Breakthroughs in Aging Research | Dr. Eric Verdin, 2024 Longevity Summit | Aviv Clinics

Good afternoon, everybody. So up first, we have Dr. Eric Verdin. He is the president and CEO of the Buck Institute for Research on Aging. He's also a professor at the Leonard Davis School of Gerontology at the University of Southern California. Last but not least, he's a professor at the University of California, San Francisco. Welcome, Dr. Verdin. Good afternoon, Villagers. I want to start by thanking Aviv Clinics for putting this meeting together. I think there's nothing that pleases me more t

han to actually meet and present the work that we're doing and to share it with you. I also want to congratulate you for being here. As you will see, lifespan, healthspan is all about taking care of your own health. And this is going to be one of the messages that I'm going to be sharing with you. And by being here, you're already showing that you're taking the first step and at least a critical step and taking your own health into your hands. So let me start by asking you a question with a rais

e of hand, who wants to live to 100? Okay, but it's high. But it's a it's not everybody. And I think it's going to be an important point that I'm going to bring back to this question later and decide, you know, why did you answer in the way you did? I have organized my presentation and a number of breakthroughs. And I think this is really one of the message I want to share with you is that there has been another growing revolution in our understanding of the science of aging. And we lie right no

w at a critical point where in the last 20 years of work, we have redefined what aging is and really what it means to grow old. And I think this revolution is slowly permeating and entering the realm of clinical medicine. And Aviv Clinic is a good example of this. And therefore, one of the messages that I would like you to leave with is to do everything to be able to capitalize on this revolution, which will really change in a dramatic way, the way we age and the future. So for breakthroughs, I'

m going to be sharing with you quite quickly, just to give you a glimpse of what aging research is today and what have we accomplished. The first finding is that we can change the rate of aging, and that's an amazing 25. 30 years ago, this was thought impossible and through the work of many colleagues, we really have been able to identify a number of dials, things that exist within the organism that we can trigger either through a lifestyle intervention or through a drug that will change the ra

te of aging. This happens in animal models. And I'm going to give you a first example of a classical experiment, which is actually almost 100 years old, where whereby we can study the aging of mice in the laboratory. And what I'm showing you here is what we call life curves. So we starting with 100 animals are on the top left, and we follow these animals. As the animals die, the curve goes down. And you can see in orange, non-CR is against their own. So apologies. Thank you. Thank you for keepin

g me on track. You can see in the top left arm, we start with 100 animals. As these animals die. Look at the line on C.R. They progressively die. And by the time they reach 36 months, this is the maximum lifespan of a mouse. All of other mice in that colony have died. Now, suppose you take these mice and measure of how much they're eating individually, what we call adlib. They're eating as much as they want. The food is always available. What we do with them is we restrict the amount of calories

that they have available by 25%. You can see the curve shifting to the right. What this means is now these mice are living longer on average. But look at what happens when you’re restricting this by 65%. The mice are living almost twice as long. So this is actually pretty amazing to think that there is all that life potential that was locked in and not made up. Now, calorie restriction as you can probably imagine, is not easy to do. There's a there's a calorie restriction society in America. So

some older people actually have taken it upon themselves to to go on calorie restriction. And it's very hard. I've met many of these people on calorie restriction and some colleagues told me one time that this might not make you live forever, but it will certainly feel that way. And so we don't recommend this as an intervention, even though it is interesting to see what happens to these individuals who do this. So this is the type of intervention that when you do it in mice, allows us not to us

e all of the modern tools of molecular biology and genetics that we do in the lab in trying to understand what are the links within the cells and within the organism that are able to recognize that there's less food and to and to transform this into an increased lifespan. And so these are the types of experiment that we can conduct in animal models. I'm showing you a little worm. C elegans, it lives 21 days. The fruit fly Drosophila, which lives 70 days. And then mice, as I mentioned that live u

p to three years. Now we can we have a calorie restriction and we have a long life underneath. So we can again, using all of the tools of molecular biology and modern biology, identify the past what we call pathways. This is certainly a series of molecules in these organism that are critical. If you remove them and you put these animal on calorie restriction, normal response. And so we and many others in the field have been busy doing this type of work. And this is what we found. Now, this looks

very complicated, but I want to point out a few critical points. You probably will notice that there's a yellow ball called TOR in every one of the organisms so that was one of the important points. We have identified pathways and molecules that are conserved between all of these organisms, indicating that the regulation of aging is something that happens, you know, from the little lonely worm that lives 21 days all the way to us. We also have TOR. You have TOR in every one of your cells. That

