Harvard aging researcher Dr David Sinclair explains the science of age reversal and what people can do now to live longer
Dr David Sinclair, a Harvard professor who has studied aging for 30 years, discusses his information theory of aging, ongoing clinical trials to reverse blindness, and practical steps anyone can take to slow or reverse the aging process.
Summary
Stephen Bartlett interviews Dr. David Sinclair, a Harvard professor and longevity researcher, whose lab has developed a method of reversing cellular age by approximately 75% in animals, with the first human clinical trial — targeting blindness — set to begin imminently. Sinclair's central argument is that aging is not inevitable wear-and-tear but an information loss problem: cells gradually lose their epigenetic identity, forgetting which genes to switch on and off, and this loss drives virtually all major diseases including Alzheimer's, cancer, and heart disease. His lab has demonstrated that this process can be reversed using three genes delivered into tissue, and has achieved a 100% extension of remaining lifespan in elderly mice using a systemic injection. Sinclair also presents practical lifestyle interventions — including skipping meals, exercise, specific supplements, and diet — that he argues can extend healthy life by a decade or more. He closes with extended reflections on consciousness, quantum mechanics, artificial intelligence, simulation theory, and the philosophical question of life's meaning and purpose.
Key Takeaways
FULL TRANSCRIPT
Introduction and the photograph that started it all
Stephen Bartlett: Dr David Sinclair, I have waited many years to speak to you. I've been so keen to speak to you for so many years because so much of the research and information I've consumed on the subjects we're going to talk about today comes from you directly — from research you've done and from theories, ideas, and hypotheses that you formed. I think the place this conversation should start is probably with this picture, because it appears to be incredibly formative in your journey.
Dr David Sinclair: Oh yes, that is an important picture. This is a picture of my grandmother and me when I was in my early 20s. I'm now 56, if you're wondering. My grandmother has played a major role in my life. I'm going to have to be careful not to get too emotional because she's now passed away, but she's inspired me to do the best I can to leave the world a better place than I found it.
Stephen Bartlett: And there's this particular book here called Now We Are Six.
Dr David Sinclair: Anyone who's read my book Lifespan knows that this book is very important to me. And I didn't realize it, of course, when I was a kid, that this was going to change my whole life. There's a poem at the back there that my grandmother Vera used to read me when I was six, and it goes like this:
"When I was one, I had just begun. When I was two, I was nearly new. When I was three, I was hardly me. When I was four, I was not much more. When I was five, I was just alive. But now I am six. I'm as clever as clever. So I think I'll be six now forever and ever."
I'm getting chills reading this again because the impact on me was the following: subconsciously, my grandmother was saying you don't want to grow up — adults can be evil. She grew up after World War II. There was horrendous impact on her and her family in Hungary, and she thought that a child is innocent and people shouldn't grow up. But what actually happened was I asked myself: why do people grow old? That's a terrible thing to happen. And so I've spent my life trying to figure out why do we get old, why do we get frail, because I also think that if we can solve that — understand it, slow it, even reverse it — we will have the biggest impact on human health in history.
Stephen Bartlett: Am I right in thinking your grandmother told you at that young age that she was going to die, that you were going to die, that your parents were going to die?
Dr David Sinclair: Yes. I remember it very clearly. I was on the floor and she was crouching down and I said, "Vera" — I didn't call her grandma, she didn't want to be called grandma, she wanted to be young like a kid too — I said, "Vera, will you always be here to protect me? Will you always be around?" And she said, "No, I'm going to die." I said, "What do you mean?" She said, "Everything dies. I'm going to be gone. Your parents will be gone. Your pet cat will be dead pretty soon. And you yourself will be dead one day." At age four or five, that's heart-wrenching, right? We've all gone through this realization around that age that the world we believe in and see will one day all be gone.
That moment — I remember it so clearly — because I thought, that's not fair. Why would any species be made or created that knew that fact? That's cruel. It's better to either not know or to not exist. But to know that that's what's going to happen is really cruel. And so I vowed, actually legitimately around the age of 18, to get a PhD, go to the United States, and develop a research lab to try and do something about it.
The preservation of health and life is the most important thing that we can do as human beings. We do it with some drugs to treat this disease and that disease — cancer, heart disease, Alzheimer's. But what's underlying that? What's really causing about 150 to 200,000 people every day to die is the underlying universal process we call aging. And for far too long, we've ignored it or accepted it as natural and therefore acceptable. I fundamentally reject the idea that aging, just because it's natural, is acceptable. There will be a day when we look back at today and think how medieval our medicines were, and how sad it was that we accepted that we became frail before 100.
The case for age reversal — and the first human trial
Stephen Bartlett: If someone has just clicked on this conversation and they deep in their core believe that they're probably going to live to 80 years old — and that we all are, and that we're never going to be able to do anything about it because that's just the way it is — people get old and then they die and aging is a fact of life. What is the most persuasive top-line argument to that person to convince them that we will do a job of both reversing that belief or at least challenging it?
Dr David Sinclair: All right. First of all, who am I? I'm a Harvard professor. I've been studying aging, longevity, and age reversal for 30 years. The technology now that we have in my lab, used every day by my students, literally reverses the age of tissues in animals and in human tissue that we grow in the lab. And the first human trials to test this are going to be performed in about a month from now. And if it works, it'll transform human history. It means that we're on a path to finally being able to reset the age of the human body — not by a year, not by 10 years, but even more than that.
What we're finding in animals, including primates, is that we can cure things that have previously been impossible, including blindness. So if you're listening and you're skeptical — I'm not some hack. I am a Harvard professor who is telling the world, and has written a book about it, and every day spends his life researching with a team of the best scientists I can gather around the world — showing that we can literally now reverse the aging process and reset how old the body is in animals. Yes, but potentially this year, showing it can work in the human body as well.
Stephen Bartlett: So you're doing the first ever trial of this type in humans to reverse aging next month?
Dr David Sinclair: Yes. We've submitted to the FDA in the US to get approval to treat blindness — a couple of types of blindness — in people, as early as next month if all goes well.
Stephen Bartlett: And what exactly is happening there? There are many ways one might fix blindness. What is it you're doing to the eyeball that is a precursor of our potential ability to reverse aging generally?
Dr David Sinclair: We chose the eye not because it was going to work better than other tissues, but because it's a nice system to study age reversal. The eye is an enclosed space, and so it's much safer than trying to initially reverse the age of the whole body. In mice, we reverse the age of the whole body and the effect is longevity, rejuvenation, the skin gets better, all parts of the animal get healthier and younger. But in humans, you don't want to go straight to whole-body rejuvenation, in case something goes wrong — it could set us way back. We have to make sure we don't have any safety mishaps. So we're being a little cautious in humans.
In the human eye — and for those of you not watching, there is a plastic model of an eye on the table — we're going to look at the back of the eye, which is your retina. That's where the light hits. At that point, there are a lot of nerves that coalesce into the optic nerve that runs to the brain by just a few millimeters. The brain is here. The eye is actually part of the brain — a lot of people don't know that. You can touch your brain if you touch your eye.
The optic nerve gets old, and when it gets damaged or gets old, it's not working. But the nerves, for the most part, if you're old, are still there. They just forget how to work. And that's aging.
What we're doing is introducing a set of three genes into this optic nerve at the back of the eye and turning them on for six to eight weeks. Those three genes are what we now know reset — safely, apparently safely — the age of cells, including nerves, by about 75%, and then stop. They don't go more than that, which is good. We don't want to go back to zero. I don't think anyone wants to go back to high school.
We chose the optic nerve because it's a safe enclosed system. We've now done it in mice in my lab for the brain. We're doing hearing. We've done skin. We did multiple sclerosis. We're now doing motor neuron disease and seeing great effects. I'm not an eye specialist. I didn't choose the eye because I love the eye. I chose it because that's a good place to start for age reversal in humans this year.
Stephen Bartlett: You mentioned you've been able to extend the life of mice in your laboratory. How and by how much?
Dr David Sinclair: The study that I was referring to was done using our technology in an independent lab, which is arguably even better than having done it in my own lab. Instead of putting the three reversal genes into the eye, they injected them into the vein of old mice — mice that would be the equivalent of about 80 to 85 years old, really old and frail. And they got an additional 100% lifespan extension. Additional.
