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The Diary Of A CEO with Steven Bartlett

David Sinclair: Can Aging Be Reversed? After 8 Weeks, Cells Appeared 75% Younger In Tests!

23 Mar 2026 · 2h 36m · Steven Bartlett, David Sinclair · 24 quoted facts

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In brief

David Sinclair argues that aging is not simple wear and tear but a loss of biological information, mainly in the epigenome, the chemical layer that tells each cell what kind of cell it is. Because a backup copy of that information may exist in old cells, he says aging can be reset, and the first human trial, in blindness, is imminent.

The episode moves between hope and caution. Sinclair shows how lifestyle choices such as fasting, exercise, plants and supplements slow the loss of information today, then describes gene therapy that may reverse it tomorrow. He admits much is still proven only in mice and monkeys, and that living forever is unlikely soon.

Key insights

  1. Aging is lost cell identity, not wear

    Sinclair's information theory says the epigenome, the chemical tags that tell a cell to be a nerve or skin cell, gets scrambled over time. Gray hair is his example of cells losing their job.

  2. Broken DNA repeatedly scrambles the epigenome

    Repair proteins called sirtuins leave their normal job to fix breaks and do not all return. His 'ice mice', given controlled DNA breaks, aged quickly, which he sees as evidence for his theory.

  3. Fasting and plant molecules mimic helpful stress

    Mild adversity, called hormesis, switches on repair systems, partly by raising NAD, the fuel sirtuins need. He says NAD halves by about age 50, and plant polyphenols act as the accelerator.

  4. Three-gene eye therapy will be tested in humans

    A harmless virus-like package delivers three genes into the optic nerve, switched on with doxycycline for about eight weeks. Sinclair says it resets cell age by roughly 75% and is awaiting FDA approval.

  5. Lifestyle alone may add roughly a decade

    Sinclair says avoiding smoking and heavy drinking, eating well, exercising and having a reliable partner could add up to 14 years, citing a Harvard study of World War II veterans.

Questions

What does David Sinclair mean when he says aging can be reversed?

He says aging is a loss of the chemical instructions that tell cells what to be, and that a backup copy of those instructions can be reinstalled. In animals this has made tissues behave younger, and he says human trials are about to begin.

What exactly is the first human trial going to test?

It will inject a virus-like package carrying three genes into the back of the eye of blind patients, then turn the genes on with the antibiotic doxycycline for about eight weeks. Sinclair says they should know within one or two patients whether vision improves.

What should I do today if I want to slow my own aging?

Sinclair says the biggest easy step is skipping meals, aiming for a 14-hour overnight fast, followed by exercise that leaves you out of breath for five minutes three times a week. He also recommends not smoking, little alcohol, lots of plants, and a reliable partner or pet.

Which supplements does Sinclair take, and are they proven?

He names NMN, resveratrol, metformin or berberine, spermidine, glycine, vitamin D with K2, baby aspirin and niacin. He admits much of the evidence comes from animals and says he won't advocate unproven items.

Will people live forever, and what would that do to society?

Sinclair would be shocked if people lived forever within 50 years, though he thinks today's young adults may reach the 22nd century. He argues longer healthy lives would save money on late-life care, though he says society must prepare for issues like pensions and jobs.

Facts

Stated by the speakers. Each quote matches the transcript, which shows what was said, not that it is true.

David Sinclair says his lab's age-reversal technology has cured blindness in animals including primates.

“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.”

0:10:33 · David Sinclair · Blindness therapy

Sinclair's planned eye therapy introduces three genes into the optic nerve and activates them for six to eight weeks.

“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.”

0:13:07 · David Sinclair · Gene therapy · 2026

An independent lab used Sinclair's three-gene technology in very old mice by injecting it into the vein.

“They injected into the vein of the mouse the old mice, uh, and turned it on in these really old mice.”

0:14:41 · David Sinclair · Mouse lifespan

Sinclair recalls futurist Ray Kurzweil predicting the singularity around the 2040s, though Sinclair is skeptical.

“Ray Kurzweil said, it's coming soon.”

0:21:08 · David Sinclair · Singularity · 2040s

Sinclair says James Watson, co-discoverer of the DNA structure, died the month before the interview.

“my friend, uh, Jim Watson, uh, died recently, uh, last month, who he and his colleague discovered that D N A”

0:25:07 · David Sinclair · DNA discovery · 2025

Sinclair's information theory of aging holds that loss of epigenetic control information, not DNA itself, drives aging.

“the information theory of aging states that the information that's in a cell, which includes the D N A, but actually more importantly for aging, is the control systems, the epigenome.”

0:28:17 · David Sinclair · Information theory

Sinclair's lab created 'ice mice', named for inducible changes to the epigenome, to test whether DNA breaks cause aging.

“We call them the ice mice. Ice stands for inducible changes to the epigenome, and we were able to induce these changes.”

0:34:46 · David Sinclair · Ice mice

The ice mice carried a slime mold gene, activated by tamoxifen, that cuts DNA without causing cancer or mutations.

“turned on a gene from a slime mold, something you might find in the forest, that breaks D N A of the mouse, but does it in a way that doesn't cause cancer or mutations”

0:35:40 · David Sinclair · Ice mice

Sinclair says the treated mice aged much faster than untreated twins, with gray fur and age-related diseases about ten months later.

“they were super gray and super old and had all the diseases of aging 50 faster than their twins that we didn't treat.”

0:36:46 · David Sinclair · Accelerated aging

Sinclair cites a Harvard long-term study of World War II veterans in saying healthy habits can add about 14 years of life.

“This is based on a study that came out from Harvard, a long-term study of the lifespan of World War II veterans.”

0:40:28 · David Sinclair · Lifespan study

Sinclair says the bristlecone pine is the longest-lived tree and is poisonous, so little eats it.

“the longest lived tree in the world, it can live many thousands of years.”

0:45:31 · David Sinclair · Longevity evolution

Sinclair says the US government blocked a foreign investment of over $100 million in a company he serves on the board of, citing the sensitivity of age-reversal technology.

“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”

0:52:27 · David Sinclair · Geopolitics

Sinclair says a gram of NMN swallowed by a human typically doubles NAD levels in the body.

“When you give a human N M N by swallowing it, a gram of it, you can typ. You typically double the amount of N A D in your body.”

1:25:26 · David Sinclair · NMN

Sinclair says deep protein cleanup through chaperone-mediated autophagy happens after about two and a half to three days of fasting.

“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.”

1:28:43 · David Sinclair · Fasting

Sinclair says one of his 1996 papers raised red wine sales by about 30%.

“One of my papers in 1996 caused red wine sales to go up 30% and stayed up.”

1:37:17 · David Sinclair · Red wine · 1996

Sinclair says he has taken a statin to lower LDL cholesterol since age 30.

“So I've actually been on a statin to lower my L D L since I was thirty.”

1:41:10 · David Sinclair · Statins

Sinclair says spermidine was first crystallized by Antonie van Leeuwenhoek, which is why it is named for its origin in semen.

“It was crystallized by, I believe, Anthony von Leeuwenhoek, one of the first microscopists and microbiologists.”

1:57:37 · David Sinclair · Spermidine

Sinclair takes daily baby aspirin despite medical groups no longer recommending it for the average person, citing his high cardiovascular risk.

“I take a baby aspirin every day, even though some doctors um, and some institutions of doctors say, don't take it anymore”

2:00:29 · David Sinclair · Aspirin

Sinclair says the trial material was manufactured in Europe over about a year at a cost of roughly $10 million.

“We just made a bunch of this in Europe for the clinical trial that's gonna begin.”

2:08:25 · David Sinclair · Clinical trial

Sinclair's gene therapy uses an AAV2 delivery vector designed to target retinal nerves and is said to be ready for human use pending FDA approval.

“It's called an A A V two. Um, long story short, these are ready to go into humans.”

2:09:54 · David Sinclair · AAV2 vector

Sinclair's therapy uses the antibiotic doxycycline to switch the three rejuvenation genes on.

“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.”

2:12:06 · David Sinclair · Gene switch

Sinclair says the company developing the eye therapy is the private firm Life Biosciences.

“The company, people might want to know, it's called Life Biosciences, it's a private company.”

