Drivers of Healthy Longevity

It is my distinct pleasure to be joined by esteemed colleagues up here for this session. My name is Suzy Hong. I'm a professor in the Herbert Wertheim School of Public Health and Human Longevity Science and also Department of Psychiatry here at UC San Diego. And I'm joined here by three active and world-renowned researchers in aging research. Our first speaker will be Dr. Andrea LaCroix. Dr. LaCroix is a distinguished professor at the Herbert Wertheim School of Public Health and Human Longevity Science here at UC San Diego. And her research centers around healthy aging and particularly women's health. Our next speaker is going to be Dr. Cheryl Anderson. She's a dean and professor at the Herbert Wertheim School of Public Health and Human Longevity Science at UC San Diego. And her expertise and her research is in nutrition science and cardiovascular health. Last but not least, Dr. Nicholas Mucey is a professor and vice chair of translational science at Cedars-Sinai Medical Center. And he is he also directs the center at the Department of Medicine there, a center for diabetes, metabolism, and endocrinology. I think I've mixed the orders a little bit. But without further ado, Dr. LaCroix. Thank you. Let's see if that works. Does that work? Okay, great. Well, I wanted to start by just saying that we three from the Herbert Wertheim School of Public Health and Human Longevity Science view the whole population as our patient. And so I'm going to focus on what we've learned about healthy aging and health span and human longevity on that population level. And I'm going to talk mainly about three things. Some of them you've heard touched on today. So I think by the end of the day you'll say, well, gee, those things really make a difference. The first thing I want to talk about is in the news this week as a major driver of longevity in the population. And that is education. If you open the New York Times this week and Google educational attainment, you'll see that a new paper just came out from Case and Deaton who were also the authors of the paper on deaths of despair in America a few years back about the opioid epidemic. They just published new data through 2021 on U.S. deaths in adults age 21 to as old as people get. And I'm going to show you some visual aids since I don't get to show slides. This picture here is life expectancy in America. And it goes from 1995 to 2021. And sadly what it shows, the top line is Americans with a college degree. And the bottom line is Americans without a college degree, which happens to be two-thirds of the population. We are the only country in the world that has a majority of the population now with a declining life expectancy. People with a college education do much better. And at the end of 2021, there's an eight and a half year difference in life expectancy in America determined by whether or not you got a college degree. Why might this be the case? Well, education is a social determinant of health. And we in the School of Public Health concern ourselves a lot with social determinants of health because there's something going on with education that is vastly affecting our health. And all other parts of our lives, it turns out, Case and Deaton are economists. And what they find is that people without a college education tend to have less access to resources. They tend to have jobs where they don't make as much money and have to work physically harder. They tend to have health behaviors that work against their living long. So education has now overtaken gender and race ethnicity as the driving force of life expectancy in our country. And it is modifiable, as you know. You've heard about lifelong education for those of us who are done getting formal education. But I would also say there's a lot for us to do in supporting good access to education that's equitable in society, making sure that every young person has access to an affordable college education, making sure that getting up to that point, we do excellent in education. These are societal level things we can do. Reading with first graders. I highly recommend it. This is what they do in the Baltimore study where they put people to work reading. And the experience course, what it's called. And there's just so much we can do to support education in our society and have that be broadly beneficial. The next thing I want to talk about, which is an overarching driver of longevity, is what the American Heart Association calls life's essential aid. So this just got modified. You can easily Google the American Heart Association and see life's essential aid. And I want to just briefly tell you what the aid things are. Some of them have already been mentioned and others not yet. The first one is eating better. And Dr. Anderson is an expert in helping us understand the morass of nutritional opportunity. And she's going to be telling us about that. One is managing your weight. And manage your weight is a complex area. The AHA says you should keep your body mass index below 25. For some of us, that's not really a possibility. I will tell you as an epidemiologist that weight stability and keeping your weight in the range of up to a body mass index of 30 to 32 is probably just fine. That's what the data show. We are addicted to thinness in America. And I could give you a whole talk on that, but not today. Be more active. You've heard several times. And the AHA will say the party line in America, which is 150 minutes of moderate to vigorous physical activity a week. And you've heard the word exercise a lot today. I'm going to tell you that our research, which is super cool and uses AI methods and machine learning has shown that you can lower