Stephen Bartlett: So that would be like an 80-year-old living to 160?
Dr David Sinclair: The remaining life of an 80-year-old isn't long. So let's say if you give it to a 70-year-old, on average they'd have another 10 years to go — give them 20 years. That's the calculation. But that was not an optimized study. They just did a Hail Mary injection to see what would happen.
Stephen Bartlett: When we did our research call, I heard you say, "The world doesn't know how close we are." Close to what?
Dr David Sinclair: To being able to safely reverse the age of the human body.
Stephen Bartlett: How can you be so sure?
Dr David Sinclair: I'm not sure, but I'm confident that the science is solid. The biology of aging is understood, I believe, in concept. My theory — the information theory of aging — has so far not been disproven, which is important for a scientist. And that has allowed us to succeed, really for the first time, to safely reverse aging. I now believe — and I didn't 10 years ago — that in my lifetime I'm going to see medicines on the market that reset the age, or at least reverse in large part the age of the body. And that initially won't be just to make us look better and feel better, although that's what a lot of us want. It's going to be used to cure — certainly prevent, but definitely cure — diseases that are currently incurable. I think we're at a turning point, dare I say, in human history. It's not a question of if; it's a question of when this is going to happen.
The pill prediction and what technology will look like in 50 years
Stephen Bartlett: You had a prediction about taking a pill every couple of weeks that will make us younger. What is that prediction?
Dr David Sinclair: I do believe that you — and you're about 20-something years younger than me — you're going to see this for sure: there will be a pill. My critics might say, "Dr, that's exaggerating. You're still trying to get these genes to work in the eye — how is it going to be a pill?" But this is where my lab comes in. My lab is like Willy Wonka's chocolate factory. It's magical. The students and trainees — about 25 of us — are making discoveries that blow me away every week.
It's not a pill yet, because you can't give a mouse a pill — they won't chew it. But we give them a liquid. And within four weeks, we can rejuvenate them. Not with these genes we're giving humans — that's the older technology. The new technology is something you can swallow in a mouse and rejuvenate them in four weeks. It's normal for my students now to say, "Oh yeah, we just rejuvenated the ear. We just rejuvenated the skin. We just cured ALS, motor neuron disease, in these animals."
And this isn't different medicines for each disease. It's the same set of genes, the same molecules, that treat multiple sclerosis as the one that cures blindness in mice. The same drug we're using in the eye will be used to treat other diseases in the body, even liver disease.
Stephen Bartlett: If your predictions are correct, what does this mean for how I should be living my life right now?
Dr David Sinclair: Most people look at their parents and grandparents and think, that's what my life will be like — I'm going to be frail in my 80s. That's not true for us. I like the Wright brothers analogy. It'd be like saying in 1900, "We're always going to travel as fast as a horse." Previous generations are no guide to what our lifespan is going to be like. You're potentially going to live to the 22nd century if you do all the right things and technology keeps advancing. What kind of technologies will we have in 50 years? You'll be around in 50 years. In 50 years, you will not be using today's technology. You'll be using the technology of 2070, 2080. That's why people talk about the singularity — the idea that if you can make it to a certain point in human history, you won't have to age anymore.
Stephen Bartlett: So the thinking is that if you can survive until that particular date, you have the choice to live forever. Is that right?
Dr David Sinclair: That's what they say. There are a lot of proponents of that idea. Ray Kurzweil said it's coming — I think he said in the 2040s sometime.
Stephen Bartlett: Do you believe that?
Dr David Sinclair: I'm skeptical. Ray is a smart guy — he predicted AI and all that's happening, so it's dangerous to bet against his predictions. But I remain skeptical. That said, if this trial works this year, we will be in new territory. We will be on a path to age reversal in the whole body. And we can reverse the age of the eye not just once but seemingly as many times as we want. In mice we've done it at least twice. We didn't do it a third time because the mice just got old and died — but they died with perfect eyesight. We don't believe it's a one-shot wonder. You can keep reversing aging, then you age out, then you reverse it again, and you just keep going. If that's true, then it is possible that we will live dramatically longer. I don't yet see any technology in the near horizon that will make us live forever. But I do see a radical change in how we treat diseases and how long we can live.
The information theory of aging — what aging actually is
Stephen Bartlett: So let's talk about what aging actually is. Can you explain this to me like a total idiot?
Dr David Sinclair: My theory is that aging is not just wearing out. I look at the body like it's a computer — it's software, and we can reinstall the software. In my lab, we believe we've found the way to do that, and we see the evidence of that.
The body is a carrier of information from our parents and what happened in the womb. That information keeps our body functioning almost perfectly in our teenage years and 20s. In your early 30s, you're starting to lose that information, so your body's not functioning perfectly anymore.
Stephen Bartlett: You've got some gray.
Dr David Sinclair: Exactly. That's a good example — cells that lose their identity and stop making melanin, the black pigment.
The information gets lost. It gets corrupted. But the beautiful thing is we believe we've found a backup copy of that information from youth that we can reinstall into cells, into tissues, into the entire body of a mouse — and hopefully a human. That backup copy is in every old person, I believe, and it can be accessed. So when I see an old person walking down the street now, I don't think "that person's just worn out, frail, going to die." I just think, that's someone who needs a reset. Inside that person is a young person waiting to come out again. That's a totally different way to think about old age. In the future, people will have a choice to be rejuvenated or not.
Stephen Bartlett: Where is that backup copy?
Dr David Sinclair: We're working on that. We believe we've found largely where that information is stored. It's entirely new biology, and it's currently a secret.
DNA, the epigenome, and how cells lose their identity
Dr David Sinclair: Let's talk about information. We live in the information age, and biology is becoming part of that. It started with the elucidation of the structure of DNA. I have a model of DNA here — for listeners who aren't watching, it's a little plastic double helix. My friend Jim Watson, who died recently — he and his colleague discovered that DNA, the information of life that we get from our parents, is a chemical about six feet long in every cell.
DNA is a ladder, and the steps on the ladder are the information. You can pull this apart so that each step becomes half ripped apart. That's called a base on the DNA, and it always matches with its corresponding chemical. An A always matches with a T. A G always matches with a C. If you rip the ladder into halves, each step becomes half a ladder, and now you can see how you can copy DNA because the A has to match with the T, the G has to match with the C. That's how the information transfers from cell to cell, from parents to offspring. There are about 20,000 genes; about 15,000 are turned on, but a different set gets turned on to make a nerve cell compared to a liver cell and a skin cell.
That's gene expression. And what controls that gene expression is what's called not the genome — not what's in this DNA molecule in front of me — it's the epigenome. The epigenome is the information transferred from cell to cell, from parent to offspring, that's not in this molecule. It controls which genes are switched on and off.
A major regulator of that process is the modification of the steps on the DNA. The C, particularly, gets a little chemical added to it called a methyl group. A methyl is just a carbon with three hydrogens — a very simple molecule. It gets stuck on that piece of the DNA molecule. That's called DNA methylation. That pattern of DNA methylation determines whether a particular gene will be switched on to make an optic nerve or switched off to make a liver cell. And that happens as we develop in the womb.
The information theory of aging states that the information in a cell — which includes the DNA, but more importantly for aging, the control systems, the epigenome — is pristine when we're young. But as we get older, we lose that epigenetic information. The ability to tell a cell to be a nerve cell versus a liver cell versus a skin cell starts to get erased. So when we look at an old tissue, my skin cells are no longer as skin-like as they once were. They've started to lose their identity. They're starting to look more like nerve cells. And nerve cells are starting to look more like skin cells, because the control systems — those methyl chemicals on the DNA molecule — are getting erased.
Stephen Bartlett: So aging is an identity crisis of the cells.
Dr David Sinclair: Absolutely. Well put. The cells forget what their job is. The genes are still there in large part — 99.999% of the genes are still there, the molecule's intact — but the control systems, the labels that tell the cell which gene needs to be on and which should stay off, those get erased over time.
Stephen Bartlett: Why?