's one finding. So aging pathways are conserved and they function pretty similarly in different organisms. The second finding is, TOR is named TOR because it means target of rapamycin. And rapamycin is actually a drug that's available in the clinics today. And the implication is that, and it's been demonstrated, that if you put at any one of these animals on rapamycin, they live longer up to 20 and 30%. So these are animals now that are living at completely normal life. We don't change anything

else to their their conditions under which they live. But simply by taking this drug, they live 20 to 30% longer. Remarkable finding. And today, after about 20 years of research, we have in mice more than 100 interventions that will do exactly this. Many of these interventions pointed on the left are actually drugs. Some of them are already in the clinic. Metformin, I suspect we have in the audience a number of you who are on glucophage. Glucophage, Metformin is a drug that it seems to be having

anti-aging effect. Acarbose is another drug in the clinic I mentioned rapamycin already and there's a whole series of them, about 100 that are slowly moving from the early lonely models to the clinic and into humans. I should say also that none of those have been demonstrated in humans yet, but the efforts are ongoing and my prediction is within the next 5 to 10 years we will have the first drug approved in the clinic. that will delay aging. So think about this and think about it, especially at

the end of the talk. Breakthrough Number two is, is the realization that aging is the largest risk factor for what we call non-communicable disease. If you think about in 1900s, actually, most of us were dying from infectious diseases, tuberculosis, pneumonia and so on. All of these infectious diseases have been replaced due to antibiotics, vaccination by a whole series of new diseases that are shown here, and you will recognize them. Atherosclerosis, heart attack, stroke, glaucoma, macular deg

eneration. Many forms of cancer are linked to aging, osteoarthritis, osteoporosis, hip fracture, knee pain, hearing loss, sarcopenia, Alzheimer, Parkinson, type two diabetes. How much fun it is to get old and the reason. So why I ask you the question who wants to live to 100? A significant fraction of you actually said yes, I do want to, but I would say pretty much half of the audience said no. And I suspect if I were to change my question and ask you, who wants to live to 100? Not afflicted by

all of these conditions, please raise your hands. Yeah. So that that is the key thing that I want you to remember. Aging is associated with diseases in a way that by the time you reach 65, 70% of the American population will suffer from one of these conditions by the time you reach 70. About most of the people will have two of these conditions. So we associate aging with disease for very good reason. We've seen our parents, we've seen ourselves, our friends suffer from these debilitating conditi

ons. And in some way they really color the way we think about aging. Aging is debilitating, it's diminished capacity and so on. Now, what I want to point out to you is that in our laboratory experiments with the animals, the equation that aging means disease is disrupted. These animals not only live longer, but they also live healthier. And we also know in our midst we have centenarians who live not only to a hundred, but they don't start being sick typically until age 95 on average. So your typ

ical centenarians will spend 5% of their lives afflicted by these conditions versus the rest of us will spend about 15% of their life, 65 to about 78, 80. So and their lives really the greatest potential of this field. People talk about longevity. Some of my more crazy colleagues talk about immortality and living to 150 or living to 200. Frankly, I think it's all nonsense. And this is not what I'm working on. I'm working on really improving the the aging experience that we all live today. And I

will make the point later that most of the people in this audience, if you were to optimize everything you can about your lifespan and could be expected to live to 90, 95 in good health. Now think about this and think about what you're seeing around you. Now, breakthrough number three is, this will lead to a reinvention of medicine. So think about how medicine works today. We call it health care. It's actually not health care. It's sick care, medicine is focused on. I'm really treating you when

you are ill. Medicine does very little prevention. It's organ based. You go see a cardiologist, you go see a neurologist. Each of these doctors is talking to you as if you were an organ, not a person. And you've all experienced this. It's reactive, that is, we wait for disease to occur and then we treat it. And medicine does an amazing job at this. I don't want to diminish the merits of medicine. We manage disease and we pretty much give almost universal treatment. If you have high cholesterol,

you get on the statins. Even though we know that only one out of 20 people who are on the statins will actually benefit from it. Now, what is the vision of this for the future? Think about a true health care system where it is system based. Remember TOR. TOR is not just in the heart or in the brain. It's in every cell in your body. So when you get rapamycin, TOR will affect-- rapamycin will affect the activity of TOR in every one of your cells. So you will prevent disease in every single organ.

