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January 24, 2024

Sicilian Secret

SSD interviews Dr. Nir Barzilai, M.D. | Biology of Aging | Centenarians



This podcast is written and presented to you by husband and wife team doctors Sandra Cammarata and Dr. Giovanni Campanile. Sandra is a psychiatrist and was born and raised in Sicily and Giovanni is a cardiologist.

They have written the Sicilian secret diet plan book and podcast in order to introduce a wider audience to the wonderful taste and health benefits of the Sicilian Mediterranean diet, which will lead you onto a path of longevity and improved health span the reduction of disease in the later part of your life. The goal is to live not only longer but better with improved vitality and joy of life. Their motto is Be well, deliciously.

Who is Doctor Nir Barzilay?

We’re very pleased to present to you, Doctor Nir Barzilay. His resume is really impressive. He is the chaired professor of medicine and genetics and director of the larger Center for Studies of the Biology of Aging. He is the principal investigator of the Einstein Nathan Shock Center and the Glen Center. Doctor Barzilay is the recipient of an NIH Married Award aiming to extend the lifespan of rodents via biological interventions. He also studies families of centenarians and his findings have provided genetic and biological insights into the mechanisms of aging. He is the author of over 270 peer-reviewed papers and a recipient of numerous prestigious. Awards. Including the 2010 Irving Wright Award of Distinction in Aging Research and the 2018 Epson Longevity Award. He’s leading the tame trial targeting taming aging with Metformin, a multi-central study to prove the concept of multi-morbidities of aging can be delayed in humans. Is the founder of Cobar and he is the medical advisor for Life Biosciences. He’s on the board of a FAR and a founding member of the Academy for Lifespan and Health Span. He has been featured in many papers, TV programs, documentaries, Edex, and Tedmed and has been consulting and speaking at the Singapore Prime Minister’s Office, several international banks, the Vatican, PepsiCo, Milking the Institute, the Economist, and World magazine, and he is the author of a wonderful book, Age Later that was published in 2020.  Yes, what an amazing bio, and this is going to be an amazing conversation with Nier.

What’s on Today’s menu?

We’re going to talk about many, many things regarding anti-aging, health span expansion, and longevity. We’re going to talk about what’s the difference between biological versus chronological age. We’re also going to talk about the global effect of modifiable risk factors on aging and cardiovascular disease. And also is it possible already to reverse aging and make an impact on aging? We’ll talk about a super interesting concept called antagonistic play atropy which means that certain things that may be good for you when you’re young may not be good for you when you’re older and vice versa. 

And this is very much associated with certain factors in anti-aging. We’ll mention the UK Biobank and the All of Us initiative in the United States the importance of insulin-like growth factors on aging, the longevities genes project Also New Year’s work on the offspring of a centenarian, how this is important and sheds light on the meaning of the genetics of becoming a centenarian. We’ll also mention the New England centenarian study and the New England supercentenarian study the concept of compressional morbidity where all the disease is concentrated at the very, very end of life and this is really the key component of improving health span. We’ll also mention Klinvar, the TAME trial which is a metformin as a tool to target aging hyperbaric oxygen, and how this shows there’s significant research showing improvement in longevity. How metformin is a drug that not only may affect aging but also is antiviral and affects COVID-19 in a positive way and can reduce the risks of long COVID-19. He’ll mention a little bit about Brian Johnson and Project Blueprint and then at the end, Nir will tell us what he does for his own life and which you may incorporate into your routine. He’ll also mention the new society that he has helped organize, the Healthy Longevity Medicine Society, and how intermittent fasting is helpful in promoting longevity. Something that I am super interested in is artificial intelligence, electrocardiograms, and how these can measure biological and chronological age. The Longevity Dividend and the work by the economist Andrew Scott and his book The 100 Year Life of how longevity could be a $56 trillion opportunity. And then finally, how centenarians or people that make it to a certain age have great outlooks on life. Their personalities are good and they’re very happy, as opposed to us fearing what can happen at the end of life. Most centenarians are very content, so without further ado, let’s listen to this amazing and super interesting conversation with Doctor Nir Barzilay.

1- Deep Dive into Anti-Aging and Health Span

Good morning, Nir. Thank you. This is an honor and a privilege. Speak to you. You know, this healthspan and longevity is very much part of Sun and I was practicing, so we’re very excited to speak to you. Well, it’s nice to be in the same army and fighting the same war. What can I tell you? We’ll win. We might not be there to see the victory lap, to participate in that, but we’re definitely going to be there. So what? Tell us, Tell our listeners, what has been your journey? What has taken you? How did you get to be so interested in this research that is so helpful to all humanity, to all of us? So, you know, I have a book age Later where I’m talking about my journey and I’ll tell you just two things about it, but all right. But I have to say, I have to say that I kind of changed how I’m talking about it instead of answering the question. If somebody asks me, and I’m not talking about you, I say just a minute, why wouldn’t you be interested in aging? I mean, what is it about aging that you like? You know, the fact that you’ll get the disease and it can be a bad disease and the treatment and you’ll get the second disease and a third disease and your quality of life will be, will be better. I mean, what is it that you don’t want to know about aging, right? And I think that’s part of the trip, is for people to accept that, OK, death, death is inevitable, I think for now and you know, for our journey. But aging is not the way it is. I think there are two things that I would mention in my journey. And the first one is that we say that kids have imagination, But I think most kids don’t see themselves becoming their grandparents, right? They’re like, where are they coming from? You know, what happened to them? And I think this is something that really stuck with me. And I have to say that it’s amazing to me how in the last 10 years, young people have been interested in aging so much more and are concerned and are seeing their grandparents. Maybe they are more grandparents around, but they are seeing the challenges of aging. But that wasn’t the case for me. I think the second most important thing was that when I was a resident in internal medicine, I had a teacher who stopped us at the beginning of the presentation. You know the presentation is you know a 68-year-old woman who came and he said just a minute, does she look older or younger or younger than her age And it takes it you know you what does it mean? She has, you know, an infection. But all of a sudden you started realizing that biological and chronological age are different and it comes into effect even in clinical practice. You see somebody who’s 80 who’s like OK, you know nothing is going to help him multi-system, right, he looks older and then you’ll see you see 80 years, OK, as architect, but the guy is an artist, right? Or something like that. And then you start saying just a minute, if people at the same age can look 20-30 years apart, we have biology here that we need to understand, right? And this is kind of why very early on I thought, you know, I would tell you another thing. I mean you’re Giovanni, you’re a cardiologist, right? So you know actually today there was a publication about the, I think it’s a New England about the five things that if you take care of it’s five things that cause 50% of the cardiovascular disease, OK, you know, smoking, hypertension, diabetes, you know, non HDL cholesterol, whatever. And OK, I’m looking at you, and I don’t know what your HDL cholesterol is. I don’t know what’s your glucose. I don’t know what’s your blood pressure, OK? But I know that you’re not 20 years old anymore, right? This is really the most interesting biology that we have, OK, not, not those things that we’re measuring. They’re actually driven by the fact that we age, but the aging is really the underlying cause. It’s what drives diseases. Yeah, that’s that’s interesting because the, you know first of all the question is, is aging a disease, Is it a disease or is it not a disease And what can we do about it? That’s the, the that’s the other. And I know you’re working on this in a big way, but the question is, you know most of us are not centenarians, right? So most of us are not genetically protected. So you know, what is the mindset And for the for the vast majority of people?