your risk of cardiovascular disease and total mortality by doing any movement inclusive of non-exercise things like getting out of bed in the morning and taking a shower and walking to the mailbox and walking down to the end of the street and doing household chores is movement. Doing gardening is movement. It doesn't have to even be called exercise. We look at this daily life movement and it's broadly beneficial. Controlling cholesterol is another one. Not smoking. Managing your blood sugar, which I think Dr. Musi might be telling us about, and your blood pressure and getting enough sleep. How much sleep is enough sleep? The American Heart Association says seven to nine hours. Let me also say that these same modifiable health behaviors are associated with a lower risk of Alzheimer's disease and are part of the biggest randomized trials going on right now, the finger trials and the pointer trials, showing that they're broadly beneficial for brain health and they're also the very same things that reduce your risk of cancer. So while Dr. Olshansky says that age is the biggest risk factor, we know there's great heterogeneity at every age in our biological aging, in our overall health, and these eight things are part of the geroscience that we can do without taking a pill to slow the aging process. So that's what I wanted to say about life's essential eight. I think the last thing I want to talk to you about is, and I'm going to try to keep everything super positive today, which is, yeah, you've heard about social engagement. There is now a huge amount of evidence, a recent paper studied over two million older individuals in 90 studies around the entire world and looking at social isolation and loneliness in relation to mortality, and based on this and all those component studies, we know that social isolation is associated with about a 30 to 40 percent increased risk of mortality and loneliness around a 20 percent increased risk, depending on adjustment. All of these things are adjusted for age, so they're independent of age, per se. The thing I want to tell you about that is this, the Surgeon General has a brand new report out on the epidemic of social isolation and loneliness in America, and I just want to say in the positive, what does it mean to not be socially isolated and lonely, and I want to advance the concept to you that there's something salutary, something beneficial about being loved and giving love throughout our lives. They don't call it that in science, but some scientists do. So there's a woman called Barbara Fredrickson. She wrote a book called Love 2.0, and she talks about the changes in our body when we have something she calls open heart, which in their open heart interventions, the easiest way I know to explain it to you is imagine you're looking at a baby who's not your grandchild, just in the grocery store, and this baby catches your eye and your attention and you're fully present, and the baby is smiling at you, and you are just, your heart just opens. That to me, that's my experience of open heart. I think when we get together in the community, there's some of that going on, and there's lots of ways in the Surgeon General's report for us to do better at being socially connected and being loved and giving love in our communities. So with that, I will pass the mic to Dr. Anderson. Well, hi everyone. Hi everyone, it's such a delight for me to be here today to talk a little bit about healthy aging. I want to say thank you to the conference organizers, and I'm so happy to be here with my distinguished colleagues. So I just want to share a little bit about positionality before I start, because I think it's really helpful to know about the person who delivers messages to you. So I grew up as the daughter of, and maybe even one might say the granddaughter of, a farmer. So my dad had a professional life as a chemist, but he also had a personal life in which we always grew food at our home. As I got older, he bought a little plot of land, and he grew food on this plot of land. And upon the death of my grandfather, who lived to be 97, I discovered that at my grandfather's home was also an extensive network of gardening going on behind the home that I never knew about as a child, because we didn't necessarily live close to my grandparents. So I, growing up in a home where food's being grown and harvested and prepared, really had a strong appreciation for food and what it meant for a home and a life. I appreciated it as being important in health. I appreciated it as being important culturally. I appreciated it in being important for how one felt mentally and spiritually. And so I am now at a place in my life where my professional life and my personal life really intersect. And I can't tell enough stories at this point. My dad's now 84 years old, and every time I visit him and I spend time in the garden with him, I think about my science, I think about administration, I think about how important an ecosystem, which you get to manage when you're farming, is in terms of how we all live together, diversity being important in a farm, the influences that you have when you shift one thing in a garden and you plant something else, you need to know what it's going to do to that thing over on the south corner. So that's who I am. I have that personal backdrop when I speak to you today. So professionally, I discovered when I trained in nutrition science and epidemiology that for decades we've been thinking about diet and health scientifically, but more specifically diet and cardiovascular health. And the classic hypothesis here is that if you have a diet that has a lot of saturated fat and a lot of cholesterol in it, you are more likely to