Episode 26: Dr. Nir Barzilai

Nir Barzilai is a doctor and he is a chaired professor of medicine and genetics and director of the biggest center in the world to study the biology of aging. He is a recipient of an NIH merit award aiming to extend the healthy lifespan in rodents by biological interventions. He also studies families of centenarians that have provided genetic biological insights on the protection against aging. Several drugs are developed based in part on these paradigm changing studies. He is a recipient of numerous prestigious awards, including the 2010 Irving S. Wright Award of distinction in aging research. Please meet Nir. He is an incredible brilliant man on the topic of aging.

Welcome, please introduce yourself.

I'm Nir Barzilai. I'm a physician scientist. I have the biggest center in the world for the biology of aging out of Einstein here in New York. And I'm trying to target aging, which means I'm trying to delay aging, maybe stop aging, maybe reverse aging in several ways. Something we didn't know that it's possible, we thought it's inevitable.

And so I guess the question is, have you done it? And is this, Can I have some?

We're making huge progress in. We really went from hope to promise. The hope was, you know, there's a biology of aging. I mean, you go, you go into a hole full of people you don't know who has high cholesterol or who has diabetes or who has hypertension, but you kind of know who's above 50 or below 50. There's a biology. And just like you can treat cholesterol and glucose, you can treat this biology. And this is something that as a community we've done for more than a decade now. And we found out not only that we could do it, that there are some drugs that are in human use that can do that. And we also created the atmosphere. So they are now biotechs and venture capitals that are looking at this opportunity to extend our health Spanish and makes us live healthier as we grow older.

That's great. So obviously then it sounds to me that some of the progress has been made in some of the lifestyle issues that come up with aging and death where it could be cholesterol, it could be diabetes, it could be a number of things. So am I wrong in assuming that this is an area that you're talking about?

So there are two things. First of all, you're absolutely right. The environment is crucial here. Okay. Of all the environments, the one thing that is most important for a successful aging is exercise. At any age, any sex, it's always the most important thing. It can Provide years to life or.

Well, I totally agree with you, but why? What can people understand about that? So that they understand their need for the motivation. What exactly happens when you exercise?

You know, there is a biology that I don't think I can, I cannot use the terms now, but I'll use the concept, okay? Because actually it seems for a biologist that exercise is the last thing you should do. You know why? Because when you exercise, you increase oxidative stress. Right? And we all are about antioxidants. We spend and we support the economy by antioxidant, and yet we do exactly the thing that can do it most. Okay, so why is it working? It's working because exercise increase our defense mechanism against stress, against the biological stress of aging. In fact, one of the theories we have now is that in order to successfully age, you need to go through periods of stress. It's called hormesis. So if you go through periods of stress, you upregulate your ability to deal with stress. That stays with you as you grow older. And I think exercise is a perfect example of something that you can do, do once a day, get stress level. It can do harm. You know, exercise breaks your tissue, does inflammation, there's a lot of things, but at the end of the day you repair better. Okay, so this is kind of the mechanism.

Yeah, I mean, that was really a good definition. I haven't heard anybody really make it as clear that the stress of working out and the repair is, is so much a part of really preserving the continuity of how strong you can be. The other thing is, and can I

just add, the stress concept is important. Look, when you have stress because you have pain 24 hours a day and you cannot sleep and sleep, that's bad stress. But to have stress during your day, to have stress that works, gives you not only exercise and to deal with issues that are difficult is actually part of how you can get to deal with aging better. So stress is a double edged sword here, okay? We kind of don't want it. We want you always to be happy. But on the other hand, when you have goals in life and you go into them and you sometimes don't sleep one night and struggle the rest, and at the end of the time you're stronger.

Yeah, I totally agree with that. And then the possibility of what you can do becomes. You become more sort of informed on what your potential is, the stress of working out, well, maybe I can do splits and I can do a standing split and all of this stuff. And I think, well, that is a pretty Big deal, because it took me time to get there. But I'm empowered by that now. And I know if I can do that, I can do more and I can do anything in my workday because physically, that's a pretty demanding thing that a lot of people can't do. And I love it. I love the power of that. So it gives you. It does so many things. Your potential is defined, your ability to go to the next place. So I have another question about exercise. Do you think that there are different types of exercise that people should do at different points in their lives? Or do you think it's like, should you run till the last day of your life? Or like, what are your thoughts about that?

So let me tell you one thing that will follow throughout this hour. I'm a scientist, I'm also a physician. And my answers to question like that are usually, do we have a clinical study that can give me a view of how it is? A clinical study means you take group of people and in some you do this intervention and the other that intervention, or you give them placebo versus drug or something like that. And to answer your question, we don't have the answer. We know that no matter what kind of exercise you do, it's beneficial. But what is the combination? But it's more than that, it's what the combination. And how does it change throughout aging? And do elderly people, elderly women, do they need a different exercise than young women? So there is a lot to do. But the bottom line is if you like one of those things, you should do it now. Because we know the benefit, we just don't know the comparison very well.

No, it's true. I think that there are so many different exercises that trying as many things as possible is a way you find out whether you like it and it's changing some part of you or enhancing your life. So I'm such a strong believer in feeling flexible and stretching and really having mobility is really incredibly powerful. So how does sleep affect aging?

