This Harvard Professor Explains the Secret to Aging in Reverse | David Sinclair on Health Theory

What gets really interesting and

this

is something that most scientists don't know yet is level three, the deep layer of

aging

. There is actually a DNA clock that tells our bodies how old we are. I could take your blood, read it and I could tell you approximately when you're all going to die, welcome to

health

theory

today's guest is

david

sinclair

is an acclaimed

harvard

professor

who is doing some of the world's most innovative work on longevity human being was named by time magazine as one of the most influential people on the planet and his new book Lifespan, the revolutionary science of why we age and why we don't have to, will permanently change the way we think about the inevitability of

aging

and possibly even death, that's exactly where I want to start.

So

this

is my favorite topic. I want to live forever. I have no doubts about it. I know that right now, even though I'm on a collision course with death, you have a really interesting

theory

about what makes us age. If I do not do it. It is a mistake to call it information theory of aging, so what exactly is information theory of aging and how can we take advantage of it? In fact, we have been working on aging for about 5,000 years or more and it is only in the last 20 years that we have come to present a set of distinctive characteristics of aging, there are about eight and I think many of you viewers will know that there is a wear and tear. of telomeres, the ends of chromosomes shorten, mitochondria, energy packets will run out of energy as we age, there's a long laundry list and most people in my field have said, "okay , we have discovered aging", we have this list, we put it on a nice pie chart and that's it, but what I'm saying is why all that happens, it's not enough to just mark what happens, you have to understand if there is a previous cause of all that and that is why in my book and in the scientific articles that we are now publishing for the scientific community to also read what I think is happening is that our bodies are losing essential information as we age, which drives many, if not all, of those features that we know exist.

So how is the epigenome involved in this? How are we losing information? little rant about the difference between genetics that I think you get and then the epigenome and epigenetics and how that develops yeah yeah sure it's not that complicated there's really only two main types of information in our body that we get from our parents: First it's genetic, we all know about DNA and the four letters atcg, it's a long molecule in the cell and it's a string of letters that is digital, it's like music playing on a DVD, those things we used to use to store movies, but there is another level. of information that is above that in the cells that is the reader of the information that is called epigenome and that is really different because it is analog information in the same way that records and cassette tapes sucked, they were terrible at storing information but the The problem is that we have an analog version of the information, the epigenome, that controls which genes in the DNA strand are turned on and off, and that's why you're considering that analog.

I don't think I understand how it really works. I can imagine DNA sequences simply arranged. of repeating the atcg code, but what is analogous about the epigenome, this reading about it in your book is the first time I began to imagine it in a different way, well, it is very clear that if you only have four letters, that is digital , so we understand. that, but the epigenome is the structure of how DNA is organized, so DNA doesn't just wave around like a thread, it's actually packaged around proteins that we call histones and it's like rolling up your hose in the garden. , you roll it up and then you can put those loops into larger structures and then you get a chromosome that you can see that any high school student can see under a microscope.

That's the chromatin structure, as we call it, it's the epigenome, and when the hose is wound tightly and coiled, that's it. stop the genes from turning red, so the genes are off when compacted, but also if the cell needs to read certain genes and a nerve cell needs to read the genes of the nerve cells and the liver cell specifically needs to read the genes of the liver cells, so open them up and now the cell can access and read them, it's an analog system because it varies all the time, it changes when you wake up, what you eat, so it's literally the amount that the DNA unwinds and the place. in which it is unrolled so that it can be read correctly and that is what determines the function and identity of the cell that we know when we are born where 26 billion cells each of those cells knows what it is and what it has to be 80 years later, he and his descendants and over time what I'm saying is that aging is due to the cells losing their envelope and then eventually the cells losing their identity.

The disease ensures that the cells become zombie-like and are now essentially senescent. and then our organs fail and we die, but until recently we had no idea why that was happening and why it's happening well, so packaging is the really important part because, just like software runs code, the epigenome controls what genes are in and out and if you stress the system and by that I mean biological stress and the biggest stress you can cause to a cell is to break its chromosome because it is going to die if that doesn't fix it or it is worse for the body.

You get a tumor so the cell has to hunker down, stop dividing, stop almost everything it's doing and then try to repair that broken DNA, but in doing so it has to do two things, first of all, it has to take proteins from somewhere else it's doing is doing a good job of preventing the cell from working or making sure that the cell is working properly and that the cell is using those proteins to repair the DNA that's broken, but also what happens in the break is that all of that It also opens because you remember if you break. a DNA and it's coiled up, you can't fix it, you can't glue it back together unless you unpack it, put it back together and then you have to repackage it so that this movement of proteins and the unpacking, the repackaging of the DNA.