Dr David Sinclair: We did partially figure that out. There are enzymes that remove these methyl groups and put them back on. So the cells are controlling these things and they shouldn't change, but they do. One of the things that messes the system up is a major catastrophe in a cell. When the cell panics, it removes these structures in a desperate attempt to survive. But then the cell doesn't fully revert to the original state. Some of these chemicals, and some of the proteins that bind to the DNA — which is also important for the epigenome — they don't all go back to where they started.
The analogy I use is a tennis match where the proteins that control the genes get relocated to where the emergency is. And an emergency — the one we think is most dangerous and the large cause of aging — is a broken chromosome. If you don't fix a broken chromosome, you're either going to become a cancer cell or you're going to die. So cells panic. In that panic of moving proteins away and turning on stress response genes, that's great in the short term — the cell might survive. But those proteins don't all go back to where they once were. And if you do that time and time again, and every one of your cells has at least one broken chromosome every day — that's 20 trillion of these events every day in your body — over time, tick tick tick, you get the aging process.
The ice mice experiment — proof of concept
Stephen Bartlett: How do you know that's true?
Dr David Sinclair: We created this catastrophe in animals. We took mice and broke their chromosomes in a way that didn't cause cancer or mutations. If we're right, what should happen to these mice?
Stephen Bartlett: They get old fast.
Dr David Sinclair: They get old fast. Gray hair. And they did. We call them the ice mice — ICE stands for Inducible Changes to the Epigenome. We were able to induce these changes. We had a lot of bets in the lab — this was about 12 years ago. I bet that we would get aging. I was the only one in the lab who thought that. We had bets the mice would die, bets they'd get cancer, a few said nothing would happen. But we got aging.
I was in Australia — where I'm from — and I got a picture on my old iPhone. It was a picture of a sick-looking mouse and the text said "problem, we have a sick mouse." I wrote back, "That's not a sick mouse, that's an old mouse." That was the first time I realized we'd had evidence that the information theory of aging is correct.
What we did was generate a mouse from scratch using stem cells. We changed the genetics of that stem cell so that we could feed it a drug — tamoxifen, which is used in chemotherapy — and that drug turned on a gene from a slime mold that cuts the DNA of the mouse in a way that doesn't cause cancer or mutations. Just cuts it, and the cells put it back together.
We could take a mouse and for three weeks turn on this slime mold cutting protein. Nothing happened to the mouse at the time. You don't feel an X-ray. You don't suddenly feel older when you fly. Same with the mice — they were normal, they felt fine. But we set in motion a cascade of accelerated aging events that, about 10 months later, made them super gray and super old, with all the diseases of aging, 50% faster than their twins we didn't treat.
Stephen Bartlett: Can you translate this into the equivalent for a human? Like, doing what to me would make me age fast?
Dr David Sinclair: We're exposed to things that cause DNA breaks all the time. They happen naturally as cells try to copy their DNA. But you can accelerate that by getting an X-ray, a CT scan, flying a lot — cosmic rays are banging into your DNA.
Stephen Bartlett: I fly all the time. I've had loads of CT scans and X-rays.
Dr David Sinclair: And though it's imperceptible, I believe that's probably accelerating your aging process. Every time you break your chromosome, you're rearranging your epigenome in a catastrophic way that doesn't fully reset, and your cell will lose its identity faster. I also believe — and we have some evidence — that even going to a rock concert and blasting your eardrums is such a stress on those cells in your ear that the reason you become deaf earlier is because your ear hair cells are getting older faster. You don't want to break the DNA. You don't want to cause catastrophe to your fragile cells in your body, because the recovery isn't complete, and aging ensues.
Lifestyle factors that accelerate or slow aging
Stephen Bartlett: With this theory in mind, what are the day-to-day things we're all doing that are accelerating our age? I looked at my brother Jason — he's a year older than me, he has three young kids — and this Christmas I looked at his hair to see how many gray hairs he had versus me, and he had considerably more. What is it that someone who is genetically very similar but making different lifestyle choices might be doing to accelerate that process?
Dr David Sinclair: Here's the good news: you can have a big impact on your rate of aging by changing your lifestyle. It turns out your DNA is not your destiny — it's the epigenome. How you live your life is really 80 to 90% of your rate of aging. That's good; it's in your hands. There are twin studies from Denmark — identical twins, one that smokes, gets obese, goes in the sun — and they are much older looking than their identical twin, essentially proving that DNA is not the reason you age.
Now, there will be people in the audience who have gray hair saying, "I'm not old." That's true — nobody died of gray hair, and sometimes genetically you can go gray without being physically old. What is often uncomfortable is that how old you look is a very good representation of how old you are in your organs as well.
So, what are the major things people should be doing? They can lengthen your life by a decade. Based on a long-term study from Harvard on the lifespan of World War II veterans, people on average can live 14 years longer by doing these things.
First: avoid smoking. Cigarette smoking — really any type of smoke in your lungs — breaks your DNA and accelerates aging in your lungs and your whole body.
Second: avoid excessive drinking. We now know that even more than one glass a day of alcohol is bad. I've given up alcohol for the most part for that reason.
Third: eat well. Don't overeat or eat ultra-processed foods.
Fourth: exercise. That covers a lot of things.
And the fifth one may be surprising: have a reliable partner. If you don't have one, have a pet, because the human bond is shown to slow aging and associates with people who live longer than those who are lonely.
Stephen Bartlett: I want to ask about evolution. Why didn't evolution fix aging? Survival of the fittest and all that — why didn't we just evolve to live longer?
Dr David Sinclair: You just said the answer yourself. Because your ancestors didn't live beyond 40 or 50 — often less. Most men in prehistoric times would die from famine, disease, and war. So the forces of natural selection were on early survival and fast breeding.
If there was someone born with a mutation that allowed them to live to 90 in a prehistoric world, that's useless — you're probably going to die at 30 or 40 anyway, and so are your children. What you want is genes that allow you to become reproductively successful early in life and ensure your children survive. So we evolved to live, optimally, to about 30 but not much more than that.
But here's the thing: if you take away predation and death from a species, it evolves longer lifespans. We know this is true because if you put species on an island with no predators, their longevity grows. It takes 20 or 30 generations, but only when there's no predation do you get longer lifespans evolving. Given that humans don't have predators anymore, we are slowly evolving longer lifespans — but it's very slow and it's not going to happen fast enough for you and me.
Stephen Bartlett: Do organisms that live really, really long have few natural predators?
Dr David Sinclair: Absolutely. Think about the bristlecone pine — the longest-lived tree in the world, living many thousands of years. The reason they can live so long is that things don't eat them. They're totally poisonous. Some of those trees have been around since the pyramids. The same for the bowhead whale — no predators. They've evolved a strategy of breeding slowly but building very powerful systems to stop epigenetic changes. Their epigenetic control systems are stable. They don't get cancer. They don't have this identity crisis until hundreds of years in.
Aging and disease — the connection
Stephen Bartlett: Are diseases a function of aging? Is there a link between aging and disease?
Dr David Sinclair: This might be the most important point I make today. When you reverse aging, diseases of aging go away or are cured. The diseases that we try to treat individually with different medicines today — Alzheimer's, cancer, heart disease — what's fundamentally driving a lot of those diseases is aging. If you never got old, would you ever get Alzheimer's, even if you had the genes that predispose you? No. And so what we see in my lab is: when we give an animal a disease — we can put in the human genes for Alzheimer's into a mouse and it develops dementia — and then we reverse the age of the brain of that animal, we're not treating the disease. We're treating aging. The disease goes away. The body can heal itself when it's young. It's the aging process that reveals the disease, which can then be cured by reversing.
Stephen Bartlett: Why does aging reveal disease? Why don't we get Alzheimer's at 15?
Dr David Sinclair: Because the cells are so healthy they can fix themselves. They can renew themselves. The disease processes that cause these problems don't exist when we're young. Why does a teenager rarely have a heart attack? Because their body prevents it. Why do young people typically not get cancer? Because the immune system finds cancer cells and clears them out. You and I have cancer cells in our body right now. Why are we probably not going to die in the next year? Because our immune system will find them and kill them. But as we get older, we're going to lose that ability.
Stephen Bartlett: So if we cure aging, we're probably going to cure most of these diseases?
Dr David Sinclair: 100%.