2 – Is Aging a Disease? 

 So there is the biological answer, you know, the genetical answer. And there’s the political answer. The biological answer is that aging is the mother of those age-related diseases. It drives them, OK. It drives the heart, the cancer, the cognition, the mortality. OK, this is aging drives those diseases. Should it be called a disease Is a very, very different question. And on that, my answer is no. Or I should reframe it and say not yet. And I’ll tell you why. Why not? Because older adults don’t want to be called sick. What, You’re 60 years old and now you’re sick? OK. And what if you’re not sick? And if you’re sick, what does that mean? We saw what it meant when COVID was around. Right. We put those elderly and isolated them and they couldn’t see their grandchildren. We put them on islands, right? So there is a consequence for calling them names. The AARP doesn’t want to call aging a disease. The American Federation for Aging Research, which I’m their scientific director, doesn’t want to call aging a disease. And most important, the FDA doesn’t want to call aging a disease. And the reason is that the people that we target don’t want us to call them a disease, but we found out and I think we all agree it doesn’t prevent the progress, OK? We know what we need to do. Maybe it’s not time to fight the political game, but we know what we have to do. And even with the FDA, when we talk to the FDA, OK, we don’t tell them. Our hypothesis is if we target aging, we prevent not one disease not to do, will prevent a lot of diseases and conditions, OK. But for them, it’s also if we can is only if we can prevent a cluster of age-related diseases. That’s OK. They’re not going to call it aging. You know for us it’s porn. We know what it is when we see it. If they if they put blinds, it’s fine. But the question is if you know we can’t prevent some of the diseases of aging that come with aging. Or premature aging. Oh, when Is the time to intervene, we start aging from day one right Day one we start our life with the process of aging. So when do we intervene and what does it mean to to be able to protect, if we can, the diseases of aging? 

Yeah, well, that’s that that’s a really good question. And I think the answer is that there’s there are stages of aging and each one is a different intervention. So let me try and give examples and this will kind of explain my weird answer. OK. It’s not, it’s not. There is one thing and it accelerates and we have to do something about it. It’s it’s a little bit more complex than then. But I will tell you this, I think if I go 50 years ahead, OK, 50 years ahead kind of put me in a position that if what I’m saying is not true, it’s not going to matter to my life anymore. So, but I think 50 years from now a 20-year-old person will come and get the treatment, might be an injection every few months or every year to kind of clean the genetic epigenetic landscape of aging and basically will grow old very, very slow, you know, if at all. OK? In other words, I think the best time to prevent aging is from the beginning. But you know what happened in the meantime to all of us who age right. and I’ll give you  2 two examples that will kind of exemplify this. So one of the and I’ll tell you this fountain of youth, this idea that we take an 80-year-old and make them 20 years old is kind of difficult biologically to accept, OK, but we can improve health at any age, OK. I think that that’s pretty clear. We improve it at any age. The biological thing at 80 years old that I think we haven’t totally proven in humans. Some things are coming up in the development of what we call senescence cells, known also as zombie cells. Those are cells that either have stopped dividing or there was something wrong that happened in the cell and it protects from cancer and it just stopped dividing. But when they accumulate, when a lot of them accumulate, they’re actually harmful to the environment. They’re associated with more cancer. So there is a way to use treatments in order to remove or kill those cells that in animals improve their health. You know, they don’t live much longer. Actually, they don’t live longer at all, but they live much better. OK, So there is a way to target something that wouldn’t be good for the 20-year-old in, in fact, could be even dangerous for 20 years. But you can intervene in this thing that’s called aging. Another example or really another concept is that there is a hypothesis in aging that’s called antagonistic pleiotropy. Things that are good for you when you’re young are bad for you when you’re old. You know, cholesterol metabolism is really terrific. You develop cells, you develop gonads, you know you, it’s important for everything. But if you have high cholesterol metabolism when you’re old, you’ll get coronary disease, right? So there is antagonism, antagonism, and this antagonism happens, let’s say somewhere at the age of 50. Now I don’t want a 50-year-old to worry because I said there’s biological age. So I’m just telling you that I’m just picking an age, but the age I’m picking is based on data that we took from a very good information source and this is called the UK BioBank. A lot of us are harvesting it. There’s actually a biobank that’s being created in the United States, I think it’s called All of Us or something like that, where, you know, a lot of people are getting kind of the same questionnaire, they’re having blood tests and there’s a sophisticated way to look and analyze and it’s open to the public. So every question that you’re interested instead of getting 50 people you’ll get, you’ll get you know thousands or 10 thousands of people for a question. Oh OK I’m, I’m, I’m telling you a big question just because I, I, I think, I think what I’m saying next is important. So we went to this UK Biobank and we found measurements of IGF one, which is a growth hormone. And we basically have shown that when you have a high IGF one level, when you have this high, the effect of growth hormone, it protects you from a variety of diseases and mortality, OK, the more the better. Then after the age of 50, it switches. All of a sudden the same high IGF one is dangerous for you, OK? It ’cause it, it’s associated with all the diseases and mortality. So this is antagonistic pleiotropy, right? Things that were good for you when you were young all of a sudden kill you. The reason I’m saying that is because some of the drugs that we have will against aging will be effective only in old age and might be dangerous to you in fact in young age. So I think between those examples of the Peter Pan that never grows old, the old people that we can do something about them there or. The fact that we have to intervene somewhere between 80 and 20 is really what we have to consider. It’s it’s all very specific and with trade-offs also. Yeah, that, you know, we interviewed Walter Longo for the podcast and he made an interesting observation on some of the people he’s worked with that the some of these very supercentenarians, and in the opposite of what you’re talking about is that something that was bad for them when you’re young may be good for you when you’re old. What he found was what he was talking about is that some of these people after a certain age, 90 or whatever, they started eating a lot more meat and a lot more things that you know, proteins that maybe when you were younger, if you did that, it would be harmful to you, but for them, it was good for them. So the sort of the opposite of this and also I’d like to have you know one of the things that I do, I’m a preventive cardiologist, I do a lot of work on reversal disease. I worked with Dean Ornish, I was the Director of the Dean Ornish program for the East Coast. So the reversal of disease like the reversal of coronary disease, you know I think would be very important for as an anti-aging. So is that something like and it can’t just be coronary disease, it has to be you know brain disease, it has to be cancer, you know reversal of disease of established diseases that part of the of this approach to anti-aging. So, first of all, I want to tell you something. it’s more, political maybe, but there’s a lot of noise around aging. and for us, biologists or academicians, anti-aging is kind of our enemy, OK? We call ourselves gero scientists. What we’re trying to talk about is gero protectors. You’re talking a lot about gero protectors or gero therapeutics. OK. So I just wanted to tell you that the second thing is again back to the point that if aging drives the diseases you hope that if you target aging in every cell, every organ then you’re going to do better all over and not only specific on on one. I would, I would take statin as an example. For me, Statin is not anti-aging as you said it or it’s not the Geroth Therapeutics and not that it’s not important, it’s an extremely important tool. But for me, the question is if I give it to animals do they live longer the answer is not, it doesn’t, it doesn’t target any of what we call the hallmarks of aging And so you know it’s not going to help the liver or the kidney or or or or something else. It’s really much more of a heart specific by the way. I know that it’s not totally the whole truth of what I’m saying because statins change inflammation, I mean there are other things. But for me the test does it target the biology of aging enough to be called Gero therapeutic So that’s the example of between specific organ stuff and targeting aging as a concept in every cell, every organ, and the whole body.

