just takes time. Speaker 2 (09:28): And I imagine it's something you have to balance when someone really might need a medication to treat something and then managing the side effects. That's really interesting. I know the second study looked at a particular intervention and this was the use of educational materials for benzodiazepines. What led you to explore this area and what did you find? Speaker 1 (09:49): Great question. So benzodiazepines are, as I mentioned earlier, medications that are often used for sleep or anxiety. The typical recommendation for benzodiazepines is that they really should be taken short term. These are medications that, you know, physicians typically recommend somebody take for a maximum of four weeks. What we have found in some of our research is that people are actually taking these for years, if not decades. And so stopping these medications can be quite challenging and sometimes patients aren't fully convinced about why they should be stopping these medications. So we took an intervention that started in Canada. It was developed by researchers in Canada, in Quebec, and this is called the Empower Intervention. And what we did is we tailored it to a health system here in the US. The Empower Intervention is a really great brochure that contains some pretty striking facts about benzodiazepines. Speaker 1 (10:45): To give you some examples of benzodiazepine, these are like your Xanax, your Ativan, your Klonopin. These are the medications that we're talking about here. These brochures highlighted some really interesting facts such as the fact that they can be harmful or linked to hip fractures and car accidents and they can make people feel very tired and weak. What we did for this intervention is we sent these brochures to about 300 people along with a letter from their primary care physician, emphasizing that these medications can be harmful if taken for too long and especially among older adults. So what we did for this study is we compared patients who had received these brochures to patients who did not receive them. So kind of they're going on their usual care, their physicians may have mentioned something to them. This was our control group, right? We didn't send anything to this particular group. Speaker 1 (11:40): We reviewed the medical records for both groups and we looked at what kinds of medications they had been prescribed. And what we found is that patients who received the brochures were really activated. You know, when they received this messaging, they would send messages in the patient portal to their physicians saying, I didn't know that there were these risks of these medications. I would really like to come in and talk to you about them. They made appointments to start tapering down these medications. What we found was for every 10 brochures that we sent, one person completely stopped taking these medications, which is a really good return on investment. This is a simple intervention. It has now been done in some other health systems in the US, particularly the Veterans Affairs health system. And you know, groups have found similar effects. We also found that the probability that someone in the intervention group completely stopped their medications was about 10% greater compared to the group that did not get the brochure. Speaker 1 (12:41): So again, you know, for a cheap simple intervention, we were pretty excited about these results. What's been really interesting is I just came back from two conferences, the US De-Prescribing Research Network and the Society for General Internal Medicine Annual Meeting. And we find that other researchers are also finding that engaging patients in reducing these potentially harmful medications is actually one of the most effective forms of deprescribing. There have been plenty of studies where researchers have actually engaged physicians and those have not been as successful. So what I'm really excited about in terms of thinking about future interventions is, how do we really engage patients in learning about what are the best options for them to manage their health? Speaker 2 (13:28): So you just said that physicians, it's been a little harder to see change in their prescribing behaviors. What do we know about ways they can introduce the idea of reducing or stopping a medication? Speaker 1 (13:39): Yeah, I think it's a great question. I think communicating when, how and why a medication should be reduced or stopped can be really challenging. What researchers have found is that when physicians focus on improving a patient's quality of life, that is what is most effective. So for example, thinking about stopping or reducing certain medications can give somebody more energy, help them move around better, they're not feeling as unsteady on their feet or dizzy. They can think more clearly because they're no longer feeling feelings of brain fog or sleepiness or drowsiness. I think these can be some really effective messages. I think some of the challenges that physicians face in de-prescribing is that de-prescribing takes a lot of time. As we all know, our primary care visits are very short. Physicians, particularly in the primary care setting, are really rushed through their visits. And so I think having some of these conversations can just be something that's challenging. Speaker 1 (14:41): I also think they're quite complex conversations to have. They may not have received the training, for example, on how to taper a medication in a safe way so that a patient does not feel withdrawal effects. And I do think that there is something about getting physician buy-in, in terms of, they are concerned about, you know, if they bring it up, the patient may be angry with them, they may be upset. And so I think really showing physicians ways in which this can be brought up that's really framed around, how do we center the patient's health and quality of life? I think those are are still questions that we as researchers are working on. Speaker 2 (15:17): We've talked about physicians and obviously patients themselves. How about caregivers? What role can they play in helping address some of these issues? And are there interventions that especially aim to include them? Speaker 1 (15:28): Yeah, great question. I think it's really important for caregivers to be aware of the medications their loved ones are taking. For many reasons. I think they can be amazing advocates in helping bring up potential side effects during doctor's visits. So for example, if a caregiver is noticing that someone is feeling drowsy or doesn't have that much energy or is feeling dizzy, any sort of cognitive impairments, right? So, such as those that may be seen in dementia, may actually be a result of medication side effects. So I think really becoming an advocate for somebody when seeing the doctor is one really important thing that caregivers can do. Another area where caregivers can play a really important role is among people with dementia. People with dementia can have some challenges in managing their medications. They may miss doses, they may take several medications twice, so they may have an overdose or they may take the wrong medication altogether. So caregivers can play really pivotal roles in helping somebody manage medication changes. There have been some early interventions looking at how to engage caregivers and persons with dementia. And some of the challenges that those researchers have seen is that there are often more than one person actually caring for somebody with dementia. And so engaging that whole group of people who may be working with that person has been a real challenge. Speaker 2 (16:54): Are there particular challenges faciing under-resourced communities or populations with language barriers? I imagine some of this communication is even harder in these cases. What do you think needs to be done in these areas? Speaker 1 (17:09): Absolutely. There is research showing that patients with language barriers have a greater risk of being hospitalized or rehospitalized because of some of the communication challenges that come with medication management. So you can imagine that for example, you know, older adults and their caregivers with language barriers may have a difficult time understanding medication instructions, which can lead to improper use. So when and how to take medications, recognizing potential side effects, understanding the purpose of each medication. And on top of that, you can layer on things like, you know, if somebody doesn't have a great understanding of the condition, right? So we call that disease literacy. Or they may have health literacy issues, or on top of that, we may even have literacy concerns where the person does not know how to read or has a limited ability to read. So layering on all these challenges can really make it difficult to both manage your medications and communicate with physicians about their concerns or side effects regarding medications. Speaker 1 (18:14): Right now, mentee and I are working on this review of interventions that have been done specifically for patients with language barriers focused on improving medication management. And what we found was that interventions that really engaged people from communities with language barriers have been some of the most effective ways to really help people learn about which medications are working really well for them, how to improve medication adherence and other important outcomes. So for example, an intervention that we found was researchers engaged folks in the community. They co-created videos about medications in the community and why it was important to take them. And then when they actually distributed these interventions, they made sure that both in terms of the videos and some of the other educational materials that were handed out to folks, that these really were very tailored both language wise, literacy wise, and culturally tailored to the communities that they were serving. Speaker 2 (19:16): Another area I wanna touch on is your work improving doctor patient communication. And I'm curious if your background as a newspaper reporter has informed your research in this area, and what are some of the ways that patients lose out when communication is not clear? Speaker 1 (19:32): So I think a lot about how we can help clinicians communicate complex information about medications and other treatments in simple, accessible ways. Which is really something that I aimed to do as a reporter, right? When I worked as a reporter, oftentimes I would take studies from medical journals and I would break them down in a way that was really easy and accessible for the public to read. And so that is really something that I'm very interested in. How do we help clinicians do the same thing? Or if we're designing interventions for patients, how do we do something similar? How do we make the risks and benefits of medications very clear to people so that they're able to make the best decisions about those for their health? So one area that I'm really interested in is these new medications for dementia that have come out, which are the anti amyloid medications. These medications have some pretty potentially serious side effects such as brain bleeding and swelling. And I'm working on a research proposal thinking about, how do we best present these medications to patients in a way that they feel like they're able to make the best decisions for themselves and their loved ones? I think it'd be really critical, particularly in terms of health equity for people to have a very good sense of how these medications can potentially help but also understand the serious risks associated with the new dementia medications. Speaker 2 (21:02): And speaking of dementia, I think you've also looked at the diagnosis of dementia and whether or not there's differences in minority populations. Is that something you can tell us a little bit about? Speaker 1 (21:14): Absolutely. So that is an area of research that I'm actually just starting to get into because what we are learning is that older black and Latino adults tend to get diagnosed with dementia once the disease has progressed more. And what that means is that they may not have received some of the services that may help them or their families. So for example, they may not have received enough support to be able to plan for the rest of their lives, or their families may not necessarily have received caregiving support early on in disease progress. I think in regards to these particular dementia medications, for example, if older adults are diagnosed with dementia at a place where they're no longer eligible to receive these medications, I think that'll be a really pretty serious health equity issue. So I am really interested in, how do we make sure that people are getting diagnosed in time to make them eligible for really potentially beneficial treatments that may help them down the road? So I'm thinking about how do we train physicians who are working in under-resourced settings, which may serve large proportions of black and Latino older adults, how to diagnose dementia in a primary care setting, and working with some colleagues in the Los Angeles Department of Health Services on how we can think about making physicians feel more confident, their diagnosis of dementia among older adults. Speaker 2 (22:40): And I wanna go back to sleep and anxiety because I know that's something that affects so many people at all ages. If these interventions are successful and people are able to stop taking some of these medications, are there strategies or interventions that we know might work for helping them with the initial conditions they were struggling with to begin with? Speaker 1 (23:01): Yeah, absolutely. I think that's a really good question because sleep and anxiety are things that can really affect somebody's quality of life and functioning, right? The most effective strategies that we see de-prescribing these medications is offering something else. So for example, some of the most evidence for insomnia really exists around using cognitive behavioral therapy. There's also been really well done systematic reviews that have found evidence that music or acupuncture may help people with insomnia. So I think one thing that's very important to think about when we de-prescribe medications is what else can we offer people? We're not just leaving people in the lurch and saying, we're taking this away and we're leaving you with nothing. We're actually able to offer them some non-pharmacological options as well. Speaker 2 (23:48): That's a really helpful note to end on. Thank you for joining us, and I know that people are really gonna benefit from learning about all you've been working on and all your work that's gonna continue in the future. Speaker 1 (23:59): Thank you so much for having me today. It's been a real pleasure. Speaker 2 (24:02): That wraps up this lesson in Lifespan Health. Thanks to Professor Michelle Keller for her time and expertise and to all of you for choosing to listen. Join us next time for another Lesson in Lifespan Health, and please subscribe to our podcast@lifespanhealth.usc.edu. Lessons in Lifespan Health is supported by the Ney Center for Healthspan Science.

Francesca Falzarano is an assistant professor of gerontology at the USC Leonard Davis School. Her research is inspired by her personal experience as a caregiver to her parents and explores how to improve the mental health and well-being of family caregivers, including through the use of technology. On young caregivers “I think right now it's estimated that five and a half million individuals are under the age of 18 are caring for a parent or some family member with chronic illness, mental health issues, dementia-related illnesses, and other age-related impairments. So, this is something that's becoming more and more pervasive, and the needs of adolescents are going to vary extremely, and they're going to be extremely different compared to what my needs were as a caregiver versus what a spouse's needs are going to be.” “I talked to a ton of first-generation Gen Z caregivers who have really been at the forefront of their loved one's healthcare interactions since they were young teens, just translating and digesting information that a doctor is saying and communicating it to the rest of the family. So there's a lot of burden that we're placing on these individuals without simultaneously understanding what their unique needs are.” On dementia caregiving “If you think about dementia itself, it's got a very unpredictable disease course where most of that time is spent in dependency, and you have a variable lifespan anywhere from four to 20 years.  So what we are learning is that there are so many things beyond just the caregiver's direct care tasks beyond what they're just doing in the care environment, like bathing or dressing or feeding that go into the caregiving role that individuals are not getting support for, whether that's managing finances, making end of life decisions, navigating the labyrinth that is Medicaid and Medicare, talking to healthcare professionals. It's essentially all of these roles and responsibilities that unfold over time is what we would dedicate one expert to take care of in our, in our school or department. And we're expecting caregivers to have learn on the fly and typically they're getting support and help in crisis.” “We learned that caregivers are expecting or anticipating the information, about what to expect about what the disease will look like and about how their responsibilities are going to unfold from the primary care physicians. But as our, my caregiver participants have said, it's a situation of diagnose and adios. So there's very little follow up, there's very little ongoing support that's provided.” On long-distance caregivers “Long-distance caregivers... their biggest challenges that they face is that intersection with the formal care system, being able to get adequate communication and information about their loved one's care.  And really just feeling involved and being able to adequately manage all of the responsibilities involved in keeping someone safe, but also in terms of their doctor's appointments and their medications and the people that are physically providing care.” “I think we need to do a better job at educating the clinicians and the care providers that just because an individual is not in person does not mean they're not a caregiver and they're not really involved in all of the work that goes into that.” “The prevalence of dementia is just going to continue to increase and the likelihood that we'll have to provide care for somebody we love is very high. The likelihood that we'll have to do it more than once is also very high. And so really kind of my goal is to normalize caregiving the way we normalize parenting the way we provide all the resources and follow up for somebody who's going on maternity leave and about to give birth to a child. And that we need to start looking and viewing caregiving in a similar way and normalizing it and reducing the stigma as much as possible so we're not embarrassed or ashamed of our circumstances, but we can use it to empower ourselves to get the support we need.” On technology “Technology has really opened a lot of doors, particularly in research and behavioral interventions to kind of alleviate stress and poor psychosocial outcomes. We've finally kind of looked at technology as a way to broaden opportunities for these individuals who might not be able to leave the house otherwise.” “I think technology can come in because a lot of the issues with the healthcare system and connecting caregivers to formal supports is we don't have enough human bodies in a room to take the time to assess each caregiver to give them the personalized support. We don't have the staffing, the time, just the capacity and technology can really help us improve and personalize that support beyond human capability.  And so if I go on Netflix and Netflix can recommend what I want to watch next, Amazon can tell me what I want to buy next. I can go online and use AI to pick out an insurance plan, to pick out what my skincare routine is or my birth control. Why are we not using technology to give more tailored, targeted and precise support to caregivers?” “I think technology can help bring their desire for personalized caregiving navigation to fruition. And I also think it could bring the possibility of a one-stop shop where caregivers can get educated, find resources, connect with other caregivers, and not struggle to find the information and help they need. I think that becomes a lot more feasible when we bring in technology.” “I’m working on two tech-focused research projects right now. One of them is kind of, alluding to what I was just talking about, is the development of a self-assessment and referral platform where caregivers can get a sense of what areas they need the most support in. And using AI and machine learning to generate targeted referrals to kind of make the pipeline between identification, assessment and referral more seamless.”  “I think this is another great thing that we can leverage technology for, is how do we engage people with dementia as well? And so a second research project I'm conducting with my colleagues at Weill Cornell, is a reminiscence therapy web-based platform where, and reminiscence therapy is pretty widely used in clinical settings. There's not as much empirical research done on reminiscence therapy, but we know that it helps the person with dementia recall memories. We know that music and all of these different interactive, prompts and activities done within reminiscence therapy could be really therapeutic for care recipients. And so, and typically in institutional settings they're kind of very general and it's facilitated by a clinician or a therapist in a nursing home. And we are creating right now a reminiscence therapy web app where caregivers are facilitating these activities and documenting meaningful memories with the person with dementia. It's something that they, they can do together. It's something that they can engage in that can promote relationship quality, help with feelings of grief that are so pervasive in both caregivers and patients.”

