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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.”
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Lauren Brown is an assistant professor at the USC Leonard Davis School. Her research uses publicly available data to uncover the unique difficulties Black Americans face in maintaining physical and psychological well-being as they age. Her lab both challenges the methods used to study older Black adults and strives to increase diversity in data science research with the goal of increasing the visibility of Black and Brown people via data and storytelling.
Quotes from the episodeOn 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.
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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.
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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.
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Dr. Roberto Vicinanza MD and PhD and instructional associate professor of gerontology at the USC Leonard Davis School, and a specialist in geriatric medicine, joins us for a conversation about healthy aging, including tips on how to keep the body and mind functioning for as long as possible.
Quotes from this episodeOn 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."
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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.”
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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.”
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Kate Wilber is the Mary Pickford Chair in Gerontology and director of the Secure Old Age Lab at the USC Leonard Davis School. She's also the co-director of the National Center on Elder Abuse, which is housed at the Keck School of Medicine of USC. She recently spoke to George Shannon about her research, including her work exploring ways to provide long-term care services and supports that allow older adults to be as independent as possible and the challenges and opportunities that technology provides in this area.
Quotes from this episode
On building on lessons learned during the pandemic
“I think a lot of what we saw were challenges that we already knew were there - how fragmented services are, how older adults can be at risk of isolation, how important the home community-based services and programs and opportunities to interact are for everybody. And I think showing the importance of community, which we didn't have during the pandemic, except a bit on social media and phone calls and maybe people getting together outside. So the key question is, how do we take the learning and the recognition of what we already knew into the future to build on these important lessons, to do better with our aging service delivery? I was going to say our aging service delivery system, but that's a huge problem. There isn't a system; there's just a lot of different components of a system.”On innovations in long-term care and supports
“We have to prepare for an aging population. And until recently I felt like we didn't do that great a job preparing, but I see a lot of exciting innovations, which to some extent may have been jump-started a little bit because of the challenges of the pandemic. We have a variety of models of senior living and I think we're going to see more innovation there or the innovations that have been developed take off because they did better in the pandemic too. So if we look at what kind of care was best for older adults who maybe were isolated or need long term services and supports during the pandemic, how do we build on that? And how do we make sure that we translate what we know into reasonable programs and policies.”
On barriers to implementing technology solutions
“People not only need to have some kind of device. They need to have broadband, it needs to work. And we've seen that in some parts of the country, especially in rural areas, broadband it's not available. All the things we take for granted, electricity, water, et cetera, how much is this an essential service that we’ll do a better job providing across the nation in areas where it doesn't exist very effectively now. And then as I said, how do we help people learn? And what are the particular cultural competencies required for trainers? What are the different uses that people want? This gets back to being person-centered and engaging the people that will be the end-user users and understanding what's most effective for them.
There are still a fairly large proportion of older adults who don't have access to any sort of computer; some have smartphones. And there is this notion, I guess, if we build it, they will come. Or if we give it to them, they'll use it, it would be the way of talking about that. But there's a variety of barriers. And if you hand somebody a box with a computer in it and say, ‘There you go, you're now going to go on the other side, the right side of the digital divide.’ They're not. So what can we learn about how to help people use technology in a way that is useful for them effective, meaningful?”
On telehealth
“So this will be a time saver. I think that's pretty clear, but the nursing facilities have to invest in it. The staff have to invest in it. They have to learn how to do it. And one of the things we're seeing is they thought the residents would be the most resistant and they're not. They're like, ’Okay, if I can see my doctor this way, fine.’ But I think the question is, how is it used, where is it most effective and where is it not a good replacement for a physician coming to the facility? So, there's a fair amount of literature developing on this, but I think there's so many exciting innovations that are rolling out and we need to build on what we're learning and make them better and be more effective in the next generation of telehealth and facilities and helping people on the digital divide connect. So all these things are really exciting opportunities to learn how to connect.”
On person-centered care
“So the idea behind person-centered care is that people have different needs. Of course, they also have different preferences, different preferences for care and for services and for supports and for contributing and giving back and primarily and mostly as with all of us, for controlling their lives and the decisions that are made. So person-centered care recognizes that the power should live with the individual in terms of the ability to make decisions about care informed decisions. But I think sometimes, we, as professionals can see, oh, this would be best for this person. And professionals are extremely busy also. And so it kind of overlooks sometimes the person's needs and preferences and working in areas like elder mistreatment and elder self-neglect. A lot of times people have legitimate reasons for wanting things that we don't necessarily think would be the best choice, but person-centered care asks us to really get in touch with what's behind those preferences. And to what extent can we ethically honor them and this is something I see the field doing a much better job thinking about and working on and great things have been written. And the American Geriatric Society a few years ago had an expert panel come together and develop a definition and sort of protocols for this. And I think that's really moving the field.
One more thing I'll say is that ageism contributes here. So we make assumptions about older people that they can't express their preferences adequately. And providers talk to the caregiver, not the older person. Or they say this is what needs to be done. So I think there's also a culture change of recognizing that it's about the older person. And we start with the older person, and that's not to say that there aren't age-related increased likelihoods, but not inevitabilities of memory issues and things of that kind. And so we need to be clear that the person has the capacity to express their preferences, but we start with person-centered. The elder is the person who whatever is happening is happening on behalf of, or for, or with. And that's where we start.”
On students
“That's our future. … Our legacy is you see the students that go through our program and they're very excited about learning and they bring innovation and enthusiasm, and then they go out and do wonderful things and they become the leaders of the field. And you could see that across the board in so many areas.”
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Rong Lu is an associate professor of stem cell biology and regenerative medicine, biomedical engineering, medicine, and gerontology at USC. She joins George Shannon to discuss her research into the complex and surprising behavior of individual blood stem cells and what it could mean for treating diseases associated with aging.
Quotes from this episode
On stem cells and what makes them so promising for medical research
Stem cells are the special cells in the body that can produce other type of cells. So in particular there are two type of stem cells, one called embryonic stem cells that only exist in the embryonic stages. And the other type of stem cells are called somatic stem cells that are also exist in adulthood. And these somatic stem cells can produce only a specific subset of the cell types in the body. For example, skin stem cells can only produce skin cells and blood stem cells can only produce blood and immune cells. But all the stem cells share the general special property called self-renewal and differentiation. So differentiation describes their ability to produce a different type of cells and self-renewal refers to their ability of making more of themselves over time and sustain the long-term differentiation and tissue regeneration.
On the ability of stem cells to regenerate as we age
…that's what makes stem cells super special because they are the only long-lasting cells in the body that continuously regenerate and sustain the tissue. But over time, stem cells capacity in terms of self-renewal are reducing and therefore the tissue as homeostasis decline when the body ages.
On whether stem cells might offer protection against age-related immune decline
Sure. So over aging stem cells become less and less competent in producing immune cells. And, the hope is if we can maintain the stem cells capacity over time then we could make the stem cells offer the protection. Again, this is very much a research in progress and many research labs are working on this important question, including my own lab.
On the focus of research in her lab
In our lab, we're interested in understanding how are individual stem cells different from each other and how different stem cells work together to maintain an overall balanced blood pool. And in particular, over aging, we want to understand how individual blood stem cells change during aging and how their change lead to the aging phenotype of the animal. And what we found is that there are a specific subset of blood stem cells that age, particularly faster than the others. And there's also another group of stem cells that actually can change in the opposite way during aging and provide more immune cells and their presence really correlate with the delayed aging phenotype of the animal. So we're very excited about this finding and we're following up on this study using our bar coding tool to track these anti-aging stem cells and study what make them so special.
On the development and use of a tool to label individual cells with unique “barcodes”
The barcoding tool was developed a couple of decades ago by several labs simultaneously. At that time they used the viral insertion site as a marker to track individual cells.
So about 10 to 20 years ago, high throughput sequencing technology started to emerge. And at that time, I started to combine the new capacity of this high throughput sequencing to quantify the cellular behavior at a single cell level. So instead of using viral insertion site, I provide a particular DNA barcode sequence into the virus and use that as a marker to track individual cells. And what this allow us is a high precise quantification of the cellular behavior and also the high throughput that is needed to track hundreds and thousands of stem cells in the body.
We can use this tool to study cancer cells and understand the heterogeneity among individual cancer cells. For example, a recent study from my group used it to track the primary acute lymphoblastic leukemia cells in xenograph mouse model. And what we found is that individual leukemia cells have different ability to grow to metastasize and to respond to the drug treatment. And we found that some cancer stem cells that are particularly resistant to drugs to drug treatment In particular, some leukemia cells that are particular resistant to chemotherapy treatment, exhibit distinct gene expression signature compared to others.
