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 [email protected]. 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.

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.

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.”