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Dr. David Sinclair: Why aging looks like software corruption

Through epigenetic information loss, cells forget their identity; fasting, eye-targeted resets, and lab work in mice point toward reversible aging.

Steven BartletthostDr. David Sinclairguest
Mar 23, 20262h 29mWatch on YouTube ↗

EVERY SPOKEN WORD

  1. 0:00 – 3:34

    Intro

    1. SB

      This is very, oh, [beep]

    2. DS

      It's bad, right?

    3. SB

      It's hard, yeah.

    4. DS

      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, it's not a question of if, it's a question of when this is gonna happen. And everyone should stick around because I'm gonna tell you some of the major things that people should be doing. They can lengthen their life by a decade. Hey, you're not taking that off, Steven.

    5. SB

      Oh, yeah.

    6. DS

      You got 10 minutes for that.

    7. SB

      Sorry.

    8. DS

      So you can accelerate aging by smoking, getting an X-ray, ultra-processed foods, excessive drinking, flying a lot.

    9. SB

      I fly all the time.

    10. DS

      That's probably accelerating your aging process. [keyboard clacking] [bell dings] 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 gonna live into the 22nd century if you do all the right things.

    11. SB

      And we're gonna 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 gonna be possible in the next 50 years for us to live forever? And then what's the best, uh, treatment you've discovered for hair loss?

    12. DS

      This is why I love your podcast, Steven. You ask the right questions. So first-

    13. SB

      This is super interesting to me. My team give me this report to show me how many of you that watch this show subscribe, and some of you have told us, according to this, that you are unsubscribed from the channel randomly. So favor to ask all of you, please could you check right now if you've hit the subscribe button if you are a regular viewer of the show and you like what we do here. We're approaching quite a significant landmark on this show in terms of a subscriber number. So if there was one simple free thing that you could do to help us, my team, everyone here, to keep this show free, to keep it improving year over year and week over week, it is just to hit that subscribe button and to double-check if you've hit it. Only thing I'll ever ask of you. Do we have a deal? If you do it, I'll tell you what I'll do. I'll make sure every single week, every single month, we fight harder and harder and harder and harder to bring you the guests and conversations that you wanna hear. I've stayed true to that promise since the very beginning of The Diary of a CEO, and I will not let you down. Please help us. Really appreciate it. Let's get on with the show. [upbeat music] 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 gonna 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.

    14. DS

      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.

    15. SB

      [chuckles]

    16. DS

      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, passed away, but she's inspired me to do the best I can to leave the world a better place than, uh, I found

  2. 3:34 – 6:27

    The Children’s Book That Quietly Shaped Everything That Came Next

    1. DS

      it.

    2. SB

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

    3. DS

      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 gonna 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, you don't wanna 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 h- we'll have the biggest impact on human health in history.

    4. SB

      Am I right in thinking your grandmother told you at that young age that she was gonna die, that you were gonna die, that your parents were gonna die?

    5. DS

      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 gonna die." I'm like, "What do you mean?" She goes, "Every, everything dies. I'm gonna 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 gonna 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

  3. 6:27 – 9:12

    Why Living To 80 Might Be Far More Alarming Than You Think

    1. DS

      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, the other disease, cancer, heart disease, Alzheimer's. But what's underlying that, what's really causing about a hundred and fifty to two hundred thousand 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 our, were our medicines, and how sad it was that we accepted that we became frail before a hundred.

    2. SB

      If someone has just clicked on this conversation now and they deepen their core, believe that they're probably gonna live to 80 years old, and that we all are, and that we're never gonna be able to do anything about it because that's just the way that it is, people get old and then they 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 top-line 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?

    3. DS

      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 thirty 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 ten 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

  4. 9:12 – 12:23

    Inside The First Human Trials Attempting To Reverse Ageing

    1. DS

      body as well.

    2. SB

      So you're doing the first ever trial of this type in humans to reverse aging next month?

    3. DS

      Yes. So we've submitted a form to the, you know, the FDA in the US to get approval to treat blindness, couple of types of blindness in people, um, as early, if all goes well, as next month.

    4. SB

      And what, what exactly is happening there? Because there's many ways one might fix blindness-

    5. DS

      Mm.

    6. SB

      You know. W-what is it you're doing to the eyeball that is a precursor of our potential ability to reverse aging generally?

    7. DS

      Yeah. Well, we chose the eye not because it was gonna 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 wanna 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-

    8. SB

      Just for those that aren't watching the video, there is a, an eye on the table.

    9. DS

      Well, a plastic eye. It's a, it's a larger version of an eye, but yes, uh, Steven's right. What we're doing, we're gonna 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.

    10. SB

      Hmm.

    11. DS

      Um, 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 gonna 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 six to eight weeks. And those three genes are what we now know reset safely, apparently safely, reset the age of cells, including nerves, by about seventy-five percent 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.

    12. SB

      Hmm.

    13. DS

      But this is the way it works. And we chose the optic nerve because it's a safe, enclosed system, not because it should work better in optic nerves. In fact, we've now done it in mice in my lab for the brain. Uh, we're doing hearing. We've done skin. Uh, we did multiple sclerosis.Uh, we're now doing motor neuron disease and seeing great effects. So it's important to know 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

  5. 12:23 – 14:51

    How Scientists Actually Slowed Ageing In Mice—And What That Means For Us

    1. DS

      year.

    2. SB

      You mentioned a second ago you've been able to extend the life of mice in your laboratory. How and by how much? Is it the same process, and by how much?

    3. DS

      Right. Well, the, the study that, that I was referring to was done using our technology in an independent lab, which is, you might argue, even better than having done it in my lab. Instead of putting the three reversal genes into the eye, they injected into the vein of the mouse, the old mice, uh, and turned it on in these really old mice. These mice would be the equivalent of about eighty to eighty-five years. So they're really old mice, they're really frail, and just any, any extension in their lifespan and health would be be- would be a great thing. And they got an additional hundred percent lifespan extension. Additional. So-

    4. SB

      That would be like an eighty-year-old living to a hundred and sixty.

    5. DS

      Well, the remaining life of an eighty-year-old isn't long.

    6. SB

      Oh, okay.

    7. DS

      Right. So let's, let's say if you give it to a seventy-year-old, on average, they'd have another ten years to go, give them twenty years. So it's that calculation. Um, but that was not an optimized study. They just did a Hail Mary injection, turn it on, see what would happen.

    8. SB

      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?

    9. DS

      To being able to safely reverse the age of the human body.

    10. SB

      How can you be so sure?

    11. DS

      I'm not sure, but I'm confident that the science is solid, right? The, 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 ten 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.

  6. 14:51 – 16:44

    Will An Anti-Ageing Pill Really Exist—Or Is That A Dangerous Myth?

    1. SB

      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 ten years' time every couple of weeks that will make us younger. Can you explain to me that prediction? What is, what is the prediction?

    2. DS

      I, I do believe that I, and you're about twenty 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 thirties and even forties, who are brilliant scientists, uh, there's about twenty-five of us, they are making discoveries that blow me away every week. It's not a pill because you can't give a mouse a pill. They won't chew it. But we give them a, a liquid down their throat, it's a drink, and within four weeks, we can rejuvenate them. Not with this, these, these genes anymore that we're giving humans, that's the old te- 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 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, Ste- Steven, 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 sclerosis 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.

  7. 16:44 – 18:34

    What Happens If You Live Long Enough To See The 22nd Century

    1. SB

      So if, if your predictions are correct, and your timeline is correct, what does this mean for the way that I should be living my life right now?

    2. DS

      Most people look at their parents and their grandparents and think, "That's what my life will be like? I'm going to be frail in my eighties." That's not true for us. I like the Wright brothers analogy. It'd be like in nineteen hundred saying railways are going to travel as fast as a horse. That's not true, right? The twentieth century saw that we could go tens of thousands of kilometers. They went to the moon, right? That's what our generation is when it comes to biology and aging. Previous generations are no guide to what our lifespan is going to be like. You're going to potentially live to the twenty-second century if you do all the right things. Technology keeps increasing, right? What kind of technologies will we have in fifty years? You'll be around in fifty years.

    3. SB

      I hope so.

    4. DS

      You're a healthy guy. I know you are.

    5. SB

      [laughs]

    6. DS

      All right? So in fifty years, what kind of things will you be able to do?

    7. SB

      Gosh.

    8. DS

      This is what most people forget, is that technology isn't static. When you're old, you will not be using today's technology. You'll be using technology of twenty seventy, twenty eighty, right?

    9. SB

      Mm.

    10. DS

      And then you'll be able to live into the twenty-second century and take advantage of those technologies. That's why people talk about the singularity. The singularity is this idea that if you can make it to a certain point in human history, you won't have to age anymore. And that, that's in the future, right? But first steps first. Let's show that we can get this to cure blindness and then get to the point where-Every year that we get one year older, we can get one year younger. When that happens, it's a very interesting world, right? You don't have to age anymore. That is the future. I don't know when we're gonna get there, but if you don't live ten to twenty years longer than your parents, something's wrong.

  8. 18:34 – 20:43

    Is Immortality Even The Goal—Or A Terrifying Possibility?

    1. SB

      On that point of the singularity, so this is a particular moment in time where we're gonna be able to make aging or age reversal, I guess, a choice, right? So the, I guess the thinking or the theory is that if you can just make sure you survive up until this particular date, then you have the choice to live forever. Is that how, is that, like, the theory?

    2. DS

      Well, that's what they say, yes. Uh, there are a lot of proponents of that, but that, that's an idea, and it's-

    3. SB

      Is it logically true, though? It's, like, logically-

    4. DS

      It's an e- yeah, it's an extension of what I'm, I'm talking about. Um, but I don't know when that's gonna be. It's... I think Ray Kurzweil said it's coming soon.

    5. SB

      Did he have a prediction?

    6. DS

      It was in the twenty-forties sometime.

    7. SB

      So Ray Kurzweil is a famous futurist that seems to predict the future really well, um, across multiple, uh, disciplines. So he said twenty-forty?

    8. DS

      Yeah, that's my recollection. It's around there.

    9. SB

      Do you believe that? 'Cause I, I'm gonna hang on till twenty-forty. [laughs]

    10. DS

      I'm, I'm skeptical.

    11. SB

      I won't leave the house. [laughs]

    12. DS

      I mean, Ray, Ray is a smart guy, right? He predicted AI and all that's happening, so it's, it's, it's dangerous to bet against Ray's predictions. I, I remain skeptical. You know, as one of the leaders in the field, I think we have a lot still to do. 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. It's gonna happen and, you know, r- and right now it's now twenty twenty-six we're talking. Twenty-forty is a number of years away. It could be that we truly are able to multiply reset the age of the body. That's, that's another thing that, that's often missed. We can re- re- 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 actually just got old, and they died, but they died with perfect eyesight. But the point is that we, we don't believe it's a one-shot wonder. You can keep reversing aging, and then you age out, and then you reverse it again, and you just keep going. And 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 that we'll have a radical change in how we treat diseases and how long we can

  9. 20:43 – 29:33

    The Real Reason Your Body Might Be More Like Software Than Biology

    1. DS

      live.

    2. SB

      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 me keep up. [laughs]

    3. DS

      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. In my lab, we believe we've found a way to do that, and we see the evidence of that. So 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, twenty. You're in your early thirties, you're starting to lose that information, and so your body's not functioning perfectly anymore.

    4. SB

      Gray hairs.

    5. DS

      You've got some gray.

    6. SB

      Yeah.

    7. DS

      Exactly. That's an, a good example of cells that lose their identity and stop making melanin, the black pigment, but it's gonna get worse, I promise you, unless, you know, unless we, we hurry up. And this information, uh, gets lost. It gets corrupted. But the beautiful thing is we believe we 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, "Oh, that person's just worn out, frail, gonna 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, and in the future, people will have a choice to be rejuvenated or not.

    8. SB

      Where is that backup copy that I need?

    9. DS

      Well, we're working on that, and, uh, if I, if I told you, my student would kill me. But we believe we've found largely where that information is stored. It's entirely new biology.

    10. SB

      And it's currently a secret.

    11. DS

      It's a secret.

    12. SB

      Okay. So you, you, you lead the way. Tell me what we should, we should talk about next as it relates to aging.

    13. DS

      Let's talk about information, right? We live in the information age, and biology is becoming part of that information age, and, uh, it started with the, uh, elucidation of the structure of DNA. Okay. And so I have a, I have a model of DNA here, so for listeners who are not watching, this is, uh, a little plastic double helix. My friend, uh, Jim Watson, uh, died recently, uh, last month, who he and his colleague discovered that DNA, the information of life that we get from our parents, is a chemical that's about six feet long in every cell. And, uh, this model here shows that DNA is a ladder, and the steps on the ladder are the information of the DNA.