On gene expression signatures
The gene expression signature means these particular subset of cells express a distinct subset of genes that make them different and potentially may cause their specific drug response behavior. So these particular gene expression signature can allow us first to identify these cells and to detect whether these cells exists and whether the patient has the potential of resist chemotherapy. And secondly, these gene expression signature can also be potential drug treatment targets to allow us to particularly target these cancer or leukemia cells in the therapeutic treatment.
On future directions in aging research
So in the context of aging, we are very excited about our recent discovery of these anti-aging, uh, stem cells. And we would like to further understand how to activate these anti-aging behavior and how to expand their function in the animal. And we are also very excited about our discovery on the cellular heterogeneity in disease, in particular, in their response to chemo drug treatment. And we would like to further identify the potential functions of the gene expression signature that we discovered. In addition, we also want to understand whether the microenvironment of the stem cell play a role in terms of instructing their heterogeneous behavior.
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Assistant Professor of Gerontology Ryo Sanabria joins Professor George Shannon to discuss their research seeking to understand why stress response pathways break down as we grow older and whether there may be ways to delay that breakdown and potentially promote healthier lifespans.
Quotes from this episode
On the definition of stress:
Stress can come in so many different forms and flavors. It can come in the form of something external, something like heat stress. For example, being out in the desert heat, it can be something as similar to cold stress of a winter storm, or even something like a bacterial or viral infection… Stress can also be internal though. It's not only external. When we think of humans, we can think of big things like mental stress, emotional stress, social and societal stressors. So really the definition of stress is pretty large. And just to say anything that causes some kind of adverse reaction to the body is a stress. And so we study all of these various types of stresses and how it impacts our bodies, our health, and of course aging.
On how our cells respond to stress:
The response to stress within the cell is simply to activate mechanisms that prevent damage. And the main way that this happens is to turn on genes. So genes encode specific types of proteins and processes and mechanisms that are important to mitigate the stress. So it's like essentially activating or turning on a switch that has some kind of functional output, similar to how you will just flip a switch to turn on a fan or an air conditioner. So you can cool down the house. Exactly in the same way, the cells will switch on jeans that can activate pathways that prevent or mitigate that is associated with exposure to stress. So for example, when we are under heat stress, our cells will turn on the mechanisms and pathways that will essentially alleviate damage associated with heat stress, such as damaging proteins or things like that, that happen under heat stress. So the cell is essentially trying to repair or discard damaged proteins that happen with exposure to heat.
On efforts to give older person to have a younger person’s ability to deal with stress
We know that the capacity to deal with stress declines during the aging process. So the question is if we give an older person, a younger person's capacity to deal with stress, would that actually combat aging? So if we go back to example again, before, if I give the grandmother her grandchild's capacity to deal with desert heat, we know that she'll be more resilient to the heat. She'll likely survive the desert, but generally, would she actually be healthier overall as well? Would she be in a sense younger? And the answer in most model organisms that we study is yes. When we give an old organism, a young organism's capacity to deal with stress, not only can they handle that specific stress better, but overall they're healthier and live longer.
So when we think about model organisms, what we're doing is activating those genes that I talked about. So essentially turning on those switches that will then activate a specific pathway, like in the example I gave earlier where heat stress causes damaged proteins, you can turn on the switches that will essentially activate pathways that will remove or repair the damaged proteins. So what happens during the aging process is that the capacity to turn on these genes switch on these genes are impaired.
So what do we do with this? We really try to increase the capacity of that gene to turn on. So it would be like increasing the electrical circuit's capacity to pump energy into your AC so we can increase the gene's output and in model organisms, this is easy. We can simply overexpress your gene. So what does that mean? If we think about the number of copies a gene has, usually one gene will have one copy, but if we give an organism 50 copies of the same gene, even if we decrease the output by half during aging, you're still having 25 times the gene expression, which will improve the overall outcome.
But of course, in humans, you can't just go in and increase the number of copies of a gene. We're not yet there for gene therapy. So what can we do in humans? Well, if we know what specific mechanisms are activated by the gene, we can try to target them with drugs. So use drugs that increase the function of one specific mechanism. So we know many of the genes and mechanisms that get activated when we're exposed to for example, heat stress. So we can try to develop drugs that activate these pathways to essentially hyper-activate the stress response and try to use this to combat aging.
On the concept of hormesis and the benefits of exercise:
Hormesis - what it means is that exposure to low levels of stress can activate a beneficial stress response that makes you more resilient to exposure to future stressors. Exercise is exactly this. When you exercise you're stressing out the body, you can get micro-tears and the muscles when you do strength training, and that's what lets the muscles grow and become stronger. Any kind of cardio or any type of fitness will make your body temperature elevate, which will cause a mild heat, stress and exposure to all of these mini stressors during exercise activates all of these stress response pathways that I talked about before. And so when your body faces stress, you essentially become more resilient to it. So athletes tend to be healthier mostly because they have a higher tolerance for stress. Their bodies are better able to mitigate damage associated with stress because their bodies can activate stronger stress responses.
So the concept of hormesis is that what doesn't kill you makes you stronger. Every hardship you face makes you more resilient and stronger to face the next one. So truly there's a connection to exercise and fitness as a model of essentially adapting to stress, to essentially combat aging.
On the benefits of stress
Yeah, I know we covered a lot today. I went into so many diverse topics, so I just want to summarize everything by, uh, saying Kelly Clarkson sings it right. For sure. She says what doesn't kill you makes you stronger. Definitely true. So while people will always tell you avoid stress, it isn't good for you. I want to just say, well, some stress isn't so bad living a completely stress-free life might actually not be so beneficial. So let yourself experience some good stress, work out, go to the gym, fight off a bully, maybe, immerse yourself in a challenging job. Everything you face in life will make you that much stronger. And who knows. It might even positively impact your lifespan.
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Research Assistant Professor Thalida Em Arpawong joins Professor George Shannon to discuss her research to better understand how our genes and environments influence how we respond to stress and adversity and impact how we age.
On the definition of bioinformatics and its use in research
“Bioinformatics is a science subfield, but really just refers to a set of tools that we use to collect, analyze, and interpret findings from large volumes of biological data. We use tools like super computers, biostatistical models, computer programming, and specific types of software, while at the same time, integrating biological concepts to guide how we use these tools. So the data we use—we call it “omics” data, for short—includes primarily genomics, transcriptomics, epigenomics, proteomics, metabolomics, that is, all the omics. Here in the school of gerontology, Dean Cohen had a vision of creating a core to help support researchers in their labs that want to use omics data but may not have the background to do so.
So, relatedly, with the Genomic Translation Core, we also use bioinformatics to work with human data, to collaborate with biologists. So these biologists work on model organisms for their research, like worms, mice, or yeast, and the biologists who have been granted pilot awards through the Nathan Shock Center because they've made some important discoveries in their model organisms, we work with them to confirm what the relevance is of their findings for human aging processes. It’s an exciting time because through this work together, we have the potential to use the expertise across different disciplines to answer some bigger questions that we haven't been able to previously with regard to cross-species effects of genomics and health.”
On her research on how experiences of stress and adversity throughout different developmental stages in life and genetic factors work together to influence emotional and cognitive health as we age
“So we used to think that genetics was much more deterministic, but we now know there are much more complex and interrelated processes occurring. We found that social structures in which we can characterize groups, such as gender, race and ethnicity or social status, are very importantly related to how genes get expressed. Similarly, people's behaviors shape levels of gene regulation and expression, then have downstream effects on immune system health, development of chronic diseases—for example, obesity, heart disease, depression—and even lifespan. So it's becoming more critical to include these key social factors in human research when we evaluate the effects of genomic data on health.”
On her research looking at how having early childhood adversity and adulthood adversities affect the level of depressive symptoms when older
“What we found were two main things. First, that there was essentially a dosage effect, so that with each additional childhood adversity, there was an even greater risk for more later-life depressive symptoms, even after the age of 50. And second, the hypothesis that was supported was called stress proliferation, which is essentially the idea that stress begets stress. So therefore, earlier-life adversities are accompanied by more adulthood adversities, and that's how they work together to impact mental health later on.”
On the mind-body connection, or the role of mental health in healthy aging
“When we think of psychological factors, such as stress and adversity and socioeconomic hardships, compared to other factors that affect aging, we're finding that there are more influential compared to genetic or biological factors. And in a recent study by Eileen Crimmins, she found that, in particular with mortality and cognitive functioning, these factors explain 25 to 30% of the variance. So that's a significant amount and often much more variance explained than we can detect for something like genetics.”
On epigenetics and how our social environment can affect our genetic expression
“We used to work under the assumption that the effect of genes was best studied at the level of a genotype or just what's encoded in our DNA sequences. But we're finding that there's so much more and we need to measure how our DNA has structural changes that occur throughout life that are not in the code itself but actually in our epigenome. So similar to using genetic risk scores, we can actually now calculate these epigenetic risk scores, and those tend to encapsulate things we've been exposed to or behaviors. … There is research on how we react to stressful experiences, how that it gets embedded into our epigenome. And we can quantify some of that using these epigenetic scores.”