3- Understanding the offspring of centenarians 

So I guess that the next question is what is the centenary? Is the centenary someone who is really truly different from all of us genetically? And my guess is that you’re studying them and you were saying you have. I have. And I liked when you said I have 750 of them, which I like because it seems that those are your babies, the ones you’re really paying a lot of attention to. So are they different from the rest of us and why are we studying them? Yeah. OK. First of all, you know I regret I said I because I have a team and it’s “we” OK. It’s always we and I and I hate when I hear myself and say I, I, but it’s really not about me there. There are tons of people who are doing this research and advancing it. And I actually have two studies. One is, you know, going to the homes of centenarians and seeing what’s happening to them and asking them tons of questions, taking their blood and seeing what’s the DNA. But actually, I think much more important is a study that I have on the offspring of their centenarians. And then you compare them to usually their spouse unless they have also longevity in their family. And I will tell you that by doing that I’ll say one thing and I can answer more questions. But the children of centenarians who are the same age are actually 10 years biologically younger and they have half the mortality, half the cognitive decline, half the, you know and we are into their late 70s now. So, and it kind of tells you also the genetics but I want to say and I’m going to tell you why and what I found in centenarians. But one point I’d like to tell you because you’re going into this venture. And I want to tell you really very bluntly that I don’t care much about what is what do I discover in these centenarians except their history and their genetics. And the reason is that if I go to centenarians and let’s take I, I take a little bit of their blood and I’m looking at something, OK. And let’s say it’s high. It’s high because of potential. Two reasons. One is it predicts their mortality and 30% of them will die next year or it presents something that got them there, right? 

The answer I know because of their offspring. Actually the best answer is HDL cholesterol. And actually HDL cholesterol is not high in centenarians, but it’s common. It’s similar to HDL centenarians of every age. But we know that actually HDL cholesterol declines by five points every eight years, so it should have been low. When we look at their offspring, HDL is very high, usually OK, statistically very high. So you can see that probably they started with high HDL cholesterol and it went down and now when they’re almost going to die, it’s kind of normal. If you’ll go down, they’ll probably die. OK. But the point is the phenotype of 100 years old when they’re hundred years old is not of so much interest. And I wouldn’t do any biological determination based on that, OK, because I don’t know if it’s because they are dying or because they got there. OK. I look at your faces. I see you’re going to cut out what I just said. But, I’m just talking from a biological perspective. I I love the centenarians, OK? Go ahead. 

Yeah, I think that’s super. Important. So we had three questions with the centenarians. Before the three questions I actually tell you the answer that is much more important because one question was the centenaries, do they get diseases when everybody gets diseases and now they live longer with the disease which is really not the point we’re trying to make. Or is there health spend and lifespan, did it go together And the answer is yes, it goes together. In fact, the centenarians have diseases 50 years later than their cohort and 20 to 30 years later than their children cohort, OK. And we’ve published it, and we’ve published it also with Tom Pearls, who has the New England Centenarian studies and we harmonize the data and it’s really incredible. So it’s not only that they live longer, they live healthier. It’s not only that they live healthier, They have a compression of morbidity. They’re sick for very little time at the end of their lives, right. We have diseases 5-8 years on average, they, few weeks or a few months. 30% of our centers don’t have any disease. They don’t take any drugs and some of them just not  waking up in the morning. So the concept that we have people in this world that are healthy, healthy, healthy and die is really the concept that we’re trying to sell, OK, That’s what we want, we want to do. We cannot promise you you’ll be 100 years old. But if you know, pick an age, if we can tell you, OK, you’ll die. I don’t know, at age 85, but you wouldn’t have a disease. I  think people will choose that. And our lifespan as a human species, statistically is 115 years, right? I mean, statistically there we know that people lived longer than that and we’re dying in the United States 876. So there’s a lot to realize even before talking about, you know, the Peter Pan. You know, maybe Peter Pan will break this 115, but there’s a lot of years that we have to realize and we have to start doing it now. Well that that’s where it’s probably could be considered a disease is that when you don’t make it beyond a certain age like 7075 then aging is a disease that rather than all aging is a disease. But the question is how do we do that? Are we doing that because we are interfering with our genetic possibility to be 150? Are we doing something throughout our lives that we are interfering with this genetic detective? You know, and that’s in the United States. There must be some potential centenaries that we are not help but to flourish into that age, or we don’t have them, or we don’t have very little of them because we know that there are pockets in the world and their pockets so. Are they pockets because they’re isolated in terms of a no pollution, good nutrition, good lifestyle or because their pockets so they are marrying each other and they have these good genes that keep on? Right, exactly the question. So let me tell you, in our population the first thing is do they do things right like we tell people to do now you know did they avoid smoking, their diet was good, you know they exercise. And the answer in our centenaries is absolutely not. Over 50% of them were overweight or obese and still 60% of the men and 30% of the women were smoking for, you know, heavy smokers for a long time. I have a woman who died at 110 and she smoked for 95 years, almost non-stop, right? So in fact, for her, what’s the story of your longevity? Smoking. OK, exercise, even moderate exercise like walking, biking houseworks, housework less than 50%, vegetarian less than 3% and you have to be very careful in how you say it. And actually Jay Leno made such a big joke out of it in The Tonight Show because he said, the secret to longevity is to smoke and be obese and say, so no, the centenarians could afford to do many things and still get to age 100. So the second question was, maybe they don’t have genes for diseases. OK, we all have genotypes, not all. Some of us have genotypes at the risk for heart and for cancer and for, you know, dementia. Maybe they had less genes for diseases and that’s all you need. You know, if you don’t have that, you kind of fly through. And the answer was so surprising for us. We did our first whole genome sequencing in 44 of our centenarians. That was long ago when it was so expensive and we didn’t have control for that. We just had the centenarians, but we had a database that had all the big the genotypes that it’s, it’s called Klimvar and it has all the genotypes that are most likely to give you a disease. And we said look, maybe centenarians will have zero of those. We didn’t expect the fact that our 44 centenarians had 230 genotypes, among them, you know, 5-6 genotypes for each one that was associated with diseases and they were not small genotypes. We have centenarians who are apple E4 homozygotes, which really apple E4 usually means that you most probably become demented when you’re 60 , 70 and dead at 80 and they’re at 100, not demented. OK. So nutrition not, they don’t have what we call the perfect genome. So what is it that protects them against aging? And then we started to find what we publicly call longevity genes. And it’s actually very misleading because it’s not that some people have an extra gene that we don’t have. It’s really changes or variants or mutations on your genes that are having consequences and. I got polygenic risk score. Will, yes. It’s like a polygenic risk for except that there are many ways to become a centenarian. OK. We have dozens of genotypes like that in groups of our centenarians that are functional, OK, they have function but not all of them are on the same pathway.