I think it leads to cells losing that original youthfulness, what we call a genetic expression pattern of how genes are turned on and off and nerve cells as they age lose their ability to remain nerve cells and liver cells lose their identity as liver cells. Do proteins the way you talk about them sound like little creatures? I think of them because of my experience as dust, as sort of inert molecules which, judging clearly from the way you talk about them, are not. I've seen them animated before with poseable shapes and they actually move, it's that precise, that's essentially it, it's super exciting when you realize that proteins aren't just blobs or powders in the cell, they're actually little machines like Pac-Man. that circulate and can change the function of other things, they can package DNA and what they do is create chemical reactions that would normally take a billion years to occur.

This is what an enzyme does, it speeds up reactions and that's why we have There are about 20,000 different types of enzymes in the body and they do different things, but what we have discovered in the last 20 years is that there are certain types of enzymes that help package DNA and help with DNA repair. These are the ones that When playing ping pong, without which we are screwed, we will basically age faster. What's really exciting is that we've discovered that you can make them more active to make sure that the DNA is packaged correctly and the repair is very efficient.

There are ways that you can do that exercise, diet, be hungry, they allow these enzymes to control our body and make us

health

ier, they make those enzymes much more active, so instead of a Pacman doing this, you exercise your diet, take them, take a molecule that we work on. and he will go around and fix everything much more efficiently and keep you young longer. We thought, why are you using the Pacman analogy? What makes me think that he's eating something is that what's happening is that he's eating cells that have a level of senescence or is it more Bob the Builder and he's going around tearing some things apart and putting some things back together?

Yeah, he's more like Bob the Builder, but I think he's a good example of at least the enzymes that we work with, called serotonins, that protect the body. They're like a little pair of scissors that cut the chemicals called acetyls and in doing so, when they cut the acetyls of those packaging proteins, the DNA becomes more compact and that's called genetic silencing and over time, as we age. This process of DNA damage, the sirtuins become inactive, they get distracted by DNA repair and the packaging of that DNA, that coiling hose starts to loosen and now genes appear that have no business being in the brain and part I think that's why we have these brain diseases that are very interesting, okay, first I want to know from a lifestyle perspective what are we doing to speed it up and then two, what can we do from a lifestyle perspective to start slowing it down and reversing it well.

I've been studying these enzymes, the sirtuins, we have seven in our bodies. I've been studying them for about 25 years and what we've learned is that they respond to the cellular environment. There is a chemical substance that they need to produce gas. Think about them. like the fuel called nad and there is another molecule that is like the accelerator of the enzymes that makes them go even faster and that is one of them is called resveratrol that we discovered years ago from red wine and together they really do really cool things in these enzymes and make them keep the body younger for at least 25 years.

We have been studying mainly animals and even small fungi and cells and what we have learned from those studies is that these are largely involved in the response when organisms are under threat of survival, so how do you make the body feel Like I'm under threat? Adversity. Then you run a lot or at least get out of breath. You know, a few times a week your body will say, "Oh, man, we had to get through one of those." Saber-toothed cats again have to go to strengthen the body. The other is to be hungry whether it's a couple of times a week or every day, you know, skip a meal or two and then your body will kick in.

These sirtuins will produce more of that fuel. Not because of the enzymes and we think that's partly responsible for the health benefits of those lifestyle choices. Well, one thing you talk about that I found really interesting is this notion of what can be good for you when you're young. it may come back to bite you in the ass when you're older, yeah, so it's like the whole hormesis notion that a little bad is actually extraordinarily good, which is exactly what you're describing now, gasp, do all the things and so when the information started flowing that the only thing in all known living organisms that extends lifespan is to eat less, which you talk about in your own book, it feels like you're saying to do it for that reason, just don't do it.

I don't stress the system that much, but now I hear you say no, no, what you really want to do is stress the system, won't that just-I-just-ran away-from-a-lion stress build up? Well, actually, if you step on a snail, it's going to die, so there are certain amounts of stress that you don't want to do, but what you want to do is make the body fear adversity in the future, but not enough to cause a lasting cause. DNA damage or uncoiling that will lead to disease and eventually death, so you don't want to overdo it, you want to be a little bloated, you want to be a little hungry, but of course, starvation, malnutrition doesn't go. to make you live longer, so it's a very fine line and what we've learned from many animal studies and an increasing number of human clinical trials is that you want to push it so that the body recovers, not constantly, we used to make the animals starve all their time. lives and it worked but it actually works better if you let them recover and I think that's the

secret

so let's dive into that so I guess you're talking about the animals being denied 20 to 30 of their calories.