On the role of education in health outcomes as we age
“Education is important for aging because it's one of the most consistent measures to relate to almost all of the health outcomes that we look at, including cognitive, emotional, physical outcomes, financial outcomes, and mortality. So it's an important aspect, and what we found is that the heritability of educational attainment has been estimated to be around 40%, which then leaves 60% attributable to social influences, or the environment, but unpacking how those genetic factors and environmental factors sort of work together is important if we're looking from the perspective of how to promote more education, especially for those at high risk for some of the negative health outcomes.”
On her research looking at psychological resilience in aging
“I appreciate that the aging field is really the only one that embraces the resilience concept in a way that there isn't a sole focus on disease or deficits, but an interest on healthier aging or successful aging from the perspective that there are different processes involved than when avoiding or preventing disease and morbidity.
A lot of my work has focused on psychological resilience in different developmental stages of life, which means evaluating what contributes to people doing better than expected in the face of adversity or challenge. So not just having greater wellbeing or greater health, but having those states despite having been exposed to having to adapt to life insults and significant stress. So what I'm focusing on now is evaluating lifelong effects from adolescents through older adulthood for psychological resilience and how that affects biological aging.”
On her research looking at the importance of physical activity across the lifespan
“One of my projects uses the Project Talent Twin and Sibling study to answer the question of ‘Does it matter when somebody is more physically active in earlier life or later life, or do you need both to result in better cognitive and emotional health later on?’ and how much of the determination of those behaviors is nature versus nurture. For instance, how much is physical activity dictated by socioeconomic adversity when growing up or [by] later-life financial constraints? And then with regard to nature, one key finding is that there seems to be very little overlap between earlier and later life physical activities that's due to genetic factors. So I didn't expect to find this, but it's interesting because from a public health perspective, I'm interested in how physical activity is a protective factor against adversity [and] results in better health and how the implications for findings from this work can inform how we design interventions to support how individuals adapt to stress throughout life.”
On the concepts of generativity and post-traumatic growth
“There has been a lot of research on generativity and how that relates to a resilience concept called post-traumatic growth. So people who've been through really intense, kind of acute stressful experiences have to reflect and rethink what their life means, what their purpose is, what their direction is in life, how they orient to people and relationships. And one of the things that is very related to gaining more post-traumatic growth is, for older individuals, having this perception of greater generativity because I think there's that relationship to purpose and meaning. And at the same time when you're talking about looking forward, there's that whole concept of future orientation that also is related to higher levels of post-traumatic growth and adaptation post-acute stress and adversity. So I think these are all very intertwined and interesting.”
On efforts to study the effects of mindfulness and meditation
“There's that whole field of psychoneuroimmunology that also bears some similar concepts [to transcendence] where there's a lot of researchers who were looking at things like mindfulness, or flow. But the concept of mindfulness, I think, relates to transcendence and there is a whole group of researchers that formed these collaborations with the Dalai Lama, and they were trying to conceptualize how to operationalize these aspects of meditation and other things that we find are beneficial, but we can't really study that clearly. And so there is a whole area that has emerged about the mind and the psyche and how we can use the mind and psyche to manipulate the effects on our immune systems and other aspects of our biology.”
On expressing gratitude to research study participants
“I'd really like to thank all the people who participate in surveys. Some who've taken part since high school, in the case of the Project Talent Studies, and allowed us to follow them up over 50 years later, and others who've answered question every two years for almost 30 years, some have given DNA and biological samples. But this method of tracking people's experiences, their natural histories, their biology, and how well these all come together has been absolutely invaluable to research across so many fields. And what we know about life course risk and protective factors for health as we age would not be where it is today without these folks, especially the diverse range of folks involved, so we can make research more relevant to addressing health needs for everyone. So if any of them are listening, a hearty, very grateful, ‘Thank you.’”
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Mireille Jacobson is an associate professor in the USC Leonard Davis School and the co-director of the Aging and Cognition Initiative at the USC Schaeffer Center for Health Policy and Economics, where she’s also a senior fellow. She joins Professor George Shannon to discuss her research using economic insights to better understand decision-making around vaccines, palliative care, Alzheimer’s disease and more.
On health economics and the role it plays in healthy aging
"Health economics really is just the application of economics to health and healthcare… So whether it's time or money or attention, we all have to kind of make what we call trade-offs. Health economics is really thinking about how to make choices in the context of healthcare and health. Economics isn't just relevant, but I think really critical to understanding things like how to incentivize healthcare providers to coordinate care or encourage people to save for retirement."
On a recent study (with colleagues at USC, UCLA and Contra Costa Health Services) looking at whether financial incentives could increase vaccination rates among the vaccine-hesitant
"What we did is we invited unvaccinated members of this health plan, this Medicaid plan, to participate in a survey. And some of the people who were in the survey were randomized to receive an offer of financial incentives, either $10 or $50, if they got vaccinated in the next two weeks. Some people saw public health messages several different kinds of public health messages that we used in the survey and others got access to kind of an easy vaccine scheduling link.
And I should say all of these, what we call interventions, were crossed. So some people got none of them, and some people got financial incentives and a public health message and an easy vaccine scheduling link and kind of everything in between. And then after the fact, we kind of looked at both what people said they would do. So did they say they were going to get vaccinated after they saw our public health message? And then, more importantly, did they actually go get vaccinated? And unfortunately, none of our nudges actually moved the needle here. So we just found that unlike in other contexts, like flu vaccinations, where we know that financial incentives can really increase uptake, that didn't work in this context.
In fact, when we kind of looked at the data more finely and tried to kind of see how different groups responded, we found something actually somewhat troubling, which was that while as a whole people didn't respond to the financial incentives, people who said that they supported Trump in the 2020 election, for example, were less likely to get vaccinated if we offered them a financial incentive. The same is true for the kind of older respondents in our survey. You know, the people 65 and over, most of them had gotten vaccinated, but if we look at the people 40 and over, if we offered them a financial incentive, they were also less likely to get vaccinated. ... This is how we interpret the data. They had very strong beliefs about COVID-19 vaccinations kind of not being a good thing, and offering money to them seemed to kind of reaffirm that for them and almost encourage them to dig in their heels further.
The reason I'm so excited about this project is there's been so much discussion about how to move the needle on vaccinations but really very, very little data on actual vaccinations. So most of the work in this area … has been focused on what people would say they would do. So you'd say if I gave you $50, would that increase your likelihood of getting vaccinated? And we were able to both ask that question, as well as look at people's actual vaccinations. And in fact, the funny thing is that we found that often people said they would do things and that just didn't show up. When we looked at their actual vaccinations. So many of the public health messages, we used seemed to increase the likelihood that people said they would get vaccinated in the next, say 30 days. But then when we looked at the actual data, that wasn't the case."
On the role of economics in understanding low rates of palliative care usage
"So palliative care is care from a team of specially trained doctors, nurses, social workers, and chaplains to focus on improving quality of life and reducing the disease burden for seriously ill individuals and their families. It can be provided alongside other treatments to people of any age facing serious ailments. The focus is really on treating pain and other distressing symptoms, addressing family needs, coordinating care, really focus on kind of the quality of life of patients and families. And there's actually a wealth of evidence that palliative care can improve quality of life. There's a now-famous study, for patients with advanced lung cancer, that showed that those receiving palliative care, in addition to regular treatment, not only had reduced symptoms of depression and a lower likelihood of hospital admission but also improved survival than those who received regular care. Kind of a stunning finding.
I would say sometimes you know, a payer's savings is a health systems loss, right? So the incentives really matter. To the extent that palliative care saves money through a reduction in kind of unnecessary treatments or hospital readmissions, I think traditionally in our healthcare system, that meant a loss for healthcare providers, our system systems really changing, and hospitals increasingly for Medicare have incentives to kind of lower spending. And so maybe we'll see more of a push towards palliative care and growth in the next decade or so, but I think really up until very recently, it was really at odds with providers incentives to widely offer palliative care."
On her research concerning Alzheimer's disease
"So this is work that I'm doing mostly with Julie Zissimopoulos at the Schaeffer Center. And she's really the kind of Alzheimer's disease kind of expert. Where I fit in is, is really thinking again about incentives that different payers face and how that kind of relates to Alzheimer's disease. So we've looked at screening and Medicare, for example, and found perhaps not surprisingly after the fact that beneficiaries who are enrolled in Medicare advantage, kind of private Medicare plans, were much more likely to say they had received cognitive screening -- so to identify or to kind of set people on the path to identifying Alzheimer's disease or other dementia-related dementias -- than individuals who are enrolled in traditional Medicare. And why I say that's not that surprising at the end of the day, is that Medicare Advantage plans get paid for their enrollees based on what we call a risk-adjusted payment, so based on the severity and extent of disease facing their beneficiaries.