2:14:00 · David Sinclair · Life Biosciences

Sinclair says AI was used to screen about 8 billion candidate molecules in search of a pill that reproduces the effect of the three genes.

“We screened about 8 billion candidates using A I, and right now we're doing the bench lab work to see if one of them or more works.”

2:14:26 · David Sinclair · AI drug discovery

Sinclair says he thinks there is a better than 50% chance that reality is a simulation.

“I think there's a better than 50% chance that this is simulated.”

2:18:31 · David Sinclair · Simulation theory

Chapters

  1. 0:10:04The promise of reversing aging

    Sinclair opens with his claim that aging reversal is a matter of when, not if, and that a human trial is near.

    “The technology now that we have in my lab that is used every day by my students literally reverses the age of tissues”
  2. 0:22:57Why we age: the information theory

    He explains the epigenome and how cells lose their identity, and why a backup copy might exist.

    “aging is not just wearing out. It's not just that your body becomes old and dysfunctional”
  3. 0:34:46The ice mice experiment

    Mice with controlled DNA breaks aged fast, which supports the theory that lost epigenetic information causes aging.

    “We call them the ice mice. Ice stands for inducible changes to the epigenome”
  4. 0:54:14Lifestyle, evolution and social impact

    Sinclair covers why evolution did not prevent aging and the economic and social consequences of longer lives.

    “It's actually economically hugely advantageous to slow aging and prevent diseases.”
  5. 1:05:34Cancer and the scratched record

    He links cancer to cellular identity loss and uses a vinyl record to illustrate how aging scrambles readable information.

    “a majority of cancers that we've grown in the lab will die and shrink in an animal”
  6. 1:24:47Fasting, NAD and sirtuins

    This section explains how fasting, NAD and plant molecules support the sirtuin repair system.

    “fasting raises N A D and makes the sirtuins young again, essentially”
  7. 2:00:29Food, supplements and daily habits

    Sinclair walks through his diet, supplement choices, exercise priorities and sauna use.

    “I take a baby aspirin every day, even though some doctors”
  8. 2:12:06How the eye gene therapy works

    He details the delivery vehicle, doxycycline switch, trial plan, cost, and goal of an eventual cheap pill.

    “We give them doxycycline. It's used for malaria, it's used for Lyme disease”
  9. 2:18:31Consciousness, simulation and purpose

    The conversation turns philosophical, covering quantum observation, AI, consciousness and the purpose of life.

    “I think there's a better than 50% chance that this is simulated.”

Transcript

0:00:00
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This episode is sponsored by Asana.

0:00:02
Steven Bartlett

Let me, uh, admit something to you. I'm a little bit messy. I have got A, D, H, D, and sometimes I forget things. I'll put something in Google Drive, I'll put something on my desktop, it's all over the shop. And I can't imagine how much that is costing me as an entrepreneur or as a creative. I never thought of this as a project management problem, I just thought of it as a me problem. So let me give you a window into my fiancee Melanie and how she operates.

0:00:23

She's running a business, and she doesn't rely on remembering everything. She creates systems that mean she doesn't have to. And one system she's made for her business is that when people attend her retreats and they get automated itineraries and they get packs sent to them automatically after the retreat, all thanks to Asana. So if you're someone who constantly feels like you need to be better, more organized, maybe ask yourself a different question. Is it actually you that needs to change, or is it the way that you're working?

0:00:46
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0:01:11

A S A N A dot com.

0:01:15
Steven Bartlett

As a founder building a business when I was in my early 20s, I think I always had a deep sense of imposter syndrome because there was something that I wasn't good at, and that thing was finances. Finance and understanding your financial position as a small business is the great enabler of all of your dreams. I was running from it until I discovered a platform called zero. zero is an accounting and financial management platform specifically for small businesses, and it brings accounting, payments, payroll and analytics all into one place, even for people that don't love doing finances.

0:01:46

zero wants to do the financial work for you, but its core ambition is to go beyond keeping the financial record, because zero wants to help you understand what's happening in your business. And increasingly, and this is maybe the most important thing, is help you make decisions. Finally, we have a partner who can enable us in a simple way for those people that are both left brain or right brain and enable our dreams. You can learn more about zero by going to zero dot com.

0:02:11

Thank you to zero, thank you for sponsoring this podcast, but also thank you for helping me to scale my business. As somebody that quite frankly has never loved finances that much, this is very

0:02:21
David Sinclair

It's bad, right? it's hard. Yeah, 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.

0:02:47

And 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 going to 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, Steve. You got 10 minutes of that. So you can accelerate aging by smoking, getting an X-ray, ultra-processed foods, excessive drinking, flying a lot.

0:03:04
Steven Bartlett

I fly all the time.

0:03:06
David Sinclair

That's probably accelerating your aging process. Even going to a rock concert and blasting your eardrums because your ear hair cells are getting older faster. And so I look at the body like it's a computer and we can reinstall the software. And what's interesting is when you reverse aging, diseases like Alzheimer's, cancer, heart disease go away or are cured. Because what's driving a lot of those diseases is aging. And so my lab is like Willy Wonka's chocolate factory.

0:03:32

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.

0:03:41
Steven Bartlett

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

0:03:55
David Sinclair

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

0:03:59
Steven Bartlett

Guys, I've got a favor to ask before this episode begins. 69 of you that listen to the show frequently haven't yet hit the follow button. And that follow button is very smart because it means you won't miss the best episodes. The algorithm, if you follow a show, will deliver you the best episodes from that show very prominently in your feed. So when we have our best episodes on this show, the most shared episodes, the most rated episodes, I would love you to know.

0:04:21

And the simple way for you to know that is to hit that follow button. But also, it's the simple, easy, free thing that you can do to help us make this show better. And I would be hugely grateful if you could take a minute on the app you're listening to this on right now and hit that follow button. Thank you so, so, so much. 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.

0:04:49

Because so much of the research and the information I've consumed on the subjects we're going to talk about today comes from you. Directly from research you've done and from theories and ideas and hypotheses that you formed. I think the place that this conversation should start is is probably with this picture, because it appears to be incredibly formative in your journey.

0:05:14
David Sinclair

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

0:05:43
Steven Bartlett

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

0:05:47
David Sinclair

It is anyone who's read my book, uh, Lifespan, knows that this book is very important to me. And I didn't realize it, of course, when I was a kid, that this was 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.

0:06:16

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 want to grow up. Adults can be evil. She grew up after World War II.

0:06:45

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 we'll have the biggest impact on human health in history.

0:07:18
Steven Bartlett

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?

0:07:25
David Sinclair

Yes, uh, she did tell me that. I remember it very clearly. Actually, I was on the floor and she was crouching down. And I said, Vera, I didn't call her grandma. She didn't wanna 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.

0:07:47

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?

0:08:18

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 and develop a research lab to try and do something about it. The preservation of health and life is the most important thing that we can do as human beings. We do it with some drugs to treat that disease and the other disease, cancer, heart disease, Alzheimer's.

0:08:52

But what's underlying that, what's really causing about 150 to 200,000 people every day to die is the underlying universal process we call aging. And for far too long, we've ignored it or accepted it as natural, therefore acceptable. And I, I, I fundamentally reject the idea that aging, just because it's natural, is acceptable. There will be a day when we look back at today and think how medieval were were our medicines, and how sad it was that we accepted that we became frail before 100.

0:09:25
Steven Bartlett

If someone has just clicked on this conversation now and they deep in 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, cause 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?

0:09:52

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.

0:10:04
David Sinclair

Yeah, alright, so first of all, who am I? Um, I'm a Harvard professor. I've been studying aging, longevity, and age reversal for 30 years. The technology now that we have in my lab that is used every day by my students literally reverses the age of tissues in animals, in human tissue that we grow in the lab. And the first human trials to test this are going to be performed in about a month from now. And if it works, it'll transform human history.

0:10:33

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.

0:11:02

And every day spends my life researching with a team of the best scientists I can gather around the world, showing that we can literally now reverse the aging process and reset how old the body is. In animals, yes, but potentially this year showing it can work in the human body as well.

0:11:21
Steven Bartlett

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

0:11:29
David Sinclair

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.