Taking it for very long periods of time extends its life by about 30 or so. It's very interesting, but you are saying that if its caloric intake over a long period of time is about the same as that of an animal that is only allowed to eat until it is satiated than if it is done in a starvation pulse pattern and almost overfeeding actually have the same benefits as the animal having aChronic calorie deficit, well let's be clear, no one knows what the perfect diet is even when it comes to it. Fasting is all based largely on rodent studies, so what I can tell you from the rodent studies that I'm very familiar with is that if you take a rodent and reduce its calories by 25 for its entire life, it will live. plus 30, but I'll be really miserable and aggressive, uh, and that's true for us too.

I tried calorie restriction for about a week and stopped. I was pretty angry, but what we discovered, my colleagues, discovered is that if it's not just what you eat, it's when you eat and what's been discovered is that as long as you have that period of hunger in a mouse to be able to feed it every two days, then they can stuff themselves as much as they want and eat. about 90 of what a mouse with free access to food would eat, but they have the same longevity benefit as a mouse that has always been hungry and if that's true, what that means for us is that we can enjoy life always We have that period of hunger once a day or maybe twice a week and I think the only reason we age is that our immune systems repair they become complacent.

You mentioned that what is beneficial to you when you are young comes back to bite you when you are old. that these repair systems are very good when we are young, so the idea is that it is called antagonistic pleiotropy and I think that is correct and that is that we evolved to stay healthy, alive and fit until we are 40 and then the forces of natural selection . decays after that because essentially we've been raised, we've often had children, but we don't need to stay beyond that and building a body that lasts a thousand years doesn't make sense, you know, most species only live as long as they need to reproduce. and then a little longer if you are a mouse you could die in two years they only build a body that lasts two years if you are a whale that has no predators you can live a couple hundred years that makes more sense why the whale lives for a couple of hundreds of years as I would say it's pretty safe to say certainly at some point in our past we became an apex predator pretty clear it's not like things couldn't take us out but I mean overall obviously look how far we've come, they didn't, so why would we only live to be 40?

Is it because whales continue to reproduce and be useful in that sense? That's really super interesting. Very few people talk about this. The reason is that we were not at the top of the food chain until recently, but in a world where we usually died of hunger or war, many men did not live to be 40 years old, so we were in the middle of the food chain. the food chain only now we barely have a chance of dying before 70 or 80 unless we are unlucky, give us another 5 million years of evolution, we could evolve with a life expectancy of 200 years, that's what should happen If evolution continues a whale has been at the apex for about 30 million years and they have been allowed to evolve those long lives we are like them we share most of their genes they are warm blooded they produce milk they are conscious basically it is us in the sea So anyone who says we've reached our ceiling doesn't know what they're talking about.

Talk to me about this notion of resetting the biological clock. How do we do it? What is the mechanism? Obviously, going hungry from time to time, exercise is going to help. help, but I know you have a regiment that I will affectionately call the regiment of drugs or precursors of things that we can take, what can we do to reset that biological clock? Well there are different levels to reset aging there are three levels we can know the first one is quite easy to reset or manipulate these are the proteins that turn genes on and off very quickly we call them transcription factors and they basically read a gene and they make a protein, that's what they do, that's level one, it's easy to get a little hungry that will change level two is a little more difficult level two is not just changing which genes are turned on and off quickly but in It actually silences the genes for a long time and this is where my enzymes that we work with, the sirtuins, come into play, let's go back to Pacman, they cut the acetyls of these packaging proteins, you roll up the hose and it gets trapped, that gene is silenced for a long time. time, so to do that you can exercise, you can diet, but I also think you need a little help.

What gets really interesting and this is something that most scientists don't even know yet is level three, the deep layer of aging. There is actually a DNA clock that tells our bodies how old we are. It could take your blood and read it and it could tell you approximately when you're going to die. What yes, we can do. What are you looking for? We are looking for chemical groups that add and subtract to our DNA, the long chain. Chemical modifications occur in the cell in a predictable way as we age from conception, so even in the womb, even when we are children, even when we are teenagers, we age according to this clock that increases linearly and where you fit on that line It is very accurate that it tells you your biological age, but how do you know when the person is going to die?

