How to Die Young at a Very Old Age | Dr. Nir Barzilai, 2024 Longevity Summit | Aviv Clinics

So next up we have Dr. Nir Barzilai. Dr. Barzilai is a founding director of the Institute for Aging Research at the Albert Einstein College of Medicine. He's a director of the Paul F. Glenn center for the Biology of Human Aging Research and the National Institutes of Health's Nathan Schoch Centers. He also discovered the longevity gene in humans. So that's quite important. Dr. Barzilai,

I thought the average age here is 68 and I don't see it. You look so much younger. First of all, thank you Aviv for this opportunity and for me, you're the people who spread the gospels. I think we're expecting very different life from now on. And this is the day that you have to decide do you want to spend your time in sick care or do you want to spend time in health care in maximizing your health as you heard from Eric, with exercise and diet and sleep and social connectivity. So I'll just bring you to my life with this following story. There's a hundred year old gentleman that walks into life insurance and he wants life insurance. And the clerk says, 100 years old, we don't give life insurance. He said that's not true because my mother is insured here. Said, how old is your mother? She's 120 and she's fine. So the clerk goes back, they talk with the boss and they said that's a great marketing, you know, we should give him life insurance and we'll, you know, we can make something out of it. So they come to the old gentleman and says, you know, we're going to give you life insurance. In fact, come on Tuesday and we have everything ready, you can just sign. He said, I'm sorry, I'm busy on Tuesday. And they say, old man, what do you have on Tuesday? He said, on Tuesday my grandfather is getting married. How old is your grandfather? He said 150, said 150 and he wants to get married. He said he doesn't want to, but his parents putting lots of pressure. So you'll understand why this is my life and this is my horizon. And I would tell you whenever we're thinking of life like that there are trade offs, right? Do you really want to be 150 year old and your in laws or mothers will tell you what to do? You know there's going to be trade offs. I also want to say I have thanks to Aviv intervention hyperbaric chamber for mice in my lab. Just like if you go for that, you can have an after work drink. Eric said what he thinks about drinks, but I'm not going to talk about it now. What I really want to talk about is this incredible fact that in 100,000 years or so of human evolution, life expectancy was between 20 and 30 years. Okay? It's only in the last 150 years. That's why it looks so steep that we made this progress. Okay, so when people are coming to me and say I have a prostate stuff, why didn't evolution figure out? Well, evolution needs those hundred thousand years to work. But if people didn't get prostate problem when they were 20, 30, we cannot solve it now. Okay? Think also you guys, not how rare you would have been during human evolution, but how many people do you think during evolution were married for more than 30 years if life expectancy was 20 or 30? Right. You're the world holder, you're doing really great. But this is the point. We got old and we started getting age related disease. We get the first disease and the treatment and the second disease and the treatment, and eventually we end up with bad quality of life. And what we've done in those first 150 years, a lot of what we have done has been prevention. Just harnessing agriculture so there's enough food, cleaning the water, building sewers, vaccination. A lot of it was prevention. Yeah, we also invented antibiotics and surgery. Okay? But it's thinking of the prevention that really makes us think that there is a new, we can create a new history here. Because if we prevent the aging process before the disease happened, then we've done a lot of things right? So if I have to summarize things that Eric basically said before or how the field, in my words, is that first of all, aging as a biology, we all know that, okay? We all know that aging is a biology. I think what we don't realize is that this biology is what drives the diseases. Okay? You can be born with genes of Alzheimer's. There's this Apoe 4. If you heard, if you have both copies of the gene, you're likely to get ALZHEIMER when you're 60 or 70 and be dead when you're 80. But when you're born, you're not demented. And when, where you're one year or 10 year or 50 years, you're not demented. You need this biology of aging to bring on the diseases. And so that's why we're talking prevention. You have to do it then. And the good news that aging can be targeted, we've done it in animals, we've done it in humans with variety of Tools. And we've showed that aging can be delayed or stopped or even reversed in several instances, if you're asking. But what is it? What is the biology? I'm really not going to tell you in a 20 minute presentation what's the biology, but just that, you know, for your eyes that we have what's called the hallmarks of aging. We kind of agree, we geoscientists agree, those are the hallmarks of aging. To be a hallmark of