have an MI and more likely to die. Well, that's the classic hypothesis developed in the 20s, and we've learned so much more about dietary intake and what it means for health since then. So I'm going to give you some broad principles around diet and what it might mean for us living longer and aging well. So the first thing that you should remember is that there's no magic potion. There's no magic supplement. There's no magic polypill that's going to help you have a better diet that's going to impact your health. It's just work. So my parents would say to us, they had four of us, the only place where success comes before work is in the dictionary. And it was something that my music teacher and my parents would always talk about. My music teacher would always say, you know, she's doing great, we know you don't like to hear all this noise around the house, but the only place where success comes before work is in the dictionary. So you're going to have to work at it. And that's important in our dietary considerations as well. So what does that mean? Well, it means if there's no single potion, single food, you know, people talk about these superfoods, etc., then we are probably going to have to focus on the patterns within which we eat, right? What do we eat most of the time that's going to impact our health outcomes? And we don't eat single nutrients. We don't eat single foods. We eat foods in patterns. And those patterns are ultimately what drive us into greater health or not. Additionally, when we think about the patterns within which we eat, we try to understand are there nutrients being consumed within those patterns that we're concerned about? Are we concerned about overconsumption of those nutrients? Things that we don't think you should eat too much of or that might confer risk for some of the factors that are important in health, like your blood pressure or your blood sugar levels or lipids or your ability to sleep well. And so overconsumption or underconsumption becomes a challenge. But you have to think about the full pattern. Now when I say you have to think about the full pattern, I'm also going to acknowledge that most of the data that we have and that we share, it's about a population level intake. So Dr. LaCroix said as public health practitioners, we think about the population as our patient. And so what might be a recommendation for the population as you read off from Life's Essential 8 doesn't necessarily get to your individual situation, right? So you go and you have a visit with a geriatrician like Dr. Moore and she might say, well, in general we would say people should do A, B, C, D, but for you, let's look at your specific circumstance and let's tailor that accordingly, right? So that's thing number two that I want you to take away. No magic potion. And number two, the recommendations are population based, but sometimes they need to be altered for you individually. The other thing that I want to acknowledge in thinking about what we know in the data around diet and outcomes is that the majority of the data show us that diet is connected to physical health. I would dare say diet is a cornerstone for physical health, right? You can't do exercise or move if you aren't well nourished. You are unlikely to be able to experience the management of the internal risk that some of us get genetically, others of us get through our genetic environment interactions. We can't manage those things without having good solid nutritional intake. So I want to just communicate, although the data are mostly around physical health, we all also know that diet's important for our mental health and diet's important for our spiritual health. And so when we're thinking about aging, I would encourage us to do what we heard, sometimes deviating from the thinking about what you're eating simply to maintain your physical health, but also thinking about what you're eating to keep your spirit healthy and alive. So from that, I want to just close out with two concepts. One is the way that we approach dietary science is often thinking about how efficacious the things that we want to communicate to the American public are, and we test them in scientific studies accordingly. So for example, an efficacy study that drives the recommendations that you hear is one called the DASH or Dietary Approaches to Stop Hypertension study. Give me a raise of hand if you've heard of this. Wow. Okay. You are a highly select group of individuals, but nonetheless, that's a really good thing for me because I can get through it faster. So through the DASH study, over a period of six weeks, individuals were fed the components of a diet that we all thought would be one that would be good for your heart health. In this case, the heart health indicator was blood pressure. It was set up to be a study where you could test the optimal diet, something that was sort of in between, and then the typical American diet. And within two weeks, the difference between those who were consuming the typical American diet and those who were consuming the optimal diet or the DASH diet in blood pressure was staggering. It was on the order of eight millimeter mercury difference, which you can't sometimes get with the pharmacologic agent, right? So because of these data, the DASH diet or DASH style diets have really become a part of our American system communication around dietary intake and health. What does that DASH diet look like? Well, it's reduced in fats, sugars, salt. It's higher in vegetables, other plants, legumes, fruits, low fat and lean proteins, animal proteins or vegetable proteins. And when those things are done in combination, most of the time, it really does have an extraordinary impact