    14. SB

      Okay.

    15. DS

      Yeah. And you can pull this apart so that each step becomes fifty, fifty percent ripped apart. So that should come apart, right? So I ripped a rung of the ladder apart, and that is called a base on the DNA, and it always matches with its corresponding chemical. So this shorthand, we'd call an A. It always matches with a T. So an A-T becomes a rung on the ladder, and down here, different color. Here I'm looking at a red and a green step. Rip it apart. This is a G and a C letter. Gs and Cs come together, and actually, when, if you, if I rip this ladder into halves-And each step becomes half a ladder. Now you can see that you can copy DNA because the A has to match with the T, wrong, and the G has to match with the C. So that's basic DNA. That's how the information is transferred from cell to cell, from mother to daughter, or parents to offspring. There are about twenty thousand genes. About fifteen thousand are turned on, but a different set gets turned on in large part, uh, to make a nerve cell compared to a liver cell and a skin cell.

    16. SB

      Mm-hmm.

    17. DS

      That's gene expression, and what controls that gene expression is what's called not, not the genome, which is what's in front of me here on the DNA molecule, it's the epigenome. The epigenome is the information we get transferred from cell to cell, from parent to offspring, that's not in this molecule. So where's this epigenetic information? Well, it controls which genes are switched on and off, and a major regulator of that process is the modification of these steps on the DNA. These chemicals, the C, particularly the C, which I'm showing you here, uh, in this red part of the, the molecule, the C gets a little chemical added to it called a methyl, and a methyl is just, if you remember from chemistry, high school, uh, it's a carbon with three hydrogens. It's a very simple molecule. It gets stuck on that piece of the, the DNA molecule. That's called DNA methylation, and that will help determine, that pattern of DNA methylation determines whether this particular gene will be switched on, say, to make an optic nerve, or switched off so that it becomes a liver cell, and that happens as we're in the womb and we become an embryo, and that's the epigenome. These chemicals that turn genes on and off is the epigenome, and the information theory of aging states that the information that's in a cell, which includes the DNA, but actually more importantly for aging is the control systems, the epigenome, that 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, it starts to get erased. So when we look at a mouse or, or an old tissue, if I took maybe not your skin f- but, but my skin, my skin cells are no longer as skin-like as they once were. They've started to lose their identity. They're starting actually to, to look more like nerve cells, and nerve cells are starting to look more like skin cells because the genes that were once turned on correctly in my young cells, that, that control system, these chemicals on the DNA molecule, these methyls, are getting erased.

    18. SB

      So aging is an identity crisis of the cells?

    19. DS

      It absolutely is. Well put.

    20. SB

      The cells forget what their job is.

    21. DS

      Yes. The genes are still there in large part, ninety-nine point nine nine nine percent of the genes are still there, the molecule's intact, but the control systems-

    22. SB

      The label thing you mentioned

    23. DS

      ... the label to tell the cell that this gene needs to be on, but this one should always stay off, that gets erased over time.

    24. SB

      Why?

    25. DS

      Uh, we, we did f-partially figure that out.

    26. SB

      And how do you know-

    27. DS

      Well... Oh-

    28. SB

      The labels-

    29. DS

      Even better. This is, this is why I love your podcast, Steven. You ask the right questions. These, there are enzymes that remove these methyl groups, um, and put them back on, so the cell's controlling these things. They shouldn't change, but they do, and one of the things that messes the system up is major catastrophe in a cell, and when the cell panics, it removes these structures to try and adapt to the stress.

    30. SB

      The label.

  10. 29:33 – 34:12

    What Happened When One Mouse Was Forced To Age Faster Than Its Twin

    1. SB

      So I g- I guess I've got two questions. Uh, I guess the first question, if I was thinking about the sequence of asking these questions, is what is increasing that stress on my cells, therefore what is increasing aging? And also, like, why didn't evolution just come up with a solution for this that stopped me aging then?

    2. DS

      Yeah.

    3. SB

      Like, evolution's very smart. Couldn't it just fix this?

    4. DS

      Well, before I get into that, uh, one of the, the reasons we know that this works, 'cause you asked me how do we know that's true, is that we created this, this catastrophe in animals. We, we took mice and we, we, we broke their chromosomes in a way that didn't cause cancer or mutations. If we're right, what should happen to these mice?

    5. SB

      They get old fast.

    6. DS

      They get old fast.

    7. SB

      Grey hair.

    8. DS

      And they did. We call them the ICE mice. ICE stands for Inducible Changes to the Epigenome, and we were able to induce these changes-And we took bets in the lab this was going back now twelve years ago. Uh, I, I bet that we would get aging, okay, but I was the only one in the lab that thought that would happen. We had a lot of bets that the mice would die, a lot of bets that the mice would get cancer, and a few said nothing would happen, but we got aging. In fact, I was, I was in Australia where, where I'm from as you know, and I got a picture on my old, old-style iPhone, and, uh, it was a picture of an old mouse. Uh, well, it was a sick-looking mouse and the, and the, the text was, "Problem, we have a sick mouse." And I wrote back, "That's not a sick mouse, that's an old mouse." And that was the first time I realized that we'd had evidence that our theory, the information theory of aging, is correct. So what we did actually, and this might satisfy your and your listeners curiosity, we generated a mouse from scratch using stem cells. And so we start with a, a mouse stem cell that we grow in the lab in the dish, and we change the genetics of that stem cell so that we could feed it a drug, uh, tamoxifen, which is used, uh, in, in chemotherapy, and that drug turned on a gene from a slime mold, something you might find in the forest, that breaks DNA of the mouse, but does it in a way that doesn't cause cancer or mutations, just cuts it, and the, the cells put it back together. So we could take a mouse and for three weeks we turned on this slime mold-cutting protein, and nothing happened to the mouse at the time. It's like a-- you don't feel an X-ray. You don't feel different when you fly except for maybe jet lag and dehydration, but you don't get old suddenly. Same with the mice. They were normal. They felt fine, and that's why at first people said, "Oh, nothing's gonna happen to these mice." After three weeks they were fine. But we set in motion a cascade of accelerated aging events that about ten months later they were super gray and super old and had all the diseases of aging fifty percent faster than their twins that we didn't treat.

    9. SB

      And you've got photos of those we could show.

    10. DS

      Yeah.

    11. SB

      Okay.

    12. DS

      Yeah. Let, let's show those. So if I was to do the experiment in you, I might have to engineer it a clone of you, but I could do that. Uh, you know, I'm not saying that it's ethically right-

    13. SB

      Yeah

    14. DS

      ...but, but theoretically we could make a clone of you, put in that slime mold gene, turn it on, and your clone would be fifty percent older than you are.

    15. SB

      Can you translate this into the equivocal for a human, that particular study that you did? So it would be like in me doing what and then me getting old fast?

    16. DS

      Yeah. Uh, well, we're exposed to, to things that cause DNA breaks all the time. They happen naturally as the cells try to copy their DNA, but you can accelerate that by getting an X-ray, a CT scan, flying a lot, and cosmic rays banging into your DNA and-

    17. SB

      I fly all the time.

    18. DS

      Yeah, it's a problem.

    19. SB

      I've had loads of CT scans and X-rays.

    20. DS

      Yeah. Uh, and, and though it's imperceptible, I believe that that's probably accelerating your aging process.

    21. SB

      What's flying doing to my... So again, you talked about flying being equivocal to what you did to the mouse. I-in what way?

    22. DS

      Well, 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, um, and we have some evidence that even going to a rock concert and, and ha- blasting your eardrums is such a stress on those cells in your ear that the reason that you become deaf earlier is because your ear hair cells are getting older faster. You don't wanna break the DNA. You don't wanna cause catastrophe to your fragile cells in your body because the recovery isn't complete and aging ensues.

    23. SB

      So

  11. 34:12 – 37:43

    The Most Overlooked Habits That Could Be Quietly Slowing Your Ageing

    1. SB

      with this theory in mind, what are the day-to-day things that we're all doing that are accelerating our age? Like 'cause I think, uh, what's really interesting is I look to my brother, Jason, he's a year older than me. He has three kids that are like under the age of s-seven or eight now, and this Christmas time, 'cause it's just been Christmas, I looked at his head to see how many gray hairs he had versus me, and I thought, "Okay, he has considerably more." [chuckles]

    2. DS

      [chuckles]

    3. SB

      Uh, he's a year older than me, and I was thinking that's like a, a proxy of aging to some degree. What is it he's potentially done on a day-to-day basis? I know you don't know him, so this is why it's not, not an offensive, uh, answer to give. What is it that someone who is generally sort of genetically very similar but is making different lifestyle choices is doing to accelerate that process of wrinkles or gray hairs or?

    4. DS

      Well, here's, here's the good news, that 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, so that how you live your life is really eighty to ninety percent of your rate of aging. That's good. It's in your hands, but it also means that some people mess up their lives. There are actually twin studies from, uh, mostly from Denmark, identical twins, one that goes and smokes and gets obese and, uh, goes in the sun, and they are much older f- looking than their identical twin, essentially proving that the DNA is not the reason you age. First of all, there are gonna be people in the audience, uh, who are listening or watching who have gray hair saying, "Damn it, I'm not old," and that's true. I mean, nobody died of gray hair, right? And, uh, sometimes genetically you can get gray, old, uh, but not be physically old. What is true that's often not comfortable is how old you look is a very good representation of how old you are in your organs as well. So d-doing the right thing. So what are those things? Let's, let's tick off some of the major things that people should be doing, and they can have a big impact. They can lengthen their life by a decade just by doing some of the major things. So we know that on average people can live fourteen years longer, this is based on a study that came out from Harvard, a long-term study of the lifespan of World War II veterans, if you avoid smoking, cigarette smoking and really any type of smoke in your lungs. Smoking breaks your DNA. It's gonna accelerate aging in your lungs, your whole body. 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. Eat well, so you want to eat healthy food. We've got some healthy food here we're going to talk about. Um, so make sure you, you don't, uh, overeat or eat ultra-processed foods. And the big one, one of the best things you can do besides all of that is exercise. Okay. And exercise covers a lot of things, so we can drill into that as well. But the fifth one is interesting. It may be surprising, but actually good news for you. Have a reliable partner.

    5. SB

      I thought you were gonna say be a podcaster. I was gonna... Okay. [laughs]

    6. DS

      Oh, no, that probably accelerates your age. Yes. So, um, 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.

    7. SB

      Interesting. We're gonna dig into all of those in great detail. Specifically very interested in, in exercise, diet, lifestyle, fasting I know is a big subject you speak about, which I'm very, very interested in. And actually, as I was doing the research for this conversation, again, my-- the way that I'm gonna approach nutrition has shifted because of some of the things I discovered there.

  12. 37:43 – 41:58

    Why Evolution Never Solved Ageing—And What That Reveals

    1. SB

      I wanna just tick off on this evolution point.

    2. DS

      Right. Let's come back to that.

    3. SB

      Yeah.

    4. DS

      Why age?

    5. SB

      I just wanna get clear. Yeah, like why didn't evolution fix it for me? Because they talk about survival of the fittest and that the very fact that I'm here is because my, my ancestors were good at survival. But listen, my ancestors all d-died at like thirty, forty, fifty, sixty, seventy, eighty years old. That's not very good. Why, why didn't they just live longer?

    6. DS

      Well, that's why. You just said the answer yourself, because your ancestors-

    7. SB

      Okay

    8. DS

      ... didn't live beyond forty or fifty, even less, right? Most men, uh, in prehistoric times would die from famine, disease, and actually a lot of them from war. So most people didn't make it to eighty. Some people did, but very, very rarely. So the, the forces of natural selection were on early survival and fast breeding. Let's put it this way, if there was someone who was born with a mutation that allowed them to live a lot longer, to ninety, in a prehistoric world, that's useless because you're probably gonna die at thirty or forty anyway, and so are your children. So what you wanna do is find genes that allow you to become reproductively successful early on in life, um, and make sure your children survive. And so we, we have children pretty early, but humans for, for s- various reasons, have a long developmental period, including education. So we don't, we don't develop very rapidly, right? We don't wake up and we can walk and run like a lot of other species and mammals. But we don't live a long time because there was... In the environment that we evolved, the Serengeti Plain is pretty much agreed upon as that's one of the places we evolved, certainly, uh, Eastern Africa, that was extremely difficult and dangerous place to live. You could get eaten by an animal, and if you didn't get eaten by an animal, you get killed by the neighboring tribe. That's super dangerous, right? And then so we, we evolved to live really at optimal to about thirty, but not much more than that. So after thirty, as you might be experiencing-

    9. SB

      Yeah

    10. DS

      ... with, with your body, we're at the forces of entropy, so the body starts to decay, the information starts to get lost in the body. But the, the good news is that if you take away predation and death from a species, it evolves longer lifespans. Now it makes evolutionary sense to have genes that allow you to put more effort into building a strong body and slowing down the aging process and preventing DNA breaks, chromosomal breaks. We know that this is true because if you put species, say, on an island where there are no predators, what happens to their longevity? They get longer lived naturally. It takes twenty, thirty generations, but only when there's no predation, when you're not under a lot of stress to, uh, breed quickly, 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 gonna happen fast enough for you and me.