So let me just tell you. I have a study of centenarians and their families. Centenarians are 100 years old. I have 700 of them.

Oh, my God.

And I have their families.

Oh, my God.

And what I'm trying to do is I'm trying to find longevity genes because in order to get hundred, you need some other help. And so those people are an opportunity for me to discover lots of things about their habits and about their biology. And early on, when I started this study, somebody came to me and said, you know, sleep is like the most important thing. I mean, if you nap during the day, that's the best thing. So I thought, I didn't know what I'm going to ask them, but then two other people said, you know, sleep is the most important thing. Look, sleep is the second question that you ask, right? And so I went to, and I was doing it on my own, so I went to the centenarians because I wanted to figure out what to ask. And I go to the centenarian and I said, so tell me, do you sleep well? Yeah, I sleep eight hours. I said, do you nap? I nap every day. I say, wow, you know, they're up to something. And then I said, so like last year also you napped. You said, no, last year I didn't nap. And the year before that, no, I didn't nap, but the year before there I napped. And then you realize you have people who lived hundred years and you're asking them about napping what now or through their life or from what age and what memory do they have at all to trust it? And so I still had the question, I had the napping and we actually wrote a paper about it because it happens that a lot of the centenarians who were napping were napping because they didn't sleep well at night. So that's not a good nap. When you don't sleep at night and you try, you fall on a couch, it's not okay. So you find it. And by the way, we don't have only centenarians, we have their children and the people who are married to their children. So we have a control group and we have generational. And it happens that our control and our centenarians and their children all, some of them all have some sleep problem. In other words, it's not typical to have better sleep because you're a child of centenarian or centenary. It's not.

But.

And that's an important but because the sleep is associated with risks for hypertension, for heart disease, from, you know, all those things, the centenarians and their children, although they don't sleep well, they don't have those diseases, they are protected against those diseases. So on one hand, sleep is not driving their longevity, on the other hand, if they have sleep disturbances, they're protected from the bad effect.

Very interesting. I asked that because I know that if you're not feeling well, if you have a cold or whatever it is, if you sleep, the more you sleep it seems to heal and restore faster.

I mean, it just, oh, I exercise

well, I Mean that, but, but I think both, I mean, I think I, I think exercise, sweated out and then sleep and restore. There's something really amazing about the miracle of the body by doing certain things that seem, you know, it's what we do.

But that's in response to provocation, right? I mean, we're looking more at the chronic, you know, what's the chronic effect? So the third part is the nutrition, right?

Yeah, that's my next.

So let me tell you a few things and then I'll tell you how everything that I said is in centenarians. Okay. So the nutrition is really interesting because we were interested from my first days in the lab. Every experiment that I had had the animals that are the control or the young, which are, and you know, rats or mice.

Okay.

And we had whatever experimental group and then we had the caloric restricted animal caloric restriction. If you take brothers, animal brothers, and half of them, you give them to eat what they want, and the others, you give them 40% less. So only 60%, they live 40% longer. Not only they live longer, they live much healthier. And this whole discovery led a lot of us to say, you know what, you have to eat less. Less breakfast, less lunch, less dinner. And by the way, when we do that, there is no end point of longevity in humans. They become leaner. And we know that not being obese is good. So then we realize that what we've done was not this. What we've done was we came in the morning and gave all the food for the day, in the morning, into the cages of the animals. Now, the animals were hungry, so they finished the food in 20 minutes and they were fasting for 23 hours.

So it's not intermittent fasting for myosin.

That's where I'm coming. That's exactly where I'm going. So when we gave them food throughout the day, they were thin, but they didn't live longer.

Wow.

So that's where the intermittent fasting is coming. And I myself am doing intermittent fasting, which I discovered is really easy to do. And the reason is I've never dieted before. But if you would have given me a three months diet, I could break any day. But if I have an hour or two to go without food, I'm not going to break. Yeah, okay. And then I can eat whatever I want.

Yeah, it's clear. No food now, food later. Okay, I'll wait.

Yeah, exactly.

It's so easy. It's really incredible when you're allowed to have a little protein or you can have a little. Then there's no sort of regulation or control. But when it's no eating, then there's no other option. So you don't look in the refrigerator. You don't think, oh, maybe I can. A carrot? Yeah, I can have a carrot. Or I can. Then you start. But then I'll just add a little of this. So the clarity of no, eat, eat is so much better. And then within that period of time that you have to eat, I think you respect the process too. You don't just eat randomly. You really think, oh, good, I'm gonna have my first meal. And you eat it with a different purpose.

And being hungry the first time in my, my life pretty much, really, but

in a hungry in a good way.

In a good way, Yeah.

I don't feel ravenous either. And what happens after a few days, it's sort of. You don't even think about.

So you do that.

Yeah, of course. I'm totally into it. I love it. And I go to bed early, so my eating time is early. And then the times when I'm going to a dinner or an event, I just switch it. So what time do you.

So, you know, so it depends when I'm having dinner, but I'm counting the 16 hours since then. Okay, so it was actually 1:30 today, but at 2:30 on the way here, I took a little vegetarian sandwich in the corner here and you know, and I'm fine.