aging, you have to show that something goes wrong when you're old. And if you fix it again in animals or humans, you get health span, most important, healthspan and also lifespan extension. As I said, targeting those hallmarks improve lifespan and health span of animal. But this is the thing, you don't have to deal with all of them at the same time. That's why there are those lines going in between. You can hit one of them and correct all of the other or most of the others. And this is kind of the promise that we have now. And we can test drugs by their ability to target those hallmarks. And if they don't hit all or many of those hallmarks, they're not really going to affect aging the way we want them to affect it. We wrote a paper and then a correction to a paper where we took all the FDA approved drugs, okay? Now when I'm saying FDA approved drugs, those drugs have been approved for some use. So they're safe, okay? We know everything about their safety. But we took all those drugs that were given to animals to test some hypotheses, extended lifespan in animals. And we took all the data that we had. And you see on the right side we have a scale that is up to 12 that looks at the hallmarks of aging in animals and also what happens to human. You see that there are five drugs that get scores between 10 and 12. In other words, those are drugs that are approved by FDA for another purpose. But if you take them for aging, you might actually really target the biology of aging. And I'll give one of them as an example. The point is, and Eric said it, we don't sell drugs here, okay? But any doctor can repurpose any FDA approved drug. And many have done that. And they've done it mainly to a drug that's called Metformin. And Metformin A is the cheapest drug in the US Formulary, okay? It's really cheap. You can get it for more expensive in Amazon. It will cost you a dollar a day. But it's really a $0.20 drug at most, or if you get it from Mexico, Metformina is even cheaper. There are two kind of evidence that you have to do about metformina. The first one that is really important for me, it showed to target all, all the hallmarks of aging. And people are saying, oh really, how does one drug do the hallmarks of aging? And this is how we understand it. There are some drugs that are going to target aging, which means they're going to take your old cell or old organ or old body and make it younger. And by that it's going to improve a lot of things. The other hallmarks, okay, so that's what it's doing on very principle way. And the reason we know that it's doing, because metformin has been out there for decades, actually for 70 or almost 80 years. By the way. It was used initially to treat. It's an extract of the French lilac, but it's modulated so it's not nutraceutical. But it was used to treat arthritis and to prevent flu. And then it was discovered that it lowers glucose in diabetics. So it went to diabetes. And in diabetes, people have noticed that it's doing really well. Why is it doing well? First of all, in non diabetic people, it will prevent diabetes, it prevents heart disease, it prevents cancer, it prevents cognitive decline and prevents mortality. The most important and really convincing data recently was from a study, a clinical study. So it's a control study, or let me say differently. Nine studies around the world during COVID have shown that people in metformin have less hospitalization and death. So in the United States, they had a controlled study where they took people, not diabetic people, and they gave them metformin within three days of a positive Covid and it decreased hospitalization by more than 40%, death by more than 40%, and long Covid by more than 40%. And this just shows you why those drugs are important. Because it's not diabetes only, it's not metabolism, it's also immunology, right? It improve your immune function and maybe it improved other things. Because Covid is a severe disease, it gives you the ability to fight the disease. So there is a lot of evidence to use use metformin. And you might ask, then why is metformin not an official target in aging? And the reason is that FDA doesn't recognize aging as a preventable condition. And if that happens, healthcare providers don't have to pay you. And if that happens, pharmaceuticals that can develop better drugs, combination of drugs and other drugs are not going to be jump in because they need a business plan. That's why what we're leading as a group, the American Federation of Aging Research, leads a group that's called tame, where we're going to do this study and we're going to show in a control study, double line control, that we're going to in one study to prevent a cluster of age related disease of cardiovascular disease, cancer, cognition, mortality. We're working with the fda. We asked the fda, is that okay? They said, well, you should do some changes. We made some changes and we're going to launch this study now. Okay, but you have to understand everybody has to be on board and we have to have this study so nobody will say you didn't prove anything. For me, we've proved everything because in different studies we showed what the cluster will do, but we