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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.

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

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

Mireille Jacobson is an associate professor in the USC Leonard Davis School and the co-director of the Aging and Cognition Initiative at the USC Schaeffer Center for Health Policy and Economics, where she’s also a senior fellow. She joins Professor George Shannon to discuss her research using economic insights to better understand decision-making around vaccines, palliative care, Alzheimer’s disease and more.  On health economics and the role it plays in healthy aging "Health economics really is just the application of economics to health and healthcare… So whether it's time or money or attention, we all have to kind of make what we call trade-offs. Health economics is really thinking about how to make choices in the context of healthcare and health. Economics isn't just relevant, but I think really critical to understanding things like how to incentivize healthcare providers to coordinate care or encourage people to save for retirement." On a recent study (with colleagues at USC, UCLA and Contra Costa Health Services) looking at whether financial incentives could increase vaccination rates among the vaccine-hesitant "What we did is we invited unvaccinated members of this health plan, this Medicaid plan, to participate in a survey. And some of the people who were in the survey were randomized to receive an offer of financial incentives, either $10 or $50, if they got vaccinated in the next two weeks. Some people saw public health messages several different kinds of public health messages that we used in the survey and others got access to kind of an easy vaccine scheduling link. And I should say all of these, what we call interventions, were crossed. So some people got none of them, and some people got financial incentives and a public health message and an easy vaccine scheduling link and kind of everything in between. And then after the fact, we kind of looked at both what people said they would do. So did they say they were going to get vaccinated after they saw our public health message? And then, more importantly, did they actually go get vaccinated? And unfortunately, none of our nudges actually moved the needle here. So we just found that unlike in other contexts, like flu vaccinations, where we know that financial incentives can really increase uptake, that didn't work in this context. In fact, when we kind of looked at the data more finely and tried to kind of see how different groups responded, we found something actually somewhat troubling, which was that while 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?"

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

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

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

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

Marc Vermulst is an assistant professor of gerontology at the USC Leonard Davis School, who focuses on the role of genetic mutations in human aging and disease. He recently spoke to us about how his research into transcription errors, essentially copying mistakes, aims to strengthen vaccines and delay or prevent diseases. 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.

Dr. 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 hyassine@usc.edu, and you can look me up at the USC directory website and I'm happy to help.

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.  

Dr. Kerry Burnight is the chief gerontologist at GrandPad, the creators of an internet-connected tablet designed specifically for seniors. She spoke to us about how the device aims to combat loneliness and abuse and about the sense of purpose that powers her gerontology career. Selected Quotes On being a gerontologist Kerry Burnight: // to this day, if anybody asks me what I do I say I'm a gerontologist // a person who studies aging. And our goal is to try to make aging a better experience for all of us. And then people are right on board. So I think there's like a million different ways to express your gerontology ness. And I honestly feel so like the world is the oyster of undergrad master’s and PhD gerontologist and the only thing that will hold you back is not going for it. On using technology to address loneliness “And so, all things being constant being lonely or socially isolated would put you at greater risk for elder abuse and exploitation, but also at significantly greater risk for cognitive impairment for stroke for heart disease and even mortality. So you're 25% more likely to pass away than those who are not lonely and something. //And so I was thinking, gosh, you know, maybe technology could help us.” On providing a vulnerable senior with a GrandPad “He was able to connect with all of us but without any of the scammers are perpetrators and so he was a guy who listened to jazz music and he loved to listen to it on his GrandPad and we did all these video calls and the reason it was so helpful is because it was so different.”  On considering seniors in technology research and development “Standard technology creates technology targeted and built for those in their 20s and 30s// It was never designed intelligently and to honor you to honor your autonomy. //Many organizations are all about “training seniors” and it's so silly. If you even take one step back and you think, don't train them. It'd be like saying let's train people to wear size two pants. No, you need to make size six pants and size eight pants and size 20 pants not shove people into the tiny pants.”  “Einstein says that the greatest sophistication is simplicity and it's true, like the hardest thing in the world that you can do is to create something simple and it's not because seniors are less than. It's because we have listened. The best thing of my job is that I employ a group of seniors ages 86 to 106 who are called our grand advisors and every step of the way. It is just by listening of what matters and what doesn't matter to people.” On the flexibility of a gerontology degree I say you can literally do anything you're interested in because aging is living// My aspect now is human connection and technology. But, if you're interested in food, you're interested in transportation, if you're interested in entertainment…basically, in my opinion, any facet of being a human in this time of demographic revolution needs a gerontologist to really be thinking at it in a systematic way from what it means from an aging perspective. On the importance of stepping up to help older adults “All you have to do is spend time with older adults and then you realize you don't have the luxury of being shy because it's not about you, it's about what you can do to serve. And actually it was a senior who told me that one time I was speaking, there was a crowd of 1000 and I was getting nervous. And so this older person said to me, ‘you need to get out of your way’. And I got really struck me that I was the one like I'm scared to talk in front of people. I don't want to, blah, blah, blah. Get out of your way because if you're going to help aging and our own aging, then you better get to work.”