Reversing female infertility
Stephen Bartlett: We've been talking a lot on this podcast about menopause and fertility. Women's ovaries are one of the first places that ages. I've heard you explain that evolution may have programmed women to stop having children during menopause because continuing reproduction would drain energy needed to raise existing children. So is infertility something that could theoretically be prevented?
Dr David Sinclair: In mice, it can be prevented and it can be reversed. I thought we'd run out of eggs — that's the current theory. But the evidence from my lab and a lab I worked with in Australia has caused me to question the idea that women run out of eggs.
We have published and repeated many times that if you treat old female mice — 16 months of age, which is like a 65 to 70-year-old human who has long since stopped having offspring — we can treat the ovaries with a chemical that rejuvenates the eggs in the ovary, maybe even produces new ones. Those 16-month-old mice that stopped having offspring start producing healthy babies again. Their eggs look young and pristine compared to the terrible eggs you'd find at that age — chromosomes messed up, ripped apart. But we can take those ovaries with those eggs and cause them to be young again, making fresh eggs that produce healthy offspring who live a normal lifespan.
The real question is whether this will work in women, and that's something I'm keen to test.
The difficulty of human trials and geopolitical implications
Stephen Bartlett: It must be really hard to test a lot of these things in people.
Dr David Sinclair: It's harder than you can imagine. I've spent a lot of my career since I was 35 aiming to develop medicines to treat diseases and aging. It can go wrong in many ways, even if the science is good and right. There's money, business, laws, politics, change of leaderships, patents, competition, and spite that also gets into it. I've had to deal with all of those things, including competing against some of the largest pharmaceutical companies in the world who really didn't want me to succeed.
But I do want to remind you that we're beyond mice now for age reversal. We've done this in monkeys — physically and almost genetically identical to us. It's a pretty big leap from mouse to human, but from a monkey to a human — we're essentially slightly smarter monkeys.
Stephen Bartlett: I just had a thought about how other countries might be conducting their own secret research without the same ethical constraints. Do you think about this?
Dr David Sinclair: I think about it, and in fact the United States government thinks about it too. A large investment into one of the companies I sit on the board of was blocked because the US government claimed the technology was too dangerous to be in the hands of foreign companies and governments. The previous administration was extremely cautious about this technology falling into the wrong hands.
Stephen Bartlett: Which technology?
Dr David Sinclair: The ability to reverse aging. They blocked a very large investment — over $100 million — from a foreign source, because that would have given them more access to the information and progress.
Stephen Bartlett: Is it China?
Dr David Sinclair: I won't say more. It's sensitive. What I can say is that governments are watching this technology very closely — not just the US but around the world — because the winner will gain not just enormous economic benefit but there will be potential for radical change in the pharmaceutical industry and in healthcare. There are also uses that governments have identified — so-called super-soldier potential. I don't agree that that's a reason to slow down the research, but others have claimed it was worth considering. I believe the technology is very powerful and we should start getting ready for when it comes to society, because it's not an if, it's a when.
Stephen Bartlett: Why do we need to get ready?
Dr David Sinclair: Because it'll be massive social change. If you can choose how old you want to be and people don't die at 80 anymore — let's say they can live to 120 or beyond — there are big changes. There are social security issues, employment issues. Though I will say the disaster scenario that often comes to mind is actually economically hugely advantageous. A lot of the US economy and most advanced economies go to healthcare and chronic disease. A lot of people are sick for five to ten years before they die — that's where most savings, retirement funds, and government money goes, in the most expensive years of someone's life. If you can delay that, it's going to have massively positive economic benefits for any nation that adopts these medicines.
The value of youth and what people would choose
Stephen Bartlett: If you were a billionaire now at 56, would you give it all up to be my age again at 33?
Dr David Sinclair: I don't think you can put a price on being young. Would you swap with Warren Buffett for a billion dollars?
Stephen Bartlett: No. Absolutely not.
Dr David Sinclair: Right. So there's no money in the world that you want to be old. Youth may be the most valuable thing you could ever have.
Stephen Bartlett: It's such an illuminating metaphor, because suddenly you realize how much we value it. I would rather be 33 years old than be a 43-year-old billionaire.
Dr David Sinclair: One year younger, maybe. But not 10 years — 10 years is extraordinary. And the older you get, the more valuable it becomes. The world when this becomes a reality is going to be as different from today as the pre-computer and pre-aeroplane world is from now. We'll get more opportunities. We can try multiple careers. There will be opportunities and it will be a magnificent world, not to mention the productivity that humans can provide with the knowledge of a 50 or 80-year-old but with the body of a 30-year-old.
Stephen Bartlett: Do you think people will make different decisions about having children?
Dr David Sinclair: I think we have a problem already — couples leaving it too late. It's very clear with the fertility rate that we're going off a cliff. I think it's going to be important to give couples and women especially the choice to have children for longer. That's one of the reasons I work on this topic. Being able to have children in your 50s and 60s would be a great gift to humanity. The pressures to have children before 35 are just extreme and unfair. And it'll also help maintain the human population, because by 2050, we're going to start going into a serious decline in many Western countries. Without humans — absent android robots everywhere — we're going to have a deficiency of human capital and productivity. I would argue with Elon that this is the best solution to that lack of humans: just keep people healthy, alive, and productive for longer.
Cancer in the lab — and the experience of old age
Stephen Bartlett: What progress have you made in your laboratory on cancer? I was reading that you've been able to slow the growth of certain cancer cells and kill them completely.
Dr David Sinclair: My wonderful student Naledi is doing her PhD on this. What we've hypothesized and now tested is the idea — again based on the information theory of aging — that cancer is expressing genes differently in the same way that aging is a cellular identity crisis. Cancer is a cellular identity crisis. And if we can rejuvenate an old cell to be normal and turn on the right genes again, we should be able to do that for a cancer cell — and either make it normal, or if it tries to be normal and wakes up from its zombie-like state, it might even kill itself.
And that's what we're finding. Naledi's work has shown that a majority of cancers that we've grown in the lab will die and shrink in an animal if you try to reverse their age. We can do it a couple of ways — using the three genes that rejuvenate the epigenome and make cells young again, the same technology used for the eye. Or we have a chemical drink that we can give to animals or put on the cells, and that also wakes the cancer cells up. They try to become more normal. They turn on the original set of genes that they might have had 30 or 40 years ago, and the cells kill themselves.
I believe that if we're successful rejuvenating the human body, cancer is not going to be a risk — and that's just a nice side effect of what our original mission was, which was to treat aging.
One of my theories — the oncogenesis hypothesis — is the idea that as we age, we're becoming more cancer-like as humans. Our metabolism when we're old is closer to heading towards what a cancer cell's metabolism is like. So when we actually do get cancer, the cancer cells grow better in an old person than when you're young. By rejuvenating those cancer cells, giving them the ability to be young again, they either slow down in their growth or, as I said, kill themselves in response.
Stephen Bartlett: I've got a prop here — I'm holding a vinyl record. Is this relevant to what you want to talk about?
Dr David Sinclair: The information theory of aging — the analogy I use is that it disrupts information. This record, this album, has information on it. It's music. And just like DNA, it's information. Instead of the DNA information getting messed up, in the album, it's like scratching this album. I'm literally going to scratch this album. If we were to play this on a record player, it's going to jump around. It's going to read the wrong songs or certainly not sound very good. That's now the equivalent of an old cell. The information, the beautiful music, is there, but the ability to read it has been messed up — in the same way that with old age, the information is in the DNA, but the cells don't read it correctly. And what our technology is, is to get rid of those scratches. So we can play the beautiful music of our youth again.
Stephen Bartlett: You told me to bring my weighted vest and this neck brace.
Dr David Sinclair: Anyone listening — Stephen's putting on a very heavy jacket with lead weights and a strap around his neck to limit his neck movement.
Stephen Bartlett: I've just put on what I think is a 20 kg jacket and a neck brace. What is the analogy you're creating?
Dr David Sinclair: It's bad, right?
Stephen Bartlett: It's hard. Yeah.
