David Sinclair: This is very bad, right?

Stephen: It's hard. Yeah.

David Sinclair: That's what it's like to be old. And for far too long, we've ignored it or accepted it as natural. And I reject the idea that aging just because it's natural is acceptable. Dying at 80 is not inevitable. Absolutely, that can be changed. So, if you're skeptical, I am a Harvard professor who has been studying aging, longevity, and age reversal for 30 years. And I've seen enough from my lab showing that we can literally now reverse the aging process. And it's not a question of if, it's a question of when this is going to happen. And everyone should stick around cuz I'm going to tell you some of the major things that people should be doing. They can lengthen your life by a decade. Hey, you're not taking that off, Stephen. You got 10 minutes for that. So, you can accelerate aging by smoking, getting an X-ray, ultraprocessed foods, excessive drinking, flying a lot.

Stephen: I fly all the time.

David Sinclair: That's probably accelerating your aging process. Even going to a rock concert and blasting your eardrums because your ear hair cells are getting older faster. And so I look at the body like it's a computer and we can reinstall the software. And what's interesting is when you reverse aging, diseases like Alzheimer's, cancer, heart disease go away or are cured because what's driving a lot of those diseases is aging. And so my lab is like Willy Wonka's chocolate factory. They are making discoveries that blow me away every week. And I think we're at a turning point in human history where you're probably going to live into the 22nd century if you do all the right things.

Stephen: And we're going to dig into all of those in great detail. But what are the unintended consequences of such a world where we all live longer? And also, do you think it's going to be possible in the next 50 years for us to live forever? And then, what's the best treatment you've discovered for hair loss?

David Sinclair: This is why I love your podcast, Stephen. You asked the right questions. So, first,

Stephen: Dr. David Sinclair, I have waited many years to speak to you and I've been so keen to speak to you for so many years because so much of the research and the 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 and ideas and hypotheses that you formed. I think the place that this conversation should start is is probably with this picture because it appears to be incredibly formative in your journey.

David Sinclair: Oh yes, that is an important picture. True. This is a picture of my grandmother and me when I was in my early 20s. I'm now 56 if you're wondering. And uh my grandmother has played a major role in my life. Uh, I'm gonna have to be careful not to get too emotional because, uh, she's now passed away, but she's inspired me to do the best I can to leave the world a better place than, uh, I found it.

Stephen: And there's this particular book here called Now We Are Six.

David Sinclair: It is. Anyone who's read my book, uh, 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. And 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 and hearing this poem again because the impact on me was the following that 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 uh 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 realized 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 grow up? Why do we get frail? Because I also think that if we can solve that, understand it, slow it, even reverse it now, we will have the biggest impact on human health in history.

Stephen: 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?

David Sinclair: Yes. Uh she did tell me that. I remember it very clearly actually. 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 will you always be here to protect me? Will you always be around?" And she said, "No, I'm going to die." I'm like, "What do you mean?" She goes, "Every 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, you know, four or five. That that's that's heart-wrenching, right? We've all gone through this realization around that age that the world that 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 I I vowed actually legitimately around the age of 18 to get a PhD to 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 that disease and the other 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, therefore acceptable. And I I 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 were were our medicines and how sad it was that we accepted that we became frail before 100.

Stephen: If someone has just clicked on this conversation now 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 cuz that's just the way that it is. People get old and then die and aging is a fact of life as the phrase goes and you just have to accept it. If that's their sort of core belief, what is the what is the most persuasive sort of topline argument to that person to convince them that in the next two hours when we have this conversation, we will do a job of both reversing that belief or at least challenging it in some way and then also presenting them with a set of possible solutions.

David Sinclair: Yeah. All right. So, first of all, who am I? Um, 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 that is used every day by my students literally reverses the age of tissues in animals 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. And what happens when you do that? What we're finding in animals, that includes primates, is that we can cure things that have previously been impossible, including blindness, by the way. And 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 my 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: So you're doing the first ever trial of this type in humans to reverse aging next month. And what what exactly is happening there? cuz there's many ways one might fix blindness, you know. What is it you're doing to the eyeball that is a precursor of our potential ability to reverse aging generally?

David Sinclair: Yeah. Well, we chose the eye not because it was going to work well, but because it's a 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. Now 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 get healthier and younger but in humans you you don't want to go straight to rejuvenation uh because in case something goes wrong it could set us way back and we have to make sure we don't have any safety mishaps. So we're being a little cautious in humans in mice it's a little different. So, in the human eye... what we're doing, we're going to look at the back of the eye, which is your retina, and that's where the light hits. And 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. So, 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. so the optic nerve gets old and what we've discovered if it gets damaged or gets old, it's not working. But the nerves for most the most part if you're old are still there. They just forget how to work. And that's aging. And later everyone should stick around because I'm going to tell you why it is we get old and how it is we reverse it. But but for this this model, what we're doing is we're introducing a set of three genes into this optic nerve at the back of the eye and turning them on for 6 to 8 weeks. And those three genes are what we now know reset safely, apparently safely, reset 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.

Stephen: And I I heard when we did a bit of a research call, you say, "The world doesn't know how close we are." The world doesn't know how close we are to what? to being able to safely reverse the age of the human body. How can you be so sure?