Professor John Walsh, vice dean of education at the USC Leonard Davis School joins Professor George Shannon, holder of the Kevin Xu chair in Gerontology for a conversation on how teachers and students can make the most of online instruction and to discuss how our life experiences can help us meet this challenging moment in time, both in the classroom and outside of it. Quotes from this episode: John Walsh On isolation Many students are feeling isolated right now and it's obviously forced isolation and they just want to connect. The  premed class I'm teaching right now, I have 50 students. And, and so here we are, two weeks into the semester and  class ends at the hour 50 minute mark, and I'm having, 10 to 15 students stay afterwards just to hang out and, talk about anything. And they just want to feel connected and, that's a good thing because we got to help them through this. On always learning I always tell my students that I’ve never stopped being a student and that I always want to keep learning. And, so I will deliver a lecture, we'll get centered on a topic and philosophically, I know from my reading and from looking at websites or watching videos about how what we're discussing applies to furthering society or  helping you in the workplace. But I love hearing the actual application from students where they're down, boots on the ground, and they've experienced this. And they may even say, ” those guidelines,  or those principles are all good, however, in my experience…“ And, and then you put that in your back pocket… and then you use that in future lectures. I'm constantly learning  and I tell the students, I don't know everything and I really want to learn from you. On online classrooms: Well, I think this is a game changer. It was forced down our throats with a pandemic, but this is a game changer. We, as a program have always been a leader at USC in terms of online education and we can't stop being a leader. We just got to  keep up on it. These platforms do offer a level of interactivity that we weren't utilizing before. On collaborative exams I was just so amazed and so excited watching the active learning that went on during these collaborative exams. I know now that when we are back in session, // I'm going to be sitting there in the auditorium, I'm going to break people up into groups of six or seven, and they're going to do the collaborative exam right there in the auditorium, because it's, I think it's a really cool way to learn. George Shannon On his transition from elevator repairman to successful actor to USC professor I was 55 years old. I didn't have an undergraduate degree. So I spent two years in undergrad getting my undergraduate degree because I had hundreds of units where they were scattered all over in different things that I had touched upon. And then I went into the  master's program and did that in two years and was accepted into the PhD program. And so yeah, so that's a long winded way of saying there are, there are lots of things that you can do that come to an unexpectedly. I always say, if someone opens a door for you, don't slam it in their face, go walk in and see what's going on, because it might be an opportunity that can change your life in a very positive way as it did for me.  I had four kids and  a couple of wives and lots of bills and, and  I survived all of that  because I  didn't turn my back on something that I had never thought of before. If something presents a change or a mode that you're not expecting, it may be something that can lead you to something that's even more exciting that gives your life more meaning. People ask me if I'm thinking about retiring and I I'm astonished. Of course, I'm first of all, astonished that I'm 80 years old, but secondly, I'm further astonished that anyone would think that I would ever consider retiring as long as I have my faculties about me and I'm able to perform. Because life is an endless performance as long as it lasts. On online classes in some ways, from my perspective, I like Zoom because I have on the screen the 40 or 50 students, so I may have in class and I can pick them out and ask them specific questions instead of being in the auditorium where they're all trying to hide in the back of the room. And so I, I find there are some really some positives from this experience.