And so people have found that they're actually kind of do a better job of screening in general and identifying health conditions of their members. And so this kind of carried over cognitive screenings in the work that we've done. We're also looking right now at, kind of the time path or trajectory of treatment for people who are diagnosed with Alzheimer's disease or related dementias in Medicare, both in, again, traditional Medicare and this Medicare advantage or Medicare managed care plans. And what we find is that actually, people in Medicare, in traditional Medicare, where care is very fragmented, are much less likely to be diagnosed outside of the hospital. Said differently, they're much more likely to be diagnosed in the hospital than those in Medicare advantage and their rate of hospitalization and other service utilization remains much higher than those in Medicare advantage. On top of that, it looks like they're also much more likely to die within a year of their diagnosis. And all of this at least seems to suggest that care really is not as well managed in traditional Medicare plans."
On her future research goals
"I think most of what I'd like to do is to try to take what people think are kind of commonly held beliefs or their instincts about, whether it's COVID-19 vaccinations or advanced care planning conversations, and try to test them with data. I think that's kind of really what motivates me at the end of the day, finding data to ask what's happening and can we improve outcomes for patients, for providers, really for everybody?"
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Assistant Professor of Gerontology Joseph Saenz joins Professor George Shannon to discuss his ongoing work on rural-urban differences in cognitive ability among older adults in Mexico, as well as whether certain personality factors make people resilient to the negative effects of early-life disadvantage.
Quotes from this episodeOn the focus of his work
I focus my research on looking at how it's socioeconomic disadvantage throughout the life course relates with cognitive ability and late life. I'm interested in education. I'm interested in income, wealth and the resources that we have available to us throughout our lives and how this relates with better cognitive functioning, as well as lower dementia risk and the population of older adults of Latino origin here at the United States and also older adults in Mexico.
On demographics and differences between rural and urban populations in Mexico
One of the things that's very important about the Mexican population is we've seen a lot of demographic changes over the past century. In addition to seeing rapid population aging with the share of the Mexican population aged 60 and over increasing rapidly. We've also seen a large urbanization process where people are going from rural areas to urban areas. For example, back in 1920, only about 70% of the Mexican population lived in rural areas, but by 2010, this had declined to only about 20%. So a lot of people have been going from rural areas to urban areas. And this is important because in Mexico we see a lot of differences of a lot of disparities between urban areas and rural areas.
Rural areas tend to be disadvantaged in several ways. They tend to have lower access to education. There's fewer schools for people to go to. And the educational quality that people got, especially if you look at several decades ago was significantly lower quality than their urban counterparts. Also in rural areas, we tend to see higher rates of poverty and various measures of SES. And we also see that the rural population tends to have less access to healthcare. This as the gap between the rural and urban areas in terms of healthcare access has shrunk a little bit over the past couple of decades, but there's still a disparity there. And so when you bring up the idea of the life course and where people live throughout life, I think this is especially important in Mexico, where we saw that rural to urban population shift, that many people who are living in urban areas now were living in rural areas as children.
On his research looking at where people live throughout their lives
In this more nuanced approach, what we see is that the people that had the lowest exposure to urban areas throughout life, those who lived in rural areas in early and late life, ended up doing the worst cognitively. And those who are doing the best are the people that lived in urban areas in early life and urban areas that late-life... And what we also see is that compared to people that stayed in rural areas throughout their entire lives, those who went from a rural to an urban area, also show advantages. So what it looks like we're finding in our current studies is that both early life, urban-dwelling and late-life urban dwelling are related with better cognitive ability. And there is an advantage that comes from moving to an urban area throughout life.
On the negative impacts of indoor air pollution
And then the other reason that we could expect to see these differences between rural and urban areas is that in urban areas, we know that people have high exposure to air pollution from the outdoor environment. When we look at pictures, for instance, say in Mexico City, we see the smoggy skies and we see this high level of air pollution that people are breathing in urban areas. However, in rural areas in Mexico, a significant portion of the population relies on solid cooking fuels. So this could be wood and coal and Mexico is primarily coal if people are using solid fuels for cooking. And when people use these solid fuels for cooking, particularly inside the house, you can imagine how quickly the pollution builds up inside the home. So people in rural areas have greater exposure to air pollution inside the home from solid cooking fuels. And we know that that exposure to air pollution is associated with poor cognitive functioning. And in my own work, looking at the effects of indoor air pollution from solid cooking fuels, I find that people who cook with these solid cooking fuels tend to have lower cognitive functioning and also more rapid cognitive.
On the potential to improve outcomes
We've seen several large policy changes in Mexico in the past couple of decades that are aimed at improving access to healthcare and primarily in rural areas. And so improvement of access to healthcare, access to health insurance, and regularly seeing doctors are something that we could use to improve cognitive ability and cognitive outcomes of older adults in rural areas. And last on the topic of cooking fuels, we know that one of the challenges and one of the reasons that people in rural areas are more likely to use these solid fuels is because maybe there's not the infrastructure to bring clean cooking fuels such as gas and electricity to more remote rural areas. Policy changes aimed at improving infrastructure to bring clean cooking fuels to rural areas and to educate people on how to cook with clean cooking fuels could be something very important to bridging these disparities that we see across rural and urban Mexico.
On the role of cognitive resilience and personality characteristics in overcoming the negative effects of early life disadvantage
What cognitive resilience is looking at is one's ability to not show the negative effects of stress. So people who are cognitively resilient can experience stress but don't show effects on cognitive functioning. They look like they're doing okay, cognitively, even though they're experiencing high levels of stress. In my work related to personality, I look at how personality characteristics are related with one's cognitive resilience or one's ability to overcome the negative effects of early life disadvantage. Early life disadvantage, being a stressor that I'm considering.
So the personality characteristics that I tend to look at include a locus of control, which is how strongly one feels that he or she has control over their lives. And people who have an internal locus of control tend to think that the things that happen to them are the results of their own work. That they're the results of their own choices. Whereas people who have an external locus of control tend to believe it's external influences that affect their life. And so they're the ones that tend to believe that maybe the bad things or good things that happened to them throughout life are the example are, are the result of luck or of chance.
Now, the other personality characteristic that I look at is conscientiousness, which has one's tendency to plan, one’s tendency to be goal-oriented and to delay gratification. And when we look at the locus of control and when we look at conscientiousness, both of these affect how people tend to cope with stressors. So in my work on personality, what I do is I look at how personality relates with one's ability to overcome those effects. And we see that having an internal locus of control and having a conscientious personality are both independently related with one's ability to overcome the effects of early life disadvantage.
On the importance of midlife research
We also see a lot of focus on early life, a lot of looking at early life SES, a lot of research looking at education and childhood, but I don't think we see nearly enough work looking at mid-life. I think there's a big gap in our understanding of the courses or the trajectories that people take throughout life. We don't see enough about midlife. So I think this is another area that I'd like to go into more in terms of looking at midlife. So what are the specific occupations that people worked? What are the levels of cognitive stimulation and those activities also looking at midlife, we could also look at people's marital histories when they got married, whether they were married multiple times. So I think there's a lot of information out there on midlife that could be very valuable in predicting where people are going to be 10, 20 or 30 years down the road.
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Assistant Professor of Gerontology Andrei Irimia joins Professor George Shannon to discuss brain imaging and brain health, including his work to determine who is most at risk for Alzheimer’s disease after suffering a concussion or traumatic brain injury.
Quotes from the episodeOn who is at risk for traumatic brain injury or TBI and adverse impacts from them
Usually, injuries sustained early in life are the least likely to cause issues down the road during the aging process. And in fact, the brain is most robust to brain injuries in the first and second decades of life and injuries sustained during that period have typically the best outcomes and the best rates of recovery. And as we age, it becomes more and more difficult for the brain to recover after a traumatic brain injury. So, older adults, especially those over the age of 65, are at the highest risk for a poor outcome after a concussion or a more severe traumatic brain injury.
After the age 40 or 45, there is a little bit of an increase in the risk for degenerative disease, including Alzheimer's disease. And that risk really increases after age 65. We have a preliminary study where we found that the biological age of the brain increases dramatically after a traumatic brain injury sustained after the age of 65, whereas for concussions sustained before that time, the biological age of the brain does not increase substantially at all.