It's also proactive and preventative. That is, we instead of waiting for you to actually be afflicted by a disease, we will start very early. And finally, it is personalized. And this is using the new tools of what we call precision medicine. So life, the last question is what drives aging? Is it genes or lifestyle? You probably have in the back of your mind a thought that, well, my parents did not live very old. So, you know, I should probably prepare to not to live very old either. And a lot

of people actually do think this is another group of people who say, no, my lifestyle is actually going to make a difference. So let me ask again another question. If you were to decide what is the most important, your genes that you've inherited from your parents about which you cannot do anything, or is it the way you live? That's going to be the major determinant in terms of your life expectancy. So first, the genes, the gene believers. Who believe it is genes? Okay, who believes it is 50/50

? Okay. And the rest, I guess, who believes it is lifestyle. Okay. Well, I'm about to surprise you. 93% non-genetics. Lifestyle. About 7% genetics, meaning that your longevity, your healthspan, your lifespan is going to be determined by how you choose to live. Now, the other thing also, it's never too late. Even late stage interventions have very powerful effect in your longevity. So I'm sorry, I guess I was missing that slide. Now, what is lifestyle? And this is what I'm going to finish in th

e next and the last 15 minutes. And look at this is what I call the five pillars of aging and these five pillars of aging. You probably know about them, at least to some degree. And I suspect many of you as retirees are actually practicing many of those. But I believe there's also an enormous gap between what we are learning that actually works and what people indeed practice in their daily lives. And this is really what the focus of my work at the Buck Institute and many of our colleagues, is t

o understand which one of all these interventions is actually functioning in the best way. So what are they on the left? Nutrition. What you eat, when you eat. Everybody knows about this. But you know, what are you supposed to do? There's a lot to be learned. Second one is physical activity, which I believe is the greatest anti-aging medicine we have today and that we're going to have for the next 5 to 10 years. Next one is our sleep. Probably one of the most important ones that you can optimize

. And stress mitigation, you know, managing your stress in a successful manner. The fourth one is what we call is human connection. And believe it or not, it is the strongest predictor of your life expectancy and the fact that you're here as a community, that you live in a wonderful community, that you have a lot of friends, that you are engaged socially is the strongest predictor of your life expectancy. This is what the data says. Now, unfortunately, it's very hard for us to study in mice. I d

on't know how mice are feeling (laughter), are feeling about each other. But we know, for example, if we if we grow our mice lonely in cages by themselves versus four or five or how we usually do it, their lifespans shorten. That's been shown in many species and there are a lot of peoples trying to understand what is it. But it's not only a human connection is also the sense of purpose. What are you here for? Are you are service to your family, to your friends, to community, to the world? These

are all sort of very hard things for scientists to study, but they are incredibly important. Last one, last bucket that I'm showing you here is the drugs. And the drugs are not here. And I think I want to be totally honest, even though, you know, some people have already started to take metformin, even though they're not diabetics. You'll hear about this from my colleague, Dr. Barzilai later. These are not proven. And so, you know, people make individual decisions in terms of whether they are wa

nting to go on these drugs at this point. But I can tell you the answers will come in the next few years. So the idea that I really want to encourage you to look at these four buckets on the left are what you should be focusing on today with all of the intention that you have, because the bucket on the right, the drugs will come in the future and might give you a further boost. So every time I give a talk, people say, well, what's the take home message? What am I supposed to do? What can I do to

day to maximize my health span in my lifespan? Now, let's start by the the worrying and the sad news today in the US, we have a shorter life expectancy than almost any any other high income countries, the Western world, including Japan. And so on. And paradoxically, we spend most in the world on health care and we are 31st in life expectancy. Let me show you what it looks like. So this is the life expectancy in the US. You can see we've been lagging for a while behind the rest of the Western wor