Reggie Tucker-Seeley, the Edward L. Schneider Chair in gerontology and an assistant professor at the USC Leonard Davis School is joined by his colleague, Jhumpka Gupta, an associate professor in the global and community health department at George Mason University. The two discuss issues of racism and hate and the implications for health across the life course. Selected quotes: Reggie Tucker-Seeley: "… with the COVID-19 global pandemic, we know that across racial and ethnic groups, that there is differential access to testing, different levels of access to quality healthcare, differences in the navigation of healthcare, differences and caregiving responsibilities, and differences and financial resources to navigate and manage healthcare and caregiving. And these differences have been shown across various health outcomes and almost always Black and indigenous people and other people of color generally fare worse than their white counterparts. Because we have seen this over and over for many health outcomes, many of us health disparities researchers, often state that we are so tired of still just describing the problem, but what does an intervention look like that addresses racism and hate towards Black and Brown people? That is, what this action and this space look like?" Jhumka Gupta: "There are certainly is not a shortage of research describing health disparities, but what I would like to see more supported is the health benefits of explicitly addressing racism, whether that's specific anti-racist policy, or if we are talking about implicit bias training of healthcare professionals, how does that not only change attitudes, if at all, among healthcare workers, but how does this training translate into patient health outcomes? How does this training translate into reduced feelings of being in fight or flight among BiPOC and especially Black patients or on a campus community or a specific city?" Reggie Tucker-Seeley: "I'm reminded of a quote that I've used several times related to when does our knowledge about health disparities move us to collective action. And it's a quote by Sir Jeffrey Vickers from an article he wrote in the New England Journal of medicine in 1958, he stated, 'The landmarks of political economic and social history are the moments when some condition passed from the category of the given to the category of the intolerable. I believe that the history of public health might well be written as a record of successful redefining of the unacceptable.' And I use this quote often. And I think the question is when will anti-Black sentiments in the US across our various systems from education to criminal justice to healthcare move from the tolerated to the unacceptable." Jhumpka Ghupta: "We also know that these circumstances don't just happen randomly. They were purposefully shaped by decades and decades of policies, and they won't be remedied with a one shot or, or simple solution to address health disparities and systemic racism." Reggie Tucker-Seeley: "My first recommendation and its related to the discussion that we are, we are indeed having in the field of public health, is not only to focus on differences across racial ethnic groups, or that is to think of race as a risk factor, but to think about racism as the risk factor - that is to think about not just group membership as being the risk factor, but the experiences of what group membership means as the risk factor." Jhumpka Gupta: (On what prompted them to write their 2016 Huffington Post piece on racism as a public health issue): "We realized that these very critical issues were being discussed more and more in high profile spaces, such as the BET awards, but what was missing was the discussion of health implications. At the same time, it was a presidential election year and the hateful rhetoric of the Trump campaign was only getting worse. And the rhetoric was targeting Black communities, Black and Brown immigrants, refugees, women, and girls, and other communities such as LGBTQ, Muslim, and disabled communities. And for those of us who are trained in and do research in examining health inequities, we could just see the crisis coming. So we wrote the Huffington Post piece to number one, bring the public health lens into the conversation around social injustices by really laying out the decades of literature on how racism and discrimination impact health inequities and 2) to mobilize the public health field to not only study the etiological role of racism and producing patterns of health inequities, but also consider the need to respond to this hateful rhetoric in all spheres of life, outside of academia in our everyday lives." Cited Works: Huffington Post To Promote Public Health, Fight Hate Where We Live, Learn, Work, And Play Health Affairs Asian Americans Facing High COVID-19 Case Fatality TEDx “Experiencing Racism in VR”,  Dr. Courtney Cogburn from Columbia University medium.com “White Academia: Do Better. Higher education has a problem. It’s called White supremacy.” by Professor Jasmine Roberts, The Ohio State University. “See No Stranger: A Memoir and Manifesto of Revolutionary Love” by Valerie Kaur