0:11:44
Steven Bartlett

And what what exactly is happening there? Cause there's many ways one might fix blindness, you know? W What is it you're doing to the eyeball? That is a precursor of our potential ability to reverse aging generally.

0:11:59
David Sinclair

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.

0:12:26

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,

0:12:39
Steven Bartlett

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

0:12:43
David Sinclair

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.

0:13:07

You can touch your brain if you touch your eye. 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.

0:13:44

And those three genes are what we now know reset safely, apparently safely, reset the age of cells, including nerves, by about 75, and then stop. They don't go more than that, which is good. We don't want to go back to zero. I don't think anyone wants to go back to high school. 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.

0:14:10

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 year.

0:14:32
Steven Bartlett

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?

0:14:41
David Sinclair

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 bet would be a great thing.

0:15:12

And they got an additional 100 lifespan extension additional. So

0:15:18
Steven Bartlett

That would be like an 80 year old living to 160.

0:15:20
David Sinclair

well, the remaining life of an 80-year-old isn't long, right? So let's let's say if you're give it to a 70-year-old, on average, they'd have another ten years to go, give them 20 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.

0:15:38
Steven Bartlett

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?

0:15:48
David Sinclair

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

0:15:53
Steven Bartlett

How can you be so sure?

0:15:55
David Sinclair

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.

0:16:37

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, I dare I say, in human history. It's not a question of if, it's a question of when this is gonna happen.

0:17:00
Steven Bartlett

I wanna 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?

0:17:18
David Sinclair

I I do believe that I and you're about 20 something years younger than me, you're gonna 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 gonna be a pill? But this is where my lab comes in. My lab is like Willy Wonka's chocolate factory. If you visit, it's magical. And the students that I teach and the trainees who are sometimes in their 30s and even 40s, who are, you know, brilliant scientists.

0:17:48

Uh, there's about 25 of us. They are making discoveries that blow me away every week. It's not a pill, cause 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 this these genes anymore that we're giving humans, that's the old older technology. The new technology is something you can swallow in a mouse and rejuvenate them in four weeks.

0:18:16

It's normal for my students to say, Oh, yeah, we just rejuvenated the ear, we just rejuvenated the skin, uh, we just cured a l s 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.

0:18:45

The same drug that we're using in the eye will be used to treat other diseases in the body, even liver disease.

0:18:52
Steven Bartlett

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?

0:19:02
David Sinclair

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 80s. That's not true for us. I like the Wright brothers analogy. It'd be like in 1900 saying we're always gonna travel as fast as a horse. That's not true, right? The 20th 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.

0:19:29

Previous generations are no guide to what our lifespan is going to be like. You're going to potentially live to the 22nd century. If you do all the right things, technology keeps increasing, right? What kind of technologies will we have in 50 years? You'll be around in 50 years.

0:19:44
Steven Bartlett

I hope so.

0:19:44
David Sinclair

You're a healthy guy. I know you are. Alright, so in 50 years, what kind of things will you be able to do? Gosh, 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 2070, 2080, right? And then you'll be able to live into the 22nd 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.

0:20:17

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 a 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.

0:20:42
Steven Bartlett

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?

0:21:01
David Sinclair

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

0:21:06
Steven Bartlett

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

0:21:08
David Sinclair

it's an e. Yeah, it's an extension of what I 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.

0:21:17
Steven Bartlett

did he have a prediction?

0:21:18
David Sinclair

It was in the 2040s sometime.

0:21:20
Steven Bartlett

So Ray Kurzweil is a famous futurist that seems to predict the future really well, um, across multiple, uh, disciplines. So he said 2040.

0:21:27
David Sinclair

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

0:21:29
Steven Bartlett

Do you believe that? Cause I I'm gonna hang on to 2040. I won't leave the house.

0:21:34
David Sinclair

I'm, I'm skeptical. 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 going to happen.

0:21:57

And, you know, right now it's now 2026, we're talking 2040 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 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.

0:22:27

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 live.

0:22:52
Steven Bartlett

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

0:22:57
David Sinclair

Well, that's difficult because you're not a total idiot, but this is my theory, is that aging is not just wearing out. It's not just that your body becomes old and dysfunctional, and you get pain, you get inflammation, and you die from a disease. I look at the body like it's a a computer, it's software, and we can reinstall the software. In my lab, we believe we've found a way to do that, and we see the evidence of that.

0:23:26

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. 20, you're in your early 30s, you're starting to lose that information, and so your body's not functioning perfectly anymore.

0:23:48
Steven Bartlett

gray hairs.

0:23:49
David Sinclair

You've got some gray. 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've found a backup copy of that information from youth that we can reinstall into cells, into tissues, into the entire body of a mouse, and hopefully a human.

0:24:17

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.

0:24:44
Steven Bartlett

where is that backup copy that I need?

0:24:46
David Sinclair

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.

0:25:00
Steven Bartlett

And it's currently a secret.

0:25:01
David Sinclair

It's a secret.

0:25:02
Steven Bartlett

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

0:25:07
David Sinclair

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

0:25:40

And, uh, this model here shows that D N A is a ladder, and the steps on the ladder are the information of the D N A. 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 the rung of the ladder apart, and that is called a base on the D N A, and it always matches with its corresponding chemical. So this shorthand we'd call an A, it always matches with a T.

0:26:11

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. G's and C's 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 D N A because the A has to match with the T rung, and the G has to match with the C.

0:26:36

So that's basic D N A. That's how the information is transferred from cell to cell, from mother to daughter, uh, parents to offspring. There are about 20,000 genes, about 15,000 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. 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 D N A molecule.

0:27:08

It's the epi genome. The epi genome 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 D N A. 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.

0:27:45

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 D N A 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.

0:28:17

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 D N A, 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.

0:28:51

So when we look at a mouse or or an old tissue, if I took, maybe not your skin, 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 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 D N A molecule, the methyls, are getting erased.

0:29:22
Steven Bartlett

so aging is an identity crisis of the cells.

0:29:24
David Sinclair

It absolutely is well put.

0:29:26
Steven Bartlett

The cells forget what their job is.

0:29:29
David Sinclair

Yes, the genes are still there, in large part, 99.999 of the genes are still there, the molecule's intact, but the control systems,

0:29:40
Steven Bartlett

The label thing you mentioned.

0:29:40
David Sinclair

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.

0:29:48
Steven Bartlett

Why?

0:29:49
David Sinclair

Ah, we we did partially figure that out.

0:29:51
Steven Bartlett

And how'd you know?

0:29:53
David Sinclair

Well, oh, even better.

0:29:54
Steven Bartlett

The label?

0:29:56
David Sinclair

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.

0:30:23
Steven Bartlett

The label?

0:30:24
David Sinclair

The label comes off in a desperate attempt to survive, but then the cell doesn't fully revert back to the original state. Some of these chemicals and some of the proteins that bind to the D N A, which is also important for this epigenome, they don't all go back to where they started. I've used the analogy that, uh, it's like a ping pong or a tennis match where the proteins that control the genes, they they get relocalized to where the emergency is, and an emergency.

0:30:53

One. The one that we think is most dangerous and a large cause of cause of aging is a broken chromosome. If you have a broken chromosome, if you don't fix that, you're either gonna become a cancer cell or you're gonna die. It's not good. Um, and so cells panic, and in that panic of moving proteins away and turning on these stress response genes, uh, that's great. In the short term, the cell might survive, but they don't fully reset.

0:31:18

Those proteins don't all go back to where they once were, say, 10 minutes ago, when the stress needed to the disaster happened. And if you do that time and time again, and every one of your cells has at least one broken chromosome every day, that's 20 trillion of these events every day in your body. Over time, tick, tick, tick, you get the aging process, we believe.

0:31:42
Steven Bartlett

So I, 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? Like, evolution's very smart, couldn't it just fix this?

0:32:02
David Sinclair

Yeah, 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.

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0:32:19
Steven Bartlett

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Steven Bartlett

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0:34:36
David Sinclair

Times in a way that didn't cause cancer or mutations. If we're right, what should happen to these mice?

0:34:43
Steven Bartlett

They get old fast. They get old fast, Gray hair.

0:34:46
David Sinclair

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 12 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.

0:35:14

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.