    11. SB

      And do the organisms that do live really, really long have a small amount of predators in nature?

    12. DS

      Absolutely. Absolutely. Think about them. The bristlecone pine-

    13. SB

      What's that?

    14. DS

      It's the longest-lived tree in the world. It can live many thousands of years. It's-

    15. SB

      Are you jealous?

    16. DS

      Not jealous, no.

    17. SB

      [laughs]

    18. DS

      No. They live a tough life. Some of those trees have been around since the pyramids.

    19. SB

      Wow.

    20. DS

      The reason they live, can live for so long and evolve to live so long is that things don't eat them. They are totally poisonous. You, you don't wanna eat a bristlecone pine. The same for a whale, right? The bowhead whale, some of these very large animals, no predators. So 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, and they, they don't lose... They don't have this identity crisis until hundreds of years. And we know that. People study the cells of whales in the dish, and those cells don't lose their identity very quickly, even when you break their DNA.

  13. 41:58 – 44:13

    If You Reverse Ageing, Do Diseases Disappear Too?

    1. SB

      So I, I guess the place, uh, also to, to go next is, uh, talking about disease generally and what disease is. So are these diseases a function of aging? Does this idea of reversing aging even matter if cancer's gonna take most of us out anyway at some point? Is there a link between aging and disease?

    2. DS

      This might be the most important point that I make today. When you reverse aging, diseases of aging go away or are cured, and in, uh, in my lab, including many types of cancer as well. The diseases that we try to treat individually with different medicines today that we think are unrelated, Alzheimer's, cancer, heart disease, you name them-Fundamentally, what's 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. Right? And so what we see in my lab is when we give an animal a disease, and we can do that, we can put in the human genes for Alzheimer's into a mouse, it becomes-- has dementia. When 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. So it's the aging process that reveals the disease that can be cured by reversing.

    3. SB

      Why does the aging process reveal a disease? Why don't we get an Alzheimer's at fifteen?

    4. DS

      Because the cells are so healthy they can fix themselves, they can renew themselves. The disease processes that cause these problems for us don't exist when we're young. Why is it that a teenager rarely has a heart attack? Because their body prevents them. 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 gonna die in the next year? Because our immune system will find them and kill them. But as we get older, we're gonna lose that ability, and we'll have a greater chance of having cancer.

    5. SB

      So are you saying that if we cure aging, we're probably gonna, by way of that, cure most of these diseases?

    6. DS

      A hundred percent.

  14. 44:13 – 47:37

    Could Age-Reversal Technology Unexpectedly Solve Infertility?

    1. SB

      We're talking about, um, menopause quite a lot on this podcast, and fertility, menopause, women's ovaries as, um, one of the first places that ages. And I've heard you explain that you think that evolution 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?

    2. DS

      In mice, which is where we live in my lab, where we work, it can be prevented and it can be reversed.

    3. SB

      I thought we'd run out of eggs. That's like the-

    4. DS

      That's the current theory. The evidence that we have from my lab and a lab that I worked with in Australia caused me to question that idea that we run-- that women run out of eggs. We have published and repeated many times that if you treat old female mice sixteen months of age, which is like a sixty-five, seventy-year-old human that has long time since given up having offspring, we can treat the ovaries with a chemical that rejuvenates the eggs that are in the ovary, maybe even produces new ones, we don't know for sure. But those sixteen-month-old mice that stopped having kids a y- uh, probably at least six months ago now start producing healthy offspring again. Their eggs look young, pristine, compared to the terrible eggs that if you try to harvest some eggs from a mouse that old, it's hard to find any that look normal. Their chromosomes are messed up, ripped apart. They're not gonna produce healthy babies. But we can take those eggs, or at least the ovaries with those eggs in them, and cause them to be young again and make fresh eggs that can produce healthy offspring that live a normal lifespan. The real question is, will this work in women? And that's something that I'm keen on testing.

    5. SB

      It must be really hard to test a lot of these things in people, right? Because we-- you've mentioned the word mice quite a lot.

    6. DS

      It's harder than you can imagine, actually, um, and I've spent a lot of my career since I was thirty-five, um, aiming to develop a medicine to treat diseases and aging. And it can be-- it can go wrong in many ways, um, even if the science is good and right. Um, and it, it's-- there's money, there's business, there's laws, there's politics, there's business strategies, there's change of leaderships, um, all sorts of human introduced variables that can get in the way. There's patents and, uh, and then there's, there's competition and spite that also gets into it. Um, and I've had to deal with all of those things, um, including competing against some of the largest pharmaceutical companies in the world who really didn't want me to succeed. But yeah, it's extremely difficult to make a drug, but I do wanna remind you and everyone listening and watching that we're beyond mice now for age reversal. We've done this in monkeys, monkeys that are physically and almost genetically identical to us. So it's not a big leap from-- It is a pretty big leap from mouse to human, but from a monkey to a human, it's-- we're essentially, you know, slightly smarter monkeys.

  15. 47:37 – 50:41

    The Controversial Reason The US Shut Down Age-Reversal Research

    1. SB

      I just had a thought about how other countries and other nations might be conducting their own sort of secret research, and they might not have the same bureaucratic-

    2. DS

      Mm.

    3. SB

      -political, ethical considerations that you have to contend with. Do you think about this much that some of the sort of geopolitical adversaries might be doing secret testing in some research lab somewhere on humans?

    4. DS

      I think about it, um, and in fact, the United States government thinks about it too. A large investment into, uh, the com- one of the companies that I, uh, sit on the board of was blocked because the U.S. government claimed that the technology was too dangerous to be in the hands of foreign companies and governments. So there-- the U.S. government, at least in, in the previous administration, was extremely cautious about this technology falling into the wrong hands.

    5. SB

      Which technology was blocked?

    6. DS

      The ability to reverse aging.

    7. SB

      So the U.S. government blocked that technology because they were scared that it might fall into the wrong hands?

    8. DS

      Well, they blocked the, the very large investment, over a hundred million dollars, into the company from a foreigner because they would have more access to the information and the progress.

    9. SB

      Is it China?

    10. DS

      Um, I won't say more-

    11. SB

      Okay

    12. DS

      ... it's sensitive. Most I can say is that governments are watching this technology very closely, not just the US, but around the world. Because the winner will make not, not just a lot of economic benefit, but there will, there will be potential for radical change in the pharmaceutical industry, in healthcare. Um, the amount of change socially will be dramatic as well. But there are also uses that the government has identified, uh, so-called super soldier potential. Now, I, I don't agree that that's a reason to slow down the research. Others claim that it was worth it, but I do believe that the technology is very powerful and we should start to get ready for when this comes to society, because it's not an if, as I said, it's a when.

    13. SB

      The technology to do what?

    14. DS

      To rejuvenate the human body.

    15. SB

      Why do we need to get ready?

    16. DS

      Well, because it'll be massive social change. If you can choose how old you want to be and people don't die as-- at eighty anymore, let's say they, they can live to a hundred and twenty or beyond, there's big changes. There's Social Security issues, there's, uh, employment. Though I will say that the, the disaster scenario that often comes to mind when I talk about this, and which I covered in, in the last part of my book, Lifespan, it's actually economically hugely advantageous to slow aging and prevent diseases. A lot of the US economy and most advanced economies goes to healthcare. And chronic disease, a lot of people are sick for five to ten years. That's where most of people's savings and retirement and government money goes in, the most expensive years of your life are the last two years. If you can delay that, it's going to have massively positive economic benefits to a nation that adopts these medicines.

  16. 50:41 – 53:52

    Would You Trade Everything You Own Just To Be Young Again?

    1. SB

      I've got a question for you that actually came to mind yesterday when I was-- I watched some, I don't know, some video on social media, and they asked a question to a guy. Um, David, if you were a billionaire now at age fifty-six, would you give it all up to be my age again, thirty-three?

    2. DS

      Um, I don't think you can put a price on being young. Another way of, of putting it, and I've, I've seen this on social media, would you-- for a billion dollars, would you swap with Warren Buffett?

    3. SB

      No, absolutely not.

    4. DS

      Right. So there's no money in the world that you want to be old, right? Uh-

    5. SB

      Yeah

    6. DS

      ... it's not worth it. In other words, youth is more valuable than a billion dollars. It may be the most valuable thing you could ever have is your youth.

    7. SB

      It, it's such an in- an interesting and illuminating analogy or metaphor or whatever, because suddenly you do realize that how much we value it, we value it more than anything. I would rather be thirty-three years old than be a forty-three-year-old billionaire. Even the ten years I value is a billion dollars. [chuckles]

    8. DS

      Yeah. One year maybe, but not ten years, right? Ten years is super... I, I totally agree with you. Um, and the older you get, the more valuable it becomes. It's important to realize the, the massive impact that this technology can have, not just economically, but on individual lives of human beings across the planet. The world when this becomes a, a reality, again, I'm speaking like it's a certainty because I'm pretty convinced it's going to happen, the-- that world is going to be so different from the world we live in. It's going to be as different as the pre-computer world and the pre-airplane world as today is.

    9. SB

      I'm trying to imagine the world where we could pick our age and maybe even, you know, you talked about earlier being able to c-continue to reset to that age.

    10. DS

      Yeah.

    11. SB

      Trying to r- imagine what the world would be like if I could be thirty-three forever, or if you could be, you know, thirty-three forever.

    12. DS

      Or even for another hundred years or something.

    13. SB

      Yeah.

    14. DS

      Yeah.

    15. SB

      I could stay thirty-three for a hundred years. Do you think that's the plausible outcome, which is we can kind of pick an age and stay there for a hundred years, like at that particular age? Or is it just that I'm going to be a hundred and fifty in my physical form? I'm going to be wrinkled and gray, but I'm just gonna continue to live. Is it looking young or is it just living longer?

    16. DS

      It's actually-

    17. SB

      Is it both?

    18. DS

      It's-- the good news is it's both. And we're doing a lot of work in my lab on skin and hair, uh, hair loss, hair graying.

    19. SB

      Yeah, please help me. Like if I... [chuckles]

    20. DS

      You don't have to worry just yet. Um, you know, we'll, we'll help your brother first.

    21. SB

      No, no. Come on. [chuckles]

    22. DS

      Yeah, we, we will. Tell him to call me. Um, so we, we've seen that we can rejuvenate the skin of, again, mice, but still we, we also grow human skin in the lab from scratch, and we can put that human skin on mice, and the mice have human skin, so we can now test age reversal in that system. I'm very optimistic that we'll be able to rejuvenate, uh, the, the external part of the body as well as the internal. If we can cure blindness, reversing the age of the skin is, is a piece of cake.

    23. SB

      What, what does

  17. 53:52 – 59:02

    What Living Longer Really Does To Meaning, Purpose, And Motivation

    1. SB

      that world look like? I'm trying to understand all of the sort of unintended consequences of such a world where we're all kind of young and we all live longer. Is there problems of meaning and purpose? Is there... What are the unintended consequences?

    2. DS

      I- I've thought a lot about this. There's this gut feeling that a lot of people have, maybe you're feeling it now, is that if I'm not worried about death, I'm not going to strive as hard or I'm not going to have as much meaning. I'm not going to have agency. I totally reject that view. I believe that every moment is special. Uh, I don't believe I would be enjoying this conversation with you any more if I could live two hundred years. I'm loving the moment.

    3. SB

      Mm-hmm.

    4. DS

      Right? And so I, I believe that we get up with purpose and that if I lived for a thousand years, I'd still enjoy every day that I lived. And even a thousand years one day may be seen as too short.No, it's twenty times my age, a little bit less than twenty. That's still not very much in the grand scheme of, you know, the age of, uh, geology and the Earth. We still are around like that. Uh, and so I think that we will still love life-- most of us will still love life and enjoy every moment, but we'll get more opportunities. We can try multiple careers. Maybe we, we, we will get divorced and find-- have a whole new life. So there will be opportunities, and it will be a, a magnificent world. Not to mention the productivity that humans can provide with the, the knowledge of a fifty or eighty-year-old, but with the body of a thirty-year-old.

    5. SB

      Do you think people will make different decisions about having children?