have to do the cluster in order for the FDA to say maybe. Maybe you're right. Is metformin the only drug now? I'll go back and connect it to the 100 years old. By the way, I appreciated how many of you want to be 100 years old. I'll talk about my study. Those are the poster child of my study. Those are four siblings that were born between 1910 and 1920 in New York. And what happened to them? All of them reached over the age of 102. In fact, when their little sister on the right died, they were shocked. Okay, the other sister, the old sister standing on the left, Helen died at 110. I met her first time in a New York apartment when she was 100 years old. She opened the door, she was smoking a cigarette. I said, helen, nobody told you to stop smoking. And she said, the four doctors that told me to stop smoking, they died. Those guys. I have 750 like that, okay? Those dyes, 60% of men, 30% of women were smokers, obesity or overweight. More than 50% exercising, even housework, walking, less than 50%, 2% vegetarian. They didn't do what they had to do. And the point here is we talked about environment is a major thing for you, but not 400 years old. Okay? With Helen, the conversation, well, if you stop smoking, maybe you live 120 years. Okay? But they were not people who were interacting with the environment. And that's why they're so special for us, because something slowed their aging. And how did it slow the aging? One of the things actually it was very important for us from the beginning to ask, did they get sick? When everybody gets sick now, they're just living with disease longer, they're sick longer, or is their lifespan and healthspan. Did it go together? What you see here on the graph, that initially everyone don't have a disease. The scale is disease free survival, everybody's okay. And then you go with the green group. The green group are what we call our control that they are age of their kids. Actually they are like regular people. And after the age of 60, they start to accumulate diseases. And at age 80, only 10% of them don't have a disease. But you see that the centenarians, they are free of disease 20, 30 years longer. For me, this is what we're trying to do. We're trying to increase health. SPANISH the side effect will be increased lifespan, but we have population that can do it. It's within our ability as humans. We actually think that we have the ability to live, at least statistically, 215 years. There's a woman that was 122 years, but we have this capacity and we're dying in the United States below the age of 76. Those centenarians live longer, they're healthier, but that's not actually the interesting thing. They have what we called a contraction of morbidity. They are sick very little time at the end of their lives. Okay, you see that even the centenarians who are 100 years old, 30% of them don't have any disease. And some of them will just not wake up one morning, okay? But they spend very little time, if at all being sick. And this is very important because even the CDC now we all know what's the CDC showed that the medical cost in the last two years of somebody who dies over the age of 100 is third of those who die when they are 70. Okay? So we know that it's true. And then comes this Professor Andrew Scott, who's economist in the London School of Economy. And he said, guys, you're out of your mind. What? You're measuring. You're measuring so they are not in the hospital. But if they're not in the hospital, what are they doing? What are you guys doing? You're traveling, you're shopping, you're building houses for your kids. There is an economical value of not being sick that we forget sometime. And he calculate that this economy value is $39 trillion. If we affect health a year, if we affect healthspan by a year or two. So we cannot afford not to do that. I would tell you that one of our major initiatives these days is, and we started it, it's called the superager Initiative, the Superager Family Study. It's led by American Federation for Aging Research. And we're trying to get 10,000 centenarians and their families. In 750 centenarians, we discovered longevity genes of which two are already went to approved drug. By the way, I should explain that when we find the genes, okay, we can do something about it. Not for the centenarians, but for others. Okay. When we find what's the gene, we see the mechanism and usually what we do is we develop a drug. Two thirds of the FDA approved drug last year were based on genetic study. So we want the genetics of the people who slows aging so much that they live 40% more than their friends. Right. This is what we want. There are several, there's not one of them. But all of them are druggable. And we'll have to find which drug is good for which people, but that could be done. So if you know any centenarians, please register them on the web. And what we do, we send them a kit and they spit into the kit and then we have their data and we find genes in them there and their families. Okay, I want to take it a notch farther and just talk a little bit about how this biology looks in the lab. What I'm showing you now is that we measured 5,000 proteins of the blood of thousand people between the ages 65 and 95. We asked what changes between 65 and 95. Those are a lot of proteins. 