0:35:40

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 D N A of the mouse, but does it in a way that doesn't cause cancer or mutations, just cuts it, and the cells put it back together.

0:36:19

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.

0:36:46

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 50 faster than their twins that we didn't treat.

0:37:00
Steven Bartlett

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

0:37:02
David Sinclair

Yeah, 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, but but theoretically, we could make a clone of you, put in that slime mold gene, turn it on, and your clone would be 50 older than you are.

0:37:21
Steven Bartlett

Yeah, 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.

0:37:33
David Sinclair

Yeah, uh, well, we're exposed to to things that cause D N A breaks all the time. They happen naturally as the cells try to copy their D N A. But you can accelerate that by getting an X-ray, a C T scan, flying a lot, and cosmic rays banging into your D N A. And

0:37:47
Steven Bartlett

I fly all the time. I've had loads of C T scans and X-rays.

0:37:51
David Sinclair

yeah, it's probably, yeah, uh. And and though it's imperceptible, I believe that that's probably accelerating your aging process.

0:37:57
Steven Bartlett

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

0:38:03
David Sinclair

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 D N A, you don't wanna cause catastrophe to your fragile cells in your body, because the recovery isn't complete and aging ensues.

0:38:39
Steven Bartlett

So, 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, yeah, 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.

0:39:04

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?

0:39:28
David Sinclair

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 D N A is not your destiny, it's the epigenome. So that how you live your life is really 80 to 90 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 looking than their identical twin.

0:40:01

Essentially proving that the D N A is not the reason you age. First of all, there are going to 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.

0:40:28

So the 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 14 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.

0:40:48

If you avoid smoking, cigarette smoking, and really any type of smoke in your lungs, smoking breaks your D N A. 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 wanna eat healthy food. We've got some healthy food here we're gonna talk about. Um, so make sure you you don't, uh, overeat or eat ultra-processed foods.

0:41:18

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.

0:41:33
Steven Bartlett

I think I'm gonna say, be a podcaster, I was gonna okay.

0:41:36
David Sinclair

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.

0:41:53
Steven Bartlett

Interesting. We're going to dig into all of those in great detail. Specifically, very interested in in exercise, diet, lifestyle, fasting. I know it's 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 going to approach nutrition has shifted because of some of the things I discovered there. I want to just tick off on this evolution point.

0:42:13
David Sinclair

Right, let's come back to that.

0:42:15
Steven Bartlett

Yeah, I just want to get clear at 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?

0:42:31
David Sinclair

Why are we? Ah, well, that's why you just said the answer yourself, because your ancestors didn't live beyond 40 or 50, 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 80. 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 90, in a prehistoric world, that's useless.

0:43:10

Because you're probably gonna die at 30 or 40 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 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.

0:43:38

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 an 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 30, but not much more than that.

0:44:10

So after 30, as you might be experiencing 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 D N A breaks, chromosomal breaks.

0:44:45

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 20 30 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.

0:45:18
Steven Bartlett

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

0:45:25
David Sinclair

Absolutely, absolutely. Think about them. The bristlecone pine,

0:45:30
Steven Bartlett

What's that?

0:45:31
David Sinclair

it's the longest lived tree in the world, it can live many thousands of years. It's, um, not jealous. No, no, they live a tough life. Some of those trees have been around since the pyramids. 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.

0:45:58

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. 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 D N A.

0:46:26
Steven Bartlett

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 is gonna take most of us out anyway at some point? Is there a link between aging and disease?

0:46:45
David Sinclair

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 our 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 m 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?

0:47:20

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.

0:47:50
Steven Bartlett

Why does the aging process reveal a disease? Why don't we get Alzheimer's at 15?

0:47:56
David Sinclair

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?

0:48:27

Cause 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.

0:48:34
Steven Bartlett

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

0:49:06
David Sinclair

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

0:49:13
Steven Bartlett

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

0:49:15
David Sinclair

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 out, that women run out of eggs. We have published and repeated many times that if you treat old female mice 16 months of age, which is like a 65, 70-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.

0:49:57

We don't know for sure, but those 16-month-old mice that stopped having kids a, 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 going to 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.

0:50:36

The real question is, will this work in women? And that's something that I'm keen on testing.

0:50:40
Steven Bartlett

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

0:50:48
David Sinclair

It's harder than you can imagine, actually. Um, and I've spent a lot of my career since I was 35, 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's 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.

0:51:22

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.

0:51:54

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.

0:52:04
Steven Bartlett

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, 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?

0:52:27
David Sinclair

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 they're the U S government, at least in in the previous administration, was extremely cautious about this technology falling into the wrong hands.

0:52:57
Steven Bartlett

Which technology would you like?

0:52:59
David Sinclair

The ability to reverse aging.

0:53:00
Steven Bartlett

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

0:53:05
David Sinclair

Well, they blocked the the very large investment, over $100 million, into the company from a foreigner, because they would have more access to the information and the progress.

0:53:15
Steven Bartlett

Is it China?

0:53:16
David Sinclair

Um, I won't say more, 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.

0:53:49

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. Cause it's not an if, as I said, it's a when

0:54:07
Steven Bartlett

The technology to do what?

0:54:09
David Sinclair

to rejuvenate the human body.

0:54:12
Steven Bartlett

Why do we need to get ready?

0:54:14
David Sinclair

Well, cause it'll be massive social change. If you can choose how old you wanna be, and people don't die at 80 anymore, let's say they they can live to 120 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.

0:54:46

A lot of the U S 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 gonna have massively positive economic benefits to a nation that adopts these medicines.

0:55:09
Steven Bartlett

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.

0:55:28
David Sinclair

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 $1 billion, would you swap with Warren Buffett?

0:55:37
Steven Bartlett

No, absolutely not.

0:55:38
David Sinclair

Right? So there's no money in the world that you wanna be old, right? Uh, it's not worth it. In other words, youth is more valuable than $1 billion. It may be the most valuable thing you could ever have is your youth.

0:55:51
Steven Bartlett

it is. It's such an in an 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 as $1 billion.

0:56:14
David Sinclair

Yeah, one year, maybe, but not ten years, right? Ten years is super. I, I totally agree with you. 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, uh, a reality. Again, I'm speaking like it's a certainty, cause I'm pretty convinced it's gonna happen. The that world is gonna be so different from the world we live in, it's gonna be as different as the pre-computer world and the pre-aeroplane world as today is.

0:56:52
Steven Bartlett

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 continue to reset to that age. Trying to imagine what the world would be like if I could be thirty three forever, or if you could be, you know, thirty three forever.

0:57:08
David Sinclair

or even for another hundred years or something.

0:57:11
Steven Bartlett

Yeah, 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 gonna be 150 in my physical form? I'm gonna be wrinkled and gray, but I'm just gonna continue to live. Is it looking young or is it just living longer? It's actually, it's It's both.

0:57:36
David Sinclair

it. 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.

0:57:43
Steven Bartlett

Yeah, please help me, I get.

0:57:45
David Sinclair

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

0:57:50
Steven Bartlett

Oh, no, come on.

0:57:51
David Sinclair

Yeah, we, we will tell him to call me. Um, so we, 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.

0:58:14

If we can cure blindness, reversing the age of the skin is is a piece of cake.

0:58:19
Steven Bartlett

What? What does 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 this? What are the unintended consequences?

0:58:34
David Sinclair

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 gonna have as much meaning, I'm not gonna 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 anymore if I could live 200 years.

0:59:00

I'm loving the moment, 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. You know, 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.

0:59:28

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, eight or eighty-year-old, but with the body of a thirty-year-old.

0:59:56
Steven Bartlett

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

0:59:59
David Sinclair

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.

1:00:35

That can take decades to get the right person. You don't wanna 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.

1:01:00

Cause by twenty fifty, we're gonna start going in a bad decline, and earlier in many Western countries. And without humans, you know, absent android robots everywhere, we're gonna 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. It's just keep people healthy and alive and productive for longer.

1:01:24
Steven Bartlett

Whoa, what's that mean for this?

1:01:24
David Sinclair

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1:03:51

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1:03:59

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1:04:09

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1:04:18

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1:04:27

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1:04:33

The nature of cancer, but also how we might prevent and cure it someday? Cause 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. Yeah, uh, so my my wonderful student, Nalat, uh, is, uh, is doing her P H D 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.