And also when, you know when you're gonna eat, you can even prepare and have good food ready for you. Do you know what I mean? Like, oh, when I break my fast, I'm going to have my favorite salad or I'm going to. So it's. I absolutely love it. And I think when you add exercise to that, you feel so much better. You don't feel bloated, you don't feel

like, well, I'm breaking my records in exercising since I'm doing it, you know, I'm doing peloton, I'm doing biking, I'm doing things. And I've been improving. So, you know, I think it's working for the aging perspective. I certainly didn't lose lean body mass, even though I lost fat mass. So, you know, I lost.

I think it comes. I think what happens is the consistency. Your body then starts to transform. And it's an interesting thing because as a woman having gone through menopause and all of, you know, through your 40s and all of a sudden, like, what's happening and then menopause and oh my God. Like this is crazy. By being consistent with exercise, I was able to manage some of the worst parts of what was happening. Even when I was exercising and feeling hot. If I just like I would say to myself, you're going to sweat anyway, so don't. So you're hot, you're already there and just go through that. So part of this thing we talked about, of barreling through an exercise and seeing what you can do, it's helpful in giving birth or in so many ways of breathing through things, going, getting to the other side of it. But I do think the conversation about eating too much food and eating round the clock, I mean getting up in the middle of the night, people eating and going to bed and eating in bed and like, whoa, wait a minute. But what will it take to kind of bring that message to everyone?

So what I'm doing, I'll tell you about messaging, how to messages. But what I'm interested is the science. Because look, the 16, 8 is just a made up. You could have said 17, 7. Okay. I mean it's just a makeup. And what I'm doing at Einstein, we're taking older and younger people and the first thing we're doing is we're doing a 24 hour fast because we are looking at that fast at the biology of aging. We're going to take their cells and see if they are getting younger or they're upregulate those defense mechanisms and if they produce ketones, which you produce when you're fasting. And what happened to the insulin levels and the glucose level and all variety of things. So we need the time course of that. Once we know the time course and based on that, and I hope it works, I hope the 12 hours is enough because then we'll design a study where we bring those people for 12 hours. In other words, eat a 6 o' clock breakfast, 6 o' clock dinner or whatever. And if that 12 o' clock works, it might be an easier message to implement. You know, so you do breakfast and you skip lunch and you do dinner or I don't know, you can choose or you can do this. 16 ate too. But it gives more options for individuals to. They're actually people who are telling me I cannot do without breakfast. I don't know why and I don't know if they really tried for a few days. Maybe the first day is hard, but there are people who said okay, but if breakfast and dinner works then that's good. Then you skip lunch, you have to skip something. So that's What I can tell you, the marketing in health care is very problematic. We're not good at that. You know, we're not good at it. Some of it because of regulation. When you see drug companies putting advertisement on television and it's more about the side effects that never happen, you know, who wants to take the drug? On the other hand, how do we make our people consumers? You know, why do they get on a Coca Cola ad and they want it? You know, we're selling them bad stuff or McDonald's, right? We're selling them poison, but they want it. How can we turn around and have some recommendation? People say, I want that. That sounds good. It's a challenge. I don't have a solution. It's a challenge. But I'll give you example. Immunization in elderly is a problem. A flu immunization, flu. First of all, people know that it's not 100%. Maybe it's only 40%. Well, for 40% I don't need pain in my arm. Okay, so do you get flu shot? Yeah, yeah, I get flu shot for years and I've never gotten the flu.

I've gotten a 65 year old plus flu shot. Did you know that there's a Stronger1 For 65 years?

Yeah, yeah, yeah, of course, of course.

I had no idea. So, so when they said to me when I got my flu shot, oh, we'll give you the 65, and I thought, me?

No.

And I was like, oh yeah, I guess that's me. Because I never think of myself as the senior in the movie theater and you know, whatever that's about.

Well, you raise another question. I want to go back to the immunization, but you raise another very important question. This is a lot on our mind. There is a chronological age and there is a biological age.

Oh, yeah.

And even you can see it in people that don't take care of themselves. Some of them just look 10 years younger and some years 10 years older. Okay. And this is something in research, by the way. That's why I'm doing centenarian studies. They look 20 years younger than their age.

Really?

That's the perfect population.

Really?

And their children too. Okay. And their children too. And by the way, their children were the same age as the control. They have less of every one of the diseases and they also have less biomarkers that are associated with.

This is a genetic thing.

Well, this is genetic, but before going to genetic, we have to identify those because it's not all genetic. Some of that is environment. I'll just Tell you. So to finish the immunization, one of the things that elderly hate is to go to the hospital. So, you know, you have to find. If you say, you know, if you don't get that, you are 10 times as likely to be in the hospital and, you know, you hate the hospitals is a better motivation than you have. Okay, now, in pediatrics, the doctors don't tell their patient to immunize. The mothers are saying, are you immunizing him? You know, but in the elderly, there's nobody who's shouting at him. So how do we, you know, with this talk, how we change our elderly to consumers so that they want to exercise, they want to do the right thing with diet, and that's a challenge. So our centenaries, if you're asking about our centenarians, they haven't done anything good in their interaction with the environment. Almost 50% of them are overweight or obese. 20% are still overweight or obese. Cigarette smoking. 60% of the men and 30% of the women. I have a woman who died when she was 110, and she celebrated 95 years of cigarette smoking.