I’ll give you an example, it’s not too complicated. But 60% of our centenarians have mutations that are making their growth hormone ineffective. 60% of our centenarians and I said before the example that growth hormone is important for you when you’re young and then turns against you when you’re old. This is a very important thing to know and to target. And we actually took it back and showed in animal that we have antagonism for the growth hormone. They live healthier and longer with a drug that was developed for humans for cancer. It didn’t work, but it’s an antibody against IGF one receptors, this growth hormone. Also in our centenarians, those that have the high, the lowest IGF one level, this the the lowest half of IGF one level. They live twice as long. They’re already centenarians, OK, so who cares? But they live twice as long as those that have the highest level. This is IGF one at rest, correct? Not when you’re exercising. IGF one is not really reactive to, it is not reactive acutely. And growth hormone in older people is also not reactive acutely. IGF one comes from growth hormone, but also is produced by cells themselves in different organs. OK. So IGF comes from different sources, but this IGF is a marker if you want of health or longevity depends what level you’re you’re looking at. And this is one of the most common, as I said, 60% of its centers have something on growth hormone receptor and IGF receptor. By the way, Volter Longo, I don’t know if he talked with you about that, but that was something that he’s interested in, the Laurent towards. 

The Laurent syndrome, yes. They have a growth hormone receptor. By the way , 11% of our centenarians have a deletion of exum three in the growth hormone receptor. OK. So we have Lauren dwarfs, we have centenarians. So this is a pathway that really comes through and so stunning a growth is something that really allows you to get to older age. So again I just talked a lot but I said that it wasn’t the environment for them and it’s still very important for us. It wasn’t for them, it wasn’t that they had the perfect genome. They actually have genetics to get them there. And so I think even in those blue zones, I think those blue zones allow more people to get to be centenaries Okay there is an environmental factor but even in the blue zones, I believe that the 100 year olds have a genetics to them. It’s not just the environment. 

Well, I think that what you’re saying is, and this is the way I look at it. You tell me if I’m wrong that centenarians are like Superman. You know, they’re super people. They whatever they do, you know, they could be obese, they can smoke and nothing. They can’t even hurt themselves. It’s the rest of us. You know what? You know, most people are not centenarians. So, I look at this as universal precautions like AIDS or something like this, you know, where it’s a terminal disease. What do we do to prevent that, you know, to mimic that? You know, what do we do? Like, is it the lifestyle changes that we do? Each and each individual doesn’t really know if they’re a centenarian or not, right? So you assume you’re not a centenarian and do all these other things. So how much does that help us when we do the correct lifestyle change? Well, how much does it help us?

4- The TAME trial

First of all, you summarize it beautifully. How much does it help us? I’m throwing it straight back to you. My mission is to find what is genetic. You know, we, I think we all agree that aging is 80% environment and 20% genetics. OK, my point of view, if I understand those 20% genetics, I can protect 80% of the environment, OK. I mean, I don’t want to say that I’ll give you a drug and you don’t have to exercise and stop smoking and stuff like that, OK. But, this is what I’m thinking. The clear thing for us is that there we can maximize our health without genes, OK, By exercising, by diet, by sleeping and by social connectivity, right. We’re on the same boat, right. And that’s huge. I’m kind of talking about, where is the next horizon for us? 

And are you talking about these Jarrow therapeutics? And I know what this gets to you, the big trial you’re doing, the TAME trial. I think if I understand it correctly, the purpose of the TAME trial, I know you’re studying metformin, but it’s really not to study metformin, it’s to study whether we can affect aging, correct. I know. So I would love to know if you can explain what the purpose of what the trial is, the purpose of the trial and and exactly what the bigger picture is in terms of the outcomes. Right. So first of all, you’re right. Metformin is a tool, OK? It happens to be the best tool because what we’re doing with metformin has already been done, OK. Metformin has prevented diabetes in a clinical trial, has prevented cardiovascular disease in a clinical trial, has prevented the cognitive decline associated with less cancer and everything. So all this has been done, we’re packaging it. So the real, the real thing that I’m doing is not what you said and it’s only to get the FDA to approve aging as an indication, OK. This is the reason we’re doing the trial because the proof of concept for me is not important. The proof of concept is important in the packaging, but it’s not really the main thing we’re doing. It’s for the FDA to come and say that because then healthcare providers will not say if there is an indication like that, healthcare providers will have to. Otherwise they’ll say you know, good for you, but this is not an approved treatment and they actually do say although metformin, one of the advantages of metformin, is that it’s the cheapest drug in the formulary. You know, I think everybody who says aging is about rich people and stuff. No, Metformin is the cheapest, OK, Everybody will afford a healthcare provider that will take you there. If healthcare providers will give you Jaroth Therapeutics, then the pharmaceuticals will jump in and develop more drugs, better drugs, combinations of drugs and we’ll really start to realize better our potential in 115 years. But this is really why we’re doing the tame to demonstrate that this revolution is possible and that we get everybody on our boat. 