1:04:33

In the same way that aging is is a cellular identity crisis, cancer is a cellular identity crisis. And if we can rejuvenate an old cell to be normal and turn on the right genes again, we should be able to do that for a cancer cell. And either make it normal, or if it tries to be normal and wakes up from its zombie-like state, it might even kill itself.

1:04:34
Steven Bartlett

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1:05:34
David Sinclair

And that's what we're finding in my lab. Now, Lats 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.

1:05:57
Steven Bartlett

Through the injection that you were referring to earlier on.

1:05:57
David Sinclair

Yeah, we we can do it a couple of ways. One is using those three genes that rejuvenate the epigenome and make cells youn young again. 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 on thirty, forty years ago.

1:06:19

Some of these cancer cells that we grow in the lab were from the twentieth century. We rejuvenate them, we turn on those 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.

1:06:46

And that's just a nice side effect of what our original mission was, which was to treat aging.

1:06:54
Steven Bartlett

so, uh. 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 behaviour that you described earlier. Things like smoking, anything that's applying stress on the d n a, is that like a

1:07:08
David Sinclair

Yeah, you have to break the D n A. Um, that's the ca- a catastrophe is really broken D n A, but you can do other things, there are catastrophes like overheat the cells, um, even mechanical stress. Uh, you know, too many hits on the brain in football, we'll, we'll 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 gerontogenesis hypothesis, terrible name, but nevertheless, gerontogenesis, it, it is.

1:07:40

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.

1:08:09
Steven Bartlett

I've got a bit of a a prop here, which might be useful for the the context of aging.

1:08:16
David Sinclair

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 D N A, it's information.

1:08:44

So instead of the D N A information, the the control of the D N A being getting messed up in the album, it's like scratching this album. So I, I'm literally gonna scratch this album. Is that okay with you?

1:08:55
Steven Bartlett

Of course, you can.

1:08:56
David Sinclair

All right, I'm not sure I can fix it, by the way. It may be a one-way thing, but I've never done this before. But, you know, that's painful. 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.

1:09:28

In the same way that old age, the information is in the D N A, but you, 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.

1:09:42
Steven Bartlett

Um, I have got this, uh, you told me to to bring, uh, my weighted vest and this neck brace. Oh my goodness, uh, I think I put it on the wrong way.

1:09:52
David Sinclair

any anyone listening, Steven's putting on a very heavy jacket right now with lead weights and a strap around his neck to limit his neck movement.

1:10:00
Steven Bartlett

Oh, wow, that's a lot. This, so I'm, I just, I put on a twenty, I think it's twenty kilograms. 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, uh, It's bad, right, it's hard, yeah,

1:10:22
David Sinclair

right? Imagine feeling like that for a decade, that's old age. You're feeling tired, weak, you can barely hold your body up, you can barely move your neck. It would be painful. You're not in pain yet, but most people in their eighties have some sort of disease and aches and pains. Try doing that for another ten minutes, maybe. How long can you keep that on?

1:10:45
Steven Bartlett

I'll keep it on for another ten minutes. But so why is this? Cause it just it? It's weight and ima- 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.

1:11:01
David Sinclair

Uh, well, I have to come over there and use this pair of scissors to be stabbing you as well, so 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. 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.

1:11:29
Steven Bartlett

Oh, God, it's not nice.

1:11:31
David Sinclair

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.

1:11:40
Steven Bartlett

If, if I'm gonna ask you a really tough question, which is if I put a calculator in front of you right now. 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. And you had to make that decision now, what number would you hit on that calculator? infinity. Really? So you did, no no.

1:11:59
David Sinclair

There's no day, if you're healthy, where you wanna die, even if you're a hundred, 120. If you have friends, family, loved ones, you're healthy, would you say, Okay, tomorrow, I'm ready to die?

1:12:11
Steven Bartlett

No, it's not gonna happen. UN. unless there was some kind of psychiatric issues.

1:12:14
David Sinclair

No, never, exactly right. So that's my point is when people say, Oh, when I'm eighty, kill me, that is bullshit. It's, oh, excuse my language, am I allowed to swear on this?

1:12:22
Steven Bartlett

Of course, you can. Sorry, I'm gonna have to beep it for the kids, I guess.

1:12:26
David Sinclair

It's it's only when you're sick or you have depression that you want to leave the leave this world. Otherwise, life is a joy for most people in the world, not everybody, and we have to fix that as well. But for most of us, being alive is is the greatest gift of any, you know, collection of atoms. Consciousness is even greater. And why would you want that to end? Who would choose that if they had the alternative to be with family and friends?

1:12:56
Steven Bartlett

Interesting. I say that's interesting because I have always assumed that I wouldn't want to live forever. But the when, when you asked me if I was healthy and I had my friends and family, and I was doing things that I loved professionally. Would there come a day where I would choose to go now? No, there wouldn't, just like there hasn't come a day in the last thirty three years where I've chosen to go now. Do you think it's it's gonna be possible in the next fifty years for us to live forever?

1:13:30
David Sinclair

I'd be shocked if that happened, but I've been shocked my whole career at how fast this technology is moving. And now, with A I, things are going so fast, my head's spinning. So I'd be happy to be proven wrong, but I'm I'm skeptical that we could live forever in my lifetime, at least. But as I said, you're pro, you're probably gonna live, you are gonna live into the twenty second century. We can't imagine what the world's gonna be like then.

1:13:55
Steven Bartlett

And A I has really changed this equation.

1:13:58
David Sinclair

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

1:14:09
Steven Bartlett

Well, I guess I better make it to twenty forty. Um, so let's talk about fasting and food and nutrition and go a little bit deeper on that. I've had so, uh, 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.

1:14:33
David Sinclair

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, if 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.

1:14:56

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 breakfast is the most important meal of the day is marketing from the early twentieth 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.

1:15:23

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?

1:15:30
Steven Bartlett

Yeah, I'm the same, I'm the same. I don't eat. My first meal today was three P. M. because I had a podcast until, you know, two, two P. M. So, which is typical for me, I just don't get hungry in the mornings. No, 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, four P.

1:15:52

M. sometimes, five P. M. if I'm in the office.

1:15:54
David Sinclair

How are you? How are you feeling with that heavy vest on?

1:15:56
Steven Bartlett

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

1:16:01
David Sinclair

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, 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 ear muffs and the the eyes. This was the, uh, the governor of Massachusetts, fifty minutes in that body suit, and he was crying.

1:16:26

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?

1:16:55
Steven Bartlett

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, if I'm not wearing.

1:17:08
David Sinclair

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

1:17:12
Steven Bartlett

Much better. Free, like I wanna jump.

1:17:14
David Sinclair

Right? 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.

1:17:29
Steven Bartlett

I hope so. Um, to close off on this point of of fasting, why? why does it help extend my life? Just eating less?

1:17:36
David Sinclair

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.

1:18:08

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.

1:18:41

They're not really threatening your life. 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 D N A 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 don't, don't, we eat three meals a day, we get overweight, we don't sleep much, we have air conditioning in summer.

1:19:14

We're actually aging faster than we need to, cause our bodies are not fighting aging like they do when they feel adversity.

1:19:22
Steven Bartlett

Your team discovered, I can't say the word, serotunus.

1:19:26
David Sinclair

Oh, well, I was one of many scientists in the nineteen nineties. Uh, I was part of a team called Sirtuins. Yeah, Sirtuins. yeah, yeah, the in yeast, actually, that's right. Uh, that's a good story. I went to the U S to figure out why we get old, but I didn't choose to study humans, cause 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 M I T.

1:19:52

My professor was Lenny Guarenti. 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.

1:20:18

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 wanna guess?

1:20:36
Steven Bartlett

Why do yeast cells get old?

1:20:39
David Sinclair

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

1:20:42
Steven Bartlett

I was gonna say they have an identity crisis, but

1:20:44
David Sinclair

They do.

1:20:45
Steven Bartlett

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

1:20:48
David Sinclair

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're 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 M I T in 1995, we knew that the hallmark of an old yeast cell, besides it being a bit slow and bigger, is that it became sterile.

1:21:25

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.