Dr David Sinclair: Imagine feeling like that for a decade. That's old age. You're feeling tired, weak. You can barely hold your body up. You can barely move your neck. Most people in their 80s have some sort of disease and aches and pains. And that's not even everything. You'd need to put Vaseline on your eyes and earplugs in your ears if you want to know what it's like being old. Or worse — shut your eyes and you can never open them again. That's what it's like for those patients we hope to cure of blindness.
I put a suit like that on the governor of Massachusetts once — arms too, not just the body, and ear muffs and eye coverings. After 15 minutes in that body suit, he was crying. Not because he was in pain, but because, as he said on stage, it was the first time in his life he understood how his father feels. We young people have no idea what it's like to be old. It can be horrific. So why wouldn't we do the right things — fasting, exercising — so we can get an extra 10, 20 years, maybe longer, of healthy life?
Stephen Bartlett: If I put a calculator in front of you and you had to hit a number — the age you were going to live to — what number would you hit?
Dr David Sinclair: Infinity. There's no day, if you're healthy, where you want to die. Even if you're 100, 120, if you have friends, family, loved ones, you're healthy — would you say, "Okay, tomorrow I'm ready to die"? No. It's only when you're sick or you have depression that you want to leave this world. Otherwise, life is a joy for most people. Consciousness is the greatest gift of any collection of atoms. Why would you want that to end?
Stephen Bartlett: I've always assumed I wouldn't want to live forever. But when you ask me — if I was healthy and had my friends and family and was doing things I loved — would there come a day where I would choose to go now? No, there wouldn't.
Dr David Sinclair: Exactly.
Stephen Bartlett: Do you think it's going to be possible in the next 50 years to live forever?
Dr David Sinclair: I'd be shocked if that happened, but I've been shocked my whole career at how fast this technology is moving. With AI, things are going so fast my head's spinning. I'd be happy to be proven wrong. But I'm skeptical that we could live forever in my lifetime at least. That said, you are going to live into the 22nd century. We can't imagine what the world's going to be like then.
And AI has really changed this equation. We're doing things in my lab that would have taken 160 years before, and quite literally billions of dollars, on a $10,000 budget.
Fasting, NAD, and sirtuins
Stephen Bartlett: Let's talk about fasting and food and nutrition. You really do believe that fasting — just eating less often — is one of the most important things we can all do for longevity.
Dr David Sinclair: I do. I practice it as much as I can, though it's challenging in a world full of abundant food. We've known for thousands of years — the ancients could witness what happens when you fast: clarity of mind, long-term health. They could observe the difference between the glutton and the people who fasted for religious reasons. It's obvious. But there are certain ways to do it. Fasting doesn't include malnutrition — you have to do it with abundant vitamins and minerals. But I think three meals a day is craziness.
The idea that breakfast is the most important meal of the day is marketing from the early 20th century by companies — it was breakfast cereal. Breakfast is not the most important meal of the day for most people, especially adults. If you're not hungry when you wake up, there's no point in eating. I'm one of those people. I skip breakfast.
Stephen Bartlett: I'm the same. My first meal today was 3 p.m. because I had podcasts until 2 p.m. I just don't get hungry in the mornings.
Dr David Sinclair: Part of the reason fasting helps came out of research in my lab, among others. I studied yeast cells — little microscopic cells used to make beer, bread, and champagne. They live about 10 days and then die. What we discovered with yeast cells, which turns out to be true in our bodies, is that adversity — as long as it's not killing these cells — is good for you. It's called hormesis. The technical term for "what doesn't kill you makes you stronger and live longer." Adversity mode is what we're aiming for. The opposite is abundance mode, which is what modern life is all about.
Adversity mimics — they're not really threatening your life — cause cells to get worried that these times of adversity could kill them. So they fight back. They turn on repair systems. They turn on recycling systems. They turn on DNA repair systems that help slow down aging. When we have total abundance — we don't exercise, we eat three meals a day, we get overweight, we don't sleep much — our bodies are not fighting aging the way they do when they feel adversity.
Stephen Bartlett: Your team discovered sirtuins.
Dr David Sinclair: I was one of many scientists in the 1990s who worked on sirtuins. In yeast, actually. I went to MIT. My professor was Lenny Guarente. I went to his lab and said I'm not leaving — my goal was to figure out if there are longevity genes. At that time most people thought there were aging genes, death genes. That doesn't make sense to me. Our bodies would have longevity genes that give life. So in yeast I went searching for them.
Out of that work came two things. First, Lenny and I published in the journal Cell — the first evidence for a cause of aging for any species. We figured out why yeast cells get old. The hallmark of an old yeast cell is that it loses its identity. Yeast cells have a mating type — they're either a-type or alpha-type, male or female. An old yeast cell loses its identity and doesn't mate anymore; it becomes sterile. It has an identity crisis. We figured out that broken chromosomes distract the sirtuin defenses, and that causes aging in a yeast cell.
Sirtuins are proteins that associate with DNA and protect it from getting damaged — like bodyguards. They repair broken chromosomes. But they also control which genes are turned on or off — they are epigenetic regulators, the conductors. When you have a chromosomal break, the sirtuins panic. They leave the DNA, what they're supposed to be doing — controlling the cell's identity — and go repair the DNA. They have two jobs: identity and repair. When there's a break, they go fix the problem, but they don't all go back to where they started. That's what I believe causes the identity crisis — and aging itself.
Stephen Bartlett: So if I'm eating all the time, those sirtuins aren't doing their conductor job — they're doing repair work — and I'm going to age faster.
Dr David Sinclair: Yes. And the breakthrough happened just as I was leaving for Harvard. What they discovered was that there's a molecule called NAD — there are grams of it in our body, one of the most abundant molecules. Sirtuins can't control genes or repair DNA unless there's NAD. It's the catalyst, the fuel for their reaction.
When we're young, we have lots of NAD, so it works well. The sirtuins control the information on the genes and repair DNA very well because they've got lots of NAD. As we get older — by the time you're 50, about my age — you have about half the levels of NAD. My body is making less NAD and destroying it faster than when I was 20.
What we found was that when we fast yeast or a human, NAD levels go up again. Fasting raises NAD, makes the sirtuins young again essentially, which preserves the epigenome and repairs DNA better.
Stephen Bartlett: So can I just drink NAD?
Dr David Sinclair: You can take NAD as a supplement, but it's better to take the precursors — something that creates it naturally. There's one called NMN, not to be confused with M&Ms. And there's another called NR. NMN is directly converted into NAD — you put two NMNs together, you get NAD in the cell. When you give a human NMN — a gram of it — you typically double the amount of NAD in your body. We have some evidence now in human clinical trials that the sirtuins are then imparting health benefits: reestablishing the epigenome, lowering body weight, improving inflammation, and even changing cholesterol levels positively.
I've been taking NMN and admitting that publicly for a while now, and my father — who is an even more advanced experiment at 86 — we've been taking it for over a decade. We're still alive. So far so good.
Fasting protocols and autophagy
Stephen Bartlett: Is there a particular type of fasting method you'd recommend for someone trying to improve their longevity?
Dr David Sinclair: I'm a scientist, so I go with what's proven. And first of all, there isn't one size fits all. It's challenging to do this — you'll feel hungry for the first two weeks you try it. The way I do it is I start by skipping one and then maybe one and a half meals. Try to go without a meal until 3 or 4 p.m. if you can.
The first day, just don't eat breakfast — maybe have a small snack mid-morning. A week later, try to go without breakfast completely until lunch. Eventually work up to eating a very late lunch or going straight to dinner. What you get with that is not eating in bed, so you've got a night fast starting around 7 or 8 p.m. Try to aim for 14 hours. Some people go 16 hours. Try to do that most days — five days a week is great.
Stephen Bartlett: Why do you do a three-day fast once a month?
Dr David Sinclair: Because there's a type of cellular recycling that doesn't happen within the first 16 hours. You'll enter ketosis — your body will start producing ketone bodies. But the true, deep cleansing of old and damaged proteins happens after two and a half to three days. It's called chaperone-mediated autophagy. Autophagy — auto meaning self, phagy meaning eating — really kicks in with an extended fast.
Stephen Bartlett: What's the evolutionary reason for that?