Yeah, I mean I think it’s a completely different concept and pharmaceutical companies have thought of up to date, you know what metformin I guess affects so many different pathways and you know up to now we focus like  1 drug,  1 pathway,  1 molecule. But this is like a real, big picture kind of thing where one drug can affect many, many different outcomes, which is not the way we, as doctors or as pharmaceutical companies. We’ve thought about these things in the past. 

So, what we’re talking about in biology, we’re talking about the hallmarks of aging. Hallmarks of aging are things that change with aging and when we reverse it in animals or in humans, we get an extension of health span or lifespan in animals. OK, that’s how we get there. The geroth therapeutic, OK. The interesting thing about those hallmarks, they’re interactive in the sense you can, you can target  1 hallmark and you’ll affect several of the others. Metformin is not the only drug. There are three drugs like that at least that affect not one, not two of the hallmarks, but all the hallmarks because I’m really responding to the fact it has so many effects now. And that’s rapamycin. And what’s the third one? Rapamycin is the same and SGLT  2 inhibitors. GLT 2, right? OK. So people are saying, oh really, metformin happens to target all all the hallmarks of aging. But really what happens, metformin is a drug that takes a cell or an organ or a body and makes it younger. And when it makes it younger, many things are improving. OK. So you get effects on the hallmarks because those hallmarks are interactive which with each other. But for me that’s exactly how I define Juror Therapeutics. Statins are not going to affect all the hallmarks, maybe the inflammation hallmark or something, OK, but it’s not going to affect all the hallmarks. The true Juror Therapeutics are affecting all the hallmarks and for me that’s the reason to go to clinical trial when I have something like that. The question is what are all the hallmarks that we’re looking at that metformin effects and are we targeting then 50 years old and and older because that’s you said when the change happens and what is the impact on the IGF which is what the the centenarian have less of correct. Right. Can you release me? I’ll show a slide. Can you release me? I need the host to allow me to do that. Sure. Let me put that up one second. 

OK, so I’m not, I’m not going to show you all the hallmarks because this will be blah blah blah, OK. If I don’t have this slide, it’s OK. So, I can answer you the second part of the question. So we’re saying that metformin targets all the hallmarks, but one of the things that so remember this antagonistic plotrophy hypothesis of aging, the things that are good for you when you’re young are bad for you when you’re old. But it’s also true that if you do something to old people, if you do the same to young people, it’s bad for them. There are trade-offs to the other side. Metformin who was studying in clinical studies usually after the age of 50 that was the, that was the cricket actually the the population where in their late 60s or 70s sometimes, which is after the age of 50, metformin decreased. For example IGF one level which we don’t want it to in young people, Metformin in some men decreased testosterone. Testosterone is good for you when you’re young. So Metformin is an example of actually a drugs that I think you should take after the age of 50 unless you’re obese, diabetic or women with PCOS that get also lower testosterone level that is good for them and good for elderly but not for the rest of us. So I think Metformin, is exactly this thing and one of the things that really makes me so upset sometimes when people are telling me, I’m a 37 year old bodybuilder and I’m getting metformin. Well that’s not I don’t think that’s good for your goals in life. OK. We know from elderly study that if you exercise elderly within without metformin, those with metformin have less muscle as response because actually metformin lowers emptor which is a sensor that is very important for muscle building. OK. 

And in fact I’m complex one, it’s that correct the way that works? I think it actually effects complex, for it’s a new thing that’s emerging that it doesn’t matter, you know, doesn’t matter really. Whatever complex he does, you know, no matter what, it would do something. But yes, he does. But among other things, OK, I mean, I cannot tell you if that’s necessary for longevity or not, but metformin can do things without the MP kindness, without mitochondria, OK, it can do things. So when people are saying we want to develop a complex one in Ibitor, I think they’re in danger of missing what metformin is doing otherwise beside targeting a complex one or complex 4. 

So, the TAME trial hopefully will show some benefit. Do you think there’s enough metformin in the world that if it’s a really positive trial, that everyone’s going to want to take this? Yes, it’s an extract of the French Lilac. It’s generic. It’s easy to produce a, you know, I think you know it’s first of all not everybody, the trial will come. New England Journal will have it. You think that the next day everybody will be on metformin, probably not. On the other hand, every day that passes, there are more elderly on metformin because kind of the thing is out, right? I mean, believe me, people will see this podcast and will ask their doctors for metformin also, right? But I want to say another thing. Metformin was used in the 1920s, the 1950s for arthritis to prevent flu, to do many other things. When it was discovered, when it was discovered in that diabetic patient it lowers glucose, OK. And then it was kind of hijacked to glucose, which is good because that’s why we have so many studies and we know what metformin is doing. I use metformin, I’m originally from Israel and when I practiced in Israel in the 80s, I had metformin as a major drug. I came to the USI came to Yale for fellowship because companies try to bring metformin to the United States, but they needed more data to see if it works on Americans also. And at that time I was looking at the mechanism of action of metformin on diabetes. I was the first one that published the the fact that metformin really targets the liver and not the muscle and but I didn’t know yet then it was serendipitous and it’s only years later that I realized this is a geroth therapeutic and not really and you know also also a glucose lowering a drug. 