Donna Benton, research associate professor and director of the USC Family Caregiver Support Center, joins Professor George Shannon to discuss the challenges faced by family caregivers during the coronavirus pandemic and how they can be addressed at individual, community, state, and national levels. Here are some highlights of what she said: On who is a caregiver “Rosalyn Carter who was the wife of one of our former President Jimmy Carter, at one time said that the world kind of divides up into four types of people. Those are people who are currently caregivers, those who will be caregivers, those who know a caregiver, or those who will need a caregiver.” On increased social isolation among caregivers due to COVID-19 “But now this is very different in our pandemic right now because, maybe before with their relative, they were able to say that you were able to go out and go shopping together. Or you could have somebody else come, a neighbor could stop by, and say you know I'm going to go out for a couple of hours, ‘Can you come and sit with mom or dad and while I go out?’ Well you can't do that. You can't bring someone into your home comfortably, safely because now you're putting that person at risk. They probably have some medical condition that makes them at a higher risk for contracting Covid-19. And so the isolation is that the caregiver really can't take what we call respite which is the ability to take a break and to get away from the caregiving situation.” On how to contact a California Caregiver Resource Center ‘Well, pre-COVID and post-COVID, I think it's important that caregivers look for support from both formal agencies that are out there such as, in California we have the California Caregiver Resource Centers that are serving— just focusing on you, the family caregiver across the states. … A lot of it starts with a phone call, so that you have someone that you can talk to that understands what you're going through. … You can start by calling even 1-800-540-4442, so that you can get connected to the right resource center.” On the need for policies to protect caregivers “But what we can do for caregiving is have policies that help relieve some of that care when we're not able— so that we don't always have to make a choice between, say a paycheck and caring for someone, going in sick to work and caring for our relative, being able to sleep and caring for our relative. So we need to have built in policies that allow for breaks, allow for alternatives when we choose to have them there. And all of those things may not be a direct pay to the caregiver, but it provides more options for care, for both the caregiver and the person they're caring for.” On how to advocate for caregivers through personal stories “People get scared about talking to a legislator or their elected official and they go, ‘Well I don't know how to develop policies.’ Well, you know what? You don't have to come up with the wording. What you can do is tell your struggle, tell your story, tell not just the struggles but also why you do what you do. And your story will be enough for the policymakers. They're the ones that need to understand where the gaps are. And to understand what your needs are. And so when you tell your story all you have to add is, ‘And I wish that someone could do blah.’ Don't worry if it's there or not right now. You just give out your wish list.” On the health impacts of caregiving “Twenty-three percent of caregivers say that just by being a family caregiver, their health has been made worse. And why is that? Because they're spending time— they're taking their relatives to the doctor and they're not going to the doctor themselves for their own health care. Because they may not have time to do it. They have to make a choice. I can either get my relative, who is sicker than I am, to the doctor. Or I can go to work. Or I can use my sick time for me. And so, you know, having to make those kinds of choices— that means that we really need to have better policies overall for long term care services and supports in our communities.” On the need for caregivers to take care of themselves too “And again, that's often because we don't see ourselves separate and apart from our role as a caregiver needing, what we call needing your oxygen— putting your oxygen on first. So if we don't care for ourselves we're not going to be there in the long run to care for the person that we want to, but we tend not to want to put the oxygen on first.” On racial and socioeconomic health disparities “You know, the pandemic right now has really just removed that very thin veil that was covering up the health disparities and disparities in social determinants of health in our society right now. Racism has always pushed our African-American, Black, Latino, and other ethnic and racial groups to the margins in terms of how we've set up policies to help them with family care overall. Even when the in-home support services were set up, part of that was that there were not reimbursements for being a caregiver in terms of benefits that you could pay into Social Security or things like that. So that people that worked in domestic work never could, kind of, build up equity for themselves— financial equity. And then when it comes to health disparities right now for the African-American community, diseases like Alzheimer's are considerably higher among that population and we're more at risk because of other health disparities. And that all comes down to the fact that we've had health policies that have not been equal or access to health care has not been equal. And so that our older adult population might be sicker than other populations. And during this during the time of COVID that health disparities have just been shown through the fact that we have much higher rates of death and infection among the African-American population… And we have to look at, you know, where people are living and do we have enough medical facilities in the neighborhood? Do we have enough adult daycares and child care centers in neighborhoods? Do we have enough grocery stores in the neighborhood? And do we have the right types of food and fresh vegetables and things in the neighborhood?” On how to better support dementia caregivers “So I think for dementia, the policies need to be there so that we get better diagnosis, that we have more physicians who are trained to recognize and help family members, that social service and physicians also know where to refer people to once they have a diagnosis of dementia and how to help the family because, you know, it's not going to be— the physician isn't going to be there to help with support groups. They're not going to become the support group person. They're not going to help them navigate, so other social services. But if they make the right referral to, say an Alzheimer's Association or AARP or a California Caregiver Resource Center system. When you make that referral, that actually helps start the process so that the caregiver will have somebody who they can call once, you know, whenever they need to— over the course of many years as the disease progresses, you're going to need different training, different information.”  