Lauren Brown is an assistant professor at the USC Leonard Davis School. Her research uses publicly available data to uncover the unique difficulties Black Americans face in maintaining physical and psychological well-being as they age. Her lab both challenges the methods used to study older Black adults and strives to increase diversity in data science research with the goal of increasing the visibility of Black and Brown people via data and storytelling. Quotes from the episode On the role of racism in biomedical and statistical sciences and disease prediction If you think about the history of statistics and where it starts from, the earliest statisticians were actually also eugenicists. And a lot of it stemmed from the fact that Black people at the time that the census had started were property. And it was a way to count and keep up with property until we get to a point in the early 1900s when we start recording actual race in the census and colored being one of the options that you could check. And that being a way we kept track of Black populations, unfree, Black populations in particular, but also freed as well. And that transition of having Black people in the census started what was eventually used as studies that were confirming or trying to confirm biological and genetic inferiority among Black people.   So once Black people were started to be included in the census and started included in medical research, clinical research, that research was usually often to compare Black people to white people with the innate goal to say Black people had more muscle mass biologically and genetically or smaller brain circumferences and justify it would a way to justify slavery by suggesting that the biological and genetic inferiority was a part of how Black people became slaves and would justify their continuation as slaves. So you fast forward to today that legacy of, of genetic and biological inferiority in medical, and statistical analyses has now manifested in things like race norming, where we're actually saying like, there are adjustments we use for Black patients in the clinic to justify whether they do or do not qualify for care strictly based on race. And a lot of it is based on false statistics that eugenicists had originally been pushing in the early 1900s. How injustice through data and storytelling affects the health and wellbeing of Black Americans When you think about like an individual, how this may affect one individual Black person, like for example, if we think about George Floyd's killing in 2020, his death originally was considered in the autopsy report performed by the medical examiners due to prior health conditions. They originally blamed his underlying health conditions and drug use as the cause of death. It was only after the family got an independent autopsy that they were able to show that the death was a homicide that then implicated Derek Chauvin and the Minneapolis Police Department, as responsible for the death and the knee on the neck. So this idea of blaming Black biology, is something that persists, I think, in larger society and that the biological inferiority is the cause and the precipice for Black death, and that it's not at all the function of society when actually now we know, you know, based on a lot of great research that the social environment is much more responsible for the fact that Black and Brown people often live shorter lives than white people or any other race and ethnic group in the US. We often live with more disease and disability at the end of life. And a lot of that we know is now it’s social conditions, it's discrimination, it's racism, those are at the forefront. But the research doesn't always follow that line of thinking because of the history and the legacy that still exists that we're still combating. And this new level of science is trying to push up against this idea. On diversity in population studies  It’s been really obvious that a lot of the measurement and the things that people use to measure the wellbeing of Black life is really centered in white populations. And it's not innate or particular to the lived experiences of Black and Brown people. And so I think oftentimes we miss the real story that's happening up underneath a lot of Black health and aging specifically because those studies weren't designed just for Black people. They were designed for all aging populations and to monitor the aging of populations over time.   The ethical considerations if you're leaving a whole group of people out or if you're not intentional about measuring their aging, is that you're not able to predict their clinical progression or able to assist their aging process in a way that's meaningful for them. We're doing everything much better for white populations than we are for minoritized populations. And so that the injustice is embedded in the structure of how these studies often come about. And the intention around what I want to do in this work is to help magnify the voices of Black people in these studies so that they more accurately represent the aging experience so that we can get better at predicting disease, preventing disease, and ensuring better aging process. On the Linked Fate Data Collective  Linked Fate Data collective is a group of activists, of scholars, of students, of people who are interested in expanding their data science tools in order to promote the accurate depiction of the aging and the living process or the lived experiences of Black and Brown people. The idea being that, you know, most of the data science spaces are very white and male and often then reflect the values of people who are white and male. And I am very passionate about creating a space that looks and feels different for the people that I would love to bring into the data science realm. And you know, how we do that, I think, you know, there's a lot of argument about the pipeline issues of how we get people into data science or how we get people the skills to be able to do this on how we get Black and Brown people interested in data work.  The inception of the name Linked Fate comes from a term that was originally used in African American studies. And the term was referring to block voting in Black populations where African Americans vote primarily Democratic with this idea that, you know, their fate is connected to the fate of the larger group. And so, there’s an interest in finding a collective voice in order to impact change and power. And that's really what I named this space after is that we have collective voice in data and it's the power of an individual magnified by many that gets people something that's powerful with the data work. And so that's really what this Linked Fate Data Collective is trying to do, is bring underrepresented groups and people and their ideas into a space that will honor the data science that we want to see in the world. And that is not perpetuating scientific racism, that's not perpetuating a lot of the genetic determinism and the things that some of the current science and medical and clinical spaces are perpetuating. On the Black mental health paradox One of the things I like to do in my work is move away from these disadvantaged narratives that really plague the aging story of Black Americans. Most people are very interested in the weathering and accelerated aging of Black Americans, when really there's a lot of trends that suggest that's not the only way that Black Americans are aging. That it's not just weathering stress aging faster, that there are also a lot of other processes that don't act so linearly. One of them is that mental health paradox, which is this data artifact that has been found in like five nationally representative samples now that despite having higher stress burdens, despite facing discrimination, despite having lower socioeconomic status, so lower education, income and wealth and despite having worse physical health, Black Americans have lower rates of depression relative to white Americans.  So this could exist for many of reasons. It could really be a data artifact and it just could be that we are not measuring either mental health and depression in Black people in the way that it manifests so that we can measure it. Or it may be that we're not measuring the stress that's most impactful for Black Americans. And so we're not really capturing the stress burden. And so, we don't understand how that translates to mental health. And a lot of the work that I'm doing on the paradox is in that exact realm, which is that the stress experience is not being fully captured for Black Americans. And it’s not acknowledging the coping response that Black Americans can use in order to fight the adversity that they're facing. So, my idea here is to restore agency to Black people. That you're not just the sum of your stress exposures, you're also able to react and respond to those. And we have a lot of agency in responding to that and a lot of historical agency and a lot of lessons generationally passed down. And that's a really important way to acknowledge both the incredible hardship that Black Americans face in this country in growing old, both psychologically and physically. But it's also acknowledging our ability to fight back at the same time. And it's already happening. You know, it's not like we need an intervention for it or something else to do for it. Black people are already doing this and you can measure that. So yeah, it's a cool project. On the Fatal Encounters research project So motivated by the George Floyd murder in 2020 me and a colleague, Dr. Terrence Keel at UCLA recently got a RSF, Russell Sage Foundation grant. We're basically going to this data source called Fatal Encounters. It is a data source that crowd sources all of the police involved deaths that have happened in the United States. So, we are going to this data source and we are looking in LA County and we are finding the names of people who've been involved in police related deaths that have not involved firearms. That's because firearm deaths are very straightforward, can typically labeled the death as a homicide because you know, the act of shooting. But for non-firearm deaths like George Floyd, those are more arbitrary and harder to prove homicide and the autopsy reports can be very misleading, especially by the medical examiner and the coroners. And those autopsies are public in LA County. We're taking the names going to get all of the autopsies from the medical examiner/coroner. So, we have like 320 autopsies from 2000 to 2020, and we're trying to create a data set that represents how people are being classified in terms of cause of death and if there's any other indication of, you know, markings on the body some type of conflict that happened during the process. So, it's any interaction with the police out on the street or in LA County Jail. So, we have both of those data sources and we're able to try to say something about what's happening to a lot of these people, especially Black men whose moms are also very interested in understanding what happened to their kid. And so, the project is really motivated from that space. On the lack of diversity in genomic data In genetic sciences, you know I think 80% of our genetic and genomic data is from European ancestry populations, even though only 16% of the world is European ancestry. So, there's this huge imbalance in what we know about genetics because we only know what's happening among European populations. It's not, they're even telling people right now to not do genetic work in Black and Brown populations because we're not sure what we're finding is accurate because we don't have good training data. And the way genetic sciences work is that training data, everything is based on a reference population and a training population. It's not dissimilar from early eugenics where everything is compared to whites. You're constantly comparing Black and Brown people to white people. And if that's the way you're starting, it's going be a story that's rooted in inferiority and rooted in comparison and not necessarily rooted in the true story that should be unfolding that you can unfold when you're not trying to make those comparisons. So that's happening really horribly in the genetic sciences where you have dominant European frameworks and genetic data. You're trying to say something about other types of people and it's really not working, and scientists know that, but they're continuing to just do work on European populations.

Patrick Corbin is an associate professor of practice at the USC Gloria Kaufman School and an internationally renowned dance artist whose career has spanned over 30 years and bridged the worlds of classical ballet, modern and contemporary dance. He recently spoke to us about his work, exploring the positive effects that dance can have on neurology. On movement and movement therapy Well, on a neurological level movement is cognition.  Movement stimulates cognition.  So that's sort of the sciencey part. The other part is that dance is a multifaceted, multilingual way of movement, and we're actually in a duet from the time your mother becomes aware of you in the womb, you're already in a duet with her. So you're dancing before you're born. We come into this world dancing and we dance through life. So, it is intrinsic to our development. So why shouldn't it be also important to therapies and things? Movement therapy can range from anything from occupational therapy and living with different disorders to dance class or performative sort of therapies. Also, movement therapy can be sports anything obviously involving movements.    Exercise can look like so many different things, and that's why we are getting in touch with each other and starting to work together. Because the more fun the exercise, the more people are going to do it. Dance is fun; therefore, people are going to do it and keep it going.  On the benefits of dance in general There are a whole host of different areas where dance brings people together.  We dance at parties; we dance at weddings we dance, and we don't even know that we're dancing. So, anybody who says, “ugh, you know, I'm not a dancer, I can't dance.” You know you don't even need two legs because that's even ableist going on.  Do you move through space and do you like music? Then you dance and it's doing something good for your brain.  Because of course, we focus on people maybe with disabilities or syndromes or some kind of situation that way, but actually dance is just really good for everybody, you know? It's all about community. You don't have to do dance in a group setting, but often we do.  So, it's always keeping that active, curious, creative form of connection going with others. And also, it makes you feel a little sexy, right? So why shouldn't somebody who's 80 years old who has Parkinson's feel a little sexy?  I think that's one of the best things that dance does, it puts us in touch with that sexier self, that sassy self, where you can express so many things through it. And I think that's one of the great gifts it can bring to anybody. On the benefits of dance for people with Parkinson’s disease and other conditions The anecdotal evidence is just massive, right? Everybody has stories about their family member who just started going to dance class and their quality of life changed.  So, the scientific evidence is quite strong. Also, especially when you're talking motor skills, gait, and speed.  When you're talking about the, the experiential evidence we want to talk about dance as, once again, this multifaceted art or form of exercise that brings together other domains other than just the motor. So, you have the sensory, you have the motor, you have cognitive, you have social, emotional, spiritual, rhythmic, and of course your creative process.  So, what does that do to the whole person, right? What does that do for somebody who may be, have become isolated for whatever reasons? And, and I'm going to go across the board here with many different kinds of disabilities that this is, these are often invisibilized populations when you're talking about elders or when you're talking about, especially in the past, children with autism, or for instance. Now, one thing I did witness at one time is sometimes what happens the slowing happens so much, or the automaticity is so in decline that an actual freeze will happen.  And so there are different ways that you can cue people out of a freeze. And this is specifically in Parkinson's. So, the person who was teaching our class said that when one of her students froze at the door, she just said, no, just do your waltz. Do your waltz and waltz into the room. And they were able to cue themselves in waltz into the room where they were completely frozen and couldn't take a step.  So those are the kind of things, immediate things that we actually see in real-time.  On USC’s Dance and Ability course focused on people with Parkinson's The goals for the course in a broad sense as far as the University and USC Kaufman goes, is that have been wanting to do something that was truly interdisciplinary since I landed here on campus eight, almost nine years ago. And it's been that gentle pressure and getting to know different people. And then that finally culminated this year in getting funded by Arts and Action, which is a great funding organization on campus here at USC that I was able to bring together Giselle Petzinger and Michael Jakowec from Keck Medicine and Neurology.  We brought the OT school; we brought the PT school into it. We brought John Walsh from Gerontology.  We worked with a community group in Pasadena called Lineage Performing Arts Center where we designed this course together. So, I want to give our students a chance to use their fierce intellects and their fiercely intelligent bodies to start changing things in the world and to start understanding that your research in the studio is real research and it has real effects on people's lives. And the best thing about it, and this was my greatest hope, and was sort of the greatest payoff, was the intergenerational connection that came with our students getting off this campus and going to work with an elder population in Pasadena. And we were just dancing together and the love that filled that room, that number one, are students valuing these amazing people, right, that are, that are dancing through this these elements of trauma in their lives. And those folks up there, you know, maybe viewing young people in a different light than they possibly have been lately…It's all about connection. So, we can sort of complain about the lack of connection because of social media, but what are we doing about it? So that's, that's the other thing I want to do is create a community. And that's what happened. It was really kind of magical up there. On the benefits for caregivers In Parkinson's the caregivers if joining into class are getting every bit of spiritual physical, feedback reward that anybody involved in the classes…The caregivers when we went to Lineage, I noticed that they were taking time to sit and read a book and maybe do a little self-care on their own if they weren't joining in, some were joining in.  And so, I know that it offers a respite, and it also offers a moment where they can view the person who's in their care as a dancer, right? As they're doing something, that maybe they're too afraid or don't feel able to do. So that's sort of a power dynamic shift that's kind of a beautiful thing too. When I was working with the children with autism, one of the services that we were providing was a respite for these parents who I mean, these were, these were working-class people in Carlstadt, New Jersey that could not leave their child unattended ever, right? Incredibly intelligent, these kids, one was a computer whiz, and he would go in and just wreck all of the computers.  So, I realized that they could go and have a cup of coffee and maybe be just a couple for 45 minutes.  So, I know that that's also something that any kind of service you're providing that, that is community and group-oriented, you're taking care of the whole family. And that's another thing that I wanted to impress upon the students. And they got it. The students really, really stepped up. On cross-campus collaboration So, the structure of the class is it's all in the studio, but we have lectures. So, we will have two lectures in a row and then a creative session, then two lectures in a row, creative session.  And then we also peppered three times throughout the through that were field trips, field work that will be again in Pasadena in the spring, and of course in the fall will be in Culver City. So, we have whoever might be available to do the lectures. What we tried to do is we tried to give some kind of background in whatever we're studying. So, we had a few lectures with the neurologists about Parkinson's, just what it is. Then we had a creative session with the practitioner from Lineage Performing Arts Center and myself, who was training in dance for Parkinson's at the time.  and then we rinse and repeat that cycle over with somebody from occupational therapy, in gerontology, in physical therapy. And then we would wrap it up again with the neurologist coming back into it.  And throughout that we're then putting it into action or putting it into practice when we, when we visit on the field trips. It's just a dream come true. And because I've been, you know, researching on my own just as a curious person in the world and doing so much reading and watching films and sort of diving in on a pretty deep level to some of these things that then when I'm sitting in a lecture with Gisele Petzinger and Mike Jakowec  or Dr. Walsh or Lisa Fukuzato from Occupational Therapy or Marisa Hentis, that as a dancer coming into this academic space that I know something and I know something that is valuable, and I've been able to bring these things together because I knew that there was a there there, and it just needed a spark to come together. So that was the most gratifying and invigorating, edifying takeaway from this whole experience is so that dancers in general, artists, I should say in general, can walk into these spaces and have a conversation with a neurologist, and we can have a real conversation about science because I've done the work. So, I want that to be apparent that we're, we're all doing our research, whether it's in the studio or whether it's in the laboratory. Yeah.  On dance and aging And of course, there are issues in the field. It's getting better.  Also, our perceptions as ourselves as aging bodies is different. You know I, as a 58-year-old going on, 59-year-old person don't feel old in this body at all. Whereas, my mom, God rest her soul, my mom at even at 40, she felt she perceived her aging body differently. So culturally that is changing in a broader sense. And so that is of course, filtering into dance in general. There are very few opportunities for aging dancers, but they are specialized and they, some of them are very high level but when you're talking about performing, it's the same sort of ageism and ableism that you have in any other sort of aesthetic process like acting, dancing, anything like that. But it's getting better. I'm working on it on a daily basis with my students. I'm like, you should be able to keep up with me, , look at me. I'm strong. You know?  And also, what I want to impart to my students in general is that if we take care and accept our bodies where they are and honor our bodies at each stage or season in life, then we can express through them instead of shutting down and becoming isolated. Share your aging body as a thing of beauty.