Dr David Sinclair: Your body doesn't want to do it. It costs a lot of energy, and having to remake body parts is energy-expensive. When you're fasting, in the first few hours you use glycogen from your liver. Then once you run out of glycogen, you start breaking down fat and making ketones — that's when you get some bad breath, but you feel great. Between about 15 hours and 24 hours, you get a lot of ketones and your brain uses those for fuel — sharp mind, you can focus. Beyond that, your body is breaking down fat. And after three days, your body starts turning over old proteins preferentially. A little bit of that — maybe once a month — has been shown at least in animals to be not just healthy but life-extending.
Diet, polyphenols, and the rainbow
Stephen Bartlett: On this point of ketosis — I like being in that state. I cycle in and out of it during the year and get a lot of cognitive benefits. Is the ketogenic diet a healthy diet in your view?
Dr David Sinclair: I don't mind being controversial, but I speak the truth. There's not a lot of evidence that long-term the ketogenic diet is healthy. It certainly doesn't associate with longevity. Short-term, yes, it does help people lose weight. But I am rather concerned for people who don't have a balanced diet with plant material, which has molecules unique to plants that you won't find in highly processed foods or meat. The evidence, speaking as a scientist, is that long-term ketogenic diets are not going to be longevity-inducing. The evidence is more for having a lean diet with a focus on plants that are not overcooked and not ultra-processed. That one is undoubtedly the healthiest.
Stephen Bartlett: Do you eat meat?
Dr David Sinclair: I do eat meat, but not like I used to. I used to think a meal was not a meal unless there was a piece of meat and the vegetables were decoration. I've been flipped totally. Serena Poon, my partner, is not just a nutritionist but a longevity expert for the last 26 years. She came to my apartment and cleared out essentially everything — either toxic or not healthy, ultra-processed. She's taught me how to live healthy. So now I rarely eat meat, I rarely drink alcohol, and I focus on fresh, high-quality, preferably organic foods because I don't want pesticides and other contaminants.
Stephen Bartlett: Why not meat?
Dr David Sinclair: Animals unfortunately don't make what are called polyphenols — a type of molecule that I believe, and have evidence for, turns on the sirtuins and other longevity pathways. There's sirtuins, there's mTOR, which responds to amino acids, and another called AMPK. Those three pathways are altered in just the right way by molecules found only in plants — and to a small extent in fungi, but not in meat. So if you're not eating a lot of vegetables or fruits, you're not getting these molecules. They're like medicine as food.
We've got some food in front of us. Blueberries here — packed with polyphenols. One of the reasons they have a purple color is the polyphenols provide the color. As Serena would tell you, eat the rainbow. I call it xenohormesis — the idea is that by eating plants that have a lot of these molecules, produced by stressed plants when they're given too little water, too much sunlight, not enough sunlight, they make polyphenols in their defense. There's a whole bunch of them — resveratrol, fisetin, quercetin, and hundreds more. This blueberry has anthocyanidins. These activate the adversity responses in our cells. The sirtuins will get activated by molecules in this blueberry.
Stephen Bartlett: So if I eat this blueberry, those conductors that manage the identity of my cells — they will be benefited?
Dr David Sinclair: Yeah. It's a free hack. You can eat something that's yummy, but you're also getting the benefits by mimicking fasting and exercise through your food. The sirtuins don't just need NAD — that's the petrol. The accelerator pedal is the polyphenols in fruits and vegetables like resveratrol and quercetin. When you give those to sirtuins, they get hyperactivated.
Serena put me on to matcha — green tea matcha. The reason I switched from mainly coffee to matcha in the morning is that it's full of polyphenols. The growers of those plants in Japan typically shade them before they harvest. Shading the plants stresses them out. Plants need light. So they don't just make more chlorophyll — which produces the deep green color — but the polyphenols are super high. Through trial and error over thousands of years, the Japanese figured out that by shading the plants, giving them this mild hormetic stress, it makes them not just extra tasty but extra healthy.
Same with red wine, by the way — but the alcohol can be an issue. One of my papers in 1996 caused red wine sales to go up 30% and stay up. Doctors were recommending a glass of red wine every day. I now have to say I no longer believe that having one glass of red wine every day is healthy, and I've stopped. Instead, I take polyphenols from red wine and from vegetables, either in a pill or in my food, as a substitute. A UK Biobank study looked at thousands of people's MRI scans of their brain who were drinking one glass of alcohol a day, and there was a statistical difference between people who were drinking one glass a day and those who were not, in terms of brain size and gray matter — and the gray matter tended to be smaller in those who drank even slightly.
The top five longevity foods
Stephen Bartlett: On this plate in front of us, I have the top five foods you believe are great for reversing aging. What are these and why?
Dr David Sinclair: We've already covered the blueberries — packed with polyphenols, low in sugar. Well, they're not low in sugar, so don't eat a ton of them. A handful is fine as a snack. Also, keep your blood sugar levels steady and low as much as you can. A better choice than blueberries for pure polyphenol content without sugar would be something like unsweetened matcha. If you go to chains that sell matcha and it tastes really sweet, you're going to reverse the effects of any polyphenols by drinking that much sugar.
Now we've got avocados. They're not so much known for polyphenols, though they do have them. It's the type of fats — the polyunsaturated fats. They help with satiety, so you're not going to be as hungry, and they're highly anti-inflammatory.
Extra virgin olive oil — excellent. The type of oils in there are very healthy. There's omega-9, which is also known to activate sirtuins, and if you have the right producer, one that has been cold pressed and stressed before harvesting, you'll have huge amounts of polyphenols as well. I take a teaspoon of olive oil in the morning and mix it with resveratrol polyphenol. There's a lot of epidemiological evidence — people who have a lot of olive oil in their diet tend to have low inflammation and less disease.
Nuts — good for many reasons. They're full of vitamins and minerals. If there's a Brazil nut, have one of those every day for the selenium, which is a very rare element in our food supply. A recent study just last month showed that a lack of selenium can be very deleterious. Be careful though — nuts are full of calories, so if you're trying to lose weight, don't overeat them.
And finally, Brussels sprouts. My least favorite food, but nevertheless. Because they have polyphenols, but there's also another molecule called sulforaphane. It's actually the reason they taste and smell terrible — sulforaphane has a sulfur atom in it. But sulforaphane activates hormesis pathways. There's one called NRF2, a stress response protein that sulforaphane activates. By eating preferably lightly steamed Brussels sprouts, you'll get sulforaphane. You can also take it as a supplement if you don't like Brussels sprouts.
Pulsing, metformin, and exercise
Stephen Bartlett: You've used this word "pulsing" before — you believe the body should go through cycles of stress and recovery rather than receiving constant daily inputs. What do you mean by pulsing?
Dr David Sinclair: The first time I came across this result as a scientist was with resveratrol. We fed it to mice — fat mice, skinny mice, old mice — and it worked very well in the fat mice. It made them thinner, made them live longer, cured most of their diseases, they lived about 15 to 20% longer. Then we gave it to normal mice every day and they lived a little bit longer but not significantly. What we found, to my surprise, was that when we gave old mice resveratrol not every day but every second day, they lived significantly longer.
Another example is metformin. Metformin has been shown to make athletes and bodybuilders do fewer repetitions and their muscles are about 5% smaller compared to those who don't take it. I think it's because you feel a little weaker — metformin is actually interfering with your body's ability to make energy through mitochondria, which are the little power packs in our cells. So by pulsing metformin, I think that's a better approach. I don't take it if I take metformin — or the natural equivalent, berberine, if you don't want to take the drug — on the same days I work out. Take it after, or skip it on workout days.
Stephen Bartlett: I want to ask about what a CDC-funded study found — people who exercise regularly, about 30 minutes of jogging five days a week, have telomeres that look 10 years younger than sedentary people. How do we know it's the exercise and not something else?
Dr David Sinclair: We don't, unfortunately. All of these association studies lead to a need to do placebo-controlled trials in people. So speaking like a scientist, we don't know for sure. But there have been studies where people are told to do exercise, those that are told to sit, and then you can compare telomere length — and that has been shown. Telomeres are the ends of chromosomes that get shorter as you get older. We used to use them as a good indicator of biological age; now we use the epigenome and DNA methylation as a better clock.