On sex differences in traumatic brain injury impacts
It appears that in males, there is a higher risk for sequelae down the road up to about age 65, but for persons who are injured after the age of 65, there's actually a greater risk for atrophy of the brain in females, which is interesting because, as you already know, the risk for Alzheimer's disease is higher in females. And also the onset of Alzheimer's disease is typically after the age of 60 or 65. So one thing that my lab is very interested in is how exactly sex interacts with hormonal changes with the rates of biological brain aging and with other factors in determining the risk for Alzheimer's disease. There have been studies indicating without a doubt that there is an increase in the risk for Alzheimer's disease after traumatic brain injury, especially moderate to severe brain injuries.
On identifying patients at risk for cognitive impairment after brain injury
We’ve done a number of studies that have been funded by the National Institutes of Health and the Department of Defense on how we might be able to predict the risk for cognitive decline after traumatic brain injury. And we have studied cohorts of patients with Alzheimer's disease and compared them to healthy control adults who are age and sex match, who did not have a history of neurological disorders or have mental health disease. And, we found that it is actually possible using some tools that involve machine learning to predict the rate of cognitive decline based on acute imaging findings shortly after the injury. And we were able using these techniques to determine that the fact that we can actually identify the patients who are most likely to, uh, be at the highest risk for accelerated cognitive impairment six months or even one year or further after injury based on imaging scans. So this value, I believe is very valuable because it can identify patients who might benefit from additional monitoring and supervision by their clinicians and who might benefit from tailored therapies and from lifestyle changes that might decelerate the rate of cognitive impairment and might decrease the risk for Alzheimer's disease or other neurodegenerative diseases.
On studying the brain and heart health of the Tsimane
This is a very interesting and very important project that's been ongoing for essentially 20 years now. And I'm very fortunate to be part of a very large and talented group of interdisciplinary researchers who study the Tsimane people of the lowland Amazon basin in Bolivia. The Tsimane are a group of forager horticulturalists who live a very traditional lifestyle that does not rely on electricity or any of the amenities that we are used to in the industrialized world. They live in villages located in the forest of lowland areas in Bolivia very far from, uh, electricity from paved roads from modern medicine.
And the reason they are very interesting to study is because they have profiles, especially pertaining to their cardiovascular health, to their neurological health and to their inflammatory profile that is very similar to that of our ancestors, many thousands of years ago. And here's a lot of interest in whether, Alzheimer's disease, whether cardiovascular disease and, and many other disorders are perhaps, at least in part, the result of a modern industrialized environment, where we have a large amount of processed foods being used, especially here in the United States where we have air pollution, water pollution where we have a lifestyle involving sedentarianism, which is, uh, very common in the United States and elsewhere in industrial life countries. And by contrast that Tsimane live a very active lifestyle and they live off the land. So, the men go hunting in the forest with bow and arrow.
Their cooking does not involve trans fats or a lot of the unhealthy fats that are included in many of the processed foods here in the United States. So it's a very interesting natural experiment so to say, because their example allows us to study how Alzheimer's disease and cardiovascular disease might be in fact, predicated on some of the environmental factors that we have here in the United States and in other industrialized countries. And, my part of this collaboration is focused again, on the brain. And we had a study recently in the Journal of Gerontology where we showed that the brain of the Tsimane people after adjusting for head size, have a rate of volume decrease, which is considerably slower than in populations from the United States and Europe. And we found this to be a significant result because the rate of brain atrophy is very highly correlated with the rate of cognitive decline and with the rate of Alzheimer's disease risk.
And, in addition to that, the Tsimane have a very low prevalence of cardiovascular disease. And in fact, a couple of years ago, our group published a paper in the Lancet showing that the Tsimane are the population at the lowest risk for cardiovascular disease out of all populations that have been studied by science. So this is a very unique group who seemed to have excellent cardiovascular health. And now with our study on the brain, we have shown that they also have a very slow rate of brain atrophy, which raises the question as to whether our lifestyle here in the United States and in other countries that are industrialized, where we have unhealthy diets and a sedentary lifestyle might actually increase the risk of Alzheimer's and risk of cardiovascular disease to extent that are highly significant.
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Instructional Associate Professor of Gerontology Paul Nash joins Professor George Shannon for a conversation on the impacts of ageism, intersectionality and LGBTQ+ issues in aging, and the importance of talking about sexual health with older adults.
Quotes from the episodeOn stereotypes and the impacts of ageism
Well, there are some huge implications when it comes to ageism. So when we look on an individual level, we know that those people who have internalized ageism, so when they've acquired ageist attitudes across the life course, and then they reach older age themselves and they start to internalize those negative perceptions. We know that people that do that tend to walk slower, they tend to be more unstable on their feet, more likely to fall. They also have reduced cognitive functioning. So we actually start to see these stereotypes as we call it embodied. So we call it the stereotype embodiment theory, and we know that older adults have this more negative opinion of aging and being older themselves also have an average life expectancy that is about seven and a half years, less than those people that have a positive attitude about aging.
When we look at society, we know that older adults make a huge contribution to society. We talk about billions of dollars a year in things like informal caregiving, even in terms of paid work, but also within the volunteer sector as well. So older adults make a continued service to society and to the economy, but it's often something that is not really discussed this often. So it's not really met. And when we start to prejudice against old people, we actually discriminate against their engagement in society. And as such what we're doing is actually making things an awful lot worse for ourselves. So what we need to do is start to actively embrace older adults and their diversity and understand accurate perceptions of aging rather than these stereotype myths that are widely held.
Ageism is essentially prejudice against your future selves. So if we set up an ageist society, now when we read later life for ourselves, then we're going to be living and growing old in that age of society. So we need to start to challenge that younger people need to appreciate that actually having no wrinkles having gray hair or whatever, having wrinkles and gray hair is not a bad thing. Being older is not a bad thing. When we start to see all these anti-aging serums, well, that's kind of a fallacy. It's not going to stop you from aging. Every moment that we're alive, we are aging. Therefore, really the alternative to aging is death. And I don't think many people would like to wish that upon themselves either.
When it comes to the wider social problems and the stigmas and things that I think we need to try and do is we need to be very much aware of our own language. And language, as you know, is incredibly powerful. So for example, we might see ageist stereotypes in greeting cards, and we will have a bit of a giggle about that, but, well, that reinforces the stereotypes. That adds to the issues that older people think that well, okay, I'm 60, I'm 70 I'm 80 as well, I must have cognitive impairment. Well, indeed, what we need to do is start to challenge these stereotypes. We have this assumption, or we paint this mental image in our head that all older people are going to be frail. All older people are going to have cognitive impairment. That's just not true. The majority of older adults, even the age of 80 are not going to be living with cognitive impairment. It's a disease state. Yes. We understand that people who, as they age are more likely to develop dementia, but the majority still don't.
On intersectionality and LGBT issues in aging
We know that the majority of older adults within the LGBT community are likely to be single. They're also less likely to have a biological family, so children of their own. And they're also more likely to be estranged from their own family, which has led really to the development of what we call family of choice, which is really where people surround themselves by friends and friends basically take that role of family within your own life. But that can be kind of challenging unless we have intergenerational family or intergenerational families of choice, because it may, be for example, that a group of people at the same age all start to require support and help at the same sort of times.
We have to be very, very conscious of this. And then as I mentioned before, with that intersectionality, when we look at how racism and sexism and homophobia has developed across the last 50 years, we can start to understand then why, for example, gay women of color, and especially trans women of color are subject to the most forms of discrimination, which leads to problems in terms of accessing services, because they don't have faith in healthcare services, in support services, in any formal structure. So we have to make sure that there are targets and health messages. We need to make sure that we are removing some of these intersectional barriers so we can try and aim for a more equitable society.
One of the problems that we have within the LGBT community is that there are very few quote-unquote safe spaces. And these often revert around bars around nightclubs, around places, for example, that you might meet with loud music and as an older adult, that might not necessarily be your ideal situation, especially if you're living with cognitive impairment, if you're living with a visual impairment or indeed issues with hearing as well. So we find that older adults often feel slightly isolated from these particular groups, which leads to larger issues with their social network, having reduced social networks and indeed self-isolate. And we start seeing then the problems around social isolation and loneliness that you mentioned earlier, George. And these are huge issues, not just within the LGBT community, but within the older adult population as well. But before we go down that rabbit hole, it is worth mentioning that older adults are not the most lonely in society. Actually, that is something that we can pass off to the younger generation, which arguably is partly down to that social comparison with social media.
On the importance of talking about sex and older adults
One of the problems that we've got and this really pervades through research as well, is we have this wide-standing assumption that older adults don't have sex. So as soon as you reach 50 ok and say, you're done, you never have sex again. We know this to be untrue, but research and mostly policy also stopped collecting data about older adults and their sexual health and their sexual behavior as well. So there's a lot of data that we just don't have on this population. So when it comes to sex and sexual health, what we need to do is make sure one, we're engaged in the older adult population and saying, well, we know you're having sex, but let's make sure we can do it in a safe way.