ld and this has been even further precipitated with COVID 19. You can see the really rapid dip down to 76 where most Western countries today are around 82. Now, I want to congratulate you for living in Florida, because I live in I live in California. You live in Florida. These are the blue areas. You can see there's incredible disparity in terms of life expectancy in this country, which is very strongly regional. But we can also see this, the level of different communities. If you do the same st

udy in Glasgow, it's been done in Glasgow, in London and in Cleveland, you can see depending on the zip code where and how long you're going to live. In fact, your zip code is one of the strongest predictor of your life expectancy, paradoxically, which means, you know, which makes sense if you live in a in a more educated, wealthy community, you have more time to exercise. You have access to organic food versus living. You know, in an urban ghetto where you actually have access to no vegetables,

where you’re working three jobs and so on. So it just makes a lot of sense. And I can say I have not seen the data for this particular area, but I'm almost ready to predict that it is a very long lived community. Now, I've made the point earlier that most of you today could expect to live to 90, 95 in good health. And I'm able to say this is that we know when we look at some unique zip codes, they are communities in the US today that lift average life expectancy is 88 and one of those is right

next to where I live is a town called Ross in northern Marin County. And I can tell you that when I go to this community, not everybody is exercising. Not everybody has a perfect diet. I mean, obviously, as a wealthy community, people are doing a lot more than other areas. But 88 is even without optimizing everybody. Hence the prediction that 95 is not a far cry from where we are. So I want to review a because you're still wondering. Each of you. Okay, what am I supposed to do? I won't be able,

unfortunately, in 30 minutes to go through everything that you should be doing. But I want to give you at least a framework in which you can think about your own longevity and what you can do to optimize it. This is a study that was published in the Journal of the American Heart Association looking at the impact of healthy lifestyle factors, because you might wonder, okay, I exercise, but I like my alcohol and I like to eat what I want. And so what is the effect of this exercise versus this one

? So what is the relative impact of each of these variables? So this is what the study did. They looked at a number of healthy lifestyle factors and measured their effect on life expectancy in the US population. And this was actually done by combining something called the Nurses’ Health Study and the Health professional follow up study. 123,000 people were studied in this. They were all sent questionnaires to try to assess. So there are some variables people may not have answered exactly, but I

think it's a pretty strong indication and that study is a landmark in the field of preventative health. So the conclusion of that paper is that what they recognize, what they recommend is a recipe for increasing your life expectancy by 12 to 14 years. They identified a number of low risk, low risk lifestyle factors that actually really maximize your longevity. Some of them are completely obvious, but some others not. So. Regular exercise. Again, I go back the best anti-aging medicine you will ha

ve ever, at least for the foreseeable future. Moderate alcohol consumption. I usually hate to bring this up to people. We have been sold the myth that alcohol actually increases your lifespan. The only thing I have to say regarding these studies is the idea that many of these studies were supported by the alcohol industry. (laughter) And so you draw your own conclusion, and I've made the point in front of audiences like this that alcohol is the new tobacco. Remember how we were sort of delusio

nal about what tobacco meant in the 70s or 60s? And then we had a movement essentially eliminating tobacco for most of our lives. And, you know, cancer rates went down and heart attacks went down and so on. The same thing will happen with alcohol. And I think I am not recommending for people to abstain from alcohol, but I'm certainly discouraging them from using alcohol, thinking that it will improve their health. It will not, and increases cancer and increases Alzheimer's and increases pretty m

uch every complication that we can think of. And the people who don't drink live longer periods so that I still drink, but I drink in moderation and I drink for various special occasions, maybe one or two glasses a week. That's and I feel a lot better. My sleep is much better. I feel stronger, healthier, clearer-minded. So take this one home and think about it. No smoking. That's a no brainer. High quality diet. I'll say a few words about this. And a healthy weight were the really the key low ri

sk lifestyle factors. Regular exercise, again, the data here is a little complicated to look at. I just want you for every one of them to look at what's happening here on the left between the people who actually are exercising for more than five and a half hours per week, gain an extra eight years of life, three and a half hours a week, almost the same thing. So there's a lot of diminishing return. Once you reach a certain peak of exercise, you can keep exercising more. You can do it because you

like it. But in terms of if you want to get the maximum bang for your buck three and a half hours a week, that's 30 minutes per day. As retirees, I would I would venture to say that you at least have an hour a day to exercise. So, I do exercise an hour, an hour a day. And frankly, it's not only thinking about longevity is just a question of wellbeing. It suppresses depression and it does everything that you can probably hope from a wonder drug. And this is true for females and males. So remembe