Connie Cortes is an assistant professor of gerontology at the USC Leonard Davis School. Her work straddles the fields of neuroscience and exercise medicine, and she recently spoke to us about her research seeking to understand what is behind the beneficial effects of exercise on the brain with the goal of developing what she calls “exercise in a pill” therapies for cognitive decline associated with aging and neurodegenerative diseases.  On brain plasticity and brain aging Brain plasticity we define as the ability of the brain to adapt to new conditions. And this can be mean something like a disease, it can mean something like stress, it can mean something like learning, and it can also mean something like aging. Our brain is actually quite plastic and can respond to a lot of these stimuli. Now, brain aging is a slightly different component to that where we think about what happens during the brain as we get older, the normal wear and tear. What are the differences and the similarities as well between a 75-year-old brain versus a two-year-old brain?  What we've come to understand is like most other aging tissues, an aging brain begins to suffer from wear and tear just like a car would and that's where regular maintenance and regular checkups come in. … But essentially things at the biological level begin to slow down and as they slow down, that can affect the way our neurons fire and therefore we get age-associated decline in cognition and memory. On why exercise is good for the brain health That’s one of the questions that my lab is trying to answer, but in the field of exercise medicine, we've come to appreciate that exercise is very good for the brain, and it appears to do so in multiple ways. It can affect your cardiovascular health, which has a direct impact on the brain as far as blood flow and essentially clearing the brain out of things it doesn't need. The other way is delivering, metabolites and essential nutrients to the brain during exercise we make a lot of these things that get into our blood and eventually transfer through the blood-brain barrier into the brain. And so as far as the biological mechanisms of how exercise is good for the brain, we really, truly don't know yet. But that is why this field is so exciting and I think we're poised to answer these questions in the next five to 10 years.  On whether exercise can prevent or slow cognitive decline or diseases like Alzheimer's that are associated with aging For actually many decades now, we have had anecdotal evidence from the clinics that aging populations that are active, physically active, and or exercise have significantly lower levels of age-associated neurodegeneration, as well as just age-associated cognitive decline. And it's only been in the past, I would say 10 years that we've come to appreciate that it is truly the exercise activity. And so what we find is that consistently, no matter what markers of brain health we look at, those aging populations that are sedentary tend to do worse than those that are physically active. And so the field now is extremely interested in trying to understand why this is happening and can we kind of use these mechanisms and these targets as new therapies down the road. On efforts to develop “exercise in a pill” therapies We all know a hope that exercise is good for us. However, the most at-risk populations that we are trying to help, especially here in the school of gerontology, are populations that usually cannot engage in the level of exercise required. Now in the field, we're still trying to define what an exercise prescription is, but you may have heard you know, three times a week, 90 minutes a day, uh, some sort of cardio. And something that raises your heartbeat, uh, that is, has come from exercise studies in young people. However, elderly populations are sometimes suffering from additional medical conditions or sometimes there's a financial constraint or even an accessibility constraint, and they just cannot engage in that level of exercise. And so what we are trying to figure out is can we design exercise in a pill to perhaps allow them to receive the benefit without having to get on a treadmill three times a week? On when to begin exercising So that's the good news. It doesn't matter when you start, you will always get benefits. So for those of us that are a little bit more on the sedentary side, that's the good news. Now the better news is, is that yes, the earlier you start, the better. But this goes back to this concept of brain plasticity. The brain will respond to these interventions that promote neurotrophic signaling no matter how old you are, which is great for us from a therapeutic standpoint. And so the recommendation of remaining physically active is, start as soon as you can. And today is a good day to start. On the muscle-brain axis and how our muscles and brains communicate One of the challenges that we face in the field of exercise medicine is that exercise changes everything. And so we are always stumbling around this roadblock of, are the changes that we're seeing in our studies, the chicken or the egg, is it a cause or a consequence? Are they driving the benefits that we see or they just a response of the system? And so by narrowing down how different tissues communicate with each other during and after exercise, we're trying to answer this question of who is responsible for driving the benefits. And we focused on skeletal muscle because as you can imagine, it's one of the biggest responders to exercise. You need it to get on the treadmill, you use it to start lifting weights. And so where, first of all, trying to figure out how skeletal muscle responds to exercise and also how this changes with age. And what we have come to understand is that during exercise skeletal muscle secretes messages into the blood circulation that we believe are essentially talking to the brain and telling it to do better. And if we can identify these messages, then we can probably deliver them in the form of medication and therapy. And so this muscle-to-brain axis we believe is essential for the brain benefits of exercise, and we're hoping to use it to start, uh, prioritizing some of these targets for therapy. On exerkines The field of skeletal muscle physiology has known for a very long time that it's an endocrine organ, that it secretes things as it communicates with the rest of the body but the fields of exercise, medicine, skeletal muscle physiology and neurobiology have only started talking to each other in the past five years. And so there's an entire field of research now, um, called the field of exerkines, exercise-associated cytokines, things that come out of skeletal muscle and other tissues during exercise that may be some of these responses that were going after. On rethinking Alzheimer's as not only a disease of the brain Since Alzheimer's disease, was first identified over a hundred years ago now, we've thought about it as a disease of the brain, but recently we've come to appreciate that it may be a disease of the body and the brain is just the most sensitive organ to it. So in Alzheimer's disease patients if you examine some of their blood markers, some of their heart markers, some of their muscle markers, they're actually very different compared to healthy control populations. And so we are coming to appreciate the fact that despite the fact that the brain resides behind the blood-brain barrier and we thought it was isolated from the rest of the body, it's actually in direct communication and conversations with the rest of the body and the periphery. And so in our lab, we truly believe that skeletal muscle can influence the rate at which the brain ages and or develops things like Alzheimer's disease. On differences in how males and females respond to exercise It is only recently that the field is realizing that we don't know what the female brain does in response to exercise. However, from the clinical perspective, we do have some indications that women might be in a position to receive the most benefits from exercise interventions. And this comes from the current understanding that, for example, uh, women are the most at risk for developing Alzheimer's, and exercise is such a potent intervention against it. And so in our lab, we're currently beginning to tease out the sex differences associated with brand responses to exercise and trying to see what might be different. And we have some really interesting findings where, um, after exercise, the hippocampus particularly, which is the area that degenerates during aging and during Alzheimer's disease, it's where we store memory and cognition and it's also the, the brain region that responds the most to exercise. We have tremendous differences in the way the hippocampus is remodeled after exercise. So the biological responses might be unique to one sex or another, which again, provides us unique areas for intervention for either men or women or perhaps combinatorial approaches across sexes.   On future work looking at circadian rhythm and exercise Yeah. So, I mentioned we're very interested in sex differences to exercise interventions. Genetics is another huge one. In the lab, we are constrained by our genetic homogeneity of some of our animal studies. And so integrating some of the human studies to bring in this genetic diversity is going be fascinating and then circadian rhythms is another one. Some of the listeners may actually notice by themselves that they prefer to exercise in the morning or at night, and that has to do with your own circadian rhythm as well. And so perhaps we could also identify not just the best type of exercise for you, but also the best time to do it to maximize the benefits that you may receive. So in the lab, the way we are approaching this is we're using this integrated approach of neuroscience, exercise physiology and gerontology, but also using across platforms.   So we go all the way from basic cellular biology to animal modeling to human studies, and then all the way back to cells in a dish. In particular, I'm very excited about a new animal model we've created that despite never running on a treadmill throughout its entire life, the brain is responding as if it's exercising. And so by using this animal model that doesn't need to exercise, but displays the benefits of exercise in the brain, we hope we can start to prioritize this chicken and the egg question that I mentioned -  what is important and what is driving the benefits? And we're going to use these animals as a platform to prioritize drug targets to start testing in the near future.   On small changes to promote brain health It's never too late to start. It's never too late to change some of your behaviors and your habits. And the power of very small things to have a huge effect is something that I don't think we quite appreciate. So something as simple as going on a walk around the block once a day, just getting some sunshine, especially now that the rain is finally breaking, that is incredibly helpful, changing your diet a little bit. You know, drinking one less soda a week can have a huge impact on different outcomes in your body. And so thinking about small changes rather than radical, big changes that are very difficult to maintain can help a lot.   On the importance of mentorship, access and diversity This is an essential component of who I am as a lab leader and as a scientist, I'm a strong believer in, um, opening doors for those coming up behind me, uh, simply because one of the reasons I'm here is because mentors open doors for me. And so I'm returning the favor. I'm particularly passionate about historically excluded minorities in STEM. I myself am a Latina scientist, and there are not enough of us out there and I truly believe that all of us belong here, and it's through diversity of ideas that we're going figure out these big questions with major impact to human health. And so ever since I was a grad student, I've worked tirelessly to, like I said, uh, bring in junior investigators, mentor junior investigators, and make sure that my lab is a welcoming place for anybody that's interested in the research that we do. I've mentored, undergraduate students, graduate students, postdocs, and now other junior faculty.  I've spoken at multiple of my professional societies. I've given career mentoring workshops. Sometimes I've come to realize a lot,  a very small thing, like I mentioned earlier, can make a huge difference. Students that look like me, that see me up there on the podium realize that they can do it too. And so that's commitment to science. Accessibility and diversity in science is a huge thing for me as well. On her Minute Science video series I started the very video series a couple of years ago because I kept seeing all of these misconceptions around science and especially about the brain. It's something I've been interested in since I was an undergraduate student, and I love the brain and so I realized that sometimes, especially as scientists, we tend to use language that's very difficult to follow. We love our acronyms, so many acronyms all the time. And even in talking to my parents and talking to my husband, they will give me a very confused look. And I've realized I've defaulted to using very complicated language, and I came to appreciate that it doesn't need to be that complicated. We are not an ivory tower anymore. We need to share our science with the public. Our research is funded by federal tax dollars, so the federal taxpayer should know what we're doing and they should be able to communicate with us and learn about what we do. And so that was the purpose of my minute science video series that I hope to continue sometime soon, um, once my schedule clears up a little bit. And so we talk about things like, you know, is it true that you, you only use, you know, you don't, you never use your entire brain at the same time. Or is it really true that you can be right brain and left brain, but not both? But does it mean when people, people say the lizard brain, um, is it true that your olfactory system is the first one to respond to memory and why? Things like that.