on blood pressure. It turns out the result on blood lipids and blood sugars is pretty good also. We don't really know whether or not that means you don't die of a heart attack down the road, but because you can't test those studies long enough, right, you have five years usually to get it done. But you do know that if people have controlled blood pressure and lipids and sugars, and now we know if you sleep well and you don't use tobacco, then you're less likely to experience the number one killer of men and women across the globe. So that's the genesis and the basis of that work. However, I will tell you where I am currently in my science and in my sort of aligning my personal life and my professional life. In 2012, I had just moved here to UC San Diego and I published a paper of a trial that was an efficacy trial. And we fed people what we thought by guidelines they should be eating. We got beautiful results at the end of feeding. People were doing and exhibiting exactly what we thought they should be doing. Then I said, let's see if people can handle this when we stop feeding them, right? So we gave them counseling and had coaches available and just compared that to doing nothing. You go with God and see how it works out. And the people who were in the intervention with the counselors and the support, they did phenomenally better than those who were trying to do it alone. However, even that group that was doing so much better than those trying to do it alone could not stay where they had been when we were doing it for them. What it did for me was it changed the entire way that I thought about my work. This study, I can't tell you how many people, I got media coverage, everyone was like, this is amazing. It made it into policy. However, that diagram, I wish I'd brought a piece of paper like Dr. LaCroix did, but that diagram looked like a checkmark, right? People started at a level, they were brought down to where we think they should be, but then they just started to tick back up. Although people didn't experience a significant check, I realized that my reading of the literature since I was in college kept showing that very same pattern. It was a checkmark. People would start in a place, we'd help them do better. In the ivory tower context, you'd send people away to try and do these things on their own and they would go sometimes even beyond where they had been at baseline. So what does this mean? This means that we are having an extraordinary interaction between what we know should be done and what we're able to accomplish in well-controlled, often university environments, and then what happens when people go back into the world. And they try to get across these various barriers that we know you have to climb in order to do better with your dietary intake. And so the birth for me was community-based participatory research that allows us to really understand the barriers and the facilitators and the systems and the structures in communities that get in the way of us being able to do what it is that we know we should or that we tell people that they should be doing. So I will leave you with this last point that when we talk about diet and healthy aging, those of you in this room sound like you know what should be happening. You're familiar with the DASH study and those guidelines. However, all of us, public health is about all of us, every single person in this town should stand a chance, no matter where they live, where they learn, where they work, play, or pray, to have a healthy diet and to age well. So I welcome questions about this when we move on to discussion, and I will pass on to my colleague, Dr. Musi. Well, thank you. It's an honor to be here with you, and I want to thank you for inviting me. And I'll start by saying that I am 100% in agreement with what Dr. Olshansky and Anderson and LaCroix have said about what we know about healthy longevity. I will probably just extend in one area of work that my team has been working on for many years, and we've continued now that we have moved to my new institution, and that has to do with physical activity and exercise, and also how it relates to aging. And we've known for many years that physical activity does not necessarily have to mean intense exercise, but activity in general, as well as more intense exercise, has profound effects on our health. Almost all aspects, every aspect of our health that has been studied moves in a positive direction with physical activity. Our metabolism, our brain function, our mood, our bones, our heart, everything really gets better. So we absolutely advocate for maintaining an active lifestyle. What is very, very intriguing is how exercise works, how it's able to do all these things. It's largely unknown from a biologic perspective, and it's important to understand how exercise works, because first, we could personalize exercise programs. It is likely that not all types of exercise cause the same benefits in each person. The amount of exercise and how to apply it, there are general guidelines, 150 hours, minutes, hours. Thank you. So that's why we have 150 minutes per week. It's very challenging. But there may be people that benefit with much less. And it is possible that 150 minutes is harmful to some people. So how can we tailor that? So it turns out that we're learning that what are the mechanisms by which exercise works. And the classical thought that we're exercising, our muscles are working hard, our heart is pumping hard, and this is just kind of magically making us feel stronger. But now we've realized that with physical activity, almost every cell in our body is reacting and improving its function, but also communicating with other cells