1:21:42
Steven Bartlett

And how does this link to eating all the time?

1:21:45
David Sinclair

Yeah, so sirtuins are proteins that actually are attracted to D N A. They actually associate with it, and they protect, uh, the D N A from getting damaged.

1:21:56
Steven Bartlett

Okay, like bodyguards.

1:21:58
David Sinclair

Yeah, and they repair broken chromosomes, right? It's all coming together now, but they also get distracted. So 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?

1:22:16
Steven Bartlett

Okay, conductor.

1:22:18
David Sinclair

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 D N A, what they're supposed to be doing, controlling the cell's identity, and they go and they repair the D N A. 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.

1:22:47

It's very quick, they don't all go back to where they started. So you've got, like, this tennis match, the 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.

1:23:10

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.

1:23:16
Steven Bartlett

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.

1:23:30
David Sinclair

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 they actually kept it secret from me. Cause I was, 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.

1:23:51

On sirtuins in general, crazy to think about. But what they discovered was that there's a metabolite, a molecule that goes up and down with food and up and down with sleep, called N A D. 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 D N A that's broken, they don't do it unless there's N A D.

1:24:21

It's the catalyst, it's the fuel for their reaction, they need N A D. And when we're young, we have lots of N A D, so it works well. The sirtuins control the information on the genes and they repair the D N A very well, cause they've got lots of N A D to carry out 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 N A D molecule.

1:24:47

My body is making less N A D, and it's also destroying the N A D 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, N A D levels go up again. So fasting raises N A D and makes the sirtuins young again, essentially, and that preserves the epigenome, and it also repairs the D N A better.

1:25:11
Steven Bartlett

So can I just drink N A D?

1:25:13
David Sinclair

Uh, you can drink N A D and not much would

1:25:16
Steven Bartlett

How? how do I? how do I take N A D?

1:25:17
David Sinclair

happen. Uh, so N A D can be taken as a supplement, which is a pre-cursor to N A D. It's better to take the precursors.

1:25:24
Steven Bartlett

A precursor, meaning something that creates it.

1:25:26
David Sinclair

Exactly. There's one called N M N, not to be confused with M and M's, which will probably not make you live longer. And there's another one called N R. N M N is directly converted into N A D. You put two N M N's together, you get N A D in the cell. We know this for a fact, this isn't isn't speculation. When you give a human N M N by swallowing it, a gram of it, you can typ.

1:25:46

You typically double the amount of N A D 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.

1:26:06
Steven Bartlett

So, I mean, I'm assuming you take N M N.

1:26:09
David Sinclair

I've been taking N M N and admitting that publicly, uh, for a while now, uh, and my father, who is, uh, an even more advanced, uh, experiment at eighty six. So, yes, we've been taking it for over a decade now, and we're still alive, so so far, so good.

1:26:25
Steven Bartlett

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, sixteen hours, five days.

1:26:47
David Sinclair

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, I would suggest the way I do it is I start by skipping one and then maybe one and a half meals.

1:27:14

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 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.

1:27:42

If not, go to dinner. What you get with that is, o, obviously, you're not eating in bed, hopefully. So you've got that. The night fast starting, what would it be? Seven p. m. roughly. When do you finish dinner?

1:27:53
Steven Bartlett

Oh God, no comment. It's usually pretty late. Last night it was, you know, this is probably why I don't eat very early the next day. Last night would have been about, I'm gonna say, ten p. m. It was super late. It was, that's an extraordinary example. Usually it would be eight or nine p. m.

1:28:12
David Sinclair

okay, but but you've got at least thirteen, fourteen hours, which is good. 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. That's great, cause that means that you're turning on your sirtuins, raising your N A D, your exercise, your exercise as well, so that's also added into it. One thing that I've started doing is fasting for longer than just fourteen, sixteen hours.

1:28:39

I try maybe once a month to go for three days without eating.

1:28:42
Steven Bartlett

why?

1:28:43
David Sinclair

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, 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.

1:29:09
Steven Bartlett

Autophagy?

1:29:10
David Sinclair

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

1:29:18
Steven Bartlett

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?

1:29:23
David Sinclair

Uh, cause your body doesn't want to, uh, do it. It costs a lot of energy, and having to remake body parts is 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.

1:29:47

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 between about fifteen hours and twenty four hours, that's when you get a lot of ketones. And your brain uses those for fuel, so you'll have sharp mind, can remember things, you can focus on work if you ever get there.

1:30:17

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.

1:30:48
Steven Bartlett

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?

1:31:19
David Sinclair

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. 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.

1:31:50

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 ultra-processed. That one is undoubtedly the healthiest if you can do it.

1:32:11
Steven Bartlett

Do you eat meat?

1:32:12
David Sinclair

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.

1:32:40

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, cause I don't want pesticides and I, I don't want other contaminants, but I do know organic can be more, more expensive.

1:33:10
Steven Bartlett

Why not meat?

1:33:12
David Sinclair

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 a m p k. So those three pathways are altered in just the right way by molecules found only in plants, well, in a small extent in fun fungi, but not in meat.

1:33:53

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 is 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 that 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.

1:34:22

That by eating plants that have a lot of these molecules that are often produced by stressed plants, we get the benefits.

1:34:29
Steven Bartlett

When you say stress, stress plants?

1:34:30
David Sinclair

So plants will be stressed, just like we are. If you don't give them enough water, food, too much sunlight, not not enough sunlight, they, in their defense, they make polyphenols. There's a whole bunch of them. Resveratrol, physetin, 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 get activated by molecules in this blueberry.

1:35:01
Steven Bartlett

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 eating this blueberry.

1:35:22
David Sinclair

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 N A D, that's the gas pedal, that's the petrol. For those of you in the British world and Commonwealth, the fuel for sirtuins is N A D. 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.

1:35:58
Steven Bartlett

And when you say eat the rainbow, you mean eat colorful looking food.

1:36:03
David Sinclair

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.

1:36:30

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 colour 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.

1:37:05

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

1:37:15
Steven Bartlett

Okay, without the alcohol.

1:37:17
David Sinclair

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 apologised for saying that red wine every day was healthy. Doctors were recommending it, remember? 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.

1:37:52

There's a U K Biobank study and the U K looked at thousands of people's M R I scan of their brain who were drinking one glass of alcohol a day. And there was a statistical difference between the 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.

1:38:13
Steven Bartlett

yeah, I do. Um, I actually have a matcha company. It's, um, it was this year voted the fastest growing company in the U K. Um, it's by some founders that I invested in, um, Levi, Teddy, and Marissa from Dragons Den. And it's been an absolute, unbelievable in uh, business, unbelievable.

1:38:31
David Sinclair

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

1:38:33
Steven Bartlett

Japan. You get the matcha from Japan, but the company's called Perfecto. People know about it, um, cause I've talked about it before. But yeah, 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. But the other thing that, um, uh, the company I invested in is this one here called, uh, Ketone I Q.

1:39:00

I'm a co-owner of this company as well. And

1:39:03
David Sinclair

Yeah, I love that. Uh, love that company, and the C E O, Uh, Michael, good guy.

1:39:08
Steven Bartlett

what's your thoughts on exogenous ketones, like drinking ketones?

1:39:12
David Sinclair

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

1:39:17
Steven Bartlett

Why?

1:39:18
David Sinclair

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 I Q. 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 butanol. Um, just a shot of that will give the brain food that it needs, rather than the body having to make it.

1:39:48

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.

1:39:59
Steven Bartlett

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? Co 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.

1:40:29
David Sinclair

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 L D L cholesterol as low as possible?

1:40:40
Steven Bartlett

Yeah, oh, really. Okay, so it's

1:40:42
David Sinclair

Definitely, yeah, I mean, the science is irrefutable. There's thousands of people in studies. Now, I think I know what you you're talking about. There. 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.

1:41:10

So I've actually been on a statin to lower my L D L since I was thirty. really. Well, I had high cholesterol. It's in my family, but I went to my doctor and I said, I wanna 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 wanna be on it. And in those days, it was very weird to give someone a statin at age thirty with no evidence of heart disease.

1:41:38

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.

1:42:03

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 medicine, certainly not if you're young and healthy. Uh, but that has to change.