    6. DS

      Well, I think we have a problem already with the decisions that a lot of couples are making, which is leaving it too late. Um, it's very clear with the fertility rate and the rate of childbirth that, that basically we're going off a cliff. And I, I think that it's gonna be important to be able to give couples and women especially the choice to have children for longer. And that's one of the reasons that I work on this topic is that I think that the world, with all of the, the training that we need to do and the pressures on finding a mate and being happily married or, or at least being partnered up, that can take decades to get the right person. You don't want to rush into it like people used to. And being able to have children in your fifties and sixties, I think, would be a great gift to humanity. That's my personal view. Some people may, you know, for whatever reason, disagree with that. But I think that the pressures to have children before thirty-five typically are just extreme and, and unfair, but also that it'll help us maintain the human population, because by twenty fifty we're going to start going in a bad decline and earlier in many Western countries. And without humans, you know, absent Android robots everywhere, we're going to have a deficiency of human capital and human productivity. And this is-- I would argue with Elon that this is the best solution to that, uh, lack of humans, is just keep people healthy and alive and productive for longer. [paper rustling]

    7. SB

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  18. 59:02 – 1:01:29

    How Slowing Ageing Might Secretly Slow Cancer Too

    1. SB

      You mentioned, uh, cancer earlier on as something that you're working on in your laboratory.

    2. DS

      Mm-hmm.

    3. SB

      What progress have you made in your laboratory, and what has that taught you about what-- the nature of cancer, but also how we might prevent and cure it someday? Because I, I was reading that i-in your laboratory, you have been able to slow the growth of certain cancer cells and kill those cancer cells completely.

    4. DS

      Yeah. Uh, so my, my wonderful student, Nalat, uh, is, uh, is doing her PhD on this. And what we've hypothesized and now tested is the idea, again, based on the information theory of aging, is that cancer is expressing those genes differently. In the same way that aging is lo-- 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-

    5. SB

      Mm-hmm

    6. DS

      ... 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 in my lab. Nalat'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.

    7. SB

      Through the injection that you were referring to earlier on?

    8. DS

      Yeah. W-we can do it a couple of ways. One is using those three genes that rejuvenate the epigenome and make cells youn-young again.

    9. SB

      Yeah.

    10. DS

      The one for the eye, the same technology for the eye we're using in cancer cells. But we also have this chemical drink that we can give to animals or to put on the cells, and that also wakes the cancer cells up, tries to-- they try to become more normal. They turn on the original set of genes that they might have had on30, 40 years ago. Some of these cancer cells that we grow in the lab were, you know, from the 20th century. We rejuvenate them, we turn on those ul- those genes that were originally in the normal tissue, and the cells kill themselves. And so I believe that we may not be able to cure all cancer using this. That would be crazy to even say that, but I do 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.

    11. SB

      So

  19. 1:01:29 – 1:02:45

    The Real Cause Of Cancer—And Why It’s Not What Most Think

    1. SB

      f- from this, we can start to try and understand what we think is causing cancer, and I guess this goes back to the, a lot of the carcinogenic behavior that you described earlier, things like smoking, anything that's applying stress on the DNA. Is that like a-

    2. DS

      Yeah, you have to break the DNA. Um-

    3. SB

      Okay

    4. DS

      ... that's the cat-- A catastrophe is really broken DNA, but you can do other things that catastrophes, like overheat the cells, um, even mechanical stress. You know, too many hits on the brain in football will, will do that. So yes, uh, that's exactly right, and that drives aging, and aging drives cancer by the way. One of my theories called the Geronculgenesis hypothesis, terrible name, but nevertheless, Geronculgenesis it, it is. It's the idea that as we age, we're becoming more cancer-like as, as a, as a human. Our metabolism when we're old is closer to heading towards what a cancer cell's metabolism is like, so that when we actually do get cancer, the cancer cells grow better in an old person than when you're young. And so by rejuvenating those cancer cells, giving them the, the ability to be young again, they actually either slow down in their growth or, as I said, kill themselves in response.

    5. SB

      I've got a bit of

  20. 1:02:45 – 1:04:17

    The Information Theory Of Ageing That Changes Everything

    1. SB

      a, a prop here-

    2. DS

      Ah

    3. SB

      ... which might be useful for the, the context of-

    4. DS

      Oh, goodness

    5. SB

      ... of aging.

    6. DS

      Does, th- uh, there are people here that may not know what I'm holding in my hands. But, uh, for those of you who don't know and who are just listening, I'm holding a record, uh, in my hands, a vinyl record, uh, that Steven just handed me. So the, the information theory of aging, uh, the analogy that I used is that it disrupts information. And so this record, this album has information on it. It's music, and just like DNA, it's information. So instead of the DNA information, the, the control of the DNA bit getting messed up, in the album, it's like scratching this album. So I'm literally gonna scratch this album. Is that okay with you?

    7. SB

      Of course you can.

    8. DS

      All right. I'm not sure I can fix it, by the way.

    9. SB

      [laughs]

    10. DS

      It may be a one-way thing, but I've never done this before. But... Ew, that's painful. [record scratching] Maybe you can hear that happening. So if we were to play this on a record player with a needle, it's gonna jump around, and it's gonna read the wrong songs or it's, it's gonna certainly not sound very good. So that's, 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 old age, the information is in the DNA, but you c- the cells don't read it correctly. And what our technology is, is to get rid of those scratches, and so we can play the beautiful music of our youth again.

  21. 1:04:17 – 1:08:43

    Why Ageing Feels Like Carrying Invisible Weight Every Day

    1. SB

      Um, I have got this. Uh, you told me to, to bring my weighted vest and this neck brace. Ugh.

    2. DS

      Oh my goodness. Uh-

    3. SB

      I think I put it on the wrong way. Okay.

    4. DS

      Any- anyone listening, Steven's putting on a very heavy jacket right now with lead weights-

    5. SB

      Ah

    6. DS

      ... and a strap around his neck to limit his neck movement.

    7. SB

      Oh, wow. That's a lot. Listen, so I'm-- I just, I put on a 20, I think it's 20 kilogram, unless I'm weak now, um, jacket and a neck brace. And ahead of this conversation, my team told me to get one of these. W- what is the analogy here that you're, you're creating? This is very... [sighs] Fucking hell.

    8. DS

      It's bad, right?

    9. SB

      It's hard, yeah.

    10. DS

      Right. Imagine do-- 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. It would be painful. You're not in pain yet.

    11. SB

      No.

    12. DS

      But most people in their 80s have some sort of disease and ache, aches and pains. Try doing that for another 10 minutes maybe. How long you, can you keep that on?

    13. SB

      I'll keep it on for another 10 minutes. But so why is this? 'Cause it just... It, it's weight and immobi- immobility. I can't move my neck the same. My shoulders feel heavier. How, how is this a relevant analogy to aging? Because it ju- it just kind of feels like im- immobility and weight.

    14. DS

      Uh, well, I have to come over there and use this pair of scissors to be stabbing you as well, so you f- you can feel pain as you move as well. That's part of old age. It is not a fun thing being old, and most old people, the reason that they don't love life anymore is because they feel like you do, or worse.

    15. SB

      [sighs]

    16. DS

      Not to mention the fact that they're-- you need to put Vaseline on your eyes, earplugs in your ears if you wanna know what it's like being old.

    17. SB

      Oh, God, it's not nice.

    18. DS

      Mm-mm. Or even worse, shut your eyes and you can never open them again. That's what it's like for those patients that we hope to cure blindness in.

    19. SB

      If, if, I'm gonna ask you a really tough question, which is if I put a calculator in front of you right now-

    20. DS

      Yeah

    21. SB

      ... and you had to hit a number on that calculator and then hit enter, and that was the age that you were gonna live to-

    22. DS

      Yeah

    23. SB

      ... and you had to make that decision now-

    24. DS

      Yeah

    25. SB

      ... what number would you hit on that calculator?

    26. DS

      Infinity.

    27. SB

      Really? So you'd hit nine, nine, nine, nine, nine, nine, nine, nine?

    28. DS

      There's no day if you're healthy where you wanna 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"?

    29. SB

      No.

    30. DS

      No.

  22. 1:08:43 – 1:13:55

    Why Eating Three Meals A Day Might Be Holding You Back

    1. SB

      Well, I guess I better make it to twenty forty. Um, so let's talk about fasting and food and nutrition and go, go a little bit deeper on that. I've had so, so many conversations over the years about this subject of fasting, but, um, as I was reading your research, you really do feel that fasting, just eating less often, is one of the most important things that we can all do for longevity.

    2. DS

      I, I do. I do, and I practice it as much as I can, though it's challenging in a world that's full of abundant food. But yes, uh, we've known for thousands of years, the ancients are not dummies. They, they could witness what happens when you fast. Uh, clarity of mind, long-term health. They could observe the difference between the gluttons and the people that fasted for religious reasons. It's obvious, but there's certain ways to do it. Fasting doesn't include malnutrition. You have to do it with abundant, you know, vitamins, minerals. You wanna make sure that you're, you, you have adequate nutrition. But I think three meals a day is, is craziness. It turns out this idea of breakfast is the most important meal of the day is marketing from the early 20th century by companies I will not name, but it was breakfast cereal. Breakfast is not the most important meal of the day for most people, especially adults, especially if you're not hungry when you wake up. There's no point in eating if you're not hungry in the morning. I'm one of those people, so I've skipped breakfast. How about you?

    3. SB

      Yeah, I'm the same. I'm the same. I don't eat. My first meal today was 3:00 PM because I had a podcast until, you know, 2:00, 2:00 PM, so which is typical for me. I just don't get hungry in the mornings. Now because of the marketing, though, for breakfast, sometime I've, sometimes I've said to myself, "Oh, you should eat," and I'll make myself eat, but it's very, very rare. I'm notoriously, people know that I'm notoriously, um, a late eater, 4:00 PM sometimes, 5:00 PM if I'm in the office.

    4. DS

      Good, good for you. How are you feeling with that heavy vest on?

    5. SB

      It's he- it's heavy, David. I've gotta be honest. It's not... I'm finding myself, like, trying to find a comfortable position.

    6. DS

      Yeah. It, it's tough being old and, and by the end of it, you will be so convinced that this research is important because to live like that-

    7. SB

      It's not great

    8. DS

      ... in most people, life is not worth living. I put a suit, a very heavy suit like that, but on the arms as well, not just the body, and he had the, the earmuffs and the, the eyes. This was the, uh, the governor of Massachusetts. Fifteen minutes in that body suit and he was crying, not because he was in pain, because he, as he said on stage, it was the first time in his life he understood how his father feels and could be empathetic. We young people, I'm relatively young, fifty-six. You're very young, thirty-three. We have no idea what it's like to be old. It can be horrific, so why wouldn't we do the right things like fasting, exercising, so we can get an extra ten years, twenty years, maybe longer of healthy life?

    9. SB

      It does also give me a lot of empathy for people that, um, have a bit more weight on them as well because of, you know... If I was, if I weighed that much, I don't know if I'd be very active, to, to be completely honest with you-

    10. DS

      Exactly

    11. SB

      ... if I'm not very active.

    12. DS

      And, and you're in pain too, don't forget. Every joint can be hurting. How do you feel taking that off?

    13. SB

      Much better.

    14. DS

      Right.

    15. SB

      Free, like I want to jump.

    16. DS

      So let's hope, pray, wish that these technologies that I'm talking about today work, 'cause that could be what it feels like to be rejuvenated when you're eighty.

    17. SB

      Hmm. I hope so. Um, to close off on this point of, of, of fasting, why, why does it help extend my life-

    18. DS

      Yeah

    19. SB

      ... just eating less?

    20. DS

      Part of it came out of research in my lab, but of course many others I need to give credit to. But in my lab specifically, what we worked on in- initially when I started, we studied yeast cells, little, uh, microscopic cells that, as everyone knows, we use to make beer and bread and champagne. These yeast cells live about ten days and then they die, and we used yeast as a model for aging, and 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. It's 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. Popcorn, movies, wheels on your suitcase, sitting down all day.It's we're in an abundance world, so adversity is something we don't often feel. We have to work at it. Fasting is adversity. Exercise is adversity. Cold plunges, saunas, adversity. Adversity mimics. They're not really threatening your life. But 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. So in this modern world, we-when we have total abundance, we don't have to exercise. We d-don't-- we eat three meals a day. We get overweight. We don't sleep much. We have air conditioning in summer. We're actually aging faster than we need to because our bodies are not fighting aging like they do when they feel

  23. 1:13:55 – 1:20:59

    The Discovery Of The Longevity Gene—And Why It Matters Now

    1. DS

      adversity.

    2. SB

      Your team discovered, I can't say the word, sirtuinus?