Dr. Pinchas Cohen, USC Leonard Davis School dean and a professor of gerontology, medicine and biological sciences joins Chief Communications Officer Orli Belman in a conversation about COVID-19 risk factors and research directions, with a focus on how research focused on delaying aging processes holds promise for improving outcomes for older adults. On the relationship between age and mortality rates: “Older adults are so much more dramatically affected by this terrible pandemic. While of course middle-aged people and young people are affected by this and their rate of infection can be very high, the mortality of younger people is very, very small, but rises dramatically as people age." On vaccine response rates and older adults: “We all know that vaccines are the number one goal for the biomedical industry right now, but some of you may or may not be familiar with the fact that vaccines are extremely efficient in young people, but among older adults, the response to vaccination is sometime very ineffective. For example, flu vaccine has a non-responsiveness rate that approaches 50% in older adults, which are of course the group that needs it the most.”  On the need to develop cytokine storm blockers: “When people look at what actually causes people to perish from COVID 19, it's not so much the viral pneumonia that they suffer from, but rather something known as a cytokine storm that the body responds to the virus was this secretion of inflammatory cytokines like, something called interleukin six and TNF alpha and interferon, which the body then responds to with really shutting down of the lung and eventually death. So the development of blockers of this cytokine storm, are going to be critical. And that's an area that geroscience has been leading for many years.” On the importance of  gerontology and geroscience research: “Post-COVID-19, I think that gerontology education will only become more important. Furthermore, research on the policy and social impact of the pandemic will be prioritized. Our leaders, our thinkers will continue to be at the forefront of that. Research into geroscience, particularly immunosenescence and inflammaging will be a major goal for the National Institutes of Health. Prevention of chronic disease, which has been really the biggest risk factor for older adults will return as a national priority." On how coronaviruses differ from influenza viruses: “Coronaviruses are quite different from influenza viruses. They're biologically unique, very separate. Also, influenza viruses affect primarily the airways, while coronaviruses can attack various parts of the body, but they're deadly when they end up attacking the lungs, which influenza does not. Influenza predisposes the lungs to bacterial infections, which could be lethal. But they're quite distinct. That’s why there are limited lessons that we can learn from influenza when it comes to COVID 19. But we do have enough previous knowledge to allow us to deal with this crisis and for future crises.” On the roles of age, genetic and underlying conditions: “Young people get infected just as easily as old people. The difference is that many young people have a completely asymptomatic course that they're able to have the virus go through their system, develop antibodies, and never have any sign or symptom. The genetic determinants of who is going to get illness as opposed to who's going to remain asymptomatic is something that we totally don't understand. Obviously having poor health is important..but there's also going to be genetic reasons why some people develop or don't develop severe disease and then whether or not you're going to survive, you know, be really sick and, and get better, whether you're going to have a very, very bad outcome." On what matters most: “At a time of great global uncertainty, what matters most is clear now than ever before. Health matters, older adults matter, science and especially geroscience matter. I think that this is going to be a challenging year ahead of us, but together we will prevail.”