David Sinclair: I'm not sure. But I'm confident that the science is solid, right? That the the biology of aging is is understood. I believe in concept. My theory called the information theory of aging has so far been not disproven, which is important for a scientist. And that has allowed us to succeed really for the first time to safely reverse aging. And I now believe and though I didn't 10 years ago, I now believe in my lifetime I'm going to see medicines on the market that reset the age or at least reverse in a large part uh the age of the body. And that that initially won't be to make us just 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. So, we're 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.

Stephen: I want to get into your theory of aging, which we talked about there. Um, but you did have a prediction before I get to there about how you think we'll be potentially taking a pill in 10 years time every couple of weeks that will make us younger. Can you explain to me that prediction? What is what is the prediction?

David Sinclair: I I do believe that I and you're about 20 something years younger than me. You're going to see this for sure that there will be a pill. So you might say, "Well, my critics might say, "Well, David, that's exaggerating, right? You're still trying to get this gene these genes to work. How's it going to be a pill? But this is where my lab comes in. My lab is like Willy Wonka's chocolate factory if you visit. It's magical. And the students that I teach and the trainees who are sometimes in their 30s and even 40s who are, you know, brilliant scientists. Uh there's about 25 of us. They are making discoveries that blow me away every week. It's not a pill cuz you can't give a mouse a pill. They won't chew it. But we give them a liquid down their throat. It's a drink. And within four weeks, we can rejuvenate them. Not with this this these genes anymore that we're giving humans. That's the old older technology. The new technology is something you can swallow in a mouse and rejuvenate them in 4 weeks. It's normal for my students to say, "Oh yeah, we just rejuvenated the ear. We just rejuvenated the skin. uh we just cured ALS, motor neuron disease in these animals. By the way, speed and Stephen, this isn't just each disease doesn't get a different medicine. Each disease doesn't get a different set of genes. It's the same set of genes, the same molecules that treat cure multiple scerosis as the same one that cures blindness in mice. So, let that sink in. The same drug that we're using in the eye will be used to treat other diseases in the body, even liver disease.

Stephen: So let's talk about what aging actually is. And can you explain this to me like I'm a total idiot because that will help.

David Sinclair: Well, that's difficult because you're not a total idiot. But this is my theory is that aging is not just wearing out. It's not just that your body becomes old and dysfunctional and you get pain, you get inflammation, and you die from a disease. I look at the body like it's a a computer. It's software and we can reinstall the software. ... the body is a carrier of information from our parents and what happened in the womb. That information is intact. Keeps our body functioning almost perfectly in our teenage years, 20, you're in your early 30s. You're starting to lose that information and so your body's not functioning perfectly anymore. Gray has... Exactly. That's a good example of cells that lose their identity and stop making melanin, the black pigment. ... but the beautiful thing is we believe we've found a backup copy of that information from youth that we can reinstall into cells... So when I see an old person walking down the street now, I don't think, oh, that person's just worn out, frail, going to die. I just think that's someone that needs a reset. And inside that person is a young person waiting to come out again. That's a totally different way to think about old age.

Stephen: So, with this theory in mind, what are the day-to-day things that we're all doing that are accelerating our age? ... how you live your life is really 80 to 90% of your rate of aging. ... what are those things?

David Sinclair: So, doing the right things. So, what are those things? Let's tick off some of the major things that people should be doing and they can have a big impact. They can lengthen your life by a decade... If you avoid smoking... Avoid excessive drinking... Eat well... don't uh overeat or eat ultraprocessed foods. And the big one, one of the best things you can do besides all of that is exercise. ... But the fifth one is interesting. ... Have a reliable partner. ... if you don't have a reliable partner, have a pet because the human bond is something that is shown to slow aging and associates with people who live longer than others that are lonely.

Stephen: fasting, I know is a big subject you speak about which I'm very, very interested in. ... why why does it help extend my life? Yeah. Just eating less.

David Sinclair: Adversity mode is what we're aiming for. The opposite is abundance mode, which is what modern life is all about. Popcorn, movies, wheels on your suitcase, sitting down all day. ... What happens at the cellular cellular level is that those cells, they get freaked out. They're worried that these times of adversity could kill us. 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. ... One thing that I've started doing is fasting for longer than just 14 16 hours. I try maybe once a month to go for 3 days without eating. ... The true real deep clean cleansing of old proteins and damage damaged proteins happens after 2 and 1 half to 3 days and it's called chaperone mediated autophagy.

Stephen: Your team discovered I can't say the word seratunis (Sirtuins). ... how does this link to eating all the time?

David Sinclair: Sirtuins are proteins that actually are attracted to DNA. They protect uh the DNA from getting damaged. And they repair broken chromosomes. But they also get distracted. ... what they discovered was that there's a a metabolite, a molecule that goes up and down with food and up and down with sleep called NAD. ... Sirtuins to control genes and to repair DNA that's broken, they don't do it unless there's NAD. It's the catalyst. It's the fuel for their reaction. ... When you give a human NMN by swallowing it, a gram of it, you can typically double the amount of NAD in your body. ... I've been taking an NMN... for over a decade now. ... Resveratrol... accelerator pedal. ... Spermidine. The reason that I take it is that it extends the lifespan of every animal that it's been given to... it seems to stimulate autophagy.

Stephen: And AI has really changed this equation.

David Sinclair: Oh, absolutely. We're we're doing things in my lab that would have taken 160 years before and and quite literally billions of dollars on a 10 $10,000 budget. ... 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 works.

Stephen: The question is, what do you believe is the purpose of life?

David Sinclair: Well, I'm going to give a different answer because there are multiple ways to answer it. 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. ... 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.