    3. DS

      Oh, well, I was one of many scientists in the nineteen nineties. Uh, I was part of a team called Sirtuins. Yeah.

    4. SB

      Sirtuins.

    5. DS

      Yeah. Yeah. In yeast, actually. That's right. Uh, that's a good story. I went to the US to figure out why we get old, but I didn't choose to study humans because I figured if we can't figure it out for little yeast cells, we'll never figure it out for humans. So I went to MIT. My professor was Lenny Guarente. I went to his lab and I said, "I'm, I'm not going. I'm not leaving." The goal was to, in my mind, was to figure out are there longevity genes? At that time, most people thought that there were aging genes that caused aging, death genes. That doesn't make any sense to me. Our bodies would have longevity genes that give life. So in yeast, I went searching for them, and out of that work came two things. The first is Lenny and I, my professor and I, published in the journal Cell, which was a massive big deal in those days. Still is, but it was my first time. The first evidence for a cause of aging for any species. We figured out why yeast cells get old. Do you want to guess?

    6. SB

      Hmm. Why do yeast cells get old?

    7. DS

      Have you been paying attention? What does the information theory of aging say?

    8. SB

      I was gonna say they have an identity crisis, but-

    9. DS

      They do.

    10. SB

      How would we know if they have- they're having an identity crisis?

    11. DS

      Oh, you can measure the identity of yeast cells. They have an identity. It's called their mating type. The main identity of a yeast cell is they are either A type or alpha type, male, female. And the hallmark of a yeast cell that's old is it loses its A and alpha identity and gets an identity crisis. It doesn't know what sex it is and it doesn't mate anymore, becomes sterile. So when I arrived at MIT in nineteen ninety-five, we knew that the hallmark of an old yeast cell, besides it being a bit slow and bigger, is that it became sterile. It had an identity crisis, so we figured out that broken chromosomes distract the sirtuin defenses, and that causes aging in a yeast cell. But we didn't know in the nineties that that was gonna be true for us as well. It took another decade or two to figure that out.

    12. SB

      And how does this link to eating all the time?

    13. DS

      Yeah. So sirtuins are proteins that actually are attracted to DNA. They actually associate with it, and they protect, uh, the DNA from getting damaged.

    14. SB

      Okay, like bodyguards.

    15. DS

      Yeah. And they repair broken chromosomes, right? It's all coming together now. But they also get distracted. So look, a, a sirtuin's normal job, if there's no crisis, is that they turn genes on and off. They are epigenetic regulators. They control the epigenome. They tell a cell what type it is. Nerve cell, skin cell, right?

    16. SB

      Like a conductor.

    17. DS

      Thank you. Conductor, exactly. But the conductor becomes demented over time. What happens is 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 they go and they repair the DNA. That's their other job. They have two jobs, identity and repair. So when you have this break, the sirtuins go away, they repair the problem, but they don't all go back in the next few minutes. It's very quick. They don't all go back to where they started. So you've got like this tennis match that the sirtuins are the balls and they get hit over to the break, then hit back. Most of them find the genes that they should go back to, but they don't all do that. And that total game of tennis or ping-pong, if you like, is what I believe causes the identity crisis and aging itself, causes aging in yeast cells. It's why yeast cells don't live longer than ten days, and I believe it's why we struggle to live beyond eighty or ninety.

    18. SB

      So if I'm eating all the time, then those sirtuins, they're not gonna be doing their job as the, um, the conductor, making sure I know the identity of my cells. They're gonna be doing repair stuff, so I'm gonna age faster.

    19. DS

      Yes, and the breakthrough happened in the lab as I was just leaving to go to Harvard. I got a job at Harvard when I was twenty-nine, super excited, and just as I was leaving, there was a big breakthrough that act- they actually kept it secret from me because they w- they were worried I was gonna work on it when I left, and in fact, my professor tried to prevent me from working on it when I left, on sirtuins in general. It's crazy to think about. But 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. We have lots of it. There's grams of it in our body. It's one of the most abundant molecules in the body. It's very ancient. It's in yeast, it's in us. And what they found was that 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. They need NAD. And when we're young, we have lots of NAD, so it works well. The sirtuins control the information on the genes, and they repair the DNA very well because they've got lots of NAD.To carry out their, their work. These are enzymes. They work, they do things. As we get older, by the time you're fifty, about my age, you have half the levels of this NAD molecule. My body is making less NAD, and it's also destroying the NAD faster than when I was twenty. That's a problem. And so what we found was that when we fast the yeast or we fast a human, NAD levels go up again. So fasting raises NAD and makes the sirtuins young again, essentially. And that preserves the epigenome, and it also repairs the DNA better.

    20. SB

      So can I just drink NAD?

    21. DS

      Uh, you can drink NAD and not much would-

    22. SB

      How, how do I-

    23. DS

      -happen

    24. SB

      ...how do I take NAD?

    25. DS

      Uh, so NAD can be taken as a supplement, which is a precur-precursor to NAD. It's better to take the precursors so that-

    26. SB

      A precursor meaning something that creates it naturally.

    27. DS

      Exactly. There's one called NMN, not to be confused with M&M's, which will probably-

    28. SB

      [laughs]

    29. DS

      ...not make you live longer. And there's another one called NR. NMN is directly converted into NAD. You put two NMNs together, you get NAD in the cell. We know this for a fact. This isn't, isn't speculation. When you give a human NMN by swallowing it, a gram of it, you can t- you typically double the amount of NAD in your body. And we believe, and we have some evidence now in human clinical trials, that the sirtuins are imparting health benefits, reestablishing the epigenome, lowering body weight, uh, improving inflammation, uh, and even changing cholesterol levels in a positive way in humans.

    30. SB

      So I mean, I'm assuming you take NMN.

  24. 1:20:59 – 1:25:23

    The Fasting Method That Could Actually Extend Your Life

    1. DS

      so, so far so good.

    2. SB

      So far so good. I do wanna get into, and I will ask you in a second about the, the supplement stack that you would recommend for the average person. Um, but that's good to know. But just to close off on this point of fasting, is there a particular type of fasting method that you would recommend for someone who's trying to, you know, improve their longevity? 'Cause there's so many that I hear.

    3. DS

      Yeah.

    4. SB

      Sixteen hours, five days.

    5. DS

      I'm a scientist, so I go with what's proven. I'm not selling anything. So what the science says, first of all, is that there isn't one size fits all for everybody. Um, it, it often depends on what you can do personally. It's challenging to do this, right? You'll feel hungry for the first two weeks you try it. So I s- I would suggest the way I do it is I start by skipping one and then maybe one and a half meals. Uh, like what you do, try to go without a meal until three, four o'clock if you can. Maybe not the first day, right? If you do that the first day, you'll say, "This is crazy. I'm, I'm gonna grab a snack," and you won't do it. So go slowly. Build up to it. So the first day, I would say just don't eat breakfast and maybe have a, a snack mid-morning. A week later, try to go without breakfast completely until lunch, and eventually work up to what you do and I do, which is eat a very late lunch, if not go to dinner. What you get with that is ob-obviously you're not eating in bed, hopefully. So you've got the, the night fast starting, what would it be? Seven PM roughly. When do you finish dinner?

    6. SB

      Oh, God, no comment. [laughs]

    7. DS

      Okay.

    8. SB

      It's usually pretty late. Last night it was, you know, it was... This is probably why I don't eat very early the next day.

    9. DS

      Mm-hmm.

    10. SB

      Last night would've been about, I'm gonna say ten PM.

    11. DS

      Okay.

    12. SB

      It was super late. It was, it-- That's an extraordinary example. Usually, it would be eight or nine PM.

    13. DS

      Okay, but, but you've got at least thirteen, fourteen hours, which is good.

    14. SB

      Yeah.

    15. DS

      Try to aim for fourteen hours. Some people go sixteen hours, but that's a good start for fasting, and hopefully you can do that most days, five days a week.

    16. SB

      Mm-hmm.

    17. DS

      That's great, 'cause that means that you're turning on your sirtuins, raising your NAD. You're exerci- you exercise as well-

    18. SB

      Yeah

    19. DS

      ...so that's also adding to it. One thing that I've started doing is fasting for longer than just fourteen, sixteen hours. I try maybe once a month to go for three days without eating.

    20. SB

      Why?

    21. DS

      Because there's a type of cellular recycling that doesn't happen within the first sixteen hours. Um, you will enter ketosis, so you'll s- your body will start to change its metabolism, produce what's called ketone bodies. But the true, real deep clean-cleansing of old proteins and damage, damaged proteins happens after two and a half to three days, and it's called chaperone-mediated autophagy.

    22. SB

      Autophagy.

    23. DS

      Autophagy is the word for auto, self-eating. And it really kicks in for, with an extended fast.

    24. SB

      What's the evolutionary reason for that? What's going on there? Why does it take me two and a half days for this deep clean to happen?

    25. DS

      Uh, 'cause your body doesn't want to, uh, do it. It costs a lot of energy, and having to remake body parts is ex- energy expensive, and our body tries to conserve energy as much as possible. Uh, when you're fasting, what it'll, it needs to do is to use your body as fuel. So it'll start breaking down proteins for fuel that you need. So first of all, what'll happen is in the first few hours, you use glycogen from your, your liver. Your liver makes glucose. You'll feel a little bit hungry, but you'll eventually be fine. Then once you run, run out of glycogen, then you're gonna start breaking down fat and making ketones. Uh, that's when you start to get a bit of bad breath from, from that and you, but you feel great. When you're in a l- between about fifteen hours and twenty-four hours, that's when you get a lot of ketones, and your brain uses those for fuels. You'll have sharp mind, can remember things, you can focus on work if you ever get there. Beyond that, you need to break down fat and, uh, that is, uh, when your body is starting to do that. But ultimately what, what, what happens after three days is your body says, "Hey, I'm gonna start breaking down protein as well." And, uh, I wouldn't do that often because I don't wanna break down a lot of protein, but your body will start to turn over old proteins preferentially and a little bit of that, that's why I do it maybe once a month, has been shown, at least in animals, to be not just healthy, but life-extending.

  25. 1:25:23 – 1:26:45

    Is The Keto Diet A Longevity Hack—Or A Misguided Trend?

    1. SB

      On that point of ketosis-Um, I like being in a state of ketosis. I kind of cycle in and out of it during the year because I get so many of the like cognitive benefits. I'm more articulate on the podcast. I can think better. I feel better. I feel more focused and more attentive. Is ketosis, is the ketone diet, the keto diet, a healthy diet in your view? Is it-- What are the benefits of it? Is it something that you think is natural to be recommended?

    2. DS

      Well, I don't mind being controversial, but I do speak the truth. Um, there's not a lot of evidence that long-term the ke-ketogenic diet is healthy.

    3. SB

      Mm-hmm.

    4. DS

      It certainly doesn't correlate or associate with, uh, longevity. Short-term, okay, it does help people lose weight, no question. Uh, but I am rather concerned for people that don't have a balanced diet with an input of plant material, which has molecules that are unique to plants and you won't find in high-processed foods, uh, or meat. The evidence, speaking as a scientist, is that the long-term ketogenic diets are not going to be longevity inducing. The evidence is more having a lean diet with a focus on plants that are not overcooked and not ul-ultra-processed. That one is undoubtedly the healthiest if you can

  26. 1:26:45 – 1:30:34

    Why Plant-Based Eating Might Be The Simplest Longevity Upgrade

    1. DS

      do it.

    2. SB

      Do you eat meat?

    3. DS

      I do eat meat, but not like I used to. I used to think that a meal was not a meal unless I had a piece of meat there, and then the vegetables were the decoration, and I'd begrudgingly eat the green stuff. I've been flipped totally. Um, Serena, my partner, Serena Poon, is not just a nutritionist, but a longevity expert for the last twenty-six years. And so she came to my apartment, uh, which is now our apartment, and she just cleared out all the food that I had. Pretty much everything was either toxic or, uh, or just not healthy. It was ultra-processed. She said, "What are you eating that kind of peanut butter, you know, full of sugar?" So she, she's taught me how to live healthy. And so now I rarely eat meat. I rarely drink alcohol. I focus on really fresh, high quality, uh, preferably organic foods because I don't want pesticides and I, I don't want other contaminants, but I do know organic can be more, more expensive.

    4. SB

      Why not meat?