No.

And when I met her first, she was 100 years old. And I said, nobody told you to stop smoking. And she said, all four doctors that told me to stop smoking, they died. Okay, if you're talking about exercise, even moderate exercise, like walking or biking, less than 50% of the people, and vegetarian is like 2% of the people. So they were not different than the population. What they did is they had protection, a genetic protection. That's what we were uncovering.

So can you.

So, okay, by the way, I have some indications that you have longevity in your family, but first you'll tell me, and if I'm right, I can tell you about it. Do you have longevity in the family?

Yeah. Yeah, tell me. My. My grandmother lived to 100 or 99 maybe she was gonna be 100. And I think I connect with her the most out of my mother's grandmother. My mother's family is Lebanese, so they have a certain diet that I think also helps with that. My mother. My mother didn't live as long as her sisters. She had. She's one of five sisters. And the four sisters all lived into their 90s. My mother lived to 88.

What did she die from?

She actually eventually died of colon cancer. She had a big colon operation. She had it when she was younger, had it again, but for a good part of her life. Her diet earlier, her diet was great, and she juiced when I was 16 and drove me crazy with this big engine in the house with the carrots. And then she sort of was eating funky food. And I think that had a part of it to what.

But you still understand that you have a strong family history of longevity with the siblings, with even your mother, 88. You know, that time, at her generation, life expectancy was at least 10 years below. And the reason I know it is that I heard in another podcast that your mother and grandmother had their children at age 55. Our centenarians typically have their first and last child later.

Really?

Sometimes it's the only child, really. And by the way, we try to understand when is menarche and when is menopause. And we wrote this paper because there is an exchange in nature. There's exchange between longevity and reproduction. If in animals, you stop the reproduction, they live longer, okay? If you increase reproduction, they live shorter. And there is evidence that it's the same in humans. And we did a study in our centenarians, and we saw that they have significantly less children, both the women and the men. And so, of course, the first question, is it raring the kids or, you know, what is it? It's the biology.

And what's the answer to that?

So because it's in men, too, we think that it's more of a biology. So we try to ask to see what's the age of menopause? And when I got the results, the, you know, the data, and I'm looking at menopause, it was 50 plus, minus zero, which basically means all the centenarians, women, had their menopause at 50 years old. Didn't make any sense. So I went to the nurse who's taking those. It's a male nurse. And he was taking those questionnaire. And I said, so tell me, how are you asking about menopause? He said, well, I asked when was your last menopause? And I said, what's the answer that you got? He said he didn't remember. They're 100 years old. So what did you do? So I said, 50. And I said, yeah, 50. You wrote 50. But it also shows you. I mean, people don't remember their menopause, certainly not 50 years later.

It's very easy to forget. And I think a lot of the reason it's easy to forget, because I have to really, for me, if I'm 74, and you think how far that was, like when I'm answering a doctor saying, are you still menstruating? And I think, how long ago? And I Think, oh, wait a minute, 10. Like, oh, that's a long time ago. And it often sort of peters out and there. Isn't it done?

Yeah, it's not one day.

It's still like puberty. Okay. It's not one day on point now. I know. No, it sort of fades. So I have a question. If shortening, if you have a hysterectomy, would that have any effect on longevity?

That's a good question. But look, the hysterectomies are happening post reproduction, right?

Or maybe not.

Well, usually so. Most of the women had their kids by then. So this is a different biology.

It's very interesting. I think the hormone phenomenon for women especially, it's such a roller coaster that women go through, and it sort of defines so much of who we are at different points in our lives. And I think that there's something to the end to menopause finishing that when you get through the transition, the relief of not having this hormonal agitation sort of making you more sensitive or things that men can't stand in women, like hyper about the littlest things or whatever. And finding that so much ruled your behavior and not having it, I think I would never want to go back to that because the peace, and I think the longer you have that for sure, has got to be beneficial.

So, you know, this is really very interesting. I'll tell you something that I'm bringing you to my perspective, and I'm talking about hormones from the perspective of aging. And this is our problem. We can measure lots of things that are happening with aging. Some of them might be the cause of aging. Some of them, we might measure them and they might even tell us what's your biological age, but they're not doing anything. But the third group is the most important. It's when we have aging and we start the breakdown of aging, there is a response. Just like when you have infection, you have inflammatory response. When you have the aging, you have a response. So what of everything you're measuring is the cause of aging? What is the response for aging? Because if it's the response to aging, you don't want to stop it, right? You want to do only what's causing age.

Right.

It's a big headache. And we're going through that and making, you know, making progress. But the estrogen is a really important story for us. Because when I came to the field, I'm an endocrinologist, okay? The reason I went to becoming endocrinologist, I was interested in aging. But I thought, you know, if we just. You just give back all the hormones, we've solved everything. And when the Women Health Initiative started, I was initially, why are they doing that? I mean, we kind of know what's happening. And then as I became an agent, I said, no, they have to do that. And when they did it, they found out that in women over the age of 60, those estrogens were causing them heart attacks and cognitive decline and brain breast cancer and all these things. Which makes me think that if it really accelerates those diseases of aging, that menopause is actually a protective mechanism. Okay, It's a protective mechanism that we shouldn't restart, because when you restart this, you get bad results. So I really think that. And by the way, it's not all or nothing. You know, estrogen has some good things, but estrogen is really a protective response. And in fact, I think more interestingly, you know, animals don't have menopause. And our thought, and several people were discussing it over beer, usually because it's not influencing our research. But why humans needed menopause, why did they need to stop reproduction? Well, the reason is that mothers, if they were pregnant all the time, they will die in birth. And why will they die in birth? Because humans went from being on four to being erect. When you're in four, your hip is opening like that. When you're erect, it's closing. So the babies became bigger and bigger because of nutrition, and the hips became smaller and smaller. And. And I think at some point in the evolution, they had to figure out who are the women. You know, how do you stop? Because otherwise you'll have no mothers and no grandmothers and all humanity would be different. Right?