There is a minimum amount that people with no disease should be taking after 50. We don’t know. I’m sure the answer is yes. And I think that there are probably ways to figure it out, but we don’t have the dose response of metformin from an aging perspective. There is a dose response of metformin for diabetes perspective, it’s 16125 milligrams, OK. But as I said, I think diabetes is not really the important target of metformin and and and we want to have metformin in non diabetic patients. I was asking what do you? Measure once you start and a healthy 50 year old on metformin. Non diabetic. Non diabetic. What do you measure? Yeah, I think that you know the biomarkers of aging is a is a huge field that I’m very much involved also because I have the centenarians and their offspring and and with biomarkers we can see that the offspring of centenarians are are are healthier but the they’re biomarkers of aging that are So biomarkers of aging will tell you what’s your biological age rather than chronological age, right. If you could take a test for a 50 year old and he’s 40, for example, maybe doesn’t need colonoscopy. On the other hand, if he’s 60, let’s try and see where is aging resides and let’s be more, let’s do more intervention. That’s why we need biomarkers. But for me, this is not the only thing you need a biomarker that will change with treatment. Not every biomarker that we have changed with treatment. We have, for example, epigenetic biomarkers,, clocks. What’s known as clocks, and they’re not going to reflect change in hemoglobin A1C. But hemoglobin A1C itself is one of the biomarkers that changes. CC steam changes with aging. TNF alpha receptor changes with aging. They’re like  5 things that will change with aging and you can measure them, but we don’t have much of that. We do have a biomarker that changed with Metformin and it’s called GDF 15. And on average, it rises by  3 and half  fold. And maybe this is going to be an important biomarker to see how much is enough, but I think we’re not there. So for me it’s 1500 milligrams because that’s that’s where that’s the dose. The studies were done when the committee met on TAME, by the way, the study is called TAME targeting aging with metformin or taming aging. But we came in and we had data on 1500 milligrams, but some said, hey, but the elderly, we should give them less and some said no, it’s longevity, we should give them more. OK. And we said OK you know we know that 1500 milligrams has an effect. So why don’t we do 1500 milligrams and by the way 1500 milligrams not everybody achieved 1500 milligrams right. And it’s his intention to treat. So,I think if you tolerate 500 go and see if you tolerate 1500 because I think it’s individual. Let me give another example with Metformin.  3 to 6% of the people with metformin have diarrhea after a week of treatment. This is the major side effect of metformin. It is kind of common to people in the first week. Certainly most people will not get diarrhea, some get early satiety or something else but three to 6% of the people will have diarrhea. The reason they have diarrhea is they don’t have either genetically or for other reasons. They don’t have the expression of the transporters that take metformin and brings it into the cell. So what happens when metformin is in the guts? It cannot be absorbed and when it’s not absorbed it causes diarrhea. So you don’t take metformin because even if it was absorbed, it wouldn’t get into your cells anyhow. OK. So I’m saying there’s lots of clinical things that we talked about metformin and although we had it for a long period of time, there was no need really to do a dose response. So you know, take 1500 milligrams for. Those patients that get diarrhea, it’s not worth for them to continue it, right? Yeah.    

5- Metformin & Vascular Age 

Right. So we, you know, in cardiology we measure, you know, I measure CIMTS and that gives us a vascular age of the carotid arteries as a reflection of the entire vasculature of the body. And now we’re doing CAT scans with artificial intelligence over read that tells the same thing about the coronary arteries. Does this first of all, is vascular age a good measure of aging in general? And #2 Does metformin affect vascular age? And so first of all, I’m going to tell you something totally unexpected. I’m not going to talk about metformin. I’m going to talk about another thing that was incredibly interesting, and it’s the effect of hyperbaric oxygen on health and on aging. And I’m sure as a cardiologist it sounds terrifying that you’ll take a person and expose them every day for weeks and months to oxygen under hyperbaric. Which means it’s not only that you saturated oxygen, but it now diffuses into the cells. So every cell is going to get oxygen, and your cardiologists believe that oxygen is a big toxic thing, right? And. And you want us to take antioxidants, right? So it makes no sense, and it makes no sense to me until I realize what’s really happening. First of all, the oxidative. The oxidative hypothesis of aging is not a strong hypothesis anymore in the sense that I told you that for us. What does it work on the lab for aging? If you get mice and increase their oxygen damage or decrease their oxygen damage by a lot of genetic manipulation, it doesn’t change their lifespan. OK, now that doesn’t mean it’s not important on their trade-offs and stuff like that. But so oxygen is not a major hypothesis of aging. 

But there are two things that are happening with oxygen and and and now you’ll see why I’m hijacking this, this metformin thing, there is a 30 to 40% decrease in small vessels disease as you age. OK. Which really means. So is it important? Yeah, very important. And. And it means that we have cells in our body that have lost vasculature. They’re not dead, but they’re not alive either. And when you give them those pulses of oxygen, all of a sudden oxygen gets there and wakes them up. I’m talking about non-biological terms, but there’s a biological way to see that. So this is one thing that’s really important and you can see in particular in the brain you see a huge effect. But, really, what happened when I started hearing clinical studies that showed the huge effect of hyperbaric oxygen, I purchased hyperbaric oxygen for my labs and we’re looking hat happened to mice and rats from an aging perspective, OK. And it’s quite incredible. There’s another thing that happens, actually. The best longevity factors are hypoxic. You know, if somebody strangulates you, actually you upgrade a lot of good, good things against aging. But of course, how do you get it? What happens in hyperbaric oxygen is it takes you to higher higher oxygen and when you go back to regular atmosphere, the body feels relative hypoxia. So it induces all those factors. So I’m really using it for two. First of all, I’m using it to answer your question, is small vessel important and telling you there’s actually a super treatment for this lack of small vessels, but also to tell you that it’s not only on metformin and some things are what, you know, we call left field. They came out, they came out somewhere, you thought it’s the most ridiculous thing. And all of a sudden, you know, there’s something that also with trade-offs probably, right? Also with trades offs, how many times can you do it? How much can you repeat it? And is there an age or a condition where actually the oxidative stress is not going to be beneficial? But I’ll tell you, it’s pretty good. Yeah, you know in cardiology there is some data showing pre-treatment ischemia helps outcomes. You know before you do a procedure you do some of you do an ischemic manipulation and then post procedure they do better. So it’s probably. Exactly, you upgrade the regulation and you increase the resiliency. And I didn’t know about hyperbaric oxygen because I have a lot of patients that asked me about it. So that’s really great information. Yeah, I want to say something else about Metformin and this is not in order, so you’ll have to edit it. But you know we have all those clinical data on metformin and something really interesting happened during COVID. There were nine papers from all over the world that showed that people on metformin had basically half the hospitalization and death. And then there were a control studies that took COVID patients and gave them Metformin within three days of being positive. And it also decreased hospitalization, death and long COVID by about 50%. And the point is when because metformin is a Geroth Therapeutics because it targets other hallmarks of aging like the immune the the the immune decline OK among other things then you see that metformin is good for many things or basically for aging. What about supplements like berberine or resveratrol, spermadine, what’s your opinion about these because we had a lot of patients that are interested in these as jaro therapeutic supplements. So for me, first of all there are big advantages that they support the economy right by all those supplements. The question that consumers should ask is what is the evidence behind it. Lack of evidence doesn’t mean that it is not good but it’s still a hope and not a promise and certainly lack of evidence also may indicate that it’s bad and you wouldn’t know. So if you want to go ahead, do a look at the clinical study.The definition of clinical study is that you have to have a control, OK, a placebo control or or another agent as a control. And if it’s a double-blind study, it’s great. If it’s a crossover, it’s even better. But you have to have a data to see if it’s working in my mind and many of those things haven’t been shown anything. I have a paper out there that gives resveratrol up to  5 grams to elderly people and there’s very little change that I’ve seen really nothing significant, although there were significant results but wasn’t significant clinically. So there’s lots out there that could be good but it may not. But this is my real problem. There is a guy, Brian Johnson. You know Brian Johnson. Yeah, I’ve heard of Brian. Right. And Brian Johnson is good for a field because it gets attention. But also it’s a problem how to handle him because he’s doing some things that we think are unsafe. One of them, he takes 105 supplements and medications 105 AM. And if you look at those 105, you might understand why he takes each one of them. And in his mind, it’s going to be either an additive or synergistic. But in fact it can be antagonistic too. OK. And I think this is something that Lex, we don’t know how medication interacts with each other, but we have a lot of data including on his 105 supplements who can be interacted with one another. So, one thing is whether the medication works, and the second thing is when you take a lot of them, what does he do? And sometimes he does the opposite and not additive. 