Just based on straight lines, they are actuarial tables, although the average human life expectancy is 86 and that's what you mean or could you? I see something specific on my line that I would say you're heading to 68, sorry no it's not specific but what it's based on is machine learning based on the genome methylation code of thousands of people and comparing it to their health and its date. of death oh, that's very interesting, so if you took my blood right now, what exactly would you look for? We would read methylation, kemp, these are chemicals, hydrogen and oxygen attached to DNA chemically physically bonded and they accumulate as you age. very predictable ways, in fact, they are so predictable that we can use the same clock to measure the age of the dog and the age of a human, it's all based on methylation, okay, what causes methylation?

Well, there are two kinds of enzymes, those that add methyl chemicals. and those who subtract it, how do I take a heap from those who subtract it? Ah, that's what we're working on now. Here's the key level two aging reset we can do with some of the things I'm doing in my life. yeah, you probably are too, those are not permanent changes, you can't just do that and expect to take treatment and you'll still live another 10 years, that's okay, because level 2 is not that permanent, it's something permanent that level one, but level three is truly permanent.

You could reset ten years and then go back and then wait another ten years and potentially reset the clock again if you know how to do it and we're just starting to figure out how to do it. level one diet exercise great got it level two uh metformin are you taking metformin okay, I talked about this on the show before, but explain what metformin is, why it's prescribed to diabetics, and now why it's apparently a rash on non-diabetics. diabetics. taking it, yes, there are three main pathways that regulate aging in animals and probably in ourselves are the sirtuins that I've talked a lot about today.

There is one called mtor that responds to the amount of amino acids or how many amino acids are in your body, it will hunker down and protect the body, the less amino acids it has access to, okay, so the third one is called ampk and this is the energy sensor, when your body has low energy levels, it will allow the body to duck and protect itself. of diseases, but the reason AMPK is worth mentioning is that this is one of the goals, as we call it, of the drug metformin. Metformin will activate this ampk pathway and make the body think it is hungry when it is often not and will also keep blood sugar levels more stable.

Why would I be hungry at a cellular level or do I actually experience hunger at a certain level? That's fine, but it also has an interesting side effect. For many people, including myself, it is a little hard on the stomach, so it also reduces my appetite, but the good thing about metformin is that it has been in millions of people for a few decades, so we know the side effects that they are relatively fast, so metformin is creating at the cellular level the sensation that I am hungry and you are. We're saying that from a bit of a bad hormesis perspective it's like stressing the system and that's why we think it works, it's exactly that and it really helps the body respond in a way to increase the energy supply so that one does it.

It does undeniably increase the level of mitochondria, it actually creates additional mitochondria so that your cells become more efficient or more capable of generating energy in the long term, but in the short term what it does is actually poison. part of the mitochondria, so it is a little bit of poison that generates benefits in the future. Which part is poisoned? It is called complex because there are protons that are in a part of the mitochondria area in a membrane region. and the cell accumulates protons, it becomes very acidic in that region, but the cell wants to release them, so what they do is put small pores between the membranes so that they can filter from the area of ​​high concentration to the area of ​​low concentration in the area. . in the middle and as they pass through that pore the pore spins and that physical spin of that protein will generate chemical energy called ATP that's how ATP is created and without ATP we're dead in about 10 seconds yeah okay , that's very interesting, uh and you're saying sorry for going back to the poison, the poison is raising those levels, which makes it go more, it's actually lowering the ATP in the short term, so the cell says man, no.

I have enough chemical energy in ATP, so that's what forces it. It's to create more mitochondria, so that's the poisoning part. The increased number of mitochondria is exactly in response to the slight poisoning, but there are two other important points: the cells in our body also think that they need to become more sensitive to insulin. yes, which keeps our glucose and sugar levels more stable, yes, that is key because that is what helps type 2 diabetics recover and prevents the disease from getting worse. Yes, the second is that it has just been discovered in humans that if you take metformin a lot and exercise it can mitigate the effects of exercise on the construction of mitochondria.

What we think is happening is that you don't always want to have metformin in your system or your body won't have a chance to recover from that mild poison. I'm not going to prescribe anything. I'm not a doctor, but we think it's best to take metformin on days when you're not exercising or recovering and hit it again so you have metformin, exercise, metformin, exercise, right? I'm not prescribing anything, but how many days are you taking it? How many days not? How often do you exercise? How often don't you do it? In fact, I spent much of my 30s and 40s not exercising at all, it's crazy, right?