We also need to make sure that sexual health screening is available for older adults because we have targeted interventions for youth groups, for hard-to-reach communities, but we don't have sexual health screening that goes around residential care, for example. And there's no reason why we build that. We also have to be very, very aware that older adults have different relationship styles. So gone are the days where every older adult is in the same relationship that they were in when they were 20 years of age. Indeed, now we're seeing increased divorce rates. We're seeing open relationships, polyamorous relationships, the same as we're seeing across other age groups as well. So we have to be very aware that for example, condoms, aren't just there to prevent pregnancy, but they're also there for sexual health. And we can take that across to, for example, HIV, where we see now that over 50%, nearly 60% of all those people living with HIV are older adults. And within this population, those are people over the age of 50. And that's been a real challenge, both in terms of healthcare providers also in terms of policy.
So really what we need to do is open our minds and address some of these ageist assumptions that we have around older adults, and actually start to work with older adults as well, rather than making these assumptions about this homogenous group, which is exactly the opposite. It's the most heterogeneous group that you're going to get and actually work with them to understand some of these intricacies and understand some of these challenges that have been faced. So again, what we can do is try to make sure that these health messages are targeted and available for these specific groups.
If we make these assumptions, the old people don't have sex well, we're automatically cutting them off from research or automatically cutting them off from health services. So really, I think one of the key lines is something that we used very, very widely in the UK. When working with older adults, we should be saying nothing about us without us. We should have that participating in inclusion work with older adults. Don't make assumptions around them and what aging actually entails when actually we've got these experts in the field, as it were, that are largely ignored from social policy and from research.
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Associate Professor of Gerontology and Sociology Jennifer Ailshire joins Professor George Shannon to discuss the impacts of air pollution, global aging and how factors like location and education can influence the way we age.
On the importance of place, or location, on aging
Well, I think of place as one of the greatest supports and constraints on the way that we want to live our lives. So we envision a life for ourselves, our daily decisions, but it's really dependent on where we live. So for instance, I have a goal to be a very physically fit person and to engage in physical activity every day because I know that's one of the best ways to support my own health and aging. But if I live in a place where there aren't a lot of opportunities for me to exercise outdoors, maybe because I don't have access to good park space or other recreational spaces, maybe because of weather problems, it's going to have a constraining power on my individual choices. So a lot of people really want to eat healthy and exercise. And some people live in places that provide a lot of opportunity for that. And other people live in places where actualizing those wishes, those goals is really quite difficult. And then of course there are other factors about environments that really matter in terms of social stressors like crime or feeling safe in your neighborhood, and also more physical characteristics like, air pollution, which is one of the things that I've spent a lot of time studying while at the school of gerontology here at USC.
On air pollution and aging
We think of air as a physical characteristic. It's something that exists in the physical environment, but actually, maybe it's because I've been trained as a sociologist. I think of the air pollution as a social phenomenon because after all it's produced by humans for the most part. And so air pollution is located in places where we have a lot of industrial activity and where there's a lot of car traffic. So some people live in areas where they're closer to those sources of air pollution, and it usually is the case that those are lower income communities because throughout much of our kind of industrialized history in this country, people who could afford to live in a nicer area that was further away from sources of pollution would move and they would end up in a cleaner air environment.
Now here in Los Angeles, we have poor air quality in a lot of places. On average, LA has worse air quality than a lot of cities in the rest of the United States, but there's also pockets of poor air quality here as well. So by the ports of Los Angeles and the ports of Long Beach, for instance, they have much worse air quality because a lot of that shipping and trucking activity, moving goods around. But living in California these days, particularly during fire season means that a lot of us are going to be exposed to poor air quality at some point during the year. And it doesn't at that point, it doesn't really matter what our own socioeconomic resources are. It's really just ways which way the wind blows and where the fires pop up around us.
Most of the research had been conducted in younger populations in children and adolescents and in younger adults, but just in the past 10 years, it's become really clear that older adults are a vulnerable population and that they're more likely to suffer adverse consequences from chronic exposure to air pollution, and also from these acute episodes. So we've done a lot of work trying to grow that area of research in public health air pollution topics. And I think that it has really caught on, and there are a lot more people who will have been working in this area, trying to understand the negative impacts of air pollution on older adults. Our group was most interested in the aging brain. And so most of my research has been in trying to understand how air pollution might impact cognitive aging, increasing risk of cognitive decline or risk of cognitive impairment or the onset of dementia, for instance.
I would say that until recently, although people understood that older adults were a vulnerable population, there wasn't necessarily a lot of direct attention on older adults themselves. So, those of us who work in this area of air pollution and its impact on health among older adults have been saying for a number of years that the federal regulatory standards that are used to regulate air quality, which had been really successful actually at improving our air quality over the past few decades since these regulations were codified and put into action at state and local levels, they tend to be driven by empirical evidence over the entire life course. They don't necessarily focus on the evidence for older adults specifically. And the problem that we've seen with that is that we tend to find that there are adverse health impacts at lower levels of pollution for older adults than there are for younger adults.
So I think that we need to have a louder voice as gerontologists, geriatricians, people who are focused on the other end of the life course, that we need to have more of a voice at the table when these conversations are occurring about how we should be improving air quality. And I think that the EPA and state and local organizations are really receptive to this idea because they also see the need for it and the importance of it. I've already noted in federal documents that they have been highlighting the need to focus more on older adults. But of course we need that expertise kind of among their ranks. So I'd like to see more partnerships between the environmental sciences side and the policymaker and programming side with gerontologists who are focused on this population.
On the protective role of education
The importance of education for healthy lives cannot be overstated. It is simply the most important factor in all of the research that we've conducted and the aging brain is certainly no exception. But actually we think education is particularly important for the brain because we think what happens is that in early life people develop a cognitive reserve or some people call it resilience, but essentially we're building capacity in the brain to be able to deal with insults that might occur later in life. So for instance, something like building up brain volume or neural connections and early life, which can happen in part through education is really important when an individual gets older and they have exposure to toxic chemicals, for instance, that might cross the blood-brain barrier or enter the brain through other means that having that underlying reserve or that ability to deal with these external threats to brain health is really important.
And people with higher levels of education seem to have a little bit more of that capacity. The other important thing about education though, is that it really sets people up for a lifetime of cognitive engagement. So people who have higher levels of education tend to engage in daily activities that are more likely to operate almost like a brain exercise, but it could be something as simple as playing instruments, speaking other languages and learning new things, taking classes later in life and, socializing with people, but anything that kind of keeps you sharp and keeps you on your feet is another good way to cope with the realities of some of the things that we're exposed to that might otherwise weaken the health of our brain.
On global aging and Colombia
I think if you ask most people, if you think of a place where there's aging happening, or there's a large population of older adults, where are those places? And they would say, think of countries like Japan, the United States, the United Kingdom, some of the countries in Western Europe, but aging is happening everywhere, everywhere, even in lower and middle income countries like Colombia that we didn't previously think of in terms of being an aging country. But Colombia, like a lot of countries in Latin America and other countries around the world, is experiencing a couple of key demographic changes like falling fertility rates and increased lifespan. And it's all happening very quickly. So Colombia will experience the same amount of aging in their population in about 20 years that the United States went through and, you know, in 50 plus years and some countries in Europe did and over a hundred year period. So this is a really opportune time to look at these countries that are undergoing this rapid transition to help us better understand aging.
I also think that there is a potential to use the unique context of Colombia to help us gain insights, to help us understand aging in the United States population. So some of my colleagues in Colombia are working on a very famous study of genetics and Alzheimer's disease that are currently the home of one of the world's most important clinical trials of drugs and interventions for Alzheimer's disease at the moment. And it's because they have a cluster of people who are genetically predispositioned to get Alzheimer's disease at a very young age, in their forties and fifties. And so it's created this real world laboratory to understand a disease that we've just really been struggling to get a handle on. The discoveries made in Colombia will have far reaching impacts outside of that country, into the United States and other countries around the world, because we're all sort of dealing with this impending challenge of an increased number of people in the population who will have some form of dementia in their lifetime.
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Julie Zissimopoulos is an associate professor in the USC Price School of Public Policy and the co-director of the Aging and Cognition Program at the USC Schaeffer Center for Health Policy and Economics, where she’s also a senior fellow and the director of two NIA-funded centers that support innovative social science research on dementia.
She recently spoke to us about her research using economic insights to better understand the impact of Alzheimer’s disease on individuals, families, caregivers, and society.
On the demographics of Alzheimer’s disease:
“People are living longer than ever. So, for example, today about 50 million Americans are aged 65 and older. It was about half that in 1950. And by 2050, US census projects about 20% of the population will be 65 and older. And age is one of the foremost risk factors for Alzheimer's and other dementias. So what does this mean for our future? Well, it means that without new treatments or innovations or ways to prevent or delay Alzheimer's and dementia, the number of persons living with this disease will be about 12 million by 2050.