r that 15 minutes of walking in the morning and at night, and I would hope that you would all commit to me that when I come back next year. This is something that has changed. And if you don't do it because you have a problem of mobility, which is become significant, get a stationary bicycle, join a gym class, do water aquatics. There's so many ways to exercise, but physical activity is the basis of healthy longevity. No smoking, no smoking period. That's an obvious one. If you are a smoker, you

lose. You can lose up to ten years of life, 12, 12 years in males. And that should be a no brainer. High quality diets. Again, people here where I'll just since I'm running out of time, about six to four years of extra life the the things that you should really be focusing on are listed here five servings of vegetables per day, extra serving of green leafy vegetable. Skip the French fries. Doesn't mean you can not-- I'm against any absolutist diets, for example, I don't support the vegetariani

sm or veganism. The question is there are a number of things that we all love. I'm Belgian, by the way, originally from Belgium, but so I love French fries. And it's a really-- for those of you who travel to Belgium, we have the best mussels and French fries. And it's impossible for me to imagine life without eating French fries from time to time. And I suspect it's the same for all of you. Just don't eat them every day. And if you eat in them twice a week, eat them once a week and enjoy them ev

en more. So four servings of fruits avoid fruit juice. This is one of the biggest myth in the world. That fruit juice is healthy. Fruit juice is like Coca-Cola. Again, there's no difference from the metabolic point of view. It's not healthy and you should never certainly not in the morning for breakfast. Second thing that I hope will change, 15 minutes of walk in the morning at night no fruit juice Eat fruits. Totally different . Eat an orange because the orange, the juice comes the same same am

ount of juice is actually present in the context of fiber in little cells. When you chew on an orange, you probably feel these little cells breaking it individually. You don't break all of them. The rest goes into your stomach, you intestine and is slowly digested. That means the sugar from the fruit sort of drips into your bloodstream very slowly. And therein lies the key five or six servings of whole grain. per day, one serving of protein from nuts, legumes or tofu. Eat fish at least once a we

ek and add healthy fats like olive oil, avocados. Skip the butter. It depends what kind of butter, but in general, try to favor these healthy oils and avoid seed oils. You're probably have heard about the seed oils. Really to be avoided. You can read more about it online. Again, moderate alcohol consumption. I've said already alcohol should be a special treat, something that you enjoy on an occasion. Not certainly not every day. I don't find it healthy or helpful and maintain a healthy weight, w

hich is going to happen as a function of all the other changes that you're making. If you're eating regularly and if you're eating a lot of fibers and vegetables, very hard to gain weight, eating vegetables. Now, here's the most important slide, because you might wonder, okay, this is nice, but I do one of these and I don't do the other. I drink I like, like three glass of wine a day. Is that the fact that these interventions stack up? So and this is shown here, each of these lower risk risk lif

e factors counts for one. And what you can see here, if you add them up eventually you get to 14 years of extra life in women, 12 years of extra life in men. And so the framework that I would like for you to think about this is I think about for my own health, I think about them as buckets. So I have a bucket for nutrition, I have a bucket for a bank account, the same way I think about them as individual accounts. It doesn't mean that I have to be perfect on everything every day, but every time

I put something in an account or a bucket, it's an investment in the future. And since we know they work together, the more you put in each of these buckets, the better you will do. So as you go through your day in the next few days, think about these five different categories and think about making one change every day about the way you exercise or the way you eat. I guarantee you that at the end of the month you will start feeling better if you're not feeling good. If you're doing all of this

already. Congratulations. You didn't even need to come today. So all of the advice, it basically adds up. Adherence to a low risk lifestyle means a longer life. This could prolong life expectancy at age 50 by close to 14 years and 12 years for men. And again, we'll be back next year. I think our work with the Aviv Clinics, who has been a pioneer in actually bringing this type of revolution to the clinic. And hopefully next year I can I can have a whole lecture about nutrition or all about exerci

se because you’re probably still left, you know, form of exercise is better. There is, this is the Last point that I'll make. Since I have 29 seconds, I want to use all of our-- Actually, I'm already over. So I will wrap up and I will thank you for your attention and see you next year.