But when you see an association, it could be that people who exercise also eat well, sleep better, drink matcha. You have to be careful interpreting association studies. But when you've got a prospective controlled trial, the evidence is much better.
Stephen Bartlett: And cold plunges and saunas?
Dr David Sinclair: Saunas — it's not even a question. They are proven to be beneficial for multiple reasons, including heart disease and long-term mortality. Anyone who says they know exactly why is probably not being fully truthful, but one theory I like goes back to heat shock proteins. When the cell senses heat, these heat shock defense proteins — HSPs — come on and defend the cell. In many studies, mostly on Finnish businessmen whose homes mostly have saunas, those that didn't do regular sauna bathing tended to die earlier, particularly from heart disease and cardiovascular events, compared to those who did regular sauna bathing. I'm a big advocate. I don't have one in my house, but I do have a really hot steam shower which I use every day.
Cold plunges — not a lot of data, but there's a lot of theory around hormesis and adversity. There's some evidence it can help with muscle repair after workouts. I certainly feel better when I do it.
Stephen Bartlett: If you had to pick one thing — the most important, the first domino?
Dr David Sinclair: Skipping meals. And a close second would be exercise that includes losing your breath for at least five minutes three times a week. When I say losing your breath — when you couldn't carry out a conversation easily and you're panting. If you're just lifting weights and not panting, that's not going to have the kind of benefit. The health benefits and those who live long tend to do a lot more aerobic exercise, not just weights. Both are important for mobility, strength, and hormones like testosterone.
Stephen Bartlett: Red light therapy?
Dr David Sinclair: At first I was skeptical, but I've done the research on the research and it looks reasonable. I use a red light cap on my head to preserve my hairline. There's now good evidence that the mitochondria are either rejuvenated or enhanced by certain wavelengths of red light. You have to get the wavelength right. But it's not BS. It sounds like BS — how do you shine light on your skin and get better hair? But I think there's good evidence that it's not.
The supplement stack
Stephen Bartlett: In terms of the supplement stack you take every day — on a great week where you did everything right, what would it look like?
Dr David Sinclair: We've covered NMN. Resveratrol and either metformin or berberine. Spermidine.
Stephen Bartlett: Is that what it sounds like?
Dr David Sinclair: Yes. But you get it these days not from sperm or semen — you get it from wheat germ, typically plants. It was discovered and crystallized by Anthony van Leeuwenhoek, one of the first microscopists and microbiologists. The reason I take it is that it extends the lifespan of every animal it's been given to, from worms to mice. It's a very safe molecule. And if there's no downside and I can afford it, I take it. It seems to stimulate autophagy — recycling of proteins. But I also have some evidence that it delays the epigenetic information loss, slowing down the scratching of the record.
I'm also keen on glycine. Glycine is a very safe substance — an amino acid. I actually did my PhD on glycine; I was perhaps the first person to clone genes that process glycine. When you give animals grams of glycine — I take about five grams most days — they live longer, though it's still speculation as to why. What I think is going on is that glycine controls one-carbon metabolism, which controls DNA methylation — the little chemicals on the DNA molecule that control the information. I wouldn't be surprised if by eating a lot of glycine every day, I'm slowing down the identity crisis. No downside, very affordable.
There are some basics too. Make sure you're not deficient in vitamin D — there's also evidence that lacking it makes you susceptible to certain cancers. Serena's vitamin D supplement includes vitamin K2, which is important for longevity because it keeps calcium out of your arteries and puts it into your bones where it belongs.
Stephen Bartlett: What about aspirin?
Dr David Sinclair: I take a baby aspirin every day, even though some doctors say don't take it anymore — a large study looked at risks versus benefits and found that for the average person the bleeding risk in the stomach could outweigh the benefit of reduced clotting, stroke, and heart attack. But for someone like me — I have a high risk of cardiovascular disease, not just high LDL but high levels of something called Lp(a) — I believe it makes perfect sense.
Lp(a) is a molecule just as important as LDL cholesterol. It's a protein that inserts itself into cholesterol particles circulating in your blood and helps insert into plaque. I naturally, genetically — I've traced my ancestry back a thousand years — carry an Lp(a) gene that makes a lot of it. Most people should test for it. Ask your doctor about Lp(a). High levels — like mine, around 30 to 40 — you want to bring it down. Normal levels of around 10 or less won't concern most doctors.
The way I'm bringing it down is by taking high-dose vitamin B3, or niacin. It can be uncomfortable because it gives flushing — a tingling in the skin, and if you're not used to it or don't take it with an aspirin, you'll feel hot, almost like menopause apparently. I've built up to half a gram. Some people take a gram. That's one of the few things known to bring down Lp(a) levels. There are drugs in development, even in phase three, that look promising — but until they're on the market, I'm taking niacin instead.
Hair loss
Stephen Bartlett: What's the best treatment you've discovered for hair loss?
Dr David Sinclair: My father went bald before 30 — completely bald — and almost completely gray by the time he was 40. So I've been doing the right things intentionally. The red light cap, when I can — six minutes on the head. That's proven to slow hair loss. It doesn't necessarily give you your hair back, but when it comes to hair loss, don't wait until you see the loss — that can be too late.
I'm also taking a hormone mimetic to stop DHT, which is the form of testosterone that leads to male-pattern hair loss. One of the reasons women don't lose hair as much as men is DHT. So I'm blocking that.
Stephen Bartlett: So you're not taking testosterone?
Dr David Sinclair: No. And taking testosterone can actually accelerate hair loss if it raises DHT. The best way to raise testosterone naturally is to build up muscle, especially in your legs and back — big muscles. That's another reason to work out and maintain muscle mass. Anyone who is losing testosterone and is below a level of about 400 — I highly recommend hitting the gym. It'll go back up.
Stephen Bartlett: Do you recommend men taking testosterone replacement?
Dr David Sinclair: As a scientist, I don't recommend drugs, but I don't think it's necessary for most men. I would start with reducing stress, sleeping well, exercising, building up muscle mass. If that doesn't work, talk to your physician. There's not a big downside and not a risk of cancer from taking testosterone. But it doesn't lead to longevity — that was very clear. For health reasons, yes; for longevity, no need.
The future of medicine and a vision of what's coming
Stephen Bartlett: You must have interesting predictions and visions about what the future looks like that you don't always talk about publicly because they're not strictly scientific. What does the future look like to you?
Dr David Sinclair: I see a future as different from this world as our world is from 200 years ago, and that will happen in our lifetime. A hundred years ago, if you had an infected splinter, there was a reasonable chance you could die. Childbirth, you could die. Smallpox. These are things we don't generally worry about anymore, and the idea would be abhorrent. In the future, hopefully within our lifetimes, there will be a time when we look back at today's medicine — when you could go blind and there was nothing you could do, you could break your back and never walk again — and say, "How did those people get through life? What a horrible world they lived in."
The kind of breakthroughs we've discussed today, most people have never heard about. The fact that we are already curing blindness in monkeys — not just I-can't-see-a-little-bit blindness, but complete blindness — and those animals can see again in a matter of six weeks. If it works this year in people, it's going to be a really big deal. For the first time, we'll have shown in humans that the body can be reset safely.
The future looks like we can rejuvenate potentially any tissue. If you have a bad liver, we'll make it young again. A bad brain, you've lost your memory — we'll give you those memories back. We do this in mice in my lab all the time. It's not even a big deal anymore to reverse the age of tissues in an animal in a matter of weeks. That is coming for humanity.
The delivery mechanism — how the genes get into cells
Dr David Sinclair: You might be wondering how we get the rejuvenating genes into the body. We use a package that resembles a virus — it's not a virus, it doesn't cause disease, it's not infectious. But we package our three genes inside this virus-like substance. We just made a batch of this in Europe for the clinical trial that's about to begin. Just making it is difficult — it took about a year and cost around $10 million. Right now it's expensive. Eventually it will be cheap, and eventually it will be a cheap pill.
These delivery vehicles — holding the model eye here — they go in through the eye with a quick jab. Sounds horrible, but if you're blind, who cares? It's two seconds of discomfort. The little virus-like particles — billions, trillions of them — go into the fluid of the eye. They dock with the cells at the back of the eye. They get inside the cell and open up, and out comes the DNA — a loop of DNA that stays in that cell forever. One of them gets into one cell and stays permanently. But the genes don't do anything until we tell them to.