Throughout his career, Dr. Tyler Evans ‘02 has been on the front lines of major disease outbreaks around the globe. He was in South Africa at the height of the AIDS crisis and he treated Ebola patients in Sierra Leone. He just joined the New York City Emergency Management Department as the chief medical officer for the COVID-19 branch. The USC Leonard Davis School “Impact Maker” joined Professor John Walsh to discuss the current pandemic, global health, and how students can best serve populations in need. Here are highlights from what he shared: On how we were not prepared for COVID-19 “Folks in public health, especially in the communicable disease world, knew that the greatest sort of threat to society was not necessarily going to be war; it was going to be a microbial onslaught. And if the infrastructure is there, I'm not saying it's not bad, but the risk is definitely mitigated. And we were not there. I mean, we're getting better now. but we were not ready.” On health disparities and vulnerabilities “When we look at variability, even between states and certainly even within states and within cities, and when you look at the granularity, you're going to see a lot of differences, and those differences, I think, really highlight the disparities that naturally exist throughout this country.” “I'm sitting here in a tennis field hospital with incredibly sick people, but they all have what we refer to it as the social determinants of health. They all have a number of chronic comorbidities. They're people that historically don't have a great access to healthcare. So there are a lot of factors involved that have led them to be more vulnerable for adverse consequences.” “We can't move forward in life being afraid to come outside. We can't move forward in life being afraid to touch other people. I do think that the shelter in place measures were a good thing. I don't think that we completely thought out all of the unintended consequences on the most vulnerable populations in the U.S. and abroad when it comes to food insecurity, when it comes to other kinds of chronic diseases or access to care.” On how we are all in this together “I think, hopefully, it'll kind of bring us all together; more solidarity across the world to better understand that we are really all in this together. Despite the fact that the term is a little cliché, I think that if people really listen to what that means, they will grasp onto it and really understand how we focus so much on differences, but the reality is we really are all potentially impacted by this.” On how students can help and find meaning in their work “There are a lot of opportunities to get involved, not just for COVID, but for the prevention or management of other diseases. You don't have to be a physician. You can be a student. But you’ve to find ways where your contribution is not just meaningful to you. I've had a number of really meaningful and translatable, sort of transformational experiences throughout my own life, but we also have to ensure that we're giving back to society when we're doing these internships or whatnot. So finding something that might not be as glamorous but could truly be meaningful and helpful is good. You might be having to create a database or code, or help to develop infrastructure. A lot of the developments are not as sexy and cool and exciting as people think they are. But all of those parts ultimately end up leading to our ability to save lives. So finding your niche, finding something that you're really good at, and doing it, and contributing is important.” “For the students that are watching this, it’s so important that throughout your career, whether it's in medicine or public health, or whatever field you decide, to just try to really do the right thing. Try to lead your career with your moral compass and ultimately try to impact populations that need it the most. And I assure you that ultimately your lives, both professionally and personally, will be very rich and meaningful.” “So the world needs you guys to help populations that are in need, whether it's now, or whether it's building it, or whether it's in acute management. Like I said, it's not just healthcare systems, it's economics… there's so many intersections in our globalized world. And as long as folks really lead with their moral compass, I think they'll have a very meaningful life.”