Dr. Roberto Vicinanza MD and PhD and instructional associate professor of gerontology at the USC Leonard Davis School, and a specialist in geriatric medicine, joins us for a conversation about healthy aging, including tips on how to keep the body and mind functioning for as long as possible. Quotes from this episode On the importance of setting small goals "People may have all the good intentions, but they might set up goals that are too ambitious and then when they don't reach that goal, they feel frustrated, and they quit… We have to let them understand that goals must be small…So, an apple a day. We have to eat the apple a day and be happy and recognize when we reach three or four days in a row that we are eating the apple, right? So celebrate the success even of small, very small goals." On keeping your diet simple "Diets cannot be too restrictive for a long period of time. The majority of people will give up.  It is important that diet needs to be easy to follow, but at the same time needs to be healthy. When we talk about a simple diet, we are now referring on something that needs to be easy to follow, but also simple in terms of the way we make food. So we have to eat in a very simple way. So, avoiding ingredients that are maybe tasty, but not that healthy. And sometimes they also cover the, the real flavor of, of food.  We have this tendency to add always sauces and creams and other things on food that actually cover the real flavor of food and also contain a lot of saturated fatty acids, heat and sodium, sometimes sugar. So, we increase these calories by adding something that we don't really need. Diet must be simple in terms of the type of diet that we have, but also in the way we cook and prepare dishes." On the benefits of the Mediterranean diet "So, the results that, that we have referred to the traditional Mediterranean diet, which is characterized by high consumptions of fruits and vegetables, cereals, legumes, extra virgin olive oil, nuts, and a moderate intake of fish, and a low intake of dairy products and meat products. So, we do have robust evidence suggesting that high adherence to these dietary patterns is linked to positive health outcomes, in particular for cardiovascular diseases, dyslipidemia and diabetes. But another important result was that the adherence to Mediterranean diet was inversely associated with a number of medications. So, patient who were more adherent to Mediterranean diet, they also used less medication.  Another interesting observation that we found was related to depressive symptoms and comorbidity. When we analyze our data, we found out that the relationship between comorbidity and depressive symptom was high in older adults…In patients with higher adherence with Mediterranean diet, this correlation was weaker. When Mediterranean diet adherence declines, this relationship was stronger. So Mediterranean diet played seems to play a crucial role in mediating the relationship between the presence of comorbidity and depressive symptoms." On the importance of physical activity "Although we don't have big clinical trials on physical activity, we have small, randomized control trials showing that certain level of physical activity, may have some benefits in terms of improving the cardiovascular health and, utilization of glucose in the muscle in modulating inflammation, improved cognitive function and physical performance. Some of the benefits that we have from being active and also exercise regularly include an improvement in the cardiac output improving the health of the heart by improving cardiac contractility, oxygen uptake. And we know that we don't have to do long sessions of exercise or being extreme physically active. Already, if we walk between 45 to 75, 85 minutes a week, we can already see some benefits. Of course, the more we exercise, the more benefits we see, but at some point we reach a plateau." On sarcopenia "With the aging process, there is a decline in our muscle mass, strength and also performance. And this phenomenon is called sarcopenia. The level of physical activity, the changes in the hormones that occurs in older adults the amount of proteins that we eat when we are old all of these factors may contribute to the onset of sarcopenia, and also the progression of some sarcopenia. In terms of dietary intervention for sarcopenia, it is important in older adults to maintain an adequate protein intake. Recent studies suggest that older adults need to ingest between one to 1.2, 1.3 gram per kilogram a day of protein to sustain their muscle mass and functionality. And this amount can also be adjusted based on the body composition." On weight management "Weight management is a complex problems and obesity is a complex condition that can lead to health problems, including cardiovascular disease, diabetes ... but weight is not the only parameter that we should take into consideration when we talk about weight loss in particularly in older adults. So, it's not only important to monitor the fat content and the weight, but also evaluate the composition of the weight. There is some studies and meta-analysis conducted in older adults showing that even if the BMI is likely higher in older adults, this is not really associated with overall risk of mortality. So, on the other hand, if the BMI is low, below 22 or 23, the risk for mortality increased. Why that happened and why this has been observed, because of course, malnutrition may have some serious consequences in older adults. Weight fluctuations is another risk factor. So not only being underweight, but also this fluctuation of weight in older adults may have a negative effect. So, it's good to have a stable weight, preserve our muscle mass, do not rely only on the weight on the scale, and have an evaluation of the body composition. " On stress "Stress is an adaptive mechanism that allows the body to perform better in certain circumstances and situations, and to cope with temporary threats. However, when process become chronic these adaptive mechanisms of the body become destructive. Chronic activation of stress can alter our metabolism, can disrupt our endocrine system, including the reproduction, the reproductive system, glucose metabolism, but it can also affect our immune system and other many cell function. And all of these can accelerate the aging process. Now we also known that chronic stress may affect also our chromosomes. A large body of evidence has linked stress with shorter telomeres, and shorter telomeres are associated with cellular, aging, inflammation and chronic diseases." On healthy aging "Aging is a dynamic and complex process where biological, psychological, environmental, and behavioral factors are involved. And the complex interactions of these factors explain, at least in part why there is significant inter-individual variability in the way we age. But it also suggests that modification of some of these factors, when possible, can also slow down the aging process. I think that we cannot feel satisfied by considering healthy aging only when there is absence of disease. I think we should be a little bit more ambitious and consider aging as a physiological process that despite all the biological changes that occurred during this process, allow us to maintain an adequate physical, mental, and social wellbeing by preserving not only our basic functions, but also our functional reserve and functional capacity as long as possible. This will have a tremendous impact not only in terms of quality of life, but also or our loved ones and the community will live."

Dion Dickman, associate professor of neuroscience and gerontology, joins George Shannon to discuss how the nervous system processes and stabilizes the transfer of information in healthy brains, aging brains and after injury or disease.  Quotes from the episode: On synaptic plasticity: “Synapses are essential, fundamental units of nervous system function and plasticity is this remarkable ability to change.  And throughout early development into maturation and even into old age, synapses just have this amazing resilience to change and adapt to different situations and injury disease, things like that. So synaptic plasticity is really the essence of what it means to grow and mature and change throughout life. Things like learning and memory all depend on changes in synaptic function and structure and it's really a key area of research for many of us.”   On challenges to maintaining nervous system stability “You can imagine in the incredibly complex environment of your brain, where neurons are making synapses with thousands of other neurons, that itself is a big challenge to maintain stability. Sometimes I'm kind of amazed that we don't walk around like raving lunatics half the time and our brains remain stable. When you think of disorders of excitability or stability, things like seizures and various forms of defects in cognition ultimately come down to not being able to stabilize or maintain your neural circuit function. And this really just comes down to normal development that all of your nervous system has to stay stable and your synapses are the key substrates to maintain stability.”  On the aging brain “.. a lot of studies are showing is that this cognitive decline that happens in aging really is ultimately due some sort of a maladaptive reduction in plasticity. And it's kind of amazing, but, young humans, our brains are remarkably plastic and resilient, and that resiliency and plasticity seems to degrade over time and into old age… We think as old age happens .. people's memories start to lapse, even in the absence of any disease, they're not quite as sharp. We think this all ultimately comes down to some limitations imposed on neuroplasticity and that's a major area of the research. On studying diseases like schizophrenia, which cannot be seen in brain imaging “There are no good biomarkers for neuropsychiatric diseases like schizophrenia and bipolar and things like that. So, there are basically two ways to study these kinds of diseases. One is through behavior where you try to get animals to model behaviors that mimic neuropsychiatric diseases. There's some good work happening rodent systems. Although I find it to be honest, very difficult to know whether a mouse is showing the defect in social interaction, for example, that are characteristic of autism or schizophrenia for that matter. So the alternative instead is not to actually model the disease in drosophila or mice, but to take humans in which we can mine their genetics to find genes highly associated with the disease in humans and find out what the fundamental function of these genes are. And that's kind of the strategy that we take. So we found about 30 genes now that when mutated in drosophila give rise to defects in this process of homeostatic plasticity at synapses, and the vast majority of these genes have links to human diseases that give rise to neuropsychiatric diseases like autism spectrum disorder, schizophrenia, seizure disorders and, bipolar disorder as well. And so I think by understanding the fundamental functions of individual genes, we can extrapolate what might be happening in humans when those genes aren't functioning properly.” On the importance of sleep “…one of the most fascinating questions in neuroscience, or really science more generally is what is the function of sleep? What is the essential function of sleep and what role does synaptic homeostasis and disease play a role in sleep behavior? So, it's quite interesting that almost every neuropsychiatric disease has a sleep disorder associated with it. That's already very interesting. If you look at schizophrenics, their sleep patterns tend to be very fragmented. Whereas people with depression, chronic depression seem to sleep too much, much more than is needed and many neurodegenerative diseases of old age like Parkinson's, and Alzheimer's one of the earliest predictors of these are sleep dysfunction at earlier stages and there's also many studies that have shown that if you treat the sleep dysfunction, you can improve the symptoms of neuropsychiatric disorders. A schizophrenic, for example, might get if you improve their sleep, their symptoms, cognitive symptoms seem to improve children with autism spectrum disorder have, big defects in sleep behavior during development. And it's thought that if you treat the sleep defect, you can improve the phenotypes of autism. So a lot of research seems to be showing that synaptic homeostasis and plasticity and sleep behavior and disease all share really important and synergistic links between them. And I think that really is the major challenge for the future is to understand what happens to synapses during sleep. What happens to synapses during various neuropsychiatric diseases and can this intimate relationship between sleep and, and synaptic plasticity be targeted as a way to improve and treat psychiatric and neurodegenerative diseases.” On bringing a multidisciplinary approach to research This is a big advantage, I think of especially working at USC, in, you know, straddling different schools like Dornsife and gerontology and really being able to throw everything we can in our toolkit at a question or a problem. So, our lab is a drosophila genetics lab. We do neurogenetics. But we do electrophysiology to understand how synapses function we do basic imaging to see synaptic structures and how they work. But we also do a lot of super resolution imaging. Now we've got a super resolution microscope that we've recently purchased that allows us to look at the nano architecture of synapses and how they might change during defects and plasticity and disease. And finally, we're doing things like calcium and voltage imaging to really see the dynamics of how, you know, visualize plasticity happening in real time or dysfunction happening as they go on. So I think having a large toolkit to throw everything we can at a question really lets you see the same problem from many different perspectives. On the value of basic scientific research “Science is for me a curiosity driven process. It's great that there are ramifications to disease and health and humans, but what initially inspired me was just to understand how does nature work and how does the nervous system work. And so I want to just say supporting basic research, basic science, even if it doesn't have any direct implications on disease right away, I think is really important as part of scholarship, as part of what we at the mission of our university, but also just as our world. I think to study basic processes and just understand how nature works and then the applications of them with all evolve. You know CRISPR CAS9, as many of you have probably heard about, all came from basic research and now it is going to revolutionize health and disease.”

Kelvin Davies is a Distinguished Professor of gerontology, molecular and computational biology, and biochemistry and molecular medicine at USC. Over the course of his career, he has played a central role in defining the pathways and mechanisms by which the body is able to maintain balance under stress and in uncovering the role aging plays in disrupting this balancing act. He recently joined Professor George Shannon to discuss his research on how the body is able to maintain balance under stress and the implications it could have for preventing age-related disease and decline.   Quotes from this episode On the concept of adaptive homeostasis “So every organism that we've looked at is able to adapt to stress. And I'm talking not about psychological adaptation, but adaptation at a cellular or molecular level. And we've been working on what are the pathways which that adaptation occurs. And what we came up with over a series of a number of years is the concept of adaptive homeostasis. “What we found with adaptation is that successful adaptation actually involves the turn-on of a number of genes, a key one being something called NRF2. And NRF is a sort of a master regulator that turns on about another 200 genes. When I say ‘turn on,’ what I mean is that those genes start making their protein products. So the code in that gene starts being read, turned into a protein product. Thousands of proteins are then made. Many of them at least are enzymes that have a job to do. And all of those enzymes have a role in enabling you to adapt.” On adaptive homeostasis and aging “As organisms age, the capacity for adaptive homeostasis declines. That's been true in everything we've looked at all the way from bacteria to yeast, to worms, to flies, to mice. “NRF2 activity is modified in aging. And so it doesn't work as well … And the reason we think that happens is that there's another gene that's turned on in aging that inhibits NRF2 responsiveness. It turns out that that gene might actually be helping to protect you against cancer. So one of the things that cancer cells are very good at is avoiding stress and adapting to stress. And in fact, NRF2 works really, really well in most cancer cells, better than in normal cells. So it looks as if the body is adapting to age by inhibiting its own NRF2 thus decreasing adaptive homeostasis in order to diminish the increase in cancer. We all know that cancer increases with age. Maybe it would increase twice as much if you didn't have this offset by inhibiting NRF2 in the cancer cells. And the price you pay is that you're also inhibiting NRF2 in your normal cells at the same time.” On understanding the role of enzymes and backup systems “What we've learned over the years is that the body treats important enzymes much more like the way that NASA treats important components in a space shuttle. In other words, if something is important, let's have a backup to it. And if it's really important, let's have a backup to the backup. And if it's life-threatening, let's have a backup to the backup to the backup. And the problem is when you knock out one enzyme if you don't know if there's a backup enzyme to that one, then, and that takes over, then you'll completely mask the effects you're seeing. “We had a great example of that in my lab several years ago where we found an enzyme that was induced during chemical stresses that stopped DNA being read. So basically protein RNA synthesis and protein synthesis were stopped by this particular enzyme that got turned on during stress situations. If you inhibited that enzyme, it didn't make any difference because there was a backup to that enzyme. And if you inhibited the backup, it didn't make any difference either because there was a backup to the backup. So it turned out what was really important in cells is that if you're being stressed to the point where it could be lethal for that cell, all of these things will get turned on simultaneously and any one of them can do the job. You're willing to spend the extra chemical energy, so to speak, to turn all of them on to make sure that you don't die from the stress. So that, that's why I think just looking at one enzyme or another is not the way to go. And I think most people would follow that ethos today.” On the role of sex in the adaptive response “What we found is that the females adapt better than males. Females generally lose less of their adaptive homeotic capacity with age than do males. So sorry, men we’re losing out there. And also curiously, and this we don't understand, female flies responded to certain oxidants very well and others less well and males responded differently to different oxidants than did females. So there were some oxidants to which males responded relatively well [and] females didn't respond well and vice versa. This is sort of the power of molecular biology. “These days, we are able to do experiments with flies, where you can switch the sex of a fly from male to female or female to male. We wanted to do that basically to see whether or not we were right about the maleness or femaleness of the adaptive response. And it turns out when you switch a male fly to a pseudo female or a female to a pseudo male, genetically, they exactly switch their adaptive homeostatic capacities to the new sex.” On future research directions “So everything basically in physiology is explained by homeostasis, but the homeostatic range is flexible and you can change it by training and by doing various other things. I think what we're seeing is the beginning of understanding how that process kicks off, or those kinds of processes kick-off, how they begin that involves NRF2 and similar enzymes and similar genes. But then after the initial response, if you're looking at a long-term adaptive response, that's a whole different set of genes and set of proteins that are involved that we're only at the very, very beginning of understanding I would say.” On the importance of being a mentor “If you're going to be an educator or a professor, it should be a major part of what you do. I've been fortunate enough to receive several mentoring awards, and I'm very proud of them. And I think they're some of the most important work that I've done. “Over 30 postdocs have gone through my lab over the years and a similar number of PhD students have done their PhDs in my lab. Many of them have gone through and done their work very well. And, and we've said goodbye, and I see them occasionally and others of them are family members … They are literally a part of Joanna, my wife and I, my family; we see them all the time. We are very close to many of them and follow their careers and have had relationships with some for over 30 years. It's a really a joy in terms of some of the best aspects of being a university professor. I think it's one of the things I've enjoyed most, I must say. And hopefully I've been able to be of some help some of those people over the years and to occasionally steer them in the right direction.”