Yeah.

So this is just a thought, right?

So what's your thought about hormone replacement therapy then? I mean, is it something. I mean, it is the topic right now. Menopause is finally being talked about. A lot of focus on it, sort of out of context with aging, which I think is a little troubling because it's not that separate. But the conversation about hormone replacement is big and there are companies being established now to distribute through very modern means. And in a way, I'm a little curious about how that's going to work for all the individual women that have different family history and have all of this. And yes, you can fill out a questionnaire, but still, knowing that person is another thing. It's an in person thing. And why should this person be a candidate and that person not? So what is the prognosis on that?

So look, I think this has to be resolved in a clinical way. So look, the argument was, you know, you, the WHI did it on 60 years old woman. But maybe between 50 and 60 there is an opportunity. Okay. And I accept it. And, and in fact there is a clinical study that shows now it's six or seven years that there are still benefits at early menopause. Okay. So I accept that this is the problem. We talked about the fact that people have their chronological age and biological age is not the same. So I think there are women that could take maybe estrogen for until they're 65, but there are women that maybe at 55 they become a risk because it is established that at average age 60, you get into trouble. So how do you decide who are you and where are you? It's exactly back to what you said in individual way.

Very specific. Yeah, I'm a little concerned about that because it does seem like the antidote when you look at the benefits. But then, you know, specifics are so, you know, important.

So look, my wife, who's going to be 60 now, I hope she doesn't

now, you know, she could be listening to this. But 60 is young and she, she

looks amazing and she decided not to take hormones. But she does have some symptoms and I do think. And she doesn't take anything. Although I think that for symptoms you can give a little bit of estrogen. Okay. I'm, I'm talking about full replacement versus helping symptoms or maybe helping symptoms at some time. So I don't see it as an all thing, but it has to be figured out.

I agree. I don't think there's an answer for everybody. I think it's impossible just the way menopause is so different for every woman. But I do know that women who drink through the process, who are not working out, who aren't being more sort of controlled about how they're eating and what they're eating, are definitely going to have a different experience than women who are not. I also feel alcohol. I personally feel alcohol is aging. You are the expert.

Well, I'm not an expert in alcohol. I don't like alcohol so much.

But what are your thoughts about it in all of these studies? Are these people, people drinking red wine or they.

Well, so our centenarians are.

Well, they're smoking, so they're probably.

Yeah, they're, they're drinking very little in, you know, very little. So you cannot do anything with that. They're just having an average of one drink a week, they say.

So that's. Yeah, well, I I think there's something.

But alcohol. But you know, the data on alcohol we, the American Medical association suggested that men should have, women should have one cup of wine or alcohol and men should have two. A day.

A day?

Yeah. And I think.

Are you kidding?

Yeah. That was the recommendation. And that's not. Oh my God, that's not the recommendation anymore. We don't know that. And by the way, remember, it was based on evidence. It was based on evidence, but the evidence was established decades ago. And we're living very different life with very different environment. And I'm not saying it wasn't right then, but I'm saying it's not right now.

Yeah, I mean, our environment is so toxic as it is that we're having to deal with layers of bad air, more food with high processed, high fructose corn syrup and everything else that to add more sugar with alcohol just doesn't feel right to me. It just doesn't seem like it. It's going to be good. But I mean, you know, I think that's another switch that has to turn in the head. So I read you're the expert on this, but I read years ago and still keep seeing this, that at 120, the cells stop reproducing. Is that a fact?

Well, dividing, right? So this is an interesting story. So, yes, our cells have ability to divide just that many times and after that many times they become a different kind of cell. We call them senescent cells. That's not the only way to become senescence. If something goes wrong in the cell, they can either commit suicide, it's called apoptosis, or they can become senescent. And both of them are actually cancer protective mechanism. Okay. Instead of, you know, something is going wrong, there is mutation and something. Instead of being cancer, let's stop it now. You're either senescent. What happened with aging? We're accumulating those senescent cells and we found out that those senescent cells are secreting proteins that are making the tissue around them old, I would just say, and actually contributing to cancer and other diseases. And when we in the lab remove those cells from animals, they are healthier, much healthier. And they live longer. On average, they live longer. They don't have maximum lifespan more, but they are living longer. And this is one of the commercial things that are happening now. There's a pharmaceuticals by the name of Unity that is really trying to figure out a treatment so that your senescence cells can be, maybe every few months can be depleted.

Oh my Goodness.

We cannot stop senescent because it's cancer protection. But we can remove them once they are there. And by the way, how do we remove them? We try to make them rather than stay senescent now to commit suicide, to do the apoptosis.