    5. DS

      So animals unfortunately don't make what are called polyphenols, which are a type of molecule that, uh, I believe, uh, and have evidence turns on the sirtuins and other pathways, biochemical reactions that delay aging. So sirtuins are just one of a few enzymes that control aging. We know this. There's sirtuins, there's mTOR, which responds to aminos, and another one called AMPK. So those three pathways are altered in just the right way by molecules found only in plants, well, and a small extent in fun-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. So right here, I hope you don't mind me mentioning that there are some, some food in front of us, and I'm looking at blueberries here. Blueberries are packed with polyphenols. One of the reasons they have purple color is the polyphenols have the color. And as Serena would tell you, eat the rainbow. I call it xenohormesis, which is not as attractive, but xenohormesis is the same idea as eat the rainbow. That by eating plants that have a lot of these molecules that are often produced by stressed plants, you get the benefits.

    6. SB

      When you say stress-stressed plants?

    7. DS

      So plants will be stressed just like we are. If you don't give them enough water, food, too much sunlight, not enou-not enough sunlight. They, in their defense, they make polyphenols. There's a whole bunch of them. Resveratrol, fisetin, quercetin, there's, there's hundreds. Uh, this one has, um, anthocyanidins, that's the color. These activate these adversity responses in our cells. The sirtuins will be get activated by molecules in this blueberry.

    8. SB

      So if I eat this blueberry, those conductors that conduct some of the aging process you talked about, making sure my cells don't have an identity crisis, fixing the, the s- the negative stress that's going on in my, um, in my cells, they will be benefited by me eat-eating this blueberry?

    9. DS

      Yeah. It's, it's like a, a, a free hack, right? You can eat something that's yummy, but you're also getting the benefits by mimicking fasting and exercise in your food as well. The sirtuins don't just need NAD. That's the gas pedal. That's the petrol for those of you in the British world and Commonwealth. The fuel for sirtuins is NAD. The accelerator pedal are the polyphenols in fruits and vegetables like resveratrol, quercetin, which we know when you give them to sirtuins, they get hyperactivated.

    10. SB

      And when you say eat the rainbow,

  27. 1:30:34 – 1:31:39

    What Makes Matcha So Powerful—And Is It Overhyped?

    1. SB

      you mean eat colorful looking food?

    2. DS

      Because that's an, an easy way to remember how to eat foods that have the most polyphenols. I'll give you a really good example, Steven. Serena put me onto green tea matcha. Right? So matcha tea, if you haven't tried it, uh, I'm sure you've tried it, but those of you who haven't tried it, I highly recommend it. It, it tastes great. The reason for it switching from coffee mainly to matcha in the morning for me is that it's full of polyphenols. Why is it full of polyphenols? It's not just because it's green tea, which is not naturally healthy, but the growers of those plants in Japan, typically, they shade the plants 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 in the tea, but the polyphenols are super high. And 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.

  28. 1:31:39 – 1:33:31

    Is Red Wine Helping Your Health—Or Quietly Hurting It?

    1. DS

      Same with red wine, by the way, but the alcohol can be an issue. But absent alcohol, red wine is very good for you.

    2. SB

      Okay. Without the alcohol.

    3. DS

      It's unfortunate. You know, I, I... One of my papers in 1996 caused red wine sales to go up 30% and stayed up. I apologized for saying that red wine every day was healthy. Doctors were recommending it, remember?

    4. SB

      Yeah.

    5. DS

      But I now changed my mind. I have to say that I no longer believe having one glass of red wine every day is healthy, in my opinion, and I've stopped drinking red wine every day. Instead, I take polyphenols from red wine and from vegetables, either in a pill or in my food as a substitute, because the evidence for alcohol is rather damning. There's a UK Biobank study, and the UK looked at thousands of people's MRI scan of their brain who were drinking one glass of alcohol a day, and there was a statistical difference between people that were drinking one glass a day and were not in terms of brain size and gray matter. Of course, the gray matter was tended to be smaller in those that drank even slightly.

    6. SB

      Hmm. Yeah, I do, um, I actually have a matcha company. It's, um, it was this year voted the fastest growing company in the UK. Um, it's by s- s- some founders that I invested in, um, Levi, Teddy and Marissa from Dragon's Den, and it's been an absolute unbelievable in, uh, business. Unbelievable.

    7. DS

      So tell us, where do, where do I get it?

    8. SB

      Japan. You get the matcha from Japan, but the company's called Perfect Tea. People know about it, um, 'cause I've talked about it before. But i- I didn't realize when I made the investment that matcha was considered by many to also be very healthy, especially a health alternative to certain energy products on the market that you get in cans that give you, um... I shan't get sued. [laughs]

    9. DS

      Yeah.

    10. SB

      But the other thing that, um, uh, the company

  29. 1:33:31 – 1:34:33

    The Truth About Exogenous Ketones And What They Really Do

    1. SB

      I invested in is this one here called, uh, Ketone-IQ. I'm a co-owner of this company as well and-

    2. DS

      Yeah. Yeah, I love that, uh, love that company and the CEO, uh, Michael. Good guy.

    3. SB

      What's your thoughts on exogenous ketones? Like drinking ketones?

    4. DS

      I do it. In fact, that I drink Ketone-IQ before I do a podcast.

    5. SB

      Why?

    6. DS

      It improves my clarity, I find. Um, I also believe the science, and there have been multiple studies now in people, in some of the, the science comes out of Ketone-IQ, but also independent studies have shown that it's extremely healthy for the heart and, uh, there's new studies that show for the brain as well, it can be healthy. The brain uses ketones like beta-hydroxybutyrate or in that one it's one three butanediol. Um, just a shot of that will give the brain food that it needs rather than the body having to make it. Um, and you get, I believe, and I feel it, I get the clarity of fasting without being in a fasted state, but I also drink it when I'm fasting to give it the body the extra boost that it needs.

  30. 1:34:33 – 1:37:13

    Why Starting Statins At 30 Might Not Be As Extreme As It Sounds

    1. SB

      Mm-hmm. And on this point of diet, one of the things that I was told by my doctor when I did a, like one of those blood tests, was he cautioned me about bad cholesterol. He said to me something along the lines that I need to be careful about the bad cholesterol, and there's been lots of conversation about cholesterol, good, bad. What's your perspective on this conversation around bad ch- cholesterol, which has been thought to increase, um, certain foods have been thought to increase bad cholesterol, um, which is very, very detrimental to our health?

    2. DS

      I didn't realize there was a debate. At least in my world, there is no debate. Um, if you're referring to, do you wanna get your LDL cholesterol as low as possible?

    3. SB

      Yeah.

    4. DS

      Definitely.

    5. SB

      Oh, really? Okay. So it's-

    6. DS

      Yeah. I mean, the science is irrefutable. There's thousands of people in studies. Now, I think I know what you were, you were talking about. There are, there are some stories that you need cholesterol in your brain, and if you inhibit it, you might affect your brain function. Um, you also need it for repair of arteries. But there's no evidence that that's a problem. In fact, it's, it's a little known fact that the brain doesn't use the cholesterol from the bloodstream. It makes its own. So I've actually been on a statin to lower my LDL since I was 30.

    7. SB

      Really?

    8. DS

      Well, I had high cholesterol. It's in my family. But I went to my doctor and I said, "I want to go on these new drugs," at the time, statins. And he said, "Why? You don't have heart disease yet." And I said, "Why would I wait? Get me on it. I want to be on it." And in those days it was very weird to give someone a statin at age 30 with no evidence of heart disease. But as you know, I'm of the opinion that we shouldn't wait till we get diseases to treat them. We should preempt that and start early in life. And so, yeah, I insisted with my doctor, initially with statins, but on all of these things, I go in and I say, "I need you to prescribe me this test. I need this medicine." And eventually, after talking it over with him, he typically prescribes me something or gets me a test. But I've been fighting the system and my doctor's at Harvard, so he's a good doctor, but conservative. The old way of doing medicine is if you're not sick, we're not gonna give you a medicine, certainly not if you're young and healthy. Uh, but that has to change.

    9. SB

      So you're saying that I should be on statins potentially?

    10. DS

      Well, what's your LDL level?

    11. SB

      Not... I don't think it's great. I think I ate too much bacon or something. [laughs]

    12. DS

      Well, we can talk about food and cholesterol 'cause it depends whether you absorb sitosterol or not. We can test for that. But if you do absorb cholesterol more than most, I would say that you may wanna change your diet at a minimum.

    13. SB

      On this plate here in front of

  31. 1:37:13 – 1:41:04

    The 5 Foods That Could Have The Biggest Impact On Your Lifespan

    1. SB

      us, I have the top five foods that I believe you think are great for reversing aging. Am I correct? Does that, does that-

    2. DS

      These are great choices, yeah.

    3. SB

      So what are these and why? So we've already done the blueberries and we've t- you've explained to me about polyphenols, and they're rich in them, which I understand.

    4. DS

      Mm-hmm.

    5. SB

      And they're low in sugar, right?

    6. DS

      Well, they're not low in sugar, so don't eat a ton of them. A handful is fine.Um, as a snack. It's also known that having too much sugar is bad for longevity.

    7. SB

      Okay.

    8. DS

      So keep your blood sugar levels steady and low as much as you can, so don't eat too many of those. A better choice than blueberries would be something like matcha, which is not full of sugar. In fact, if you go to some of these chains that sell matcha and it tastes really sweet, you're gonna reverse the effects of any polyphenols by drinking that much sugar. So I always have unsweetened matcha.

    9. SB

      Okay.

    10. DS

      So now we've got avocados here.

    11. SB

      Yep.

    12. DS

      Yep. Avocados, um, they're not so much known for their polyphenols, though they do have them. It's the type of fats, the polyunsaturated fats. They help with satiety, so you're not gonna be as hungry. Uh, so if you put that on your sandwich at lunch, you're not gonna feel peckish. And they're, uh, highly anti-inflammatory as well. The molecules are in there, and the fats are very good for you.

    13. SB

      Extra virgin olive oil?

    14. DS

      Oh, yeah. Excellent. The, the type of, uh, oils that are in there are very healthy. There's omega-9, which is also known to activate sirtuins, and again, if you have the right, uh, grower and this has been cold pressed, not too processed and stressed before harvesting, you'll have huge amounts of polyphenols as well.

    15. SB

      I really hope that this is what the team said it was. [laughs] This has happened before where I tried something and I thought-

    16. DS

      Yeah

    17. SB

      ... it was something else, but it, it was some... Basically, it was a white powder-

    18. DS

      Uh-huh

    19. SB

      ... and it was labeled with something for original-

    20. DS

      What, what could it be? Yeah, yellow liquid

    21. SB

      ... urine.

    22. DS

      Yellow liquid. [laughs]

    23. SB

      It could be urine or something. Ah, urine. It's urine. No, I'm joking. It's not. [laughs] I can-

    24. DS

      I don't think drinking urine, uh-

    25. SB

      [laughs]

    26. DS

      ... is, is longevity. But yeah, on and off, I, I do take a teaspoon of olive oil in the morning and mix it with, uh, resveratrol, uh, polyphenol.

    27. SB

      Oh, in... Okay, interesting.

    28. DS

      Mm-hmm.

    29. SB

      Okay, so extra virgin olive oil. Good. Good.

    30. DS

      Yeah.

  32. 1:41:04 – 1:46:45

    Why Taking Fewer Supplements Might Actually Be Better

    1. SB

      You've used this word pulsing before. Uh, you believe that the body should go through cycles of stress and recovery rather than receiving constant daily inputs. When you say pulsing, what do you mean? What-- Give me an example of pulsing and why I need to do that.

    2. DS

      Well, there's, there's a few examples. The first time I came across this result as a scientist was resveratrol. So resveratrol is found in red wine, among other things.

    3. SB

      Mm-hmm.

    4. DS

      And, uh, it's thought to give the health benefits of red wine, and we fed it to mice, fat mice, skinny mice, old mice, and it worked very well in the fat mice. It made them thinner. It made them live longer. It cured most of their diseases. They lived about, I think it was fifteen, twenty percent longer. Then we gave it to normal mice every day, and they lived a little bit longer, but not significantly.

    5. SB

      Resveratrol?

    6. DS

      Resveratrol. What we found, to my surprise, w- does-- when we gave old mice resveratrol, not every day, but every second day, then they lived significantly longer. So then I thought, "Well, maybe giving them a foreign substance every day is not good. Maybe there's some side effect that's counteracting the benefit." The other thing I wanna mention, I said there's a few examples. Another good one is metformin. Metformin has been shown to make athletes and bodybuilders and people who go to the gym, weightlifters, um, do less repetitions, and as a result, their muscles are about five percent less compared to those that don't take metformin in size. I don't think it's molecular. I think it's because you feel a little bit weaker with metformin because it's actually interfering with your body's ability to make energy through mitochondria. Mitochondria, I think most people have heard of the little power packs living in our cells, originally bacteria that came into our bodies. The point is that by pulsing metformin, I think that's a better way to do it for longevity.