The risk of Alzheimer's is really a risk at older ages and it rises dramatically with age. So for individuals 65 to 79, about 7% of them will have dementia. But in your eighties, the risk of dementia is about 20% prevalence. And by 85 and older, if you live that long, about 40% of those persons will have Alzheimer's. It's also much higher for women than men. And that difference is not explained just by the longer lifespans of women compared to men. It's also about one and a half to two times higher for Blacks, Hispanics, American Indians, and indigenous Americans compared to whites. And we know a little bit about what explains some of the differences by race. Some of its explained by education and prevalence of chronic conditions that are associated with higher risk of dementia, like hypertension and diabetes, but it does not explain it all.”
On cognitive assessments at wellness visits
“We collected data from a nationally representative sample of older Americans to understand better their use of annual wellness visit and the cognitive assessments. And what we found that was only about a quarter of them who received an annual visit also reported receiving a cognitive assessment. And this was higher for beneficiaries who were in Medicare Advantage-type plans versus those who were in the traditional Medicare plans. And this might have an important indication that these traditional benefit plans, the Medicare benefit plans, where there's direct service-related payment for a set of bundled services, like at the annual wellness visit, may not be a very efficient way to increase our cognitive assessments. We also, I think, have some opportunities to improve our policy around cognitive assessments. Right now there's no guidance about what constitutes a cognitive assessment or how it should be performed. So a clinician can use a structured tool, which we have many of, or they might just ask the beneficiary, the patient, if they're concerned about their memory. And so all of these factors may affect whether we are actually providing good early detection or not.”
On the costs of Alzheimer’s
“Along with the incredible health toll that Alzheimer's and dementia takes on a person and their families, it also takes an incredible, tremendous financial on the person who's living with dementia and their family. Alzheimer's disease leads to cognitive decline slowly destroying the brain functioning. It also leads for many to behavioral and psychiatric disorders and declines in ability to self-care, functional status. And all of this is extremely, extremely costly. So we estimated the costs for all the persons with Alzheimer's disease, other medical care costs in long-term care costs, and it's about $200 billion. But that's only a partial a portion of the costs. So as I mentioned persons with dementia need a lot of care and much of this care is provided by family members, unpaid care. And if you value the hours of family members caregiving, that's about a hundred billion dollars So we're talking about over $300 billion in costs of care for dementia. And this is more than the cost of cancer and heart disease combined .
There is a growing literature… looking at what are these impacts on the unpaid care provided by family members and other caregivers. And there's very consistent evidence that there is negative health effects, particularly on mental health. Caregiving for a person with dementia, particularly as the disease progresses from mild symptoms to severe is a very stressful type of caregiving. There's a very long arm of financial impacts. For spouses, wealth is consumed to pay for long-term care. So care in a facility such as a nursing home can cost anywhere between $50-100 thousand a year. And most families don't qualify for Medicare that reimburses for the cost of long-term care. And for adult children who are caregivers there's impacts on their work productivity, their ability to maintain work in the labor force on their income. We don't have, as a nation, national family leave policies to support and pay for time away from work for caring for older family members with dementia or other conditions.”
On the need for policy changes
“I think one important policy change is we need solutions to support family caregivers in the workplace, compensation programs. But this isn't going to be enough. Demographic trends suggest that family caregiving as the main source of care is likely not sustainable. People are having fewer children and they are more Americans with dementia. So we really need an insurance system to cover long-term care. The current system does not function well who, who take it up, tend to only be those at high risk with very high healthcare costs. So we need to be a little innovative here, maybe consider a voluntary auto enrollment in long-term care insurance with an opt-out much like what has worked well in the retirement savings market. Medicare could also help; we had a new benefit of Part D that covers drug expenditures and protects against very high out-of-pocket spending for those beneficiaries with high drug expenditures. This was very successful. Medicare could do something similar for long-term care, but it will be very costly. So we will need to figure out who will pay, how we will finance this and, and, and who is going to bear the costs of this. Will it be the younger generation through taxes on, say, health insurance premiums? If so, how are we going to make sure that they don't bear the full burden?”
On future research goals
“I'm very interested in continuing to try to understand how drugs for our chronic conditions are affecting our risk of Alzheimer's. Looking at anti-diabetics right now, and some of those drugs that are potentially increasing risk of Alzheimer's and dementia. I've been working on understanding and reducing barriers to early detection, how we might improve that and have some real impact there. And then there are many policy changes that are happening to Medicare, new benefits and Medicare advantage and these could all impact the care and quality of life for persons living with dementia. And it's important for us to understand what care systems best serve the needs of those individuals, protect against financial impacts for them and their families.”
On the importance of social science research
“…Social science has a lot to offer in terms of identifying opportunities to reduce risk, reduce disparities in risk and improve quality of life and care, and really reduce financial burden. And at the USC Schaeffer Center for Health Policy and Economics and in collaboration with the school of gerontology, we have two NIH funded centers that support grant awards and mentorship opportunities for social science scholars who are interested in this area of research. Through efforts like this and growing this area of research, I think we can make immediate impact while we hopefully wait for clinical development of that drug that everyone is hoping for.”
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Marc Vermulst is an assistant professor of gerontology at the USC Leonard Davis School, who focuses on the role of genetic mutations in human aging and disease. He recently spoke to us about how his research into transcription errors, essentially copying mistakes, aims to strengthen vaccines and delay or prevent diseases.
On transcription errors
…when you go from DNA to a protein, there's a short intermediate molecule that needs to be created, and that is an RNA molecule. And so conceivably you can make the wrong proteins … if a mistake occurs in the process of making an RNA molecule and that process is called transcription. So we study how frequently mistakes occur when RNA molecules are generated and what type of impact that has on aging and disease.
When I first started this project the reason why it hadn't been studied much was because there was no technique capable of actually finding them, so it was something that we just could not see. So what my lab did is was we designed a novel tool, a molecular biology tool, that allowed us to find these transcript errors across the entire genome. So it was this massive improvement, and suddenly we could observe things that were previously unobservable and what we discovered with it was that these errors are really, really frequent and when they happen, there are a couple of impacts that they have.
The most important one probably is that they result in incorrect proteins and those proteins tend to fold in the wrong way. Proteins are large 3d molecules. In order to function, this long molecule needs to fold in a particular structure. And when you make a mistake in the generation of that protein, because of a transcript error, the protein tends to misfold and as it turns out, misfolded proteins are a key component of numerous age-related diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis. All of these diseases are caused by misfolded proteins. So, what I think that we really found is a new component of the etiology, the origin of all of these diseases.
… transcription errors occur a hundred to a thousandfold more frequently than genetic changes. So most of the mistakes that occur in proteins are not due to genetic changes, they are due to these transcript errors.
One of the things I'm really interested in is the occurrence of age-related diseases for example Alzheimer's and Parkinson's disease. And one of the major questions is why do people get these diseases? There are families that have a mutation that makes them more predisposed to getting these diseases, but that really only explains five to maybe 15% of all of the cases. The remaining 85 to 95%. We really have no clue why these people get these diseases. So what I'm trying to do is I'm trying to explain these remaining 85%.
Because all of these diseases are caused by misfolded proteins, and transcription errors cause these misfolded proteins, I think that we have found a new mechanism that can cause these diseases. And if the mechanism is indeed correct that means we can now do something about it. So it's really about finding the origin of the disease itself in order to be able to design medicine for it. That's one of the major goals. We're also asking when aging actually happens. We have reason to believe that the events that lead to aging can occur many, many years earlier, probably decades. And perhaps in certain cases, the pace of aging is actually set in our twenties or thirties. And that's one of the things we're trying to prove as well,
On COVID-19
… one of the reasons why viruses become resistant to vaccines or to drugs is because there is always one viral particle that happens to get a mutation that allows it to be resistant. So one of the major things people want to know about viral particles and different kinds of viruses is how fast do mutations accumulate in the genome of these viruses. And they want to do that for two different reasons. First of all, they want to know that because they want to be able to predict how quickly viruses might get resistance to certain treatments or vaccines. The higher the mutation rate, the faster that would happen. Secondly, they want to be able to predict what type of viruses might erupt in the future. So we now know that for example, that a coronavirus has a certain genetic composition, but that composition might be completely different next year or the year afterward. So by doing these mutational analyses, we're able to predict hopefully what the virus might look like in the future. So we can better prepare for an outbreak in 2022 or 2023. It's been a really rewarding project. So the reason why I got into it is because of my interest in genetic mutations and that's a key component of the viral particles.