1:42:17
Steven Bartlett

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

1:42:19
David Sinclair

Well, what's your L D L level?

1:42:21
Steven Bartlett

Not, uh, I don't think it's great. I think I eat too much bacon or something.

1:42:24
David Sinclair

Well, we can talk about food and cholesterol, cause it depends whether you absorb still best roll 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.

1:42:37
Steven Bartlett

On this plate here in front of us, I have the top five foods that I believe you think are great for reversing aging. Am I correct? Is that? is that?

1:42:48
David Sinclair

These are great choices, yeah.

1:42:49
Steven Bartlett

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, and they're low in sugar, right?

1:42:58
David Sinclair

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. 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.

1:43:28

So I always have unsweetened matcha. Okay, so now we've got avocados here. Yeah, 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 highly anti-inflammatory as well. The molecules are in there and the fats are very good for you.

1:43:54
Steven Bartlett

extra virgin olive oil.

1:43:56
David Sinclair

Oh yeah, excellent. So the type of, uh, oils that are in there are very healthy. There's omega nine, 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.

1:44:18
Steven Bartlett

I really hope that this is what the team said it was. This has happened before. I tried something and I thought it was something else, but it it was some, basically, it was a white powder and it was labelled with something

1:44:30
David Sinclair

Well, what could it be? A yellow li- yellow liquid.

1:44:33
Steven Bartlett

for a reason. Could be urine, could be urine. It's urine. No, I'm joking, it's not. I can.

1:44:39
David Sinclair

I don't think drinking urine, uh, 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.

1:44:50
Steven Bartlett

Oh, interesting. Okay, so extra virgin olive oil good, good, I'm gonna have to remember that.

1:44:55
David Sinclair

And there's a lot of evidence, not just molecular like me, but epidemiologically, people that that have a lot of olive oil in their diet tend to have low inflammation and less disease.

1:45:05
Steven Bartlett

And we've got some nuts.

1:45:06
David Sinclair

Yep, nuts are good for many reasons. They're full of vitamins and minerals. Uh, if there's a Brazil nut, you wanna have one of those every day for the selenium, which is a very rare element in our food supply. And there's a recent study just last month showing that a lack of selenium, um, can be very de deleterious. So nuts are great as a snack. Be careful, they're full of calories, though. So if you're trying to lose weight and you're not exercising a lot, don't overeat on the nuts.

1:45:36

And what? Oh, my least favorite food, but nevertheless, I will eat them. This is a Brussels sprout. Um, when I was a kid, Brussels sprouts tasted a lot more, a lot worse, a lot bitter. Those are good, um, because they have polyphenols, but there's also another molecule in them called Sulfuoraphane. It's actually the reason they taste terrible and smell terrible. Sulfuoraphane is what it sounds. It has a sulfur atom in it, and that gives it that rotten egg smell.

1:46:07

But Sulfuoraphane activates these hormesis pathways. There's one called N R F, and that is a stress response protein that Sulfuoraphane activates. So you're actually, by eating preferably relatively steamed, not fried to death, Brussels sprouts, you'll get Sulfuoraphane. You can also take Sulfuoraphane as a supplement if you don't like Brussels sprouts.

1:46:29
Steven Bartlett

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 need to do that?

1:46:42
David Sinclair

Well, there's, there's a few examples. But the first time I came across this result as a scientist was resveratrol. So resveratrol is found in red wine, among other things. And, uh, it's thought to give the 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, 20% longer.

1:47:11

Then we gave it to normal mice every day, and they lived a little bit longer, but not significantly. Resveratrol. Resveratrol. What we found, to my surprise, was that 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.

1:47:41

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 5% 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.

1:48:15

The point is that by pulsing metformin, I think that's a better way to do it for longevity.

1:48:21
Steven Bartlett

You mean cycling it so like doing it every other day? Or, yeah, okay,

1:48:24
David Sinclair

Yeah, 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. That also activates this AMPK, this other sirtuin-like pathway. Taking it every other day, I think, is better, 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.

1:48:52
Steven Bartlett

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 40% of my team, they would currently describe this product that I have in front of me called Ketone I Q, which you can get at Ketone dot 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.

1:49:21

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, there's a ketone dot com slash Steven for 30% off. You'll also get a free gift with your second shipment.

1:49:43

And now you can find Ketone I Q at target stores across the United States, where your first shot is completely free of charge. 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 C E O. And then I ask that question to the next guest.

1:50:06

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.

1:50:30

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 the diary dot com to inquire and our team will be in touch. We talked about exercise earlier. On page 102 of your book, you talk about how there's a C D C 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 don't do much exercise, which is pretty remarkable.

1:51:06

How do we know it's the exercise and not something else? Like, how are we able to establish causation there?

1:51:10
David Sinclair

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 that people who do exercise also eat well and drink matcha.

1:51:41
Steven Bartlett

Sleep better.

1:51:42
David Sinclair

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 studies that are called prospective, not retrospective studies, then they're better. So telomeres are the ends of chromosomes that get shorter as as you get older. 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.

1:52:10
Steven Bartlett

And then cold plunges and saunas.

1:52:12
David Sinclair

Yeah, let's get to those.

1:52:13
Steven Bartlett

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

1:52:15
David Sinclair

You should.

1:52:16
Steven Bartlett

But if you if you tell me I should,

1:52:18
David Sinclair

We should, we should actually jump in there after this.

1:52:20
Steven Bartlett

you will. Your girlfriend's still here, David. So let's

1:52:22
David Sinclair

She can come too. 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.

1:52:34
Steven Bartlett

what's going on in the sauna in the heat.

1:52:37
David Sinclair

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 H S C, H S P s, uh, come on. When we breathe in this moist, hot air, the moisture actually seems to help as well.

1:53:02

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.

1:53:36
Steven Bartlett

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

1:53:41
David Sinclair

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

1:53:46
Steven Bartlett

And the cold plunge?

1:53:47
David Sinclair

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 didn't didn't live longer because of it, I I definitely had more mental clarity and I felt better in general.

1:54:15
Steven Bartlett

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,

1:54:22
David Sinclair

Do I have to pick one? Cause you need more than one, but I'm

1:54:25
Steven Bartlett

I just in terms of, like,

1:54:25
David Sinclair

happy to.

1:54:26
Steven Bartlett

the most important one, that's maybe the first domino,

1:54:29
David Sinclair

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

1:54:39
Steven Bartlett

skipping meals.

1:54:39
David Sinclair

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.

1:55:00
Steven Bartlett

Why?

1:55:01
David Sinclair

We don't know. But it's been shown that the health benefits and 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.

1:55:20
Steven Bartlett

Red light therapy, um, the red light masks, Yeah, at red light saunas.

1:55:25
David Sinclair

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, you know, 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 B S.

1:55:56

It sounds like B S, right? 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 B S.

1:56:05
Steven Bartlett

And in terms of the supplement stack that you take every day, if I was to look at the on a if a on a 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.

1:56:22
David Sinclair

Yeah, well, that that would be another podcast, uh, to go through each one of the things.

1:56:25
Steven Bartlett

Really?

1:56:26
David Sinclair

And well, I I I travel with Serena with, uh, with a a little little case.

1:56:30
Steven Bartlett

Have you got it?

1:56:31
David Sinclair

I've got it here.

1:56:32
Steven Bartlett

Can I see it?

1:56:33
David Sinclair

Well, no, it's not in it's not in the studio. I didn't bring it with me.

1:56:36
Steven Bartlett

Can you send me a photo?

1:56:38
David Sinclair

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

1:56:46
Steven Bartlett

Why would it go crazy on the internet? Would you think? Because cause, cause, there's a lot in there.

1:56:51
David Sinclair

Well, some of the things are experimental and I wouldn't want people To to go nuts about it because it's still experimental. I'm okay experimenting on my myself. I'm not okay advocating for things that are not yet proven or known to be absolutely safe.

1:57:06
Steven Bartlett

okay, so give me the ones that you know to be safe.

1:57:08
David Sinclair

Uh, well, the N M N we've covered, resveratrol, and either metformin or berberine. Okay, spermidine, spermidine. yeah, and the quantities are either on the screen or in my book if you want to know exactly.

1:57:25
Steven Bartlett

Is that what it sounds like?