Yeah, I mean that’s you know by definition that’s a tremendous amount of stuff that you’re just taking. And, we don’t know if that, you know, like you’re saying we don’t know what it’s what it’s doing. You know, there’s no way to know that because you know who’s ever studied so many different supplements and medications? Right.  

So I guess the question will ask you at this point, is there anything that you have, I mean that you do take because you believe and you have the studies that supported and do you take Metformin, do you take any other supplements and have you changed your lifestyle based on the studies on your centenaries that you have Done? 

6- The Path to Centenarian Living

Yeah. So I’m doing two things. First of all, exercise, nutrition, sleep and social connectivity. OK, not only am I working on them, but I’m trying to maximize them. If I have 7000 steps, I’ll do 3000 more. There’s always more than you can do. I’m a council on a new medicine society and actually I think maybe you should join that. It’s called the Healthy Longevity Medicine Society. It’s an International Society was formed last week. The president Co president are two incredible women. One is in Singapore and one is in Shanghai. Although she moved to Israel yesterday. But they are creating data for longevity. They have, they create their own longevity clinic and educate people. Future physicians, there’s lots of longevity physicians, you know what’s out there, what we know, what we don’t know. There’s CME courses, there’s a green rounds or or case studies every few weeks And so I’m very excited that we’re preparing the consequences of our research and trying to make it actually responsible and conservative. And for me conservative, people said Metformin has no indication for aging. Well, you can repurpose any drug that is FDA approved and he’s safe, right. So I mean we have many things that we actually can do and then conservative is something very subjective if you’re conservative or not, but we are there yet. So I’m, I’m taking Metformin and I’m also doing intermittent fasting and I want to explain why I’m doing intermittent fasting. It’s not because of my Sentinel, because of my rats, because the experiment that I’ve done when I started my career was like everybody else. it’s our positive control if you take animals, brothers, half of them eat whatever they want, the other half get 60% of that. And those that are caloric restricted, they leave much, much healthier and like 40% longer. OK. Instead of dying in two years, they die in three years. You know, pretty much really a major effect. And people said, OK, you have to have less for a lot breakfast, lunch and dinner. But that’s not what we’ve done. We brought all the food in the morning and they were hungry. They ate all the food. And if we give them food throughout the day, little food throughout the day, they don’t live longer. So fasting is important. OK, So the idea that we need to spend less time eating, you know, Volta Longo is doing  5 days past, I don’t know,  3  * a year, right? There’s a lot of variability of what you could do with fasting, but I think fasting for aging is very important thing and intermittent fasting is one of the easiest interventions to do. Most people, not all, but most people can do it. It’s like finishing dinner at 8:00. You can have coffee in the morning without sugar or milk. You can have water. You can have diet sodas. And 16 hours later you can have lunch. And even if you feel like, oh, I’m hungry now, OK, you have an hour to go. What are you going to break? So I think many people feel it’s easy. We’ll never know if it increased lifespan, but there’s lots of obvious changes that are happening, including weight loss more in men than women. But it’s not for weight loss, it’s really for aging. 

I can tell you from the cardiology point of view, the Mayo Clinic has taken 250,000 E kg S and gave them to AI people, OK? And all of it suddenly became a cardiac biomarker. It tells you 100% if you’re a male and female. I read this. This is amazing. Yeah, I always knew if my patients are male and female because I saw the name, right. It’s not always, but they do it. And when you ask how do you know that? I don’t have an answer. The cardiologist doesn’t really know what is there in the waves that does it, but you can, you can do it. So I’m 100% male, but also the age of your muscles. OK, now, now let’s make sure the age of the muscle doesn’t mean that the next day you’re not going to have a coronary and destroy it, right? But the age of the muscle, so when I was 58 years old, I had an EKG at the Mayo Clinic and my biological age was 55, so I was three years younger. What I’ve done then is basically exercise mainly. Since then I started Metformin about the same year and before COVID I started intermittent fasting. And last I’ve been in the Mayo Clinic. I was 68 and my biological age was 58, right? So I was now 10 years younger and I believe for me, and it’s only for me,, it’s N equal 1, but for me I kind of saw it as a sign that the intervention worked with both those things. 

That’s that, yeah, we believe those things also so and then and the data on the EKGAI is is amazing because I read a lot about this and it apparently can even predict how long you’re going to live. I don’t know how it does that. Right. That’s what you do. So you can train, you can train those data on just biological versus chronological age, OK. Orin in other words, you have the data, so do you fall higher or lower on the curve. But more important is to take the data and have information the people who died and see really how the biomarker predicts longevity And they also predict I mean how many years left and it also can predict that again I’m always worried about the cardiac ones because you know they’re bicycle riders 3 hours a day that get this massive coronary and and so that you have to adjust for a few things. Yeah. And then lastly it, you know one. I think one of the major things about this work is that if you decrease morbidity at the end of life there, there should be an amazing savings of money from the healthcare system. You know that because if you’re sick. For all those. Years. If you’re not improved in health span versus, there must be an incredible at the you know that if everyone did did this, you know the health cost savings will be astronomical, I think. Well, you’re absolutely right. And in fact we started I I told you that our centenaries don’t only live longer. They have a compression of morbidity. The CDC have looked at the medical cost in the last two years of life of somebody who died over the age of 100 to 70, It’s third the cost, OK. And those people? That’s amazing. That’s a measure of the benefits of health. Right, right. So we called it Longevity Dividend, but this is where it becomes astronomical. There is a professor of economy in London School of Economy, Andrew Scott, who comes and says you’re out of your mind. You’re so underestimating. We say why? We’re underestimating, he said Because you’re talking about the dollars in the two years, right, the medical cost, that’s what you’re talking about. But just a minute. OK, so those guys are not in the hospital. What are they doing? They’re traveling, they’re shopping, they’re buying houses for their grandkids and kids. So from economic value, we’re talking about, and he has a number $380 trillion by the year 2030 if we extend health spend even by two years. Look, health spend is such a big deal of the economy of every country, we really cannot afford not to start making progress there. 