That's the mechanism. So it's a pill.

It will be a pill. There are some weak pills now that are in clinical studies. They work in animals. We don't know if they work on humans.

So is this like a 10 year old, 5 year, 20 year, like what, what's sort of the study period?

So, you know, I want to see. I always, I, oh my life. I said five years and I'm still saying five years for the same thing. But I would say we're, we're catching a wave and we are in the moment. So what I would say is what Bill Gates says. We are overestimating what will happen in two, two years and underestimating what happens in 10 years. And I think that's the timeline now. So I think it's relevant to all of us. And by the way, it's never too late to target aging.

Really?

Yeah.

So when, when I heard about this, the cell thing, I said, okay, all right, so I'm gonna say I want to live to 120, and I may not make 120, but at least it's sort of like when you have a target and if you fall a little short and it's that far out, it's better than not having a target. And when you have a target like that, if you live a lifestyle that's anti, you know, getting there and it's sort of definitely not going to get you to that. But if you try to sort of follow what you think is a healthy lifestyle and keep curious about it, then maybe you can get closer to it. So is this a fallacy? In my head, is it all about genetics? And I'm like, you're crazy.

No, no, it's not a fallacy. Okay. So we think that humans maximum lifespan as a species is about 115 years. Now there is a woman that lived 120 years, but you know, about 115 years. And we die now before the age of 80. So there's a low hanging fruit that we can do in addition to exercise and diet and all things we can do much better. And so some of the challenges are. And by the way, I should say 115 doesn't have to be the end, it's just, it's a different stage. Okay, now I'll give example of what will happen soon in order to break this barrier. But part of the challenges is not that we don't have way to do that. But aging is not considered a target, an indication for drug. So let's say I have something and I'm publishing it. And the patient come to his healthcare provider and say, I want this drug. And the healthcare provider said, I'm sorry, there's no indication for this drug. We're not going to pay for that. If that's not going to happen, the pharmaceuticals are not going to come and look at those biotechs and. And develop better drugs, more potent drugs, combination of drugs that we can really improve healthspan by a lot. And one of my efforts and successful one is to start a study that's called tame. It's targeting aging with metformin. Metformin is a drug that you give to all animals. They live longer and healthier, even much more healthier than longer. And we went to the FDA and there are two issues. The first one is what's the indication? The FDA didn't want aging to be a disease and we didn't want aging

to be a disease.

Okay. Because there's ageism. Right. And people are fired and not hired and stuff. So you call them sick now. And AARP didn't want it. American Federation of Aging Research. So. Okay. But we both discover it's not really necessary. What we want to do is to really prevent aging, but we want to prevent age related diseases. And we have a study that will show that we can do that. And once we do that, there will be a template to pharmaceuticals to do the same. So I think it's an obstruction that we can overcome and we're going to launch this study soon. We are missing a little bit.

Here I am.

Few million.

Here I am.

You know, it's interesting. This was.

Am I too old for this?

No, it's 65 to 80. 65 to 80. Okay. And chronological, not biological, but what happens. It's really interesting that you're saying we're going to do it in 14 centers across the United States that are going to get their own patients. And one of the reason is once I started talking about this study, Wall Street Journal wrote about it.

Oh my God.

And I got 3,000 emails and phone calls and stuff. I want to be in the study. I want to be in the study. And at first I said, we recruited everyone. We're done.

Right.

And then we thought, just a minute, those are people who read the Wall Street Journal.

Yeah.

We didn't have our emails there. They found our emails. Okay. So the point is they're doing many other things for their health. Okay. Yeah, we don't want that. Okay. And not only then. Then it started to become apparent because people said, I'll volunteer to your study as long as I'm not in the placebo group. Okay. Okay.

Talk about it. They're probably New Yorkers, entitled New Yorkers, and, you know, me being one of them.

And because they're New Yorker, you kind of start thinking if they discover they're not in metformin, they'll get Metformin anyhow. So those people now are excluded from our study. Okay. We need to do it somewhere around communities that are not sort of out of the. They don't care that much about aging, but they will take the drug if we fail. Yeah.

Wow, that's amazing. And it's. When? Soon.

Yeah, we hope to do it soon. In the meantime, there's lots of people who are taking metformin.

Oh, they are.

The sales of metformin. It's a generic drug. It's very cheap.

And so what does that do again?

It targets the important hallmarks of the biology of aging. Okay. Without being.

Who is prescribing this?

This is a drug that is used for diabetes. Most of the patients with type 2 diabetes are on Metformin. And it's interesting because those patients on Metformin, they have less cardiovascular disease, they have less cancers, they have less Alzheimer's, and they die. They die less. Their mortality is less than people without diabetes.

Okay, here's the real question. Are you taking this drug?

Yeah, I'm taking metformin.

Oh.

I'm taking metformin because I was pre diabetic. Pre diabetic is one of the indication of metformin. And when I became pre diabetic, my doctor prescribed Metformin. Since then, I'm on metformin. I lost some weight. I'm not close to pre diabetic, but I'm not off the drug either.

So what if I took it and I'm not pre diabetic?

So you know, I'm not sell. You understand that? I'm not selling it because I need.