5,000 times 1,000 proteins. We put them in this mountain where there are computers and they throw up lava stones. Those are the red dots that you see. The higher it goes, the more statistical it is. And the statistics here are 10 to the minus 80. Okay. It's very highly statistical. And the farther it goes to the left and the right is more effect. It is. Now those that goes, the lava stones that go to the right, they increase and those that go to the left is decreased. Because your protein, when you age, go both direction. Some of them you're losing, some of them you're gaining. Some of them are good, some of them are bad. It's a whole other things. But what we've done in a Nature paper that was published last week, we found out not only what's the total proteins that determine your biological age, but also where they're coming from. A lot of that is breakdown of tissues. So where are those proteins coming from? Some are coming from the brains and some from the liver and some from the kidney. When we do that, we see that generally the Age of your liver is like the age of your whole body 80% of the time. But sometimes we see that, that, hey, your kidney is aging faster than the rest of the body, or your brain is aging faster. And so maybe we should look at the brain, and maybe that's where your aging is led by, and maybe that's where we need to intervene first. And maybe there are better drugs for the brain and others for the kidney or for your heart. Okay, so this is where the research is highly AI. There's a lot of data coming in, but we've become really good at that, and we're accelerating our discoveries. Can we develop gerotherapeutics? We do, and we have developed gerotherapeutics. And those gerotherapeutics in next few years will be validated, will get blessing of the fda, and will enable us to stunt your aging much more effectively. As I said, the results of centenarians have been translated into drugs. Where do we stand now on other parts of aging? I'll just make really several small comments. But. But what you see on the left side is the three major category that we're dealing with. One is what I describe as compression of morbidity, with example of metformin. The other is reversing aging. By the way, we call it Dorian Gray. Dorian Gray stopped aging, but when he looked at the mirror, he saw his right age. Okay, When I'm looking at Zoom, I'm saying, oh, that's the Dorian age. I'm much younger. But, you know, reversing aging is the Wolverine or the fountain of youth. It's not happening, and it's not happening soon. But there are drugs that are being developed that are going to make you healthier, even if they're not going to extend your lifespan so much, but they're going to make a difference. So we're making. It's called senolytics. We're making program with them. And then, and I'm talking 50 years from now, there is the forever young, the Peter Pan. Okay? And with Peter Pan, we're making some progress, but not in whole body. The idea is, is that you'll come when you're 20 years old and you'll get the treatment and you'll repeat the treatment every few months or every few years. And it will stunt, you know, it will reverse your aging enough so that you can live healthier without growing old. For me, it's 50 years away. Okay. Because I don't want to be alive to see what happens and to be blamed if it's not or. Yes, but it's really happening in the sense that in organ specific way and in animals we're making progress. And I'm sure that some of it will be okay. Let me explain it though, in a different way. I showed you. We can measure biological aging. We can take a sperm of a 90 year old man, or maybe the 100 year old man that wants a life insurance and fertilize an egg of a 50 year old woman. And we will know the age of the egg and the sperm. But when you form a baby, the stem cells that form a baby, they go to zero. They don't remember our aging. They totally go to zero. And then they start the clock. We figured out how to do it in our own body. We have this biological capacity, this biological capacity we want to really make relevant for all of us in the future. This is my hyperbaric chamber for mice and rats. I didn't talk about it, but could our kids and grandkids be healthy centenarians? I think absolutely. I also want to say that this is not only about you guys. It's not only about getting old. People who survived cancer, kids who survived cancer are aging rapidly. What did we do? We give them radiation and chemotherapy. We age them, they get heart disease when they're 35 years old. People who have HIV getting disease 10 years before their friends. People who are disabled because they cannot move, because they eat so much, because they cannot exercise. Right. They die sooner. Or let's look at another extreme. If we want to go to Mars, we are not going to get there before we stop aging with radiation, we'll have cardiovascular disease, cancer by the time we get to Mars. And we're not going to come back. So for all those reasons, we have to stop aging. So wish us a new luck and thank you very much for listening.