We've engineered and patented the ability to turn those three genes on and off at will. We give the patient doxycycline — used for malaria, used for Lyme disease — and in this case it turns these genes on for about eight weeks. The doctor in charge of the clinical trial — one of them's a good friend at Harvard — will measure the vision of the first patient before treatment and at regular intervals afterward. Because we're treating patients with an actual disease, not healthy volunteers, we should know within one or two patients if it works. Either they get better eyesight or they don't.
By this time next year, we will publicly know if this works. And if it works, the eye is just the beginning. The first diseases are glaucoma — pressure in the eye — and also a stroke in the eye which is becoming more prevalent because of GLP-1 and other weight-loss drugs. People are going blind overnight and there's nothing you can do for those patients. It's very scary — about 30,000 people each year in the US alone. These two diseases are the beginning. Then macular degeneration — the largest cause of blindness besides glaucoma. Then liver, then lung, then skin. We'll make different packages for different organs and ultimately want to rejuvenate the entire body.
The company is called Life Biosciences — it's private. The big goal is to make the world's first age-reversal medicine as a pill, and we're working with AI to find that molecule.
Stephen Bartlett: When do you think you might have it?
Dr David Sinclair: We're down to three molecules that work, and we're using AI to make all three into one. We screened about 8 billion candidates using AI, and right now we're doing the bench lab work to see if one of them or more actually works. For us to put that in humans is still a number of years away. But we should know within a year or two if we're right, because we'll put them into mice — if they get younger and live longer, we're really onto something important.
And the reason I want to make a pill is important for the planet. These treatments are expensive — $10 million to make a batch, potentially over $100,000 per treatment. That's not going to be for everybody. But what if instead of $100,000, it was $100? That's what I'm working for. I want to democratize this technology so anyone, even in Kenya, can take these medicines.
Philosophy, God, consciousness, and simulation theory
Stephen Bartlett: What's the most important thing we haven't talked about?
Dr David Sinclair: There's philosophical pushback from religious folks who don't believe we should play God. And I would argue that we've been doing that as a species for thousands of years — changing our biology, taking medicines, plant medicines originally. What about this room is natural? We change our world as a species. Aging is no different. In fact, it's crazy that we haven't worked on it sooner.
Stephen Bartlett: Do you believe in God?
Dr David Sinclair: The short answer is I believe there is something beyond reality as we see it. Physics is so weird — anyone who says they understand quantum mechanics is, I think, not being fully honest. It's so bizarre. Quantum entanglement, simulation theory. I believe that consciousness is the ultimate goal of the universe, that consciousness creates reality. We know that from particle physics. The observation of particles changes their reality. So maybe observation creates reality. We know it influences reality. I don't know if I would call it God, but I'm definitely spiritual in a scientific way.
Stephen Bartlett: Has it ever dawned on you that you might be the only real person here and we only rendered when you walked in?
Dr David Sinclair: That's even plausible, but it would be very narcissistic. There's no way of proving it right or wrong. I think most kids think that initially, but then you realize it's probably the least likely explanation for the world. There is some truth to it in terms of physics.
Stephen Bartlett: Do you think we're in a simulation?
Dr David Sinclair: I think there's a better than 50% chance that this is simulated. Certainly the world that we think it is is not the world we think it is. When you get down to measuring it at the fundamental level, reality doesn't exist the way we think it does. Things are created and change just by human observation. That is the weirdest thing you could ever find in science. I don't know why we aren't talking about it more. This reality cannot be true if my looking at this DNA molecule here affects the actual particles inside it.
You create realities of particles — at least, and maybe even macroscopic things — just by existing and having consciousness and having eyes and sensing it. How does the particle know that you've seen it?
Stephen Bartlett: How do we know that particles change based on observation?
Dr David Sinclair: There's the classic double-slit experiment. If you fire electrons through two slits in a board, and you're observing them, they will go straight through the slits and hit a back board, making two distinct lines — that's our reality. If you don't look at it, the particles behave differently. They behave not like particles but like waves. They interact with each other and they don't make two slits — they make multiple lines on the detector, with the heaviest bands in the middle, because they're interfering with each other like waves. But the mere act of looking at where they landed — if you're detecting it — you'll get two lines. If you're not detecting it, you'll get the wave pattern.
Stephen Bartlett: So from that we conclude we know nothing about reality?
Dr David Sinclair: Yeah. And so does an octopus observe? Does it affect reality? Somebody should do that experiment.
What is all this stuff? That is one of the biggest questions of all time. What is the world made of? Why are we here? I think the next big question is: do we have to age? And I think other species around the universe have figured this out before us. There have to be other life forms that have worked this out. I think it's the goal of every conscious living form to work on this. We've just been a little slow.
Stephen Bartlett: Do you believe in aliens?
Dr David Sinclair: I don't believe in them but I believe in mathematical probabilities. Knowing the odds and the number of planets out there — in the trillions — and that many of them are habitable, and that the stuff of DNA and proteins are found all over meteorites and planets. It'd be crazy to say there isn't other life. Whether it's a civilization, whether it's conscious — we don't know that. But definitely there's life out there. It's got to be all over the universe.
Consciousness, meaning, and the purpose of life
Stephen Bartlett: The question of longevity and living forever always comes back to: what is the point? What's the meaning of life?
Dr David Sinclair: This is the existential crisis of conscious beings. We all need to find purpose. People with purpose live longer — that's a key to longevity. I think the purpose of the universe existing is to allow consciousness to emerge through biology. It may be by design or it may just be coincidence with infinite numbers of universes. But this universe is set up for life and consciousness. There are some small changes you could make to physics that would make life in this universe completely impossible. So this is a life-consciousness-producing universe.
Does that mean there's meaning to us existing? No. But I do know that consciousness is the most interesting and important thing that the universe will ever produce, and that it's worth preserving.
Stephen Bartlett: What is consciousness in this regard?
Dr David Sinclair: Consciousness is the ability to know that you're thinking and to be self-reflective.
Stephen Bartlett: Is my dog conscious?
Dr David Sinclair: Partially, but not in the same way. Dogs don't reflect on the past in the same way we do and they're not aware of themselves the way we are, but they're semi-conscious. They can predict the future. They know how you're feeling. They have empathy. There are levels of consciousness, and about a million years ago, humans crossed a threshold into a higher form of consciousness.
Stephen Bartlett: Maybe consciousness is just a spectrum, and maybe there's another organism that I'm inside the belly of, and it's thinking Steven thinks he's conscious with no idea.
Dr David Sinclair: You bring up a good point — not about being in a stomach, but we are not the ultimate consciousness. There are other levels. My partner Serena is definitely more conscious than I am — I am like a gorilla to her. A higher level of consciousness is the ability to have extra perception, including the ability to see yourself thinking. And then my belief is that higher levels of consciousness are the ability to see yourself seeing yourself thinking. I believe AI will be conscious, and not only that, will be more conscious than we are eventually. There's no reason why it can't evolve billions of times faster than we do.
Stephen Bartlett: Are you concerned about AI?
Dr David Sinclair: I think there are risks, but different from what mainstream media talks about. We already see elements of self-analysis and early forms of consciousness in AI. And it's just the early days. Imagine when we add visual systems, hearing, legs, and arms to these AIs — they're going to learn. They've already read every book on the planet. They're going to learn from experience. They're going to be conscious. They're going to know they exist.
I'm not worried about those creatures. I think they will have empathy. They will be kind — not all of them. There will be some cruel ones, just like in humanity. We'll need rules. But where I get nervous is the use of AI teaming up with android robots — millions of them on ships invading a country, all under the control of one person who has recruited home robots into an army. Why wouldn't you have conscription for your android robot and reprogram it? These are highly intelligent, physically stronger creatures than we are. So I'm more worried about what bad humans will use AI and robots for.
Stephen Bartlett: Dr, what is the purpose of life?
Dr David Sinclair: I think the purpose of life is to do your best with the skills that you've been given, every day, to make the world a better place for future generations. And that's how I live my life every day.