No, no, no. But I'm just curious, has there. Do you know of people who are taking it who aren't?

Oh, there are tons of people who are taking it. There are tons of people, but you have to understand it's for diabetes. So you're, you're thinking, will it lower my glucose? Right? It doesn't lower glucose. It doesn't work on lowering glucose. It's not a hypoglycemic agent. It's anti hyperglycemic. It really decreases your insulin levels. Okay? That's all it does. So you have the same glucose but with less insulin.

So that's an interesting conversation. So I have always sort of not being a scientist at all, but when I think of insulin and I think of being healthy or insulin and diet or whatever, I think of it as being a negative. So tell everyone about insulin and what and how you measure it.

Well, you know, you can measure insulin level, but it's not a standardized test. Okay? You have to measure the insulin and glucose. Every lab is measuring different, so it never became a standardized test. Okay, but what happened? Insulin resistance, okay. The resistance to the action of insulin has become a hallmark of this metabolic abnormality of aging. Okay. And so people who are insulin resistant need more insulin in order to get this glucose into their muscle. But this high insulin has effects all over the body, and it's thought to contribute to development of atherosclerosis and some other problems. So we always want to be more insulin sensitive. With low level of insulin, we want a little insulin to do the job. One of the things though, that people have to know is that insulin resistance is also a protective mechanism. Just as I told you, we don't know what's causing and what's not. It's a protective mechanism. In other words, when you have too much food and the glucose goes into the muscle and it stores as glycogen, it is used, there's no more space. So the muscle has to be insulin resistant and say, I'm not getting in more glucose. You go and store it in fat or somewhere, okay? So once it's a defense mechanism, you also don't want to move it to remove it. Because if you remove a defense mechanism, you just get more things.

And some of it do need a level of insulin. That's fascinating. That's really an interesting thing that.

But, you know, I think the important thing to remember is that aging or this biology of aging drives the diseases and the risk of age to diseases is much more than the risk factors that you know. In other words, cholesterol is a threefold risk for heart disease, but aging is a thousand fold risk risk for heart disease when we go from young to old. And it's the same with cancer, and it's same with diabetes and same with Alzheimer's. So the only way to take care of it is to target aging itself. If we're going to be Successful only in heart disease. Then actually, what happened now when you have a stent, you had heart attack and a stent. Then in two years you'll get either another heart attack or diabetes or Alzheimer or something. Because we never fix the aging. We only fix locally the heart. So we have to recognize that we are in this stage now where all of us are getting old. And this idea that you get old and get disease and treat the disease and accumulate diseases and things is not reasonable when we know we can target the aging process itself and prevent those diseases and increase the health.

Spanish. It's holistic. Totally.

Right?

Yeah. That's amazing. That's really fantastic. Is there anything I didn't ask you?

Well, I'll tell you just one thing. We missed a lot in our science by studying only male animals. The biology.

Sexist.

The biology. No, there were reasons. None of them is justified. For example, we didn't want to study mice because maybe they have their menstruation then. And that will change. Okay. We had lots of excuses like that. And also with the money, we needed to think where we're going to put the money. But we discovered in aging that the aging of. There's a lot of commonality, but there's a lot of differences between male and female. Only the fact that females live so much longer should have altered us. And it's around most species. It's like that.

Yeah.

And some of the drugs that we know can target aging. Not Metformin, actually, but some of the other drugs work either on male or female.

Really.

So there is a lot of us still to discover.

Wow.

Metformin is one of the drugs that work equally on both. But even that we're not totally sure. I mean, the extent it might be more sensitive to men or women, we don't really know because nobody thought of it like that.

Wow. And so is there any difference in women age because of the sort of the environment and the more aggressive role women have? Do they still live that much longer than men or is that changing at all?

I don't think. I don't have any indication it's changing. I just want to say one thing of our centenarians, Centenarians around the world, it's different with our centenarians. Centenaries around the world, 80% of them are women.

Whoa.

Okay. However, the men who makes it are much more robust.

Really?

Yeah. In our study, it's more like 35, 65, because. And that's important because we need centenarians who have children, because we need their children in Our study, and a lot of the women centenarians don't have children. Okay, Exchange of reproduction.

Why is that? See, now I don't have children.

So we.

Is there any relationship?

We don't know. We don't totally understand the mechanism.

I mean, a, they never had children.

Yeah.

A.

Right. A, you know, how many of them didn't get married or how many of them didn't get married because something was wrong with them or how many were. Are fertile. Okay. We just cannot get this information.

Really? That is fascinating. You know, I never thought that I wanted to have children, to be honest. From the time I was a little girl. I remember at 6 years old being asked, you know, about having children. I was like, no, I don't want to do that. And so it was never something that, you know, little girls all want to be mommies. And so I never thought about it. And then I thought, you know, when I had so much pressure, aren't you going to have kids? And I would start to lie and then believe it and say, well, yeah, of course, someday I will. And then when a guy got older, well, maybe I'll adopt. I can always adopt. And then it was like, hell, no, I don't want kids. Like, why am I lying? And then I would look at the stress of running a company by myself and being in business this long without partners or anybody helping me do it, and extremely stressful, extremely committed to everything. And I would look at mothers and I would say to myself, I have an extremely difficult job, but that is connected to the emotion in a way. And this is very. It's an extension of me, but it's connected in some way, an intrinsic kind of connection to the psyche. That child is an extension of you. Everything. You know, it's so complicated. And how does that. Does that not affect the stress I have? And it always isn't bad stress. It's good stress, too. But do you think there's a difference in aging?