Kate Wilber is the Mary Pickford Chair in Gerontology and director of the Secure Old Age Lab at the USC Leonard Davis School. She's also the co-director of the National Center on Elder Abuse, which is housed at the Keck School of Medicine of USC. She recently spoke to George Shannon about her research, including her work exploring ways to provide long-term care services and supports that allow older adults to be as independent as possible and the challenges and opportunities that technology provides in this area. Quotes from this episode On building on lessons learned during the pandemic “I think a lot of what we saw were challenges that we already knew were there - how fragmented services are, how older adults can be at risk of isolation, how important the home community-based services and programs and opportunities to interact are for everybody. And I think showing the importance of community, which we didn't have during the pandemic, except a bit on social media and phone calls and maybe people getting together outside. So the key question is, how do we take the learning and the recognition of what we already knew into the future to build on these important lessons, to do better with our aging service delivery? I was going to say our aging service delivery system, but that's a huge problem. There isn't a system; there's just a lot of different components of a system.” On innovations in long-term care and supports “We have to prepare for an aging population. And until recently I felt like we didn't do that great a job preparing, but I see a lot of exciting innovations, which to some extent may have been jump-started a little bit because of the challenges of the pandemic. We have a variety of models of senior living and I think we're going to see more innovation there or the innovations that have been developed take off because they did better in the pandemic too. So if we look at what kind of care was best for older adults who maybe were isolated or need long term services and supports during the pandemic, how do we build on that? And how do we make sure that we translate what we know into reasonable programs and policies.” On barriers to implementing technology solutions “People not only need to have some kind of device. They need to have broadband, it needs to work. And we've seen that in some parts of the country, especially in rural areas, broadband it's not available. All the things we take for granted, electricity, water, et cetera, how much is this an essential service that we’ll do a better job providing across the nation in areas where it doesn't exist very effectively now. And then as I said, how do we help people learn? And what are the particular cultural competencies required for trainers? What are the different uses that people want? This gets back to being person-centered and engaging the people that will be the end-user users and understanding what's most effective for them. There are still a fairly large proportion of older adults who don't have access to any sort of computer; some have smartphones. And there is this notion, I guess, if we build it, they will come. Or if we give it to them, they'll use it, it would be the way of talking about that. But there's a variety of barriers. And if you hand somebody a box with a computer in it and say, ‘There you go, you're now going to go on the other side, the right side of the digital divide.’ They're not. So what can we learn about how to help people use technology in a way that is useful for them effective, meaningful?” On telehealth “So this will be a time saver. I think that's pretty clear, but the nursing facilities have to invest in it. The staff have to invest in it. They have to learn how to do it. And one of the things we're seeing is they thought the residents would be the most resistant and they're not. They're like, ’Okay, if I can see my doctor this way, fine.’ But I think the question is, how is it used, where is it most effective and where is it not a good replacement for a physician coming to the facility? So, there's a fair amount of literature developing on this, but I think there's so many exciting innovations that are rolling out and we need to build on what we're learning and make them better and be more effective in the next generation of telehealth and facilities and helping people on the digital divide connect. So all these things are really exciting opportunities to learn how to connect.” On person-centered care “So the idea behind person-centered care is that people have different needs. Of course, they also have different preferences, different preferences for care and for services and for supports and for contributing and giving back and primarily and mostly as with all of us, for controlling their lives and the decisions that are made. So person-centered care recognizes that the power should live with the individual in terms of the ability to make decisions about care informed decisions. But I think sometimes, we, as professionals can see, oh, this would be best for this person. And professionals are extremely busy also. And so it kind of overlooks sometimes the person's needs and preferences and working in areas like elder mistreatment and elder self-neglect. A lot of times people have legitimate reasons for wanting things that we don't necessarily think would be the best choice, but person-centered care asks us to really get in touch with what's behind those preferences. And to what extent can we ethically honor them and this is something I see the field doing a much better job thinking about and working on and great things have been written. And the American Geriatric Society a few years ago had an expert panel come together and develop a definition and sort of protocols for this. And I think that's really moving the field. One more thing I'll say is that ageism contributes here. So we make assumptions about older people that they can't express their preferences adequately. And providers talk to the caregiver, not the older person. Or they say this is what needs to be done. So I think there's also a culture change of recognizing that it's about the older person. And we start with the older person, and that's not to say that there aren't age-related increased likelihoods, but not inevitabilities of memory issues and things of that kind. And so we need to be clear that the person has the capacity to express their preferences, but we start with person-centered. The elder is the person who whatever is happening is happening on behalf of, or for, or with. And that's where we start.” On students “That's our future. … Our legacy is you see the students that go through our program and they're very excited about learning and they bring innovation and enthusiasm, and then they go out and do wonderful things and they become the leaders of the field. And you could see that across the board in so many areas.”

Rong Lu is an associate professor of stem cell biology and regenerative medicine, biomedical engineering, medicine, and gerontology at USC. She joins George Shannon to discuss her research into the complex and surprising behavior of individual blood stem cells and what it could mean for treating diseases associated with aging. Quotes from this episode On stem cells and what makes them so promising for medical research Stem cells are the special cells in the body that can produce other type of cells. So in particular there are two type of stem cells, one called embryonic stem cells that only exist in the embryonic stages. And the other type of stem cells are called somatic stem cells that are also exist in adulthood. And these somatic stem cells can produce only a specific subset of the cell types in the body. For example, skin stem cells can only produce skin cells and blood stem cells can only produce blood and immune cells. But all the stem cells share the general special property called self-renewal and differentiation. So differentiation describes their ability to produce a different type of cells and self-renewal refers to their ability of making more of themselves over time and sustain the long-term differentiation and tissue regeneration. On the ability of stem cells to regenerate as we age …that's what makes stem cells super special because they are the only long-lasting cells in the body that continuously regenerate and sustain the tissue. But over time, stem cells capacity in terms of self-renewal are reducing and therefore the tissue as homeostasis decline when the body ages. On whether stem cells might offer protection against age-related immune decline Sure. So over aging stem cells become less and less competent in producing immune cells. And, the hope is if we can maintain the stem cells capacity over time then we could make the stem cells offer the protection. Again, this is very much a research in progress and many research labs are working on this important question, including my own lab. On the focus of research in her lab In our lab, we're interested in understanding how are individual stem cells different from each other and how different stem cells work together to maintain an overall balanced blood pool. And in particular, over aging, we want to understand how individual blood stem cells change during aging and how their change lead to the aging phenotype of the animal. And what we found is that there are a specific subset of blood stem cells that age, particularly faster than the others. And there's also another group of stem cells that actually can change in the opposite way during aging and provide more immune cells and their presence really correlate with the delayed aging phenotype of the animal. So we're very excited about this finding and we're following up on this study using our bar coding tool to track these anti-aging stem cells and study what make them so special. On the development and use of a tool to label individual cells with unique “barcodes”  The barcoding tool was developed a couple of decades ago by several labs simultaneously. At that time they used the viral insertion site as a marker to track individual cells. So about 10 to 20 years ago, high throughput sequencing technology started to emerge. And at that time,  I started to combine the new capacity of this high throughput sequencing to quantify the cellular behavior at a single cell level. So instead of using viral insertion site, I provide a particular DNA barcode sequence into the virus and use that as a marker to track individual cells. And what this allow us is a high precise quantification of the cellular behavior and also the high throughput that is needed to track hundreds and thousands of stem cells in the body. We can use this tool to study cancer cells and understand the heterogeneity among individual cancer cells. For example, a recent study from my group used it to track the primary acute lymphoblastic leukemia cells in xenograph mouse model. And what we found is that individual leukemia cells have different ability to grow to metastasize and to respond to the drug treatment. And we found that some cancer stem cells that are particularly resistant to drugs to drug treatment In particular, some leukemia cells that are particular resistant to chemotherapy treatment, exhibit distinct gene expression signature compared to others. On gene expression signatures The gene expression signature means these particular subset of cells express a distinct subset of genes that make them different and potentially may cause their specific drug response behavior. So these particular gene expression signature can allow us first to identify these cells and to detect whether these cells exists and whether the patient has the potential of resist chemotherapy. And secondly, these gene expression signature can also be potential drug treatment targets to allow us to particularly target these cancer or leukemia cells in the therapeutic treatment. On future directions in aging research So in the context of aging, we are very excited about our recent discovery of these anti-aging, uh, stem cells. And we would like to further understand how to activate these anti-aging behavior and how to expand their function in the animal. And we are also very excited about our discovery on the cellular heterogeneity in disease, in particular, in their response to chemo drug treatment. And we would like to further identify the potential functions of the gene expression signature that we discovered. In addition, we also want to understand whether the microenvironment of the stem cell play a role in terms of instructing their heterogeneous behavior.

Assistant Professor of Gerontology Ryo Sanabria joins Professor George Shannon to discuss their research seeking to understand why stress response pathways break down as we grow older and whether there may be ways to delay that breakdown and potentially promote healthier lifespans.    Quotes from this episode On the definition of stress: Stress can come in so many different forms and flavors. It can come in the form of something external, something like heat stress. For example, being out in the desert heat, it can be something as similar to cold stress of a winter storm, or even something like a bacterial or viral infection… Stress can also be internal though. It's not only external. When we think of humans, we can think of big things like mental stress, emotional stress, social and societal stressors. So really the definition of stress is pretty large. And just to say anything that causes some kind of adverse reaction to the body is a stress. And so we study all of these various types of stresses and how it impacts our bodies, our health, and of course aging. On how our cells respond to stress: The response to stress within the cell is simply to activate mechanisms that prevent damage. And the main way that this happens is to turn on genes. So genes encode specific types of proteins and processes and mechanisms that are important to mitigate the stress. So it's like essentially activating or turning on a switch that has some kind of functional output, similar to how you will just flip a switch to turn on a fan or an air conditioner. So you can cool down the house. Exactly in the same way, the cells will switch on jeans that can activate pathways that prevent or mitigate that is associated with exposure to stress. So for example, when we are under heat stress, our cells will turn on the mechanisms and pathways that will essentially alleviate damage associated with heat stress, such as damaging proteins or things like that, that happen under heat stress. So the cell is essentially trying to repair or discard damaged proteins that happen with exposure to heat. On efforts to give older person to have  a younger person’s ability to deal with stress We know that the capacity to deal with stress declines during the aging process. So the question is if we give an older person, a younger person's capacity to deal with stress, would that actually combat aging? So if we go back to example again, before, if I give the grandmother her grandchild's capacity to deal with desert heat, we know that she'll be more resilient to the heat. She'll likely survive the desert, but generally, would she actually be healthier overall as well? Would she be in a sense younger? And the answer in most model organisms that we study is yes. When we give an old organism, a young organism's capacity to deal with stress, not only can they handle that specific stress better, but overall they're healthier and live longer. So when we think about model organisms, what we're doing is activating those genes that I talked about. So essentially turning on those switches that will then activate a specific pathway, like in the example I gave earlier where heat stress causes damaged proteins, you can turn on the switches that will essentially activate pathways that will remove or repair the damaged proteins. So what happens during the aging process is that the capacity to turn on these genes switch on these genes are impaired. So what do we do with this? We really try to increase the capacity of that gene to turn on. So it would be like increasing the electrical circuit's capacity to pump energy into your AC so we can increase the gene's output and in model organisms, this is easy. We can simply overexpress your gene. So what does that mean? If we think about the number of copies a gene has, usually one gene will have one copy, but if we give an organism 50 copies of the same gene, even if we decrease the output by half during aging, you're still having 25 times the gene expression, which will improve the overall outcome. But of course, in humans, you can't just go in and increase the number of copies of a gene. We're not yet there for gene therapy. So what can we do in humans? Well, if we know what specific mechanisms are activated by the gene, we can try to target them with drugs. So use drugs that increase the function of one specific mechanism. So we know many of the genes and mechanisms that get activated when we're exposed to for example, heat stress. So we can try to develop drugs that activate these pathways to essentially hyper-activate the stress response and try to use this to combat aging. On the concept of  hormesis and the benefits of exercise: Hormesis - what it means is that exposure to low levels of stress can activate a beneficial stress response that makes you more resilient to exposure to future stressors. Exercise is exactly this. When you exercise you're stressing out the body, you can get micro-tears and the muscles when you do strength training, and that's what lets the muscles grow and become stronger. Any kind of cardio or any type of fitness will make your body temperature elevate, which will cause a mild heat, stress and exposure to all of these mini stressors during exercise activates all of these stress response pathways that I talked about before. And so when your body faces stress, you essentially become more resilient to it. So athletes tend to be healthier mostly because they have a higher tolerance for stress. Their bodies are better able to mitigate damage associated with stress because their bodies can activate stronger stress responses. So the concept of hormesis is that what doesn't kill you makes you stronger. Every hardship you face makes you more resilient and stronger to face the next one. So truly there's a connection to exercise and fitness as a model of essentially adapting to stress, to essentially combat aging.   On the benefits of stress Yeah, I know we covered a lot today. I went into so many diverse topics, so I just want to summarize everything by, uh, saying Kelly Clarkson sings it right. For sure. She says what doesn't kill you makes you stronger. Definitely true. So while people will always tell you avoid stress, it isn't good for you. I want to just say, well, some stress isn't so bad living a completely stress-free life might actually not be so beneficial. So let yourself experience some good stress, work out, go to the gym, fight off a bully, maybe, immerse yourself in a challenging job. Everything you face in life will make you that much stronger. And who knows. It might even positively impact your lifespan.