within the same tissue, organ, and also other organs, and really working as what we classically will think as a gland, you know, like our thyroid gland produces a hormone that signals to other organs, the pancreas, et cetera. Now we're learning that every cell in our body is functioning like a gland that is producing substances that is communicating, sending them to other cells and tissues. About 20 years ago, when I started working on this field, we learned that the muscle starts sending signals to other tissues. And then a few years later, that the heart also was communicating. But now studies done in very recent years, we're learning that almost every tissue is sending signals. Now the heart and the muscle are sending signals to the brain, which is probably one of the reasons. By signals, I mean specific substances that we now identify that is making the brain function better. But it also turns out that the brain, as we're exercising, is also sending signals to the muscle and the heart, which is kind of fascinating. Why is it doing? And even the bones, as we're exercising, is sending signals to the heart to regulate its function and also our immune system. The kidneys are activated as we're exercising and sending signals to other parts. So it's a really fascinating time in the world of exercise science. And we and others are actively doing clinical trials in patients, in which we're trying to understand what are the signals, which exercise is best to activate those signals, and how we can use this knowledge to tailor the best exercise, the right dose, for each specific person, and how that relates to nutrition and other important aspects of health. So I would say, in general, and that it could potentially, although we never advocate for substituting exercise for a pill, there may be clues that this can give us to design new treatments. And that takes me to the next theme, which is development of drugs to promote healthy aging. Again, we understand that we're not going to find a magic pill to substitute the importance of lifestyle, social, emotional, psychological, all the key factors of healthy longevity. But it is likely that certain aspects of aging can be improved through new medications. And it turns out, for example, that metformin, that Dr. Olshansky mentioned as one of the key candidates to promote healthy lifespan, many of the effects that metformin has, they're actually similar to the effects of exercise. It turns out metformin, to some degree, mimics the effects of exercise. And some of diabetes drugs also seem to be working through like an exercise mimetic. So they're kind of like exercise pills, to some degree, although not as force potent or effective of exercise. So we're also working, doing trials in patients, trying to understand and test certain drugs that have an exercise-like effect, like metformin, senolytics, which are these drugs that kill senescent or zombie cells, and drugs that promote our metabolism, like NAD boosters you might have seen in commercials, although certainly trying to do it, doing it through a very rigorous scientific process and other trials that we're doing to try to understand how drugs that may mimic the effect of exercise could potentially be used to promote healthy lifespan. But certainly, we recognize the importance of lifestyle interventions and trying to promote, trying to design the best exercise lifestyle interventions based on the specific biological and social properties of each person. And I will stop there. I'm happy to answer any questions. Thank you very much to all three speakers for sharing your insight about the importance and significance of lifestyle modifications and factors for healthy lifespan. To keep us on time, I'll just pose one question to the panel members to discuss briefly, and then we'll go straight to the audience questions. So what I've heard from all of you is iterating that we are what we eat. We knew that. We are where we live. We are with whom we hang out. So thinking about these healthy lifestyle changes, we also thinking about how Dr. Olshansky had mentioned how hostile environment can form our biology. In that case, it was a reproduction. But let's think about in terms of a healthy aging and healthy lifestyle. Individuals' healthy behaviors are formed also in constantly influenced by our environment. And when I say our environment, it's not just the physical environment. It's a social environment, social structure. So how can we make sure from both precision medicine, individual health, as well as public health, how can we make sure that we are interacting as an individual with an environment to modify our behavior to achieve health outcomes that we really want to achieve? Maybe I'll take a stab at this one first. So what I hear you saying, I think about in terms of, again, sort of seeds and growth. So let's say the seeds are your dietary intake are the seeds that you need for healthy lifespan. And then the environment is really the fertilizer of those seeds that either promote good health outcomes or bad health outcomes. And you can't have one without the other. You'll need to have those seeds present. You'll need to have the fertilizer necessary. And so in the case of diet as a lifestyle factor, we have a broken system in so many ways of food delivery, of healthful food delivery to the majority of the American public. What we find is that it's incredibly easy to get all the wrong things on your plate. And it's really difficult to have all the right things on your plate, right? A fiber rich, beautifully plant based, lean proteins. If you're like animal proteins, the ones that are better, better cuts and, you know, available, lots of vitamins, nourishment, etc. It's