    7. SB

      You mean cycling it, so like doing it every other day or-

    8. DS

      Yeah.

    9. SB

      Yeah. Okay.

    10. DS

      Yeah, I don't take-- If I take metformin or the natural equivalent, which is berberine, if you don't wanna take the drug, you can take berberine, um, that also activates this AMPK, this other sirtuin-like pathway. Taking it every other day I think is better, and, and particularly if you like to work out, don't take the metformin a few hours before you work out. Take it after or maybe skip it that day. I think that's a better approach.

    11. SB

      You know, every once in a while you come across a product that has such a huge impact on your life that you'd probably describe it as a game changer, and I would say-For about thirty-five to forty percent of my team, they would currently describe this product that I have in front of me called Ketone IQ, which you can get at ketone.com, as a game changer. But the reason I became a co-owner of this company and the reason why they, they now are a sponsor of this podcast is because one day when I came to work, there was a box of this stuff sat on my desk. I had no idea what it was. Lily in my team says that this company have been in touch. So I went upstairs, tried it, and quite frankly, the rest is history. In terms of my focus, my energy levels, how I feel, how I work, how productive I am, game changer. So if you wanna give it a try, visit ketone.com/stephen for thirty percent off. You'll also get a free gift with your second shipment. And now you can find Ketone IQ at Target stores across the United States, where your first shot is completely free of charge. [page flipping] We have finally caved in. So many of you have asked us if we could bundle the Conversation Cards with The 1% Diary. For those of you that don't know, every single time a guest sits here with me in the chair, they leave a question in the Diary of a CEO, and then I ask that question to the next guest. We don't release those questions in any environment other than on these incredible Conversation Cards. These have become a fantastic tool for people in relationships, people in teams, in big corporations, and also family members to connect with each other. With that, we also have the 1% Diary, which is this incredible tool to change habits in your life. So many of you have asked if it was possible to buy both at the same time, especially people in big companies. So what we've done is we've bundled them together, and you can buy both at the same time. And if you wanna drive connection and instill habit change in your company, head to thediary.com to inquire, and our team will be in touch. [page flipping] We talked about exercise earlier. On page one hundred and two of your book, you talk about how there's a CDC-funded study that found people who exercise regularly, about thirty minutes of jogging five days a week, have telomeres that look ten years younger than sedentary people, people that just sit around all day and do-- don't do much exercise, which is pretty remarkable. How do we know it's the exercise and not something else? Like, how are we able to establish causation there?

    12. DS

      Yeah, we don't. We don't. Unfortunately, all of these association studies just lead to a need to do placebo-controlled or at least controlled trials in people. So we don't know for sure, speaking like a scientist. But there have been studies where people are told to do exercise and those that are told to sit, and then you can compare telomere length, and that has been shown. So that's a much better evidence of causation. But you're right. When you see an association, it could be the people who do exercise also eat well and drink matcha.

    13. SB

      Sleep better.

    14. DS

      Exactly. So you have to be careful interpreting these association studies always. But when you've got a placebo-controlled trial or, you know, these stu- these studies that are called, uh, prospective, not retrospective studies, then they're better. So telomeres are the ends of chromosomes that get shortened as you, as you get older. Um, we used to use them really as a good indicator of age, biological age. Now we use the epigenome and the DNA methylation chemicals as a better clock.

    15. SB

      And

  33. 1:46:45 – 1:49:56

    Do Saunas And Cold Plunges Deliver Real Results—Or Just Hype?

    1. SB

      then cold plunges and saunas.

    2. DS

      Yeah, let's get to those.

    3. SB

      I've got a sauna in the house, but I never use it, to be honest.

    4. DS

      You should.

    5. SB

      But if you, if you tell me I should-

    6. DS

      You should

    7. SB

      ...maybe I'll give it a shot.

    8. DS

      We should actually jump in there after this.

    9. SB

      Well, [chuckles] your girlfriend's still here, David Sinclair. [laughs]

    10. DS

      She can come too.

    11. SB

      Okay. [laughs]

    12. DS

      Uh, so saunas are, in my mind, it, it's not even a question. They are proven to be beneficial for multiple reasons: heart disease and even long-term mortality.

    13. SB

      What's going on in the sauna, in the heat?

    14. DS

      Anyone who says they know is lying. We don't know. But one theory that I like, and it also goes back to yeast cells, there are what are called heat shock proteins that come on and defend the cell when they-- the cell senses heat. And it may be that these heat shock defense proteins, called HSC-- HSPs, uh, come on when we breathe in this moist hot air. The moisture actually seems to help as well. And in many studies, mostly on Finnish men, businessmen, uh, those that go into their home saunas, and the majority of homes in Finland do have saunas, so they can do these studies pretty easily. The bottom line is that those that didn't do regular, quote-unquote, "sauna bathing," uh, tended to die earlier, uh, in particular from heart disease and cardiovascular events than, than those that did regular sauna bathing. So I'm, I'm a big advocate of sauna. I don't have one in my house, but I do have a really hot steam shower, which I use regularly every day.

    15. SB

      And is there a difference between the steam room and the sauna in terms of the impact here?

    16. DS

      I think a sauna is better 'cause it gets hotter. Yeah, and I, I would have a sauna if I had my choice.

    17. SB

      And the cold plunge?

    18. DS

      Not a lot of data, but there's a lot of theory that, again, hormesis, adversity, feeling better. There's, there's some evidence that it can actually help with muscle repair after workouts, but I think we need a lot more research in that regard. But then nevertheless, I used to do it, um, before I was so busy and traveling the world. Um, and I certainly feel better. So even if I don't-- didn't live longer because of it, I, I definitely had more mental clarity, and I felt better in general.

    19. SB

      But if, but if you were, if you were prioritizing all of the things we've talked about so far and you had to pick one...

    20. DS

      Do I have to pick one? 'Cause you need more than one. But I-

    21. SB

      But just-

    22. DS

      ... I'm happy to-

    23. SB

      Just in terms of, like, the most important one that's maybe the first domino.

    24. DS

      Yeah. I, I would say that the... A combination of what the easiest, biggest impact you can have, combine that, that would be skipping meals.

    25. SB

      Skipping meals?

    26. DS

      Skipping meals. And then a close second would be exercise that includes losing your breath for at least five minutes, three times a week. So what do I mean by losing your breath for five minutes? When you couldn't carry out a conversation easily, that you're panting. If you're not panting and you're just lifting weights, that's not gonna have the, the kind of benefit.

    27. SB

      Why?

    28. DS

      We don't know. But it's been shown that the health benefitsAnd those that live long tend to do a lot more aerobic exercise, not just weights. But both are important for mobility, strength, falling in older age, and hormones like testosterone.

    29. SB

      Red light therapy. Um,

  34. 1:49:56 – 1:50:41

    Does Red Light Therapy Actually Work—Or Is It Wishful Thinking?

    1. SB

      the red light masks.

    2. DS

      Yeah. Um-

    3. SB

      Red light saunas.

    4. DS

      At first I was skeptical, uh, but I've done the research on the research, um, and it looks reasonable. I, I use a red light cap on my head to preserve my hairline. And, uh, there's some now good evidence that the mitochondria, which are the power packs and a lot of good things come from mitochondria, they actually are rejuvenated, either rejuvenated or enhanced by this certain wavelengths of red light. You have to get the wavelength right, but, uh, it's not BS. It sounds like BS, right? Oh, you shine light on your skin and it gets better or you get your hair. But, uh, I think that there's good evidence now that, that it's not BS.

    5. SB

      And in terms of the supplement

  35. 1:50:41 – 1:55:01

    What A “Perfect” Supplement Stack Really Looks Like

    1. SB

      stack that you take every day-

    2. DS

      Mm-hmm

    3. SB

      ... if I was to look at the-- on a, if a, on a g- great week where you just did everything right, what would your supplement stack look like? And I know this evolves over time, so I'm very keen to hear what it is right now.

    4. DS

      Mm-hmm. Yeah. Well, that, that would be another podcast, uh-

    5. SB

      [laughs]

    6. DS

      ... to go through each one of the things.

    7. SB

      Really?

    8. DS

      Well, I, I, I travel with Serena with a, with a, a little, little case.

    9. SB

      Have you got it?

    10. DS

      I've got it here.

    11. SB

      Can I see it?

    12. DS

      Well, no, it's not in, it's not in the studio.

    13. SB

      Oh, okay.

    14. DS

      I didn't bring it with me.

    15. SB

      Can you send me a photo?

    16. DS

      Sure. Uh, I couldn't publicly share it because it, it would be posted all over the internet. Would- Things would go crazy. But I can tell you the, the main things.

    17. SB

      Why would it go crazy on the internet? What do you think? Because it's, because it's, because there's a lot in there?

    18. DS

      Well, some of the things are experimental, and I wouldn't want people-

    19. SB

      To-

    20. DS

      ... to go nuts about it-

    21. SB

      Yeah. Okay

    22. DS

      ... because it's still experimental. I'm okay experimenting on mym- myself. I'm not okay advocating for things that are not yet proven or known to be absolutely safe.

    23. SB

      Okay. So give me the ones that you know to be safe.

    24. DS

      Uh, well, the NMN we've covered.

    25. SB

      Yep.

    26. DS

      Resveratrol and either metformin or berberine.

    27. SB

      Yeah.

    28. DS

      Okay. Spermidine.

    29. SB

      Spermidine?

    30. DS

      Yeah. And the quantities are either on the screen or in my book, if you want to know exactly.

  36. 1:55:01 – 1:57:48

    Aspirin: Miracle Drug Or Risky Habit?

    1. SB

      What about aspirin? I read that somewhere.

    2. DS

      Yeah, that, that, that could be a whole podcast actually. But the briefly, I take a baby aspirin every day, even though some doctors, um, and some institutions of doctors say don't take it anymore, even though it used to be prescribed and recommended. Why? A large study looked at the risks versus benefits. So the known benefits are you inhi- inhibit platelets, you get less clotting, you get less potentially, uh, stroke and heart attack. But there are also some downsides in some people. You can have more bleeding in the stomach. And when the doctors association weighed up those risks versus benefit, they said, "Oopsie, we're not gonna recommend aspirin anymore."But that's for the average person. Someone like me, I believe it makes perfect sense to take aspirin every day, most days at least, when I remember, and that's because I have high risk of cardiovascular disease. I don't just have high cholesterol naturally, I have high levels of something called Lp little a. Capital Lp, parentheses, little a. And this is a molecule that's just as important as cholesterol, LDL. Um, Lp little a is a protein that inserts itself into cholesterol particles that circulate your blood and gets in- helps insert into plaque. So I naturally, genetically, having an ancestry of, um, Judaism and going back to my great ancestors, which by the way I traced back a thousand years during, during Christmas, those people that I descended from have this Lp little a gene that makes a lot of it. And so I try to bring Lp little a levels down. Most people should test for it. Ask your doctor about Lp little a and get it tested. High levels like me, thirty, forty, uh, you wanna bring it down 'cause it, it's actually very important for longevity. Uh, normal levels of around ten or so or less than a doctor wouldn't panic. So Lp little a, uh, get it tested. The way I'm bringing it down, just a little, uh, tidbit, again, 'cause I love you, Steven, is I'm taking high dose vitamin B3 or niacin. Now, it can be uncomfortable for some people to take it because it gives flushing. You get little tingling in your skin, and if you're not used to it or you don't take it with an aspirin, you'll feel hot, almost like menopause, apparently. And so I, I, I take it, I built up to it. I'm taking half a gram. Some people take a gram, and that's one of the few things that's been known to bring down the levels of Lp little a. There are drugs that are in development, even in phase three, that look promising, but until they're on the market, I'm taking niacin instead.

    3. SB

      What's the best, uh, treatment you've discovered for hair

  37. 1:57:48 – 1:59:24

    The Real Way To Fight Hair Loss Before It’s Too Late

    1. SB

      loss? Hair loss-

    2. DS

      Ooh

    3. SB

      ... hair graying, that kind of thing.

    4. DS

      Yeah. So my father went bald befo- before thirty. Like completely bald.

    5. SB

      Wow.

    6. DS

      Right? And completely, almost completely gray by the time he was forty. So I'm super lucky, right? I thought I'd be bald at thirty. I was pretty worried about it. So I've been doing the right things intentionally. So what I do is this red light cap, when I can, I don't travel with it, but, uh, when I can, that's for six minutes. Stick it on there.

    7. SB

      Proven? Is it effective?

    8. DS

      Yes, proven. It's proven to slow... It doesn't necessarily give you your hair back, but when it comes to hair loss, don't wait till you see the hair loss. That can be too late, okay? You're, you're good.