I agree. And in France, they’re arguing about one year of when people retire. You know, this would make a huge difference. You know you can retire at 70, 75. You know why not work? Exactly. And I think that the maze major lesson in centenaries is maybe not how they are now, but how happy and productive they were at any age. When they’re healthy, it’s really the health that causes the bad quality of life. But you’re if you’re healthy, even at age 100, you have good, you have a good life. 

And that’s the other thing. At the end of life, are people happier? You know, are they happier? Well, that was going to be my question to you. When you’re not necessarily at the end of life, but the centenarian, do they have a different outlook at life or not throughout their lives? Is that part of you looking at their personalities? 

Yes, so there are two answers here. And I have to say I was on a podcast with Sanjay Gupta just a few weeks ago and he says, you know, my father when he worked, I said this guy is such a miserable old man, I don’t know what will happen to him at retirement. And he said my father is now 88 years old. And I asked him, how is life? And he said, this year was like the best year ever in my life. I heard the podcast with Jane Fonda who said, it’s much better from the inside than from the outside. When I was younger, I thought, if I’m 85, I’m going to be so miserable, she said. No, it’s not so bad, so bad. But there’s a reason for that. So I’ll give you this example which hit me because we have like 3 papers about personality. The personality of Centenario is great because they’re hopeful. They’re extroverts. They’re lots of good stuff and of course people say that’s why they’re there. OK. But, we know about personality basically until age 60. Maybe now a little bit longer and we said personality doesn’t change. So, let me give you this story, some people are telling me you have to see these centenarians is so great. All the scenarios are great. I I know. But they said no, you have to meet him. So I’m meeting this guy, 104 years old, really a great guy. OK. I’m sitting. I have this beautiful conversation with him. He’s philosophical. He’s grateful. He doesn’t complain about his daughter-in-law or anything else, right? So it’s just this great thing and I’m leaving the room and I’m bumping into his son, 82 years old. And I’m telling the son what I just told you. And he looked into my eyes and he said, you should have seen him when he was my age. He was a miserable guy. And then you discover that personality actually changes. And think of it, they, I mean, they somewhere, sometime retire. They lost their spouse. They moved to a house. They moved to a facility. There’s a lot of environmental changes that they had to adopt. And in the meantime, no matter what we think, they get older in their brain too, right? It became older. So it reminded me of a study they did at the University of Pennsylvania where they took young and old people and they showed them slides. Some slides were good islands in the Caribbean, sunset, whatever. And others were really bad pizza with cockroaches, things like that. And they asked them to recall what they’ve seen. And the young people recalled more and from everything, and the old people recalled less, but mainly the good things. So there’s some adaptation I’m waiting for that to know to rear only the good things. And I think maybe that’s how it works for the people who are at the end of their life and they’re pretty happy, right, if they’re not sick. 

So I think there’s biology, there’s psychology and there’s changes that brings me back to the first point. When you see a centenarian, you don’t know if what you see is the old part that killing them or the good things that brought them alive. And that’s why we have now a longitudinal study where we can see what happens to their personality also. I think there was a saying, I don’t know if I’m misquoting this from Aristotle, where he said at 80, he stopped thinking about women. So he started living his life.

7- Microbiome & Aging

So, we can’t end it without talking about the microbiome of course. I read a recent study that says the Super centenaries have the microbiome of the 20 year old. Is there anything that you’re investigating looking at then it that is that true?

I have to say I’m not, because it’s hard for us. It’s not part of our style. We’re going to their homes. We’re not asking. But you know that the remember we talked about the hallmarks of aging and what changes with aging and if you fix it your animals will live longer and healthier. There’s no proof yet and I’m ready for that. I’m not against it but there’s no proof that this microbiome is really a cause and could change. I think it could change aging. I think it’s an attractive hypothesis and whether the biology of aging affects the microbiome or whether the microbiome affects the biology of aging is for me a question of interest. And the second thing is that I think sauerkraut and kimchi are probably the one of the things that are changing microbiome more than other things. So maybe that’s the advice for all of us, but the microbiome really doesn’t change with age so much. Until you get to an age where you get antibiotics or you move to another place, it’s not so simple to identify what influences a microbiome. That doesn’t mean that there’s no better or worse microbiome for health. I’m just not there yet from a geoscience perspective. I’m not on the boat of microbiome because I’m lacking the geoscience connection. It clearly helps in so many ways. 

Well, maybe that the centenarians don’t get as sick, they don’t get antibiotics as frequently, they don’t get chemotherapy as frequently. So, you know, that may affect their microbiome. Or their microbiome was like that, you know, like that. Because their environment was like that when they started. One of the interesting things about the microbiome, is that it doesn’t change, really. It doesn’t change with age. It’s as if you’re stuck with your original microbiome. OK, what was the original microbiome of 100 years old different than what it was for us? So I don’t know. So you know, this has been really truly fascinating, interesting and we’re deeply honored to have had you today. And I’m sure this is a field that will continue to grow and change and we’ll hopefully have you many more times to tell us, you know all the new findings in your personal research and the world of research and will definitely participate you know in this new venture with. The Healthy Longevity Medicine Society. We’ll definitely join that. Listen, thank you also, look, we have to spread the Gospels, right? I mean one of the things that we’re missing is the public is still not recognizing that we can maximize our health. And what you’re doing is very important and giving me this opportunity to talk like that was really great and I wish you luck and good health. 

If you are new to the show, welcome and if you are returning, we are so grateful for your participation and support. We hope you go to iTunes or Spotify and subscribe to the show, leave feedback, write a review, or send questions. They love questions and look at every question that is submitted. The content of the Sicilian Secret Diet are meant for educational purposes only and are not meant to be a medical diagnosis or treatment advice. A doctor patient relationship is not created and any questions related to your specific physical or mental health should be directed to your healthcare practitioner. So hello and thank you for joining Sandra and Giovanni for another episode of the Sicilian Secret Diet Plan Podcast.









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