just hard to do it, whether it's because it costs a lot or because people don't have access in the communities that they spend most of their times in or because they're unsheltered. And so when it comes to managing dietary intake, we have to think so much beyond the individual and so much beyond the data that you see sitting in front of you. And so it, as we all know, in public health, it really requires that we do our work at the intersection of community. So when we are, you know, looking at data, we're also thinking, how do we get this to city planners so that this can be incorporated into how you build and design cities? How can we get it into the hands of policymakers? In Los Angeles, South Central Los Angeles to be specific, about 12 years ago, they actually put a policy in place that no additional fast food restaurants could be built because it was a swamp. I mean, it was just full of access to things, easy access to things, cheap, convenient, that do not necessarily promote your dietary health. And so it is in the diet space, it's that we have a big job ahead of us. And I think through advocacy groups, through our science that we generate, and through really working in science at the intersection of community, we can try to make a better case. As Dr. Olshansky said, maybe for the children, you know, and that would hopefully lead to greater benefits down the road and challenges. Thank you very much. Let's make the environment not hostile for certain people to live a healthy life. The first question that we got, do you still recommend Mediterranean diet for improved aging for all? Yeah, so I love this question. And the first thing that I would do is to change your question a bit, which is the worst thing a responder can do. But I would add an S to the end of diet. There is no such thing as a Mediterranean diet per se. It is a way of eating that we characterize largely by a region of the world. But it can be done in so many different ways. Just think about how important culture is, how important our taste preferences are, and then use that as an umbrella in thinking about the kinds of things that are healthful, again, like lots of color in your meals, and then substitute the foods that you like, that you prefer, that are culturally important to you in their most healthful form. But to just get right to the heart of the question, yes, following a Mediterranean-like dietary practice, the data show consistently improves health outcomes, whether it's mortality or cardiovascular health. Thank you very much. We'll move to the next question, which I thought might come up. Metformin was mentioned in Dr. Olshansky's video. Do any panelists recommend it? If so, how to convince primary care physician to prescribe it? And there was another question to Dr. Musi. Is metformin given to non-diabetic patients? If yes, in what setting? Yes, so these are very important questions. Metformin has been shown to have broad benefits on metabolism, some forms of cholesterol, heart disease, and possibly cancer. And it also has a mild effect for weight loss, and possibly to reduce inflammation. And I'm talking about data, clear data in human trials. Now, in rodents and other species, it also has clear benefits, many aspects of aging. And also epidemiological data, which is essentially analyzing large data sets in humans, also point to beneficial effects on aging and lifespan. However, and Dr. Olshansky was mentioning, and that was the point of the presentation of FDA, is that before widely recommending its use beyond its classical effects, indication of diabetes, really it's our role as healthcare providers to go with what the evidence is based on clinical trials, which a clinical trial is taking patients with a specific characteristics and treating them against a placebo, ideally, because the placebo effect can be very strong, to make sure that it's better than a placebo in what is called a randomized trial. And so until that is done, which is the importance of TAME, it's very challenging for a healthcare provider to, in good faith, recommend it and prescribe it beyond its indications or clear effects. So clearly indicated and beneficial and tied to diabetes, so unless it cannot be tolerated or it's a good reason, everyone, or it should be the first line tied to diabetes, although now there are all other excellent drugs. Also for very early, what is called pre-diabetes, which is between normal glucose, normal sugar and diabetes, and that, it's also recommended in pre-diabetes. I think in obesity, being people that are overweight, even if they're not pre-diabetic, I would not have a problem with its use, because it can help a little bit with the weight, but also it could potentially have heart difficulties. Certain forms of other hormonal problems, what is called polycystic ovary syndrome, in young women that can cause some metabolic abnormalities, and it can help with that, and also some of the reproductive effects of this disease, it is probably beneficial. Outside of that, I think that, and there are different opinions on this, I tend to be more conservative and wait for the large, robust clinical trials before. I should also emphasize, we are doing a finishing trial, it's much smaller in scope and size than the TAME trial on metformin indication for evaluating frailty and physical function in older adults, and we're about to finish that trial. Our hope is that it's positive in terms of frailty and physical function, and that would further provide support for larger trials for TAME. Thank you very much. We're at the end of the session, and thank you so much for your level of engagement and interest, and thank you to all for your wonderful talks.