We've used this super powerful big data tool to study how the virus mutates inside cells and we have a couple of different goals with it. First of all, we want to determine how quickly these mutations actually happen. Right? So that will give us an answer as to how quickly viral particles might come up with mutations that make it resistant to certain pigments and vaccines. And we've already heard in on the news that new mutant versions of the virus have come up, right. , it's a strain from Brazil, there's a strain from England that are more virulent and more dangerous and the initial coronavirus. So that is one of the consequences of the genetic changes.
The virus has a key protein that it needs to make in order to produce the envelope of the virus itself, all kinds of surface proteins and these proteins are essential. So certain genetic changes will destroy those proteins, and that will result in the death of the virus. So if we do a massive analysis of the entire genome of this virus, and we do that over time, what will find is that there are mutations present everywhere on the viral genome, except for those few spots where the mutation kills the actual virus.
So by virtue of looking at locations in the genome, or finding them where mutations do not occur, we can find these Achilles heels of the virus. And that would allow us to guide the development of vaccines to that specific spot. … if we target the vaccine to a spot that cannot be mutated, that means that the virus has two choices. It can either be destroyed by the vaccine or a treatment itself, and in an effort to try to get out of it, it could mutate that position of its genome, but in doing so, it will kill itself, so it's a no win situation for the virus. That is one of the goals of this project also.
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Hussein Yassine is a professor of medicine at the Keck School of Medicine at USC and is uncovering links between nutrition, genes, and risk for Alzheimer's disease. He spoke to us about his research on APOE4, omega-3s and inflammation in the brain.
On APOE4 and Alzheimer’s risk
So APOE is a gene on chromosome 19. It exists in the population in three different forms. The two form, not very common, the three form, the most common and the four form, which makes about 20% of the population. The four form, if you get one copy from your parents, your chances of getting Alzheimer's disease increased two to four times. If you inherit two copies, meaning you get one copy from mom and one copy from dad, your chances of getting Alzheimer's, or the odds ratio, goes to 12 times, meaning an APOE4 E4 homozygote, uh, 50% of those homozygotes by the age of 80 will have Alzheimer's disease.
On the work of his lab
My lab is working to understand whether omega-3s can slow down cognitive decline in people at high risk of Alzheimer's disease, based on APOE4. We are working on three different fronts. One, we have basic science models where we study the brains of APOE4 targeted replacement mice. We use brain imaging to study labeled DHA brain uptake in the human brain, and we do clinical trials where we give people omega-3 supplementation and look at outcomes.
On omega-3 supplements versus dietary interventions
At this point in time, we do not have high quality evidence to suggest that supplements make a difference. But we know from landmark observational cohorts, for example, the Framingham in the US, the Triple C in France, the Rotterdam in the Netherlands, and many others that people who consume at least one serving of fatty fish per week have lower risk of developing Alzheimer's disease. In contrast trials that have involved omega-3 supplements have not panned out. And as we discussed, omega-3 supplements might be too late to be given to patients with neurodegeneration because they may not reverse neuronal death. Giving omega-3s to the general population may prove to be very difficult because the majority of people do not develop Alzheimer's. So we need more research before we can recommend supplements. In addition, we don't know exactly what kind of supplements we should be providing, the exact dose, the composition that duration. More research is needed to figure out those questions.
On what can people do to reduce Alzheimer's disease risk
I think timing is key. I think if you know that you are at increased risk based on family history or APOE4 genotype nutritional and lifestyle interventions during middle age will provide you likely the most benefit. Our research and others suggest that between the ages of 45 and 65, those at risk individuals should be on certain lifestyle modifications, whether it is at least one serving of fatty fish per week, or some good exercise regimen. We're not talking about marathon running, maybe three times a week, 15 minutes per day is good enough. Lifestyle modifications, no smoking, reduced consumption of simple sugars to avoid complications of diabetes and obesity, increased intake of green leafy vegetables, which are enriched in polyphenols and antioxidants, good sleep, listening to music, certain forms of meditation, or in some individuals praying. And, uh, all of these factors, we know that have positive effect on mitigating or decreasing the chances of getting Alzheimer's.
One additional factor that I did not discuss is hypertension or blood pressure control. Blood pressure is known as a silent killer, because people have blood pressure, but they don't know that they do so. Blood pressure control, diabetes control, cholesterol control in middle age together with these lifestyle changes can really pay dividends decades later. Once people start having symptoms and we're talking now 60 to 80, they often come to us and they're talking to us about omega-3 intake, about all these changes. And unfortunately at this time, the interventions are not very effective.
On the most important points Dr. Yassine hopes people understand from his research?
The biggest takeaway is that there is a life-course risk of Alzheimer's disease risk in APOE4 carriers that starts shortly after birth. But mainly it takes decades before symptoms start. We know from imaging studies, between the ages of 20 all the way to 60, that the APOE4 brain is compensating to maintain cognition. Once this compensation fails, APOE4 carrier brains starts deteriorating, and you see signs of neurodegeneration and Alzheimer's dementia. Our research emphasizes the importance of a healthy lifestyle, which includes sufficient omega-3 consumption, defined as at least one serving of fatty fish per week, lifestyle factors such as exercise, sleeping, music, meditation, family connections, combating depression, and social isolation, and social isolation is a problem now with COVID. And in addition to that, not smoking and reducing the amount of simple sugars consumed to reduce diabetes and cardiometabolic risk. Those interventions, we all know that they are critical, but our research suggests that there's a critical time to do these interventions during middle age, to prevent the progression to Alzheimer's at the age of 65 to 75. Once patients develop this disease, those interventions become less effective. So this is the greatest takeaway from the research we are doing.
On his message to young people
So my message to young people is that if you have a family history of Alzheimer's disease, or that you know that you are an E4 carrier, plan in advance. Learn about the risks of Alzheimer's disease, learn about the risks of carrying the APOE4 genotype and get informed, because we have cutting-edge research to help you out in preventing the risks of this disease early on.
On the importance of Alzheimer’s research
Up to 25% of individuals carry APOE4. So in a room of a hundred people, 25 people will have one copy of APOE4, that's enormous. And they make the bulk, up to 50%, of patients with Alzheimer's. We have so many APOE4 carriers in the community, and I think more research in this area is very important to the future of mitigating or changing the risk of Alzheimer's disease. We should start early and we should try the best we can to prevent this disease because we know once it happens, it's very difficult to treat.
On how to reach Dr. Yassine
If anybody listening to the podcast has family members with Alzheimer's disease, they are concerned about being an APOE4 carrier and would require more advice or perhaps participate in any of our trials. Please feel free to email me. My email is [email protected], and you can look me up at the USC directory website and I'm happy to help.
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John Tower is a professor of biology and gerontology. He spoke to us about his research on the roles of sex differences and mitochondria in aging.
Highlights from our conversation:
As you may know, in humans, women live longer than men. And the reason for that is not entirely understood and also malfunction of the mitochondria, which is also called the powerhouse of the cell is, directly implicated in aging and multiple aging-related diseases, including Parkinson's disease and Alzheimer's disease and cancer. And so we'd like to understand at a very basic level, why does the mitochondria malfunction during aging and does this, or does this not have, uh, is this related to, or a result of sexual differentiation of the male and female?
While there's no consensus in the aging field on pretty much anything. But, I would say at this point, antagonistic pleiotropy is the most favored model for how the genetics of aging works across species. And the idea is that genes can be beneficial in one context, but detrimental in another context. Specifically they're likely to be beneficial early in life, promoting things like differentiation and growth and sexual reproduction and in the long term, the same genes are detrimental and have a cost during aging.
I've made a complete about face, from thinking that sexual differentiation was not important, to thinking that well, maybe sexual differentiation is actually causative to a large part in the aging process. In other words, in differentiating the male and the female, you set up the situation for sex specific trade-offs between reproduction and aging, and some aspects of these trade-offs are common between the male and the female. And some of them are unique to either the male or the female in that there are pathways that promote a reproduction, but then have a cost for the long-term maintenance of the animal. That's the kind of antagonistic pleiotropy my lab is focusing on right now which is the idea that a gene can be beneficial to one sex, but detrimental to the other, or a gene could be detrimental to each sex in different ways
Across species, we see a decrease in mitochondrial gene expression and mitochondrial gene function during aging and the relevance to sex is that the mitochondria is transmitted to offspring only through the mother. And so this means natural selection can only optimize mitochondrial gene function for the female. This means that the male inherits a mitochondria that is less optimal for his physiology than, than it might be. And so what we see is that mitochondria isolated from female mammal tissues function better than mitochondria isolated from males consistent with this hypothesis. And so this may be one reason why females tend to live longer than males
I think what I would expect is we're going to see sex-specific interventions in aging and aging-related diseases, even diseases common to the male and the female, like Parkinson's and Alzheimer's, that having an intervention that's tailored, to the male or the female will be more efficacious.
- Visa fler