Me, but I've gotten better at it now that you know, I was approaching 50. Now I'm 50. So I spend about four hours at the gym on the weekends with my son Benjamin, like two hours a day, no. four hours straight, but it's not all exercise, so it's an hour with my trainer Sean, who does mostly a combination of weights and stretching, some weights, some machines, then it's another hour just with my son, we do some treadmill running, a little more stretching and Basically, we just have fun doing things that are fun for him and then we also do some yoga at the gym, a little relaxing, but the most fun part that I really love is that at the end we do a cold bath in a jacuzzi and sauna. sauna, jacuzzi, cold bath for about an hour and I feel fantastic, tell me about that, so in your book you expose yourself to the cold, you said you moved to Boston, it sucked coming from Australia and you bundled up and now you wish you hadn't.

Well, there are a few reasons, one is the high-level view, is that anything that stresses your body puts it into shock is good in the long run, but a little bit of perceived adversity is a little too hot, a little too much. cold and especially the gradient between those two, so we jump from one to the other. The next point is that I looked at the literature and at the beginning, when they asked me. By my editor to investigate this scientifically they told me: do you know what happens with this cryotherapy? What do you think? A couple of years ago I had no idea this was real.

I thought I looked into it and there were two. important things, one is cryotherapy or exposure to cold, we will accumulate what is called brown fat. We didn't know brown fat existed in humans until about five years ago. It is usually located on the back and for other reasons can be seen with a pet scan, but otherwise. It's pretty invisible, it just looks like fat,But brown fat is particularly healthy because it has a lot of mitochondria and we think it also

secret

es small proteins that tell the rest of the body to be healthy and how to be healthy, we're not sure.

We're not sure it's interesting yet, oh man I want the answer to that question, but it certainly speeds up your metabolism and will burn energy if you're looking to stay lean, having a little bit of brown fat is okay, so my friend Ray. cronus and I have written about this and andrew bremer and at the nih we call it the metabolic winter hypothesis and it essentially says that in our lifestyles these days we are always warm I'm wearing this jacket we sleep with the blankets on we become We never expose ourselves to charcoal unless we force ourselves to do it and we think that's possibly largely responsible, if not, maybe partially, maybe largely, responsible for the diabetic problem that we have.

Alright? So if you're cold at night, we're going to burn a lot more energy by staying warm, yes we activate brown fat, that will keep people thin if we bundle up and eat the kind of diets we see in the supermarket, which will be doubly bad for our health. bodies, yes, we are warm, we are not losing energy and we are eating a lot more, yes, this is, this is very interesting, okay, so what is your advisor? Whatever you're about to tell me, no, I'm going to do it. So how often do I want to do it?

Is it every day? What's that look like?well what I do is because I'm busy and I don't have a sauna or a cold tub at home I subject myself to these things um for about an hour on Sundays and what I do is I spend about 15 minutes at 150 degrees Fahrenheit, well , that's reasonably intense, but you get used to it and then we go into the steam room, you know, we're sitting there chatting, it's great, the temperatures are lower in the steam room because the humidity is saturated, the ceiling drips on you, hot water uh but that I don't know if the steam helps but I certainly love the feeling of being there and my skin starts to get healthier because of course it's cleaning itself and then the last thing I do is a jacuzzi with water hot pretty hot. and then and then I go and I go underwater a couple of times in water that's less than four degrees Celsius, so it's so cold that it takes your breath away, yeah, yeah, but it's very interesting if there was something else at level three we should know about each other, so the work we've done recently, just in the last year, is finding ways to modify the cells and tissues of mice to at least reset the clock.

We've been working for 10 years, like I said, speeding up the clock. We can move that clock hand forward now if we cut the animal's DNA, let it heal, and in doing so we distract those proteins from where they come from, so we're disrupting this survival circuit so much that we disrupt the DNA winding process and what what we got was an old mouse by all accounts based on histology, which is looking at tissues based on their physiology, they turned gray, they got arthritis, they even got heart disease and when we looked at the molecular clock, that methylation clock, they were communications that were 50 percent older, they were more like lumps everywhere, those methyl groups were added to the DNA, okay, so we had given them heart disease and Alzheimer's or dementia, we had given them all these diseases, but by measuring the clock it was Actually what I did was age them, but that was the first step that took 10 years.