Well, then I'll ask you, how do you know that whatever thoughts you had are not part of the longevity genes that you're carrying?

Really?

Right.

Really?

I don't know.

No, That's a fascinating fact, because we

don't know if you wanted kids, if you could have kids, right?

Oh, I could have kids.

You could.

I just didn't have kids.

But I don't know what's the mechanism of fertility? So I have to tell you this story. And we land. Okay.

No, I'm gonna kidnap you.

You know, everybody who has centenarian knows centenarians. And they call me and everybody, you have to see this person and they're amazing, okay? And there's one guy who says a family who said, you know, our aunt is In Florida, she's 104 years old. Believe me, I have. You haven't seen anything like that. And I, yeah, I have. No, no, you haven't seen anything. I said, okay, when I'll be in Florida, I'll see her one day. I'm going to see this 104-year-old woman. She's outside of her house in Fort Lauderdale or somewhere, West Palm beach, outside of a beautiful house. She's dressed really, really nice, doesn't look her age at all. She just came from Plain Bridge and we're going into her house and we're sitting down and I'm asking her some questions. And then she says, you know, you didn't ask me everything you could have asked. And I said, really? What? She said, you didn't ask about sex. So I'm in Florida sitting with 104 year old old and I'm like, I don't know, what's that? And I said, you know, but you know, you're widowed and stuff, we don't ask, but what do you want to tell me? So she says, so I became sexually active when I was 16. It was actually 1917.

Okay, wow.

And I was thinking, wow, that's really early I thought. And she said, until, oh, you have until, until I was 93.

Get out.

And then I started yoga, but it's not the same.

Yoga is great though, I have to say. I've just started and I.

Did you take it for what it is?

But I, I, I think there's something to that. I think on a lot of levels, I think just connecting with another human being intimately in any way is life giving. You know, I think there's so much to that. Out of all the Centagenarians you've met, besides having some of this commonality, what's the most extraordinary experience you had in or sort of revelation?

Well, I'll tell you one example that is on my mind because you know, again, I'm meeting them when they're 100 years old and I'm trying to figure out their life, which they don't remember so well anymore. But just to show the complexity, I went and met another 104 or maybe was 102 years old and he was like the nicest man I've seen.

Oh really?

He was very thoughtful. He talked about his family with love. His daughter in law didn't do anything wrong to him. You know, it wasn't like. And so I'm having this discussion with him and I go outside and I go to the first floor and his son is there. Of course, his son is 80.

Right.

So I'm telling the son what I'm telling you, okay, this is the nicest guy I ever met. So the son looks at me and says, you should have seen this son of a bitch when he was my age. He was a terrible, terrible person, really. So then you realize that, you know, personality, people say that don't change with aging, but they looked only until age 60 or 70. In the older brain, there are changes. Even if you're okay, there are changes and the things that happen between 60 and 100, you know, there's a lot of things. You lose your spouse and you go to another old age home and you have to adopt and adopt it, adapt. And at the end, you might not be the person, I might not depict the personality that brought them here. So when I have papers out there that said the centenarians are really, they're optimistic and they're good and they're good attitude and stuff. It's true. But I don't know that that was crucial for them to get there.

Yeah, yeah, they probably had to adapt to that. And you have to be compliant in a way when you are dependent, maybe more on other people.

But the adaptation is good.

People would like to adopt, I think. So it's a survival technique that's critical. I know when my mother went through menopause, she had a terrible time of it. She was just ornery and tough. And so it was so difficult. I got married at 19 to get out of the house because you would never just live with somebody.

You were all in the United States,

you were born in Canada. So it progressively did not get better. It got a little worse. So finally I said to her doctor, when she started to get ill, it got worse. And I said, I don't mean to be a bad daughter, but is there any way you can give her a hormone replacement or something? Can we just try that? And he did. And she was a funny, kind, smart, sweet, happy person. And fortunately we had a great till the end of life experience together. So there's so much that affects how you feel and, you know, whether it's hormones or environment or whatever, being compliant that I think it's again, it's such an individual thing. Right, right.

But you know, there are still common things for everyone of why they age. I mean, at the end, you can age at different rates, but it's very common. And by the way, it's similar in animals and in humans. Okay. The skin, the hair, the skeleton, the diseases, it's all similar. And there's individual variation. But my optimism is that there is a very common mechanism to that. And I'll tell you why I'm so hopeful for being achieving even more. You know, you can take a sperm of a 70 years old and an egg of a 50 years old and you can fertilize the egg. Right. People have done that. Okay. People that age have babies. And we can actually measure the age of the sperm and egg.

Oh, you can?

Yeah.

Wow.

But when after fertilization, the blastocystis form and those cells that are going to become the new baby don't have the memory of the age of the parents, they erase it.

Wow.

Okay. So we figured out how to do that ourselves in this context. So we should figure out how to do it. Okay. So that we can really regress ourselves to be young again. And I think that's the future.

I want to be your assistant. Please let me be your assistant.

It.