    9. SB

      I'm okay. [laughs]

    10. DS

      You're good. But I know a lot of men are, are concerned. It's understandable. I'm taking a hormone mimetic to stop, uh, DHT, which is the form of testosterone that leads to men-related hair loss, right? So o- one of the reasons that women don't lose hair as much as men is this DHT. So I'm, I'm, I'm blocking that.

    11. SB

      So, so let me get that straight. You're not taking testosterone?

    12. DS

      No. No.

    13. SB

      Because that's gonna accelerate your hair loss.

    14. DS

      Well, it can if it raises, uh, DHT. The best way to raise testosterone naturally is to build up muscle, especially your legs, your back, big muscles. That's another reason to work out and maintain muscle mass, which I need to do more of. You look like you're in good shape already. But yeah, anyone who is losing testosterone is, is below a level of about four hundred, highly recommend hitting the gym. It'll go back up.

    15. SB

      Do you recommend men taking testosterone replacement?

  38. 1:59:24 – 2:00:02

    Should Men Take Testosterone—And What Are The Trade-Offs?

    1. DS

      Um, well, I'm a scientist, so I don't recommend drugs, but, um, I don't think it's necessary for most men. I would start with, uh, reducing stress, sleeping well, exercising, building up muscle mass, uh, and then if that doesn't work, yeah, talk to your physician. There, there's not a big downside. There's not a risk of cancer to taking testosterone. Um, uh, one of my good friends has done many clinical trials with testosterone. So I think there's a use of... use for it, but it doesn't lead to longevity. That was very clear. So for, for health reasons, yes. For longevity, no need.

    2. SB

      What are, what are some of the, um...

  39. 2:00:02 – 2:10:39

    The Future Of Ageing: What Happens Next Will Surprise You

    1. SB

      You know, when I started watching your, your videos many years ago and listening to your podcast and following you on Twitter, I, I wondered, you know, there's so much information you can put out there because you're a scientist and scientists are very rigorous, but you also must have a set of really interesting predictions or visions of the, what the future looks like that you don't probably always talk about because they're not scientific. They're not based on anything. They are maybe first principles in your own mind that formed where you go, "Actually, I think the world might look like this, and I think it might happen then." I'd love to hear about some of these.

    2. DS

      Yeah. Well-

    3. SB

      And I understand they're not rigorous and they're not scientific.

    4. DS

      I, I, I'm happy to. Uh, what happens to me, 'cause I'm a scientist and, you know, I'm, I'm part of this ivory tower at Harvard where we can only stick to facts, and if you go beyond that, it's, it's a, it's a crime. And I've been criticized for that. Um, but I think, you know, as humans, life's interesting when it comes to predicting the future, and like you, I'm very curious, where is humanity headed? I see a future as different from this world as our world is from two hundred years ago, and that will happen in our lifetime. Different in that a hundred years ago or more, if you had an infected splinter, there's a reasonable chance you could die. Childbirth, you could die. Smallpox. These are things that 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. We will look back at today and say, "How did those people get through life? What a horrible world they lived in." That, I believe, is, is the future that humanity is headed for and way faster than most people realize is coming.The kind of breakthroughs that we've discussed today, most people have never heard about the fact that we are aiming and already do cure blindness in monkeys, like pure blindness. This isn't just, "Oh, I can't see a little bit." These are completely blind animals, um, and that they can see again in a matter of six weeks. This is remarkable stuff, right? And if it works this year in people, it's gonna be a really big deal because for the first time, we'll have, we have, we'll have shown in humans that the body can be reset safely. And it-- the eye is just the beginning, right? The future looks like we can rejuvenate potentially any tissue. If you have a bad liver, we'll make it young again. Bad brain, you've lost your memory, we'll give you those memories back again. We do this in mice in my lab all the time. It's not even a big deal in my lab anymore to reverse the age of tissues in an animal, in an animal in a matter of weeks. That is coming for humanity, hopefully initially this year, but even if that doesn't work, it's only a technical issue. We'll solve that. You might be wondering, how do we get the rejuvenative genes into the body? And what we do is we use a package that, uh, is able to get into cells, and this is a package that, uh, resembles a virus. It's not a virus. It doesn't cause disease. It's not infectious. But we package our three genes inside the virus, uh, the virus-like, uh, substance, and we close it up. We just made a bunch of this in Europe for the clinical trial that's gonna begin. Just making this is difficult. It took us about a year to make it and was about, I think it was ten million dollars. Right now it's expensive to do this. Eventually, it will be cheap, and eventually it will be a cheap pill, hopefully. We have trillions of these molecules, these delivery vehicles that will go... Steven, pass me the eye. We're getting back this eye model. These delivery vehicles with our three genes will be delivered, obviously these are microscopic. They go in through the eye with a, with a quick jab, right? It sounds horrible, but a quick jab into the eye. If you're blind, who cares?

    5. SB

      Yeah.

    6. DS

      It's two seconds of discomfort. Now you've got the little virus, which I'm going to break off the stand here. The little virus, there's billions of them, trillions of them in the eye. Now they infect specifically the nerves at the back of the eye and the retina.

    7. SB

      How do they know what to infect?

    8. DS

      Because these little balls on the, on the package direct it specifically by design, by our lab's design, just to those nerves at the back of the eye. If we change these little proteins on the surface, we can send it to the liver or to the brain. This is the zip code, the post code for where we want to send our three genes.

    9. SB

      Mm-hmm.

    10. DS

      But this one's designed for the eye. It's called an AAV2. Um, long story short, these are ready to go into humans. We're just waiting for FDA approval to inject it into a blind patient to see what happens.

    11. SB

      And then inside there is the protein which is gonna fix the-

    12. DS

      Yeah. Well, actually, not the protein. What actually happens is when this goes in the eye, this-- what I'm-- So what I'm holding up looks like a little ball with red dots on it. Um, it looks like a virus, but it's not. It's a package. Now, what happens is these trillions of little packages go into the fluid. Now they, they dock with the cells at the back of the eye. They get inside the cell, and they open up, and out comes this little package that we've made. This is a protein package. Each one of these little dots on this little s-soccer ball is a protein. That's now inside the cell. This is a little spaceship that opens up, and out of that comes the DNA. This is a loop of DNA just here. These are-- this is the DNA package that we put in there, trillions of them. One of them gets into one cell and now stays in that cell forever. So that person or the monkey or the mouse that we've treated becomes a transgenic person with genes that we've put in permanently into the back of the eye. But they don't do anything until we tell them to. That's now just sitting there. We've engineered it uniquely and patented it, the ability to turn on those three genes whenever we want and turn them off again whenever we want.

    13. SB

      How?

    14. DS

      We give them doxycycline. It's used for malaria, it's used for Lyme disease, and we're using it in this case to turn these genes on. So the patients will get their doxycycline. Uh, we'll give them some probiotics to restore... Hopefully, we'll, we'll restore their microbiome, of course. But the idea is that this doxycycline will turn on these three genes for about eight weeks, and the doctor in charge of the clinical trial, one of them's at Harvard, a good friend of mine, he'll measure the vision of the first patient before the treatment and of course, regular intervals. And if all goes well, because we're treating patients, not healthy volunteers in the first trial, we should know within either one or two patients if it works. Because we're not drawing a graph, it's either gonna work or it isn't.

    15. SB

      Mm-hmm.

    16. DS

      The patient gets better eyesight or d- or they don't. So by this time next year, we will know if it works or not, maybe even sooner. But publicly, we may know if this works, and if it works, the eye is just the beginning. So the first disease to treat is glaucoma, pressure in the eye. There's also a stroke in the eye, which is becoming more prevalent in the world because of the Ozempic and other weight loss drugs, and people go blind overnight, and there's nothing that you can do for those patients.They're blind, and their other eye cannot-- can go a few months later. It's very scary for them. These are young people. A friend of mine had it happen. Pretty common these days, about thirty thousand people each year in the US alone. But these two diseases are the beginning. If they work, then we go on to macular degeneration, which is the largest cause of blindness besides glaucoma. Then we'll go on to liver, then maybe the lung, the skin, and we'll keep going from there. We'll make different packages for different organs, and ultimately, we want to rejuvenate the entire body. The company, uh, people might wanna know, it's called Life Biosciences. It's a private company. But Life Biosciences, I'm very proud of the scientists who are doing this work. Their goal is to really make the world's first age reversal medicine as a pill, and we're working with them using AI to find that molecule.

    17. SB

      And when do you think you might have it, if you had to forecast?

    18. DS

      Uh, well-

    19. SB

      The world's first age reversal molecule that's...

    20. DS

      Well, we have-- Right now we're down to three molecules that work, and we're using AI to make all of those three in one, and we're, we're in the middle of it. We screened about eight billion candidates using AI, and right now we're doing the bench lab work to see if one of them or more works. And for us to put that in humans is still a number of years away, but we should know within a year or two, uh, if we're right, because we'll, we'll put them into mice, and if they get younger and live longer, then we're really onto something important. And the reason that I wanna make a pill, um, is, is important for the planet. These drugs are expensive. I mentioned ten million bucks to do a clinical trial. These are expensive. They could cost over a hundred thousand dollars per treatment. That's not gonna be for everybody. It's worth it if you're blind. It's worth it for the country to cure blindness. But what if it could be, instead of a hundred thousand dollars, a hundred dollars? That's what I'm working for. I wanna democratize this technology so anyone, even in Kenya, can take these medicines.

    21. SB

      David, what's the most important thing we haven't talked about that we should have talked about as it relates to-

    22. DS

      Mm.

    23. SB

      -the future, longevity, and these adjacent subjects?

    24. DS

      There's a lot of things. And there's, there's pushback, there's philosophical pushback from religious folks who don't believe that we should play God, and I would, I would argue to them that we've been doing that as a species for thousands of years, changing our biology, taking medicines,

  40. 2:10:39 – 2:39:28

    Are Scientists Crossing A Line—Or Pushing Humanity Forward?

    1. DS

      plant medicines originally. What about this room is natural?

    2. SB

      Hmm.

    3. DS

      Right? We change our world as species. Aging is no different. In fact, it's crazy that we haven't worked on it sooner.

    4. SB

      Do you believe in God?

    5. DS

      So the, the, the, the short answer is I believe that there is something beyond reality as we see it. You know, I study physics. Physics is so weird, and anyone who says they understand the quantum world or quantum mechanics is, I think, is also lying. It's, it's so bizarre, quantum entanglement, simulation theory. So I believe that, that this, this is not a solid desk. I believe that there are multiple versions of it, maybe infinite number of versions of this desk. Um-

    6. SB

      We've got four.

    7. DS

      You do?

    8. SB

      We've got four of them.

    9. DS

      Yeah.

    10. SB

      [laughs]

    11. DS

      Then it's four times infinity. Um, I also, I also 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, even retrospectively in time, apparently.

    12. SB

      When you look at them?

    13. DS

      When you observe them. You can use a camera or you can use your eyes. Usually it's a d-detector. But the, the m-detection and then conscious interpretation of a particle's behavior changes how it acts. So does, does this mean that there's something behind this wall unless we look at it? Maybe. Maybe. Maybe observation creates reality. We know it influences reality. So I don't know if I would call it God, but I'm definitely spiritual in a scientific way.

    14. SB

      Has it ever dawned on you that actually you might be the only real person here, and actually we only-- we all render when you walked in, David.

    15. DS

      Mm.

    16. SB

      I wasn't here before.

    17. DS

      Yeah. Uh, well, that's even plausible, but that would be very narcissistic. [laughs]

    18. SB

      [laughs] I, I actually-- I just rendered when you walked into the house today. I, I, I've-- I don't exist.

    19. DS

      Well, there's no way of proving it right or wrong, actually. Um, I think most kids think that initially-

    20. SB

      [laughs]

    21. DS

      -but then you, then you realize it's probably the least likely explanation for the world. But there is some, there is some truth to that, uh, in terms of physics. Um-

    22. SB

      Do you think we're in a simulation?

    23. DS

      I think there's a better than fifty percent chance that this is simulated.

    24. SB

      So you think it's probably a simulation?

    25. DS

      That's another way. I think it's probably a simulation. Certainly, the world that we think it is is not the world we think it is.

    26. SB

      How can you be so sure?

    27. DS

      Because when you get down to measuring it at the fundamental level, reality doesn't exist the way we think it does. Things are created, things change just by human observation. That is the weirdest thing that you could ever find in science. I don't know why we aren't talking about it more. This reality cannot be true if me looking at this DNA molecule here affects the, the, the actual particles inside it.

    28. SB

      So I'm-- I might be sort of projecting it.

    29. DS

      Yeah. You create realities of particles, at least, 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?

    30. SB

      How do we know that that's true? How do we know that particles change based on observation?

Episode duration: 2:29:06

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