Last year we were asking how to make the hands go back, that's much more difficult, but we were lucky that the 2012 Nobel Prize winner was one. for the ability to

reverse

that clock in the cells it is called uh, it was the prize awarded to shinya yamanaka, a very intelligent Japanese guy and he found at least four genes that when put in the skin cells of an adult, if you give me your skin. cells, I could go back to Laven, basically clone you, I could take your cells, make a bunch of stem cells and I could turn you into a little new liver or a little new kidney, that's all easy, it's not easy, but it's doable, it's feasible, what does that tell us? is that those four yamanaka genes can reset the age if I can take someone like you who is in his early 40s and create a new self like we have done now with many species, dogs, cats, sheep, monkeys, those animals we can reset the watch one hundred percent. and those animals actually live a normal life that tells us that the instructions for being young are still somewhere in the cell, as if there is a backup hard drive that tells the epigenome that those reels had to become young again and recover those methyl groups. to be young again, not up here but back there, but don't remove them too much to be a stem cell or I'll basically turn you into the world's giant tumor, yeah, okay, so why do I turn into a tumor? why is it a tumor? a cell that doesn't know how to stop properly, so what are you breaking down in that process that makes it so dysfunctional?

Yes, in terms of the clock, let's start with that brilliant yamanaka that turned the clock back so far. It went back to zero, it came back at midnight, we don't want to do that because the cells lose their identity and that's the last thing we want to do, we don't want to go back to ourselves because it's dangerous to have a pluripotent stem cell in the wrong place in the body, so Of course it will grow, it won't stop growing, but why not? why does it become a tumor? Why doesn't it become a liver or a lung as if it had the problem of having a liver? they develop in my brain, but I'm just saying why it turns into a tumor cell instead of an actual functioning liver.

Well, when you go back far enough and it loses its identity, it will simply multiply into a mass with no cellular identity, so there is something else going on that prevents it from understanding itself well, so in the laboratory, if we take a pluripotent stem cell and we want to turn a liver cell or a neuron into a nerve cell, we give it a bunch of chemical signals in what we call a niche and when one of these cells lands in a niche around those old cells, they will use that stem cell to rebuild the tissue , but imagine if we could reset the clock not completely back to a stem cell, but only partially. that you could be 20 years old again, that's what we can do in some mouse tissues right now.

You do it en masse when it's cell by cell, DNA strand by DNA strand, how the hell do you get this done? It has an effect throughout an entire joint let alone the entire body, yes right now the way we do it is by injecting a virus called aav and this virus will target certain tissues and deliver the genes to most of the cells in that tissue, for example, we are treating eye aging in mice so we can take an old mouse, we apply a virus, the av, to the eye, a small prick, it is the same virus that is used to correct deficiencies genetics in the eye, right now, FDA approved drugs, so this is not science fiction, this is available in the world right now, we give it to old mice, we give them an answer about it, an antibiotic called doxycycline Okay, the same thing you might take if you have Lyme disease and that activates these reprogramming factors. do not use the four oskm factors, they are called because one of them causes cancer, we leave it out, we put it in the eye, we activate it, we leave it for a few weeks, it measures what happens to the eye and those mice can see again as if they were young, so we have tested three different types of eye damage.

The first one we made was a Hail Mary for a lab near ours, across the street, to work on spinal and optic nerve rejuvenation, which is crazy, yeah, because we know that as soon as you have A couple of months will not regrow your spine, it is one of the first parts of the body to age, in fact, but jellyfish can regrow, axolotls can regrow an arm. We lose that ability when we're very, very young, so the question was if we turned back the clock too much without osk genes, would those nerve cells be young enough to grow back in the brain if we damaged them, and that was the experiment they did. we pinched the back of the optic nerve so that the nerves were defective and started to die back towards the brain, of course the mice lost their vision, then we activated our reprogramming factors, now we see the nerves rejuvenate again, we turned back the clock and they grow back in the brain, we could give ourselves the healing ability that we only had when we were embryos and you start to think about what this could lead to if we can do it safely, of course, safe is the important word around the body, imagine one. day you could rejuvenate every cell in your body that way you cut yourself you break a bone you lose your mind you have dementia you take a doxycycline treatment for a few weeks and then you stop it, you disconnect it again and it is cured if you activate it at high levels.

There is a laboratory in Spain that has shown that in some animals small tumors can develop in the kidney, so we have been very careful not to destroy the cell with these factors permanently. titled or say we lower the levels to very low levels and turn it off when we don't need it, but we have given mice this virus all over their body, injected it into a vein and turned it on, left it Now I hope the mice die a year later they are perfectly fine so it seems safe but of course there is a lot more work to do.