Research Assistant Professor Thalida Em Arpawong joins Professor George Shannon to discuss her research to better understand how our genes and environments influence how we respond to stress and adversity and impact how we age. On the definition of bioinformatics and its use in research: “Bioinformatics is a science subfield, but really just refers to a set of tools that we use to collect, analyze, and interpret findings from large volumes of biological data. We use tools like super computers, biostatistical models, computer programming, and specific types of software, while at the same time, integrating biological concepts to guide how we use these tools. So the data we use—we call it “omics” data, for short—includes primarily genomics, transcriptomics, epigenomics, proteomics, metabolomics, that is, all the omics. Here in the school of gerontology, Dean Cohen had a vision of creating a core to help support researchers in their labs that want to use omics data but may not have the background to do so. So, relatedly, with the Genomic Translation Core, we also use bioinformatics to work with human data, to collaborate with biologists. So these biologists work on model organisms for their research, like worms, mice, or yeast, and the biologists who have been granted pilot awards through the Nathan Shock Center because they've made some important discoveries in their model organisms, we work with them to confirm what the relevance is of their findings for human aging processes. It’s an exciting time because through this work together, we have the potential to use the expertise across different disciplines to answer some bigger questions that we haven't been able to previously with regard to cross-species effects of genomics and health.” On her research on how experiences of stress and adversity throughout different developmental stages in life and genetic factors work together to influence emotional and cognitive health as we age: “So we used to think that genetics was much more deterministic, but we now know there are much more complex and interrelated processes occurring. We found that social structures in which we can characterize groups, such as gender, race and ethnicity or social status, are very importantly related to how genes get expressed. Similarly, people's behaviors shape levels of gene regulation and expression, then have downstream effects on immune system health, development of chronic diseases—for example, obesity, heart disease, depression—and even lifespan. So it's becoming more critical to include these key social factors in human research when we evaluate the effects of genomic data on health.” On her research looking at how having early childhood adversity and adulthood adversities affect the level of depressive symptoms when older: “What we found were two main things. First, that there was essentially a dosage effect, so that with each additional childhood adversity, there was an even greater risk for more later-life depressive symptoms, even after the age of 50. And second, the hypothesis that was supported was called stress proliferation, which is essentially the idea that stress begets stress. So therefore, earlier-life adversities are accompanied by more adulthood adversities, and that's how they work together to impact mental health later on.” On the mind-body connection, or the role of mental health in healthy aging: “When we think of psychological factors, such as stress and adversity and socioeconomic hardships, compared to other factors that affect aging, we're finding that there are more influential compared to genetic or biological factors. And in a recent study by Eileen Crimmins, she found that, in particular with mortality and cognitive functioning, these factors explain 25 to 30% of the variance. So that's a significant amount and often much more variance explained than we can detect for something like genetics.” On epigenetics and how our social environment can affect our genetic expression: “We used to work under the assumption that the effect of genes was best studied at the level of a genotype or just what's encoded in our DNA sequences. But we're finding that there's so much more and we need to measure how our DNA has structural changes that occur throughout life that are not in the code itself but actually in our epigenome. So similar to using genetic risk scores, we can actually now calculate these epigenetic risk scores, and those tend to encapsulate things we've been exposed to or behaviors. … There is research on how we react to stressful experiences, how that it gets embedded into our epigenome. And we can quantify some of that using these epigenetic scores.” On the role of education in health outcomes as we age: “Education is important for aging because it's one of the most consistent measures to relate to almost all of the health outcomes that we look at, including cognitive, emotional, physical outcomes, financial outcomes, and mortality. So it's an important aspect, and what we found is that the heritability of educational attainment has been estimated to be around 40%, which then leaves 60% attributable to social influences, or the environment, but unpacking how those genetic factors and environmental factors sort of work together is important if we're looking from the perspective of how to promote more education, especially for those at high risk for some of the negative health outcomes.” On her research looking at psychological resilience in aging: “I appreciate that the aging field is really the only one that embraces the resilience concept in a way that there isn't a sole focus on disease or deficits, but an interest on healthier aging or successful aging from the perspective that there are different processes involved than when avoiding or preventing disease and morbidity.  A lot of my work has focused on psychological resilience in different developmental stages of life, which means evaluating what contributes to people doing better than expected in the face of adversity or challenge. So not just having greater wellbeing or greater health, but having those states despite having been exposed to having to adapt to life insults and significant stress. So what I'm focusing on now is evaluating lifelong effects from adolescents through older adulthood for psychological resilience and how that affects biological aging.” On her research looking at the importance of physical activity across the lifespan: “One of my projects uses the Project Talent Twin and Sibling study to answer the question of ‘Does it matter when somebody is more physically active in earlier life or later life, or do you need both to result in better cognitive and emotional health later on?’ and how much of the determination of those behaviors is nature versus nurture. For instance, how much is physical activity dictated by socioeconomic adversity when growing up or [by] later-life financial constraints? And then with regard to nature, one key finding is that there seems to be very little overlap between earlier and later life physical activities that's due to genetic factors. So I didn't expect to find this, but it's interesting because from a public health perspective, I'm interested in how physical activity is a protective factor against adversity [and] results in better health and how the implications for findings from this work can inform how we design interventions to support how individuals adapt to stress throughout life.” On the concepts of generativity and post-traumatic growth: “There has been a lot of research on generativity and how that relates to a resilience concept called post-traumatic growth. So people who've been through really intense, kind of acute stressful experiences have to reflect and rethink what their life means, what their purpose is, what their direction is in life, how they orient to people and relationships. And one of the things that is very related to gaining more post-traumatic growth is, for older individuals, having this perception of greater generativity because I think there's that relationship to purpose and meaning. And at the same time when you're talking about looking forward, there's that whole concept of future orientation that also is related to higher levels of post-traumatic growth and adaptation post-acute stress and adversity. So I think these are all very intertwined and interesting.” On efforts to study the effects of mindfulness and meditation: “There's that whole field of psychoneuroimmunology that also bears some similar concepts [to transcendence] where there's a lot of researchers who were looking at things like mindfulness, or flow. But the concept of mindfulness, I think, relates to transcendence and there is a whole group of researchers that formed these collaborations with the Dalai Lama, and they were trying to conceptualize how to operationalize these aspects of meditation and other things that we find are beneficial, but we can't really study that clearly. And so there is a whole area that has emerged about the mind and the psyche and how we can use the mind and psyche to manipulate the effects on our immune systems and other aspects of our biology.” On expressing gratitude to research study participants: “I'd really like to thank all the people who participate in surveys. Some who've taken part since high school, in the case of the Project Talent Studies, and allowed us to follow them up over 50 years later, and others who've answered question every two years for almost 30 years, some have given DNA and biological samples. But this method of tracking people's experiences, their natural histories, their biology, and how well these all come together has been absolutely invaluable to research across so many fields. And what we know about life course risk and protective factors for health as we age would not be where it is today without these folks, especially the diverse range of folks involved, so we can make research more relevant to addressing health needs for everyone. So if any of them are listening, a hearty, very grateful, ‘Thank you.’”

Mireille Jacobson is an associate professor in the USC Leonard Davis School and the co-director of the Aging and Cognition Initiative at the USC Schaeffer Center for Health Policy and Economics, where she’s also a senior fellow. She joins Professor George Shannon to discuss her research using economic insights to better understand decision-making around vaccines, palliative care, Alzheimer’s disease and more.  On health economics and the role it plays in healthy aging Health economics really is just the application of economics to health and healthcare…So whether it's time or money or attention, we all have to kind of make what we call trade-offs. Health economics is really thinking about how to make choices in the context of healthcare and health. Economics isn't just relevant, but I think really critical to understanding things like how to incentivize healthcare providers to coordinate care or encourage people to save for retirement. On a recent study (with colleagues at USC, UCLA and Contra Costa Health Services) looking at whether financial incentives could increase vaccination rates among the vaccine-hesitant What we did is we invited unvaccinated members of this health plan, this Medicaid plan to participate in a survey. And some of the people who were in the survey were randomized to receive an offer of financial incentives, either $10 or $50 if they got vaccinated in the next two weeks. Some people saw public health messages several different kinds of public health messages that we used in the survey and others got access to kind of an easy vaccine scheduling link. And I should say all of these, what we call interventions were crossed. So some people got none of them, and some people got financial incentives and a public health message and an easy vaccine scheduling link and kind of everything in between. And then after the fact, we kind of, looked at both what people said they would do. So did they say they were going to get vaccinated after they saw our public health message. And then, more importantly, did they actually go get vaccinated? And unfortunately, none of our nudges actually moved the needle here. So we just found that unlike in other contexts, like flu vaccinations, where we know that financial incentives can really increase uptake, that didn't work in this context. In fact, when we kind of looked at the data more finely and tried to kind of see how different groups responded, we found something actually somewhat troubling, which was that while, while as a whole people didn't respond to the financial incentives, people who said that they supported Trump in the 2020 election, for example, were less likely to get vaccinated if we offered them a financial incentive. The same is true for the kind of older respondents in our survey. You know, the people 65 and over,  most of them had gotten vaccinated, but if we look at the people 40 and over if we offered them a financial incentive, they were also less likely to get vaccinated. ... This is how we interpret the data. They had very strong beliefs about COVID-19 vaccinations, kind of not being a good thing and offering money to them, seemed to have to kind of reaffirm that for them and almost encourage them to dig in their heels further.  The reason I'm so excited about this project is there's been so much discussion about how to move the needle on vaccinations but really very, very little data on actual vaccinations. So most of the work in this area … has been focused on what people would say they would do. So you'd say if I gave you $50, would that increase your likelihood of getting vaccinated? And we were able to both ask that question, as well as look at people's actual vaccinations. And in fact, the funny thing is that we found that often people said they would do things and that just didn't show up. When we looked at their actual vaccinations. So many of the public health messages, we used seemed to increase the likelihood that people said they would get vaccinated in the next, say 30 days. But then when we looked at the actual data, that wasn't the case. On the role of economics in understanding low rates of palliative care usage So palliative care is care from a team of specially trained doctors, nurses, social workers, and chaplains to focus on improving quality of life and reducing the disease burden for seriously ill individuals and their families. It can be provided alongside other treatments to people of any age facing serious ailments. The focus is really on treating pain and other distressing symptoms, addressing family needs, coordinating care, um, really focus on kind of the quality of life of patients and families. And there's actually a wealth of evidence that palliative care can improve quality of life. There's a now-famous study, for patients with advanced lung cancer, that showed that those receiving palliative care, in addition to regular treatment, not only had reduced symptoms of depression and a lower likelihood of hospital admission but also improved survival than those who received regular care.  Kind of a stunning finding. I would say sometimes you know, a payers savings is a health systems loss, right? So the incentives really matter. To the extent that palliative care saves money through a reduction in kind of unnecessary treatments or hospital readmissions, I think traditionally in our healthcare system, that meant a loss for healthcare providers, our system systems really changing,  and hospitals increasingly for Medicare have incentives to kind of lower spending. And so maybe we'll see more of a push towards palliative care and growth in the next decade or so, but I think really up until very recently, it was really at odds with providers incentives to widely offer palliative care. On her research concerning Alzheimer's disease So this is work that I'm, I'm doing mostly with Julie Zissimopoulos at the Schaeffer Center. And she's really the kind of Alzheimer's disease kind of expert. Where I fit in is, is really thinking again about like incentives that different payers face and how that kind of relates to Alzheimer's disease. So we've looked at screening and Medicare, for example, and found perhaps not surprisingly after the fact that beneficiaries who are enrolled in Medicare advantage kind of private Medicare plans were much more likely to say they had received cognitive screening. So to identify or to kind of set people on the path to identifying Alzheimer's disease or other dementia-related dementias, um, then individuals who are enrolled in traditional Medicare. And why I say that's not that surprising at the end of the day, is that Medicare Advantage plans get paid for their enrollees based on what we call a risk-adjusted payment. So based on the severity and extent of disease facing their beneficiaries. And so people have found that they're actually kind of do a better job of screening in general and identifying health conditions of their members. And so this kind of carried over cognitive screenings in the work that we've done. We're also looking right now at, kind of the time path or trajectory of treatment for people who are diagnosed with Alzheimer's disease or related dementias in Medicare, both in, again, traditional Medicare and this Medicare advantage or Medicare managed care plans. An what we find is that actually, people in Medicare in traditional Medicare, where care is, is very fragmented,  are, are much less likely to be diagnosed outside of the hospital or said differently. They're much more likely to be diagnosed in the hospital than those in Medicare advantage and their kind of rate of hospitalization and other service utilization remains much higher than those in Medicare advantage. On top of that, it looks like they're also much more likely to die within a year of their diagnosis. And all of this at least seems to suggest that care really is not as well managed in traditional Medicare plans. On her future research goals I think most of what I'd like to do is to try to take what people think are kind of commonly held beliefs or their instincts about whether it's COVID-19 vaccinations or advanced care planning conversations, and try to test them with data. I think that's kind of really what motivates me at the end of the day, finding data to ask what's happening and can we improve outcomes for patients, for providers, really for everybody?  