Cary Kreutzer, associate professor of gerontology and pediatrics and the director of the USC Leonard Davis School’s master of science degree program in Nutrition Healthspan and Longevity, joins Chief Communications Officer Orli Belman in a conversation about how to eat healthy, shop smart, reduce stress and stay connected through food as we practice social isolation due to the Covid-19 virus. Cary Kreutzer quotes from this episode: On staying connected through food                                                                                                                    “I think as we all are sequestered to our homes and may or may not be with extended family, using whatever sources of media to make those connections with family members and reaching out to them to either have them on the line as you're preparing an old family recipe or having them on the line as you're enjoying a meal and feeling as if they're there with you at that meal are all great ideas of how you can bring family in.” On what food items to have on hand “I think as we try to eat more at home, or are in a position where we need to be eating more at home, and are less able to make quick trips to the grocery store, which probably isn't a smart idea, [we should be] looking for foods that have a longer shelf life: those that need to be refrigerated, those that we can store in our freezer, or even looking to canned goods that we can have as a backup plan should we need to grab for those items.” On canned fruits and vegetables “A vegetable is a vegetable, and they all are going to provide vitamins and minerals. [In terms of] the processing of frozen and the processing of canned vegetables or fruits, we lose minimal amounts of nutrients in that processing. Many items are either quick-canned or quick-frozen and we're losing very little nutritional value. … For those that worry about their salt intake, my only caution I would say for canned foods would be to rinse the foods that are canned, that can be rinsed. Many foods like soups or even sauces, you can now buy low salt versions of those just as a way of decreasing and salt intake.” On choosing prepacked fresh produce “I would choose bagged or fresh fruits and vegetables that are in containers, whether it's a bag or whether it's plastic containers. I've toured those food preparation sites where lettuce and other foods are put together, and they're very sanitary with their practices. In a grocery store, we don't know whether people are carrying this virus while they're shopping. If you're going to buy loose carrots and your plan is to cook those carrots, I think you would be fine. But I would not buy something like a raw head of lettuce that I was going to rinse and then chop and put in a salad. I would probably stick to bagged lettuce just to be safe.” On safe supermarket shopping strategies “I would suggest trying to limit the number of times you're going to a store right now. ... It is probably is prudent to try to get what you need once a week, or longer if you can do that. And definitely have a shopping list. Sometimes if it's the store I always go to, I'll try to write things on my list in the order of where I pretty much know they are in the store: all the dairy together, all the canned foods together, all the breads together, meats together so that I can quickly get through that list. … [If you can’t find an item], find someone who you can ask where to find that item so that you can get in and get out quickly.” On take-out food “With picking up food or even having food delivered, try to stay focused on warm foods that you can reheat in the oven or heat up to 180 degrees, which is a warming temperature in the oven. I would only use raw ingredients that you're preparing at home to add to those foods. And I definitely would throw out any packaging that comes with those foods. I'd use my own dishes. I would also throw out bags or plastic or things that they come in and make sure I wash my hands well because we do know that the virus can live on some surfaces longer than others.” On staying hydrated “Avoid foods that cause you to be dehydrated; coffee, as a natural diuretic, as well as alcohol can be dehydrating. Try to focus more on water. Herbal teas are good. You can add squeezed fruit or frozen fruit to a juice if you need to add some flavor for those. With diabetes, you need to watch the amount of sugar-sweetened beverages you're consuming. So limit the juices; while those are good in terms of nutritional value, they're usually pretty high in sugar, and a little bit every day is really all we should be consuming.” On ways to avoid stress eating “I think, for all of us, being aware and recognizing that this can be stressful and coming up with plans for activities … to think of ‘What are all the things that I've been putting off that I can do around the house?’  [such as] weeding, or planting my garden a little bit earlier. Thankfully, we're not restricted with our ability to go out. That could be riding bikes, that could be going for a walk. It doesn't have to be intense exercise. … In my neighborhood, there were some neighbors that were going to have a meet and greet. Many of us have seen the video of Italy and people on their balconies singing together. In my neighborhood, that there were people that were going to go out on their porch and just wave to one another across the street. … You can use all types of social media, whether it's calling friends or family on phones now we can do video chats, we can do Skype through our computer. So lots of ways to connect with other people. I would also say, I know for my religious affiliation, they have sent lots of ideas of how I can stay connected to my religious beliefs and not feel alone. So, reach out to those resources that are provided for whatever your religion may be and work on trying to destress your environment.”