I am a scientist and I am developing medications that I must be very aware of. The dangers, of course, please no one go out and try this at home until we know more, but the eye is a good test area because it's protected and if there's a problem, you know it's protected from the rest of the body, no. it will. go too far, but all we know now is that it appears to be very safe, at least to the naked eye, this is crazy, so there is an element of enhancing human performance or anything you can make fun of us with, well , we.

In fact, I've published results that in mice, if you give them a booster molecule that will activate these pac-man enzymes called sirtuins, those mice when they're old can now run 50 more, in fact, some of our old mice ran that much. to where the treadmill stopped because mice are not supposed to run more than three kilometers which we haven't talked about yet and still tell me what it is and what the precursors are how do I complement it uh so there are some on the market that don't By the way, I don't promote or sell anything, even if you see me online, that's not me, so there is one called nr, which is stan, which stands for nicotinamide riboside, which is a very early precursor to making nad in the body. an intermediate of that called nmn which is not to be confused with m ms please don't do that that's not healthy and then the cell converts nmn to nad and you can take all three actually or each of those three and raise the levels of nad in animals. and now we are doing it myself and many others are doing human studies and we have seen that nr and in my case nmn raises the energy levels of older people and young people alike to levels that we believe could rarely be achieved.

Being a marathon runner is crazy so bringing this home to have people tell me about your dad and his experiment with nmn yeah so my dad has been in the same regiment as me with resveratrol for more than a decade, red. Wine molecule, he has been on metformin longer than me because he had borderline type 2 diabetes and now he is also on a man and seems to be doing great. He is now 80 years old. When he was 70 years old, he was slowing down. He was starting to say the same things twice, you know, typical 70-year-old man.

He is doing very well now that he is 80. He has a new lease on life. He started a new career in Sydney. He's touring the world right now. He's traveling around America driving his elderly friend, uh, around his friend, unfortunately he ended up going to the hospital the last few days, so my dad is taking care of his friends who he sees declining and if anything getting better every year. I would love to know more about resveratrol which is something I had completely ruled out until I started researching you um for a minute it seemed like it was real and then it seemed to completely die and I know you got caught in the middle of some of this stuff , so where is everything that pop culture thinks about it forgotten?

What is the reality? Yeah, so resveratrol was a proof-of-concept molecule back in 2003, the first of its kind that could mimic calorie restriction and make mice healthy on a high-fat Western diet. It was a great test of something we were trying to discover, and it led to drugs that were given to humans that looked really promising. I found myself caught up in a scientific and corporate war song. In the case of Pfizer, they published a scientific song. article that said essentially everything David has saidit's wrong, well, and then that was a big headline, Harvard scientists founded companies it's wrong, well, and you know, and then I spent about a week in bed telling the world, you know, why am I doing this? ?

I'm working very hard for society if you don't mind, but I managed to get out of bed. I thought I'd dig deeper and see if they're right or if we're right, so for another three years we worked really hard in my lab at Harvard to see if we were right, so the question was with this DNA-coiling Pac-Man, Does resveratrol work on it or is it working on something else and that for scientists is really important because if it doesn't work on this, all the drugs we're trying to work on are probably working the wrong way, so we thought we'd summarize What we found and published in Science magazine, which is one of the best things you can do and I say this because it is validated science is that we showed that resveratrol binds to Pacman and is responsible for this and now we have new information that does not we have published, but I will tell your audience.

We have created a mouse that is resistant to Pacman activation, we can modify the enzyme only in one amino acid in that protein of approximately one thousand that blocks this activation of movement, normally it chews like this, but if we add resveratrol to a normal mouse, it will do the same to our mutant mouse. is this and which is better to eat fast eating fast is better, because we believe that fast was responsible for the health and longevity benefits, so what you are showing is that by decreasing it you cause real problems and, therefore, if you have resveratrol there and make it chew very quickly you have done something positive and right and our mutant mouse should be resistant to the benefits of resveratrol if we are right but if pfizer is right then resveratrol should still provide benefits even though this enzyme is working. in some other way he managed it, so the mouse that couldn't speed up, the mutant mouse, no longer lives when resveratrol is administered in its high-fat diet, interesting, that will be the punctuation mark of the fu that we will put together, but , interestingly, the The world has moved on, well, I have to clean up the pieces, yeah, and when you say the world has moved on, you're talking about people like me who just assumed it was rubbish and that it's not real and right, so , you have said that the only supplement you take is vitamin D.