Assistant Professor of Gerontology Joseph Saenz joins Professor George Shannon to discuss his ongoing work on rural-urban differences in cognitive ability among older adults in Mexico, as well as whether certain personality factors make people resilient to the negative effects of early-life disadvantage. Quotes from this episode On the focus of his work I focus my research on looking at how it's socioeconomic disadvantage throughout the life course relates with cognitive ability and late life. I'm interested in education. I'm interested in income, wealth and the resources that we have available to us throughout our lives and how this relates with better cognitive functioning, as well as lower dementia risk and the population of older adults of Latino origin here at the United States and also older adults in Mexico. On demographics and differences between rural and urban populations in Mexico One of the things that's very important about the Mexican population is we've seen a lot of demographic changes over the past century. In addition to seeing rapid population aging with the share of the Mexican population aged 60 and over increasing rapidly. We've also seen a large urbanization process where people are going from rural areas to urban areas. For example, back in 1920, only about 70% of the Mexican population lived in rural areas, but by 2010, this had declined to only about 20%. So a lot of people have been going from rural areas to urban areas. And this is important because in Mexico we see a lot of differences of a lot of disparities between urban areas and rural areas. Rural areas tend to be disadvantaged in several ways. They tend to have lower access to education. There's fewer schools for people to go to. And the educational quality that people got, especially if you look at several decades ago was significantly lower quality than their urban counterparts. Also in rural areas, we tend to see higher rates of poverty and various measures of SES. And we also see that the rural population tends to have less access to healthcare. This as the gap between the rural and urban areas in terms of healthcare access has shrunk a little bit over the past couple of decades, but there's still a disparity there. And so when you bring up the idea of the life course and where people live throughout life, I think this is especially important in Mexico, where we saw that rural to urban population shift, that many people who are living in urban areas now were living in rural areas as children.  On his research looking at where people live throughout their lives In this more nuanced approach, what we see is that the people that had the lowest exposure to urban areas throughout life, those who lived in rural areas in early and late life, ended up doing the worst cognitively. And those who are doing the best are the people that lived in urban areas in early life and urban areas that late-life... And what we also see is that compared to people that stayed in rural areas throughout their entire lives, those who went from a rural to an urban area, also show advantages. So what it looks like we're finding in our current studies is that both early life, urban-dwelling and late-life urban dwelling are related with better cognitive ability. And there is an advantage that comes from moving to an urban area throughout life. On the negative impacts of indoor air pollution And then the other reason that we could expect to see these differences between rural and urban areas is that in urban areas, we know that people have high exposure to air pollution from the outdoor environment. When we look at pictures, for instance, say in Mexico City, we see the smoggy skies and we see this high level of air pollution that people are breathing in urban areas. However, in rural areas in Mexico, a significant portion of the population relies on solid cooking fuels. So this could be wood and coal and Mexico is primarily coal if people are using solid fuels for cooking. And when people use these solid fuels for cooking, particularly inside the house, you can imagine how quickly the pollution builds up inside the home. So people in rural areas have greater exposure to air pollution inside the home from solid cooking fuels. And we know that that exposure to air pollution is associated with poor cognitive functioning. And in my own work, looking at the effects of indoor air pollution from solid cooking fuels, I find that people who cook with these solid cooking fuels tend to have lower cognitive functioning and also more rapid cognitive. On the potential to improve outcomes We've seen several large policy changes in Mexico in the past couple of decades that are aimed at improving access to healthcare and primarily in rural areas. And so improvement of access to healthcare, access to health insurance, and regularly seeing doctors are something that we could use to improve cognitive ability and cognitive outcomes of older adults in rural areas. And last on the topic of cooking fuels, we know that one of the challenges and one of the reasons that people in rural areas are more likely to use these solid fuels is because maybe there's not the infrastructure to bring clean cooking fuels such as gas and electricity to more remote rural areas. Policy changes aimed at improving infrastructure to bring clean cooking fuels to rural areas and to educate people on how to cook with clean cooking fuels could be something very important to bridging these disparities that we see across rural and urban Mexico. On the role of cognitive resilience and personality characteristics in overcoming the negative effects of early life disadvantage What cognitive resilience is looking at is one's ability to not show the negative effects of stress. So people who are cognitively resilient can experience stress but don't show effects on cognitive functioning. They look like they're doing okay, cognitively, even though they're experiencing high levels of stress. In my work related to personality, I look at how personality characteristics are related with one's cognitive resilience or one's ability to overcome the negative effects of early life disadvantage. Early life disadvantage, being a stressor that I'm considering. So the personality characteristics that I tend to look at include a locus of control, which is how strongly one feels that he or she has control over their lives. And people who have an internal locus of control tend to think that the things that happen to them are the results of their own work. That they're the results of their own choices. Whereas people who have an external locus of control tend to believe it's external influences that affect their life. And so they're the ones that tend to believe that maybe the bad things or good things that happened to them throughout life are the example are, are the result of luck or of chance. Now, the other personality characteristic that I look at is conscientiousness, which has one's tendency to plan,  one’s tendency to be goal-oriented and to delay gratification. And when we look at the locus of control and when we look at conscientiousness, both of these affect how people tend to cope with stressors. So in my work on personality, what I do is I look at how personality relates with one's ability to overcome those effects. And we see that having an internal locus of control and having a conscientious personality are both independently related with one's ability to overcome the effects of early life disadvantage. On the importance of midlife research We also see a lot of focus on early life, a lot of looking at early life SES, a lot of research looking at education and childhood, but I don't think we see nearly enough work looking at mid-life. I think there's a big gap in our understanding of the courses or the trajectories that people take throughout life. We don't see enough about midlife. So I think this is another area that I'd like to go into more in terms of looking at midlife. So what are the specific occupations that people worked? What are the levels of cognitive stimulation and those activities also looking at midlife, we could also look at people's marital histories when they got married, whether they were married multiple times. So I think there's a lot of information out there on midlife that could be very valuable in predicting where people are going to be 10, 20 or 30 years down the road.

Assistant Professor of Gerontology Andrei Irimia joins Professor George Shannon to discuss brain imaging and brain health, including his work to determine who is most at risk for Alzheimer’s disease after suffering a concussion or traumatic brain injury. Quotes from the episode On who is at risk for traumatic brain injury or TBI and adverse impacts from them Usually, injuries sustained early in life are the least likely to cause issues down the road during the aging process. And in fact, the brain is most robust to brain injuries in the first and second decades of life and injuries sustained during that period have typically the best outcomes and the best rates of recovery. And as we age, it becomes more and more difficult for the brain to recover after a traumatic brain injury. So, older adults, especially those over the age of 65, are at the highest risk for a poor outcome after a concussion or a more severe traumatic brain injury. After the age 40 or 45,  there is a little bit of an increase in the risk for degenerative disease, including Alzheimer's disease. And that risk really increases after age 65. We have a preliminary study where we found that the biological age of the brain increases dramatically after a traumatic brain injury sustained after the age of 65, whereas for concussions sustained before that time, the biological age of the brain does not increase substantially at all. On sex differences in traumatic brain injury impacts It appears that in males, there is a higher risk for sequelae down the road up to about age 65, but for persons who are injured after the age of 65, there's actually a greater risk for atrophy of the brain in females, which is interesting because, as you already know, the risk for Alzheimer's disease is higher in females. And also the onset of Alzheimer's disease is typically after the age of 60 or 65. So one thing that my lab is very interested in is how exactly sex interacts with hormonal changes with the rates of biological brain aging and with other factors in determining the risk for Alzheimer's disease. There have been studies indicating without a doubt that there is an increase in the risk for Alzheimer's disease after traumatic brain injury, especially moderate to severe brain injuries.   On identifying patients at risk for cognitive impairment after brain injury We’ve done a number of studies that have been funded by the National Institutes of Health and the Department of Defense on how we might be able to predict the risk for cognitive decline after traumatic brain injury. And we have studied cohorts of patients with Alzheimer's disease and compared them to healthy control adults who are age and sex match, who did not have a history of neurological disorders or have mental health disease. And, we found that it is actually possible using some tools that involve machine learning to predict the rate of cognitive decline based on acute imaging findings shortly after the injury. And we were able using these techniques to determine that the fact that we can actually identify the patients who are most likely to, uh, be at the highest risk for accelerated cognitive impairment six months or even one year or further after injury based on imaging scans. So this value, I believe is very valuable because it can identify patients who might benefit from additional monitoring and supervision by their clinicians and who might benefit from tailored therapies and from lifestyle changes that might decelerate the rate of cognitive impairment and might decrease the risk for Alzheimer's disease or other neurodegenerative diseases.   On studying the brain and heart health of the Tsimane This is a very interesting and very important project that's been ongoing for essentially 20 years now. And I'm very fortunate to be part of a very large and talented group of interdisciplinary researchers who study the Tsimane people of the lowland Amazon basin in Bolivia. The Tsimane are a group of forager horticulturalists who live a very traditional lifestyle that does not rely on electricity or any of the amenities that we are used to in the industrialized world. They live in villages located in the forest of lowland areas in Bolivia very far from, uh, electricity from paved roads from modern medicine. And the reason they are very interesting to study is because they have profiles, especially pertaining to their cardiovascular health, to their neurological health and to their inflammatory profile that is very similar to that of our ancestors, many thousands of years ago. And here's a lot of interest in whether, Alzheimer's disease, whether cardiovascular disease and, and many other disorders are perhaps, at least in part, the result of a modern industrialized environment, where we have a large amount of processed foods being used, especially here in the United States where we have air pollution, water pollution where we have a lifestyle involving sedentarianism, which is, uh, very common in the United States and elsewhere in industrial life countries. And by contrast that Tsimane live a very active lifestyle and they live off the land. So, the men go hunting in the forest with bow and arrow. Their cooking does not involve trans fats or a lot of the unhealthy fats that are included in many of the processed foods here in the United States. So it's a very interesting natural experiment so to say, because their example allows us to study how Alzheimer's disease and cardiovascular disease might be in fact, predicated on some of the environmental factors that we have here in the United States and in other industrialized countries. And, my part of this collaboration is focused again, on the brain. And we had a study recently in the Journal of Gerontology where we showed that the brain of the Tsimane people after adjusting for head size, have a rate of volume decrease, which is considerably slower than in populations from the United States and Europe. And we found this to be a significant result because the rate of brain atrophy is very highly correlated with the rate of cognitive decline and with the rate of Alzheimer's disease risk. And, in addition to that, the Tsimane have a very low prevalence of cardiovascular disease. And in fact, a couple of years ago, our group published a paper in the Lancet showing that the Tsimane are the population at the lowest risk for cardiovascular disease out of all populations that have been studied by science. So this is a very unique group who seemed to have excellent cardiovascular health. And now with our study on the brain, we have shown that they also have a very slow rate of brain atrophy, which raises the question as to whether our lifestyle here in the United States and in other countries that are industrialized, where we have unhealthy diets and a sedentary lifestyle might actually increase the risk of Alzheimer's and risk of cardiovascular disease to extent that are highly significant.