Sean Curran, the Associate Dean of Research at the USC Leonard Davis School and an Associate Professor of Gerontology and Molecular and Computational Biology, joins Professor Geroge Shannon in a conversation about his research toward generating blueprints that can allow an individual to maximize health over the course of their lifespan. Informed by genetics, he is developing the capacity to predict which diets are ideal for a healthy life and which should be avoided. Sean Curran quotes from this episode: On the effect genetic makeup has with fad diets “I think everybody knows somebody who's done a fad diet that had amazing results. And then similarly either tried that diet themselves or knows someone who did the exact same diet, only to find it didn't work at all. I would argue that those two diets or those two ways of changing what you eat probably had the same effect overall. But the reason that the results were different was because of the genetic makeup of the individual. So I think this is a new way of thinking about personalized medicine but taking it from a personalized diet standpoint, where rather than prescribing a one size fits all diet, looking at the genetic makeup of an individual and then one day being able to prescribe to them— here are the types of food that you should avoid and here are the types of food that you should increase consumption of on a daily basis.” On the past research of diets and genetics for aging “So I don't think anyone would argue that both diets and genetics play important roles in how our cells metabolize things and, and how healthy we are and how long we're gonna live. But in the past, the studies that had been done usually look at one specific mutation and in the context of one individual diet. So these are all traditional classical genetic studies. But what we found is actually that diet has a much more powerful role over the lifespan than we originally thought. We've actually found conditions where a diet can be used to mask a genetic mutation.”   On his research of worm’s diets “A lot of studies have shown that worms can actually make a choice to pick one diet versus the other. But I think it's interesting what hasn't really been studied yet is whether or not worms make that decision based on the information that's given to them. Is this diet actually better for them? Is it nutritionally more readily available for them or does it just smell and taste better to them?”   On why food is hard to study with regard to aging “So I would argue food is probably one of the most variable aspects of any individual's life compounded across differences and food that you made over the lifespan. Food and diet is integrated into our society on multiple levels. It's deeply rooted in what your personal tastes are. It's rooted in what your economic status is, what you have the availability to, to actually purchase in the market as well as cultural and family influences as well. So because of this, I think a lot of the research early on focused on changing sort of large factors in diet, particularly studies that either changed the amount of food that you're going to eat or when you were given access to the food.”    On how ‘yoyo’ dieting can be hard to keep up “I think there's a lot of aspects of diet that make changing behavior complicated. One, the thought of depriving yourself of something, whether you really want it or not, I think perhaps has a psychological effect on a lot of people. I also believe that a lot of changes that you'll have to your diet work in the first couple of weeks. So I think the existence of what people think of as yoyo dieting is because when you exert a massive change on what your normal behavior is, your body is trying to adapt to this new and different types of nutrients that you're giving it. Because of that, you probably lose a little bit of weight in the first couple of weeks. After that, your body is used to using the types of nutrients, the types of foods, the amount of calories that you're giving it. It is adapted to the new diet you have.”

Paul Irving, chairman of the Center for the Future of Aging at the Milken Institute and distinguished scholar in residence at the USC Leonard Davis School of Gerontology, joins Professor George Shannon in a conversation that sheds light on the need to prepare for growing older, reasons to resist retiring, the value of volunteering and other opportunities of aging. Paul Irving quotes from this episode: On the importance of planning and preparation “This is the single thing that we all have in common, if we're lucky. We don't have race and gender and ethnicity and religion, but we all have aging. And yet, for some reason, this is something that people don't want to talk about as much as they should [and] don't want to prepare for. So, I think that for all of us who spend time thinking about this, [we should be] talking about it, communicating about it, [and] expressing that urgency. Not just for older adults, but for young people as well.” On the value of volunteering     “[It’s] not just that volunteering and service to youth is good for the beneficiaries, which is kind of intuitive. … The health benefits for the older volunteers are mind blowing. So the point is doing this work is not just good for the world. It's not just good for young people. It's good for your health. Every year, in addition to taking blood and doing all the other things that the doctor does when he or she pushes and prods and pokes, the doctor should say to you, ‘So, tell me about your volunteering,’ and maybe give you a prescription for a little bit more time with young people.” On the benefits of employing intergenerational teams “Older workers and younger workers bring different things to workplaces, different characteristics. The speed, the creativity and the risk-taking characteristics of youth; the balance, multi-sectoral problem solving and opportunity-creating understanding of age; and the understanding of how to navigate environments and get things done. There's some research that suggests that intergenerational teams, that mixed-age teams, actually outperform same age teams of any age. … I think that global employers are beginning to get it. It's beginning to happen in the United States.” On the power of positive portrayals of aging                                                                                                      “Older adults are as diverse as any other population with the same ups and downs. And I think Hollywood can play a really, really important role — and Madison Avenue too — in changing attitudes and, frankly, changing attitudes faster. I'll just add that I think things actually are moving. There's organic change going on now, and the only thing that concerns me is I think it's not going fast enough. So the question is, what can we do to catalyze it, accelerate it, [and] push it?” On the business case for catering to older consumers                                                                                     “Older adults make up a growing percentage of the population.. It's the market of the future. Get over the notion that older adults aren't consuming; get over the notion that older adults can't be attracted to travel and cars and clothes and food and all the rest. Enlightened executives in show business, advertising, etc. should be looking at that market and saying, ‘how do we produce more for this group?’”