So how do you get resveratrol into your system? Is it a medicine? Do you have to prescribe it? Well, I'm taking resveratrol. um and we would call that a safe supplement and it's commercially available uh if it's a legitimate seller and it's over 98 percent pure, it seems to be similar to what I take and about how much do you take? um I take a teaspoon in my yogurt which is probably about a gram every day every day yeah okay uh resveratrol about a gram are you taking nmm or is it nmn or is it just your dad? uh, we're both fine and then metformin, of course, those three, anything else, those are the main things.

I think that's helpful and I've been monitoring my blood through chemistry, so you and I said you had an MRI of your heart, which I love. What are the things we should try? I guess for a second I'm willing to go all out. The way to do any crazy test to know if what I'm doing is working. What would you recommend? I avoid x-rays and CT scans unless I have to be sure. If your doctor says to do it, don't refuse it, but. otherwise, don't do it for fun, don't do it because you're curious, uh, because those CT scans will break your DNA and when we break the mouse's DNA, its age increases by 50 percent, so, of course, avoid the DNA breaks.

As much as possible, what I do is get a blood test from a company called Inside Tracker that, to be honest, I invested in years ago and they analyze about 30 parameters in your blood and give you information that it is monitored by a doctor, so it's legit and it's based on a lot of science and that at least gives you some information about your body about what really happens if you change your lifestyle or take a supplement or even a new medication, so you have to have it. you have to be monitoring because you don't want to fly blind you don't know if you're hurting yourself or well so get a blood test at least go to your doctor and get a blood test For the love of god you could sequence your genome or do something that analyzes variation in your genome for a relatively low cost.

I think it's 99. Now I gave such a test to my entire family as a Christmas gift and what I've learned is that some of our members, the lab members, are not lab members, the lab members. family have variants that predict longevity, some don't, some have mutations in their genome that are a little scary. In the future, they could determine their DNA methylation age. the truth is what's called Horvath's clock some people measure the length of their telomeres um did you have a biopsy to do that or can you do it from blood? The blood test is okay, yes, it's very interesting, where can people learn more about you?

Okay so The main site is lifespanbook.com, that's where you can subscribe to the newsletter and buy a copy of the book if you're interested, I highly recommend it, thank you. I'm also on social media now, so I have a Twitter account. I try to talk about science, new findings, things I just learned and things like this that you might want to tune in to, so my Twitter account is David A Sinclair and I have Instagram where I send out some, you know, unfunny ones. The thing to do is not do this kind of thing and that's David Sinclair Phd.

Okay, what's the impact you want to have on the world? Well, that's been easy since I was four years old. I've wanted to find out why we die so quickly and you know. In my opinion, I think it is cruel to have a sentient being who knows that he is going to die in such a short time. 80 years is nothing, it passes in the blink of an eye, even a thousand years will pass in the blink of an eye, it is only 20 times what I have lived so I want to be able to leave a mark on the planet.

I hope I have moved the needle a little on the course of human history. I think we've come further than I thought. in my entire life and I still have a few years left to try to make what I'm talking about a reality, I certainly hope so, if people would make a change that would have the greatest impact on their health. What change would you like them to make? Having read tens of thousands of articles and doing this for 30 years and talking to people, I know what's cutting edge, the simplest thing you can do, and what would be the biggest investment.

It's being a little hungry, not eating, but that doesn't mean you're nourished, you're not starving, there are a lot of teenage girls, particularly, who don't eat enough, so I'm not saying that at all. You have to have minimal nutrition but for those of us including myself who like to eat those who don't mind a little dessert try to skip a meal I skip breakfast besides that little yogurt I often do too busy for lunch at dinner I eat a normal meal I don't gorge myself because that will trigger all these defensive pathways that will rebuild the body or at least keep it pristine until we have things like the level three reversal that we're working on now, that's awesome , David, thank you so much for being here, that's amazing and guys, read the book, dive in if you're like me and want to live forever.

I'm telling you this guy is on the cutting edge of a very exciting sphere so check them out if you haven't already make sure to subscribe and until next time my friends are going to be legendary take care buddy that was awesome thank you so much to everyone for watching and being part of this community, if you have. Don't be sure to subscribe, you'll receive weekly videos on how to develop a growth mindset, cultivate determination, and unlock your full potential.