Instructional Associate Professor of Gerontology Paul Nash joins Professor George Shannon for a conversation on the impacts of ageism, intersectionality and LGBTQ+ issues in aging, and the importance of talking about sexual health with older adults. Quotes from the Episode On stereotypes and the impacts of ageism Well, there are some huge implications when it comes to ageism. So when we look on an individual level, we know that those people who have internalized ageism, so when they've acquired ageist attitudes across the life course, and then they reach older age themselves and they start to internalize those negative perceptions. We know that people that do that tend to walk slower, they tend to be more unstable on their feet, more likely to fall. They also have reduced cognitive functioning. So we actually start to see these stereotypes as we call it embodied. So we call it the stereotype embodiment theory, and we know that older adults have this more negative opinion of aging and being older themselves also have an average life expectancy that is about seven and a half years, less than those people that have a positive attitude about aging. When we look at society, we know that older adults make a huge contribution to society. We talk about billions of dollars a year in things like informal caregiving, even in terms of paid work, but also within the volunteer sector as well. So older adults make a continued service to society and to the economy, but it's often something that is not really discussed this often. So it's not really met. And when we start to prejudice against old people, we actually discriminate against their engagement in society. And as such what we're doing is actually making things an awful lot worse for ourselves. So what we need to do is start to actively embrace older adults and their diversity and understand accurate perceptions of aging rather than these stereotype myths that are widely held. Ageism is essentially prejudice against your future selves. So if we set up an ageist society, now when we read later life for ourselves, then we're going to be living and growing old in that age of society. So we need to start to challenge that younger people need to appreciate that actually having no wrinkles having gray hair or whatever, having wrinkles and gray hair is not a bad thing. Being older is not a bad thing. When we start to see all these anti-aging serums, well, that's kind of a fallacy. It's not going to stop you from aging. Every moment that we're alive, we are aging. Therefore, really the alternative to aging is death. And I don't think many people would like to wish that upon themselves either. When it comes to the wider social problems and the stigmas and things that I think we need to try and do is we need to be very much aware of our own language. And language, as you know, is incredibly powerful. So for example, we might see ageist stereotypes in greeting cards, and we will have a bit of a giggle about that, but, well, that reinforces the stereotypes. That adds to the issues that older people think that well, okay, I'm 60, I'm 70 I'm 80 as well, I must have cognitive impairment. Well, indeed, what we need to do is start to challenge these stereotypes. We have this assumption, or we paint this mental image in our head that all older people are going to be frail. All older people are going to have cognitive impairment. That's just not true. The majority of older adults, even the age of 80 are not going to be living with cognitive impairment. It's a disease state. Yes. We understand that people who, as they age are more likely to develop dementia, but the majority still don't. On intersectionality and LGBT issues in aging We know that the majority of older adults within the LGBT community are likely to be single. They're also less likely to have a biological family, so children of their own. And they're also more likely to be estranged from their own family, which has led really to the development of what we call family of choice, which is really where people surround themselves by friends and friends basically take that role of family within your own life. But that can be kind of challenging unless we have intergenerational family or intergenerational families of choice, because it may, be for example, that a group of people at the same age all start to require support and help at the same sort of times. We have to be very, very conscious of this. And then as I mentioned before, with that intersectionality, when we look at how racism and sexism and homophobia has developed across the last 50 years, we can start to understand then why, for example, gay women of color, and especially trans women of color are subject to the most forms of discrimination, which leads to problems in terms of accessing services, because they don't have faith in healthcare services, in support services, in any formal structure. So we have to make sure that there are targets and health messages. We need to make sure that we are removing some of these intersectional barriers so we can try and aim for a more equitable society. One of the problems that we have within the LGBT community is that there are very few quote-unquote safe spaces. And these often revert around bars around nightclubs, around places, for example, that you might meet with loud music and as an older adult, that might not necessarily be your ideal situation, especially if you're living with cognitive impairment, if you're living with a visual impairment or indeed issues with hearing as well. So we find that older adults often feel slightly isolated from these particular groups, which leads to larger issues with their social network, having reduced social networks and indeed self-isolate. And we start seeing then the problems around social isolation and loneliness that you mentioned earlier, George. And these are huge issues, not just within the LGBT community, but within the older adult population as well. But before we go down that rabbit hole, it is worth mentioning that older adults are not the most lonely in society.  Actually, that is something that we can pass off to the younger generation, which arguably is partly down to that social comparison with social media. On the importance of talking about sex and older adults One of the problems that we've got and this really pervades through research as well, is we have this wide-standing assumption that older adults don't have sex. So as soon as you reach 50 ok and say, you're done, you never have sex again. We know this to be untrue, but research and mostly policy also stopped collecting data about older adults and their sexual health and their sexual behavior as well. So there's a lot of data that we just don't have on this population. So when it comes to sex and sexual health, what we need to do is make sure one, we're engaged in the older adult population and saying, well, we know you're having sex, but let's make sure we can do it in a safe way. We also need to make sure that sexual health screening is available for older adults because we have targeted interventions for youth groups,  for hard-to-reach communities, but we don't have sexual health screening that goes around residential care, for example. And there's no reason why we build that. We also have to be very, very aware that older adults have different relationship styles. So gone are the days where every older adult is in the same relationship that they were in when they were 20 years of age. Indeed,  now we're seeing increased divorce rates. We're seeing open relationships, polyamorous relationships, the same as we're seeing across other age groups as well. So we have to be very aware that for example, condoms, aren't just there to prevent pregnancy, but they're also there for sexual health. And we can take that across to, for example, HIV, where we see now that over 50%, nearly 60% of all those people living with HIV are older adults. And within this population, those are people over the age of 50. And that's been a real challenge, both in terms of healthcare providers also in terms of policy. So really what we need to do is open our minds and address some of these ageist assumptions that we have around older adults, and actually start to work with older adults as well, rather than making these assumptions about this homogenous group, which is exactly the opposite. It's the most heterogeneous group that you're going to get and actually work with them to understand some of these intricacies and understand some of these challenges that have been faced. So again, what we can do is try to make sure that these health messages are targeted and available for these specific groups. If we make these assumptions, the old people don't have sex well, we're automatically cutting them off from research or automatically cutting them off from health services. So really, I think one of the key lines is something that we used very, very widely in the UK. When working with older adults, we should be saying nothing about us without us. We should have that participating in inclusion work with older adults. Don't make assumptions around them and what aging actually entails when actually we've got these experts in the field, as it were, that are largely ignored from social policy and from research.

Julie Zissimopoulos is an associate professor in the USC Price School of Public Policy and the co-director of the Aging and Cognition Program at the USC Schaeffer Center for Health Policy and Economics, where she’s also a senior fellow and the director of two NIA-funded centers that support innovative social science research on dementia. She recently spoke to us about her research using economic insights to better understand the impact of Alzheimer’s disease on individuals, families, caregivers, and society. On the demographics of Alzheimer’s disease: “People are living longer than ever. So, for example, today about 50 million Americans are aged 65 and older. It was about half that in 1950. And by 2050, US census projects about 20% of the population will be 65 and older. And age is one of the foremost risk factors for Alzheimer's and other dementias. So what does this mean for our future? Well, it means that without new treatments or innovations or ways to prevent or delay Alzheimer's and dementia, the number of persons living with this disease will be about 12 million by 2050. The risk of Alzheimer's is really a risk at older ages and it rises dramatically with age. So for individuals 65 to 79, about 7% of them will have dementia. But in your eighties, the risk of dementia is about 20% prevalence. And by 85 and older, if you live that long, about 40% of those persons will have Alzheimer's. It's also much higher for women than men. And that difference is not explained just by the longer lifespans of women compared to men. It's also about one and a half to two times higher for Blacks, Hispanics, American Indians, and indigenous Americans compared to whites. And we know a little bit about what explains some of the differences by race. Some of its explained by education and prevalence of chronic conditions that are associated with higher risk of dementia, like hypertension and diabetes, but it does not explain it all.” On cognitive assessments at wellness visits “We collected data from a nationally representative sample of older Americans to understand better their use of annual wellness visit and the cognitive assessments. And what we found that was only about a quarter of them who received an annual visit also reported receiving a cognitive assessment. And this was higher for beneficiaries who were in Medicare Advantage-type plans versus those who were in the traditional Medicare plans. And this might have an important indication that these traditional benefit plans, the Medicare benefit plans, where there's direct service-related payment for a set of bundled services, like at the annual wellness visit, may not be a very efficient way to increase our cognitive assessments. We also, I think, have some opportunities to improve our policy around cognitive assessments. Right now there's no guidance about what constitutes a cognitive assessment or how it should be performed. So a clinician can use a structured tool, which we have many of, or they might just ask the beneficiary, the patient, if they're concerned about their memory. And so all of these factors may affect whether we are actually providing good early detection or not.” On the costs of Alzheimer’s “Along with the incredible health toll that Alzheimer's and dementia takes on a person and their families, it also takes an incredible, tremendous financial on the person who's living with dementia and their family. Alzheimer's disease leads to cognitive decline slowly destroying the brain functioning. It also leads for many to behavioral and psychiatric disorders and declines in ability to self-care, functional status. And all of this is extremely, extremely costly. So we estimated the costs for all the persons with Alzheimer's disease, other medical care costs in long-term care costs, and it's about $200 billion. But that's only a partial a portion of the costs. So as I mentioned persons with dementia need a lot of care and much of this care is provided by family members, unpaid care. And if you value the hours of family members caregiving, that's about a hundred billion dollars So we're talking about over $300 billion in costs of care for dementia. And this is more than the cost of cancer and heart disease combined . There is a growing literature… looking at what are these impacts on the unpaid care provided by family members and other caregivers. And there's very consistent evidence that there is negative health effects, particularly on mental health. Caregiving for a person with dementia, particularly as the disease progresses from mild symptoms to severe is a very stressful type of caregiving. There's a very long arm of financial impacts. For spouses, wealth is consumed to pay for long-term care. So care in a facility such as a nursing home can cost anywhere between $50-100 thousand a year. And most families don't qualify for Medicare that reimburses for the cost of long-term care. And for adult children who are caregivers there's impacts on their work productivity, their ability to maintain work in the labor force on their income. We don't have, as a nation, national family leave policies to support and pay for time away from work for caring for older family members with dementia or other conditions.” On the need for policy changes “I think one important policy change is we need solutions to support family caregivers in the workplace, compensation programs. But this isn't going to be enough. Demographic trends suggest that family caregiving as the main source of care is likely not sustainable. People are having fewer children and they are more Americans with dementia. So we really need an insurance system to cover long-term care. The current system does not function well who, who take it up, tend to only be those at high risk with very high healthcare costs. So we need to be a little innovative here, maybe consider a voluntary auto enrollment in long-term care insurance with an opt-out much like what has worked well in the retirement savings market. Medicare could also help; we had a new benefit of Part D that covers drug expenditures and protects against very high out-of-pocket spending for those beneficiaries with high drug expenditures. This was very successful. Medicare could do something similar for long-term care, but it will be very costly. So we will need to figure out who will pay, how we will finance this and, and, and who is going to bear the costs of this. Will it be the younger generation through taxes on, say, health insurance premiums? If so, how are we going to make sure that they don't bear the full burden?” On future research goals “I'm very interested in continuing to try to understand how drugs for our chronic conditions are affecting our risk of Alzheimer's. Looking at anti-diabetics right now, and some of those drugs that are potentially increasing risk of Alzheimer's and dementia. I've been working on understanding and reducing barriers to early detection, how we might improve that and have some real impact there. And then there are many policy changes that are happening to Medicare, new benefits and Medicare advantage and these could all impact the care and quality of life for persons living with dementia. And it's important for us to understand what care systems best serve the needs of those individuals, protect against financial impacts for them and their families.” On the importance of social science research “…Social science has a lot to offer in terms of identifying opportunities to reduce risk, reduce disparities in risk and improve quality of life and care, and really reduce financial burden. And at the USC Schaeffer Center for Health Policy and Economics and in collaboration with the school of gerontology, we have two NIH funded centers that support grant awards and mentorship opportunities for social science scholars who are interested in this area of research. Through efforts like this and growing this area of research, I think we can make immediate impact while we hopefully wait for clinical development of that drug that everyone is hoping for.”

Marc Vermulst is an assistant professor of gerontology at the USC Leonard Davis School, who focuses on the role of genetic mutations in human aging and disease. He recently spoke to us about how his research into transcription errors, essentially copying mistakes, aims to strengthen vaccines and delay or prevent diseases.\r\n On transcription errors\r\n …when you go from DNA to a protein, there\'s a short intermediate molecule that needs to be created, and that is an RNA molecule. And so conceivably you can make the wrong proteins … if a mistake occurs in the process of making an RNA molecule and that process is called transcription. So we study how frequently mistakes occur when RNA molecules are generated and what type of impact that has on aging and disease.\r\n When I first started this project the reason why it hadn\'t been studied much was because there was no technique capable of actually finding them, so it was something that we just could not see.  So what my lab did is was we designed a novel tool, a molecular biology tool, that allowed us to find these transcript errors across the entire genome. So it was this massive improvement, and suddenly we could observe things that were previously unobservable and what we discovered with it was that these errors are really, really frequent and when they happen, there are a couple of impacts that they have.\r\n The most important one probably is that they result in incorrect proteins and those proteins tend to fold in the wrong way. Proteins are large 3d molecules. In order to function, this long molecule needs to fold in a particular structure. And when you make a mistake in the generation of that protein, because of a transcript error, the protein tends to misfold and as it turns out, misfolded proteins are a key component of numerous age-related diseases, including Alzheimer\'s disease, Parkinson\'s disease, amyotrophic lateral sclerosis. All of these diseases are caused by misfolded proteins. So, what I think that we really found is a new component of the etiology, the origin of all of these diseases.\r\n … transcription errors occur a hundred to a thousandfold more frequently than genetic changes. So most of the mistakes that occur in proteins are not due to genetic changes, they are due to these transcript errors.\r\n One of the things I\'m really interested in is the occurrence of age-related diseases for example Alzheimer\'s and Parkinson\'s disease. And one of the major questions is why do people get these diseases? There are families that have a mutation that makes them more predisposed to getting these diseases, but that really only explains five to maybe 15% of all of the cases. The remaining 85 to 95%. We really have no clue why these people get these diseases. So what I\'m trying to do is I\'m trying to explain these remaining 85%. \r\n Because all of these diseases are caused by misfolded proteins, and transcription errors cause these misfolded proteins, I think that we have found a new mechanism that can cause these diseases. And if the mechanism is indeed correct that means we can now do something about it. So it\'s really about finding the origin of the disease itself in order to be able to design medicine for it. That\'s one of the major goals. We\'re also asking when aging actually happens.  We have reason to believe that the events that lead to aging can occur many, many years earlier, probably decades. And perhaps in certain cases, the pace of aging is actually set in our twenties or thirties. And that\'s one of the things we\'re trying to prove as well,\r\n On COVID-19\r\n … one of the reasons why viruses become resistant to vaccines or to drugs is because there is always one viral particle that happens to get a mutation that allows it to be resistant. So one of the major things people want to know about viral particles and different kinds of viruses is how fast do mutations accumulate in the genome of these viruses. And they want to do that for two different reasons. First of all, they want to know that because they want to be able to predict how quickly viruses might get resistance to certain treatments or vaccines. The higher the mutation rate, the faster that would happen. Secondly, they want to be able to predict what type of viruses might erupt in the future. So we now know that for example, that a coronavirus has a certain genetic composition, but that composition might be completely different next year or the year afterward. So by doing these mutational analyses, we\'re able to predict hopefully what the virus might look like in the future. So we can better prepare for an outbreak in 2022 or 2023. It\'s  been a really rewarding project.  So the reason why I got into it is because of my interest in genetic mutations and that\'s a key component of the viral particles.\r\n We\'ve used this super powerful big data tool to study how the virus mutates inside cells and we have a couple of different goals with it. First of all, we want to determine how quickly these mutations actually happen. Right? So that will give us an answer as to how quickly viral particles might come up with mutations that make it resistant to certain pigments and vaccines. And we\'ve already heard in on the news that new mutant versions of the virus have come up, right. , it\'s a strain from Brazil, there\'s a strain from England that are more virulent and more dangerous and the initial coronavirus. So that is one of the consequences of the genetic changes.\r\n The virus has a key protein that it needs to make in order to produce the envelope of the virus itself, all kinds of surface proteins and these proteins are essential. So certain genetic changes will destroy those proteins, and that will result in the death of the virus. So if we do a massive analysis of the entire genome of this virus, and we do that over time, what will find is that there are mutations present everywhere on the viral genome, except for those few spots where the mutation kills the actual virus.\r\n So by virtue of looking at locations in the genome, or finding them where mutations do not occur, we can find these Achilles heels of the virus. And that would allow us to guide the development of vaccines to that specific spot. … if we target the vaccine to a spot that cannot be mutated, that means that the virus has two choices. It can either be destroyed by the vaccine or a treatment itself, and in an effort to try to get out of it, it could mutate that position of its genome, but in doing so, it will kill itself, so it\'s a no win situation for the virus. That is one of the goals of this project also.\r\n