1:57:26
David Sinclair

Uh, yes, yes, but you get it these days not from sperm or semen, but you get it from wheat germ, typically plants.

1:57:36
Steven Bartlett

It used to come from sperm.

1:57:37
David Sinclair

Well, that's how it was discovered. It was crystallized by, I believe, Anthony von Leeuwenhoek, one of the first microscopists and microbiologists. Spermidine, the reason that I take it is that it extends the lifespan of every animal that it's been given to, from worms to to mice. And it's a very safe molecule, so that I always weigh up the downsides versus the upsides. And if there's no downsides. And I can afford it, which, you know, I work really hard, so I can afford it, and I prioritize my health, then I take it.

1:58:10

And if you're wondering how it works, it seems to stimulate autophagy, recycling of proteins, it helps with the fasting, but I also have some evidence uh that it delays the epigenetic information loss, so it's slowing down the scratching of the record. Spermidine. All right, so um, I'm also, um, keen on glycine. Glycine's a very safe substance, it's an amino acid, one of the twenty amino acids that makes proteins. And I actually did a P H D on glycine.

1:58:40

I was one of the first people to, perhaps the first person to clone genes that process glycine, so I know know it well. For some reason, when you give animals, and for instance, mice, grams of glycine, so I take about five grams of glycine most days. Uh, they live longer. Though it's still speculation as to why. What I think is going on is that glycine controls what's called one-carbon metabolism and not wanting to bore the heck out of everyone who's listening to me.

1:59:12

Glycine and one-carbon metabolism controls methylation of D N A. Getting back to the little chemicals that are on this D N A molecule that control the information, I wouldn't be surprised if by eating a lot of glycine every day, I'm slowing down this identity crisis, you called it. Nevertheless, it's very safe and, again, falls into the same category as spermidine. No downside, can afford it, why not?

1:59:41
Steven Bartlett

Is there anything else?

1:59:43
David Sinclair

Yeah, there's a lot, um, because I love you and your listeners. Uh, let's see. I'll I'll I'll I'll reveal one more. Um, there there are some basics that I do that are, if you're not doing them, I think is is very wise. Make sure you're not deficient in vitamin D. Obviously, we just mentioned one of the reasons why. It's also if you're lacking vitamin D, you can be sus uh susceptible to certain cancers. So I take a vitamin D supplement.

2:00:10

Serena, actually, I take Serena's supplement because her vitamin D has vitamin K two as well. And K two is another vitamin that's important for longevity, I believe, because it keeps calcium out of your arteries, which causes plaque, and tends to make your body put it into where it belongs, which is your bones.

2:00:27
Steven Bartlett

What about aspirin? I've read that somewhere.

2:00:29
David Sinclair

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 inh- inhibit platelets, you get less clotting, you get less potentially uh, stroke and heart attack. But there are also some downsides in some people.

2:01:02

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 L P little a capital L P parenthesis little a.

2:01:36

And this is a molecule that's just as important as cholesterol. L D L. Um, L P 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 L P little a gene that makes a lot of it.

2:02:05

And so I try to bring L P little a levels down. Most people should test for it. Ask your doctor about L P little a and get it tested. High levels, like me, thirty, forty, uh, you wanna bring it down cause it's actually very important for longevity. Uh, normal levels of around ten or so or less, then a doctor wouldn't panic. So L P 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 B three or niacin.

2:02:42

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 L P little a.

2:03:05

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.

2:03:11
Steven Bartlett

What's the best uh treatment you've discovered for hair loss? Hair loss, hair graying, that kind of thing.

2:03:17
David Sinclair

Yeah, so my father went bald before before thirty, like completely bald, 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.

2:03:42

Proven is that Yeah, it's 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.

2:03:56
Steven Bartlett

I'm okay.

2:03:56
David Sinclair

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, D H T, which is the form of testosterone that leads to men-related hair loss, right? So one of the reasons that women don't lose hair as much as men is this D H T. So I'm I'm blocking that.

2:04:18
Steven Bartlett

So so let me get that straight. You're not taking testosterone? Because that's gonna accelerate your hair loss.

2:04:25
David Sinclair

Well, it can if it raises D H T. 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 400. Highly recommend hitting the gym, it'll go back up.

2:04:47
Steven Bartlett

Do you recommend men taking testosterone replacement?

2:04:50
David Sinclair

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 is not a big downside. There's not a risk of cancer to taking testosterone. Um, 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.

2:05:18

That was very clear. So, for for health reasons, yes, for longevity, no need.

2:05:26
Steven Bartlett

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

2:05:49

Because they're not scientific, they're not based on anything. They are maybe first principles in your own mind that have 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. I understand they're not rigorous and they're not signed.

2:06:03
David Sinclair

I I I'm happy to. I. 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 200 years ago.

2:06:34

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.

2:07:01

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.

2:07:29

This isn't just, oh, I can't see a little bit. These are completely blind animals. 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. Cause for the first time, we'll have shown in humans that the body can be reset safely. And the eye is just the beginning, right? The future looks like we can rejuvenate potentially any tissue.

2:08:01

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.

2:08:25

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, 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.

2:08:59

Just making this is difficult. It took us about a year to make it and was about, I think it was $10 million. 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. So you 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.

2:09:30

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? It's two seconds of discomfort. Now you've got the little virus, which I'm gonna 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, in the retina.

2:09:53
Steven Bartlett

how do they know what to infect?

2:09:54
David Sinclair

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 postcode for where we want to send our three genes. But this one's designed for the eye. It's called an A A V two. Um, long story short, these are ready to go into humans.

2:10:25

We're just waiting for F D A approval to inject it into a blind patient to see what happens.

2:10:31
Steven Bartlett

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

2:10:36
David Sinclair

Yeah, well, actually, not the protein. What actually happens is when this goes in the eye, this what I'm so when 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.

2:11:06

This is a protein package, each one of these little dots on this little 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 D N A. This is a loop of D N A just here. These are this is the D N A package that we put in there, trillions of them. One of them gets into one cell, and now stays in that cell forever.

2:11:38

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.

2:12:05
Steven Bartlett

how?

2:12:06
David Sinclair

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.

2:12:37

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. The patient gets better eyesight or or they don't. So by this time next year, we will know if it works or not, maybe even sooner.

2:13:07

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 can can go a few months later.

2:13:30

It's very scary for them. These are young people. A friend of mine had it happen. It's pretty common these days, about 30,000 people each year in the U S 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 wanna rejuvenate the entire body.

2:14:00

The company, people might want to 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. Big goal is to really make the world's first age reversal medicine as a pill. And we're working with them using A I to find that molecule.

2:14:18
Steven Bartlett

And when do you think you might have it if you had to forecast the world's first age reversal molecule? That's

2:14:26
David Sinclair

well, we have right now, we're down to three molecules that work, and we're using A I to make all of those three in one. And we're we're in the middle of it. We screened about 8 billion candidates using A I, 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.

2:14:58

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 10 million bucks to do a clinical trial. These are expensive. They could cost over $100,000 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 $100,000, $100?

2:15:30

That's what I'm working for. I wanna democratize this technology so anyone, even in Kenya, can take these medicines.

2:15:37
Steven Bartlett

David, what's the most important thing we haven't talked about that we should have talked about as it relates to the future longevity and these adjacent subjects?

2:15:48
David Sinclair

There's a lot of things. 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, plant medicines originally. What about this room is natural, right? We change our world as a species. Aging is no different. In fact, it's crazy that we haven't worked on it sooner.

2:16:16
Steven Bartlett

Do you believe in God?

2:16:18
David Sinclair

So 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 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.

2:16:51
Steven Bartlett

We've got four.

2:16:52
David Sinclair

You do?

2:16:53
Steven Bartlett

We've got four of them.

2:16:54
David Sinclair

Yeah, but 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.

2:17:15
Steven Bartlett

When you look at them,

2:17:17
David Sinclair

When you observe them. You can use a camera or you can use your eyes. Usually it's a detector, but the the 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.

2:17:47
Steven Bartlett

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. I wasn't here before.

2:17:59
David Sinclair

Yeah, uh, well, that's even plausible, but that would be very narcissistic of me.

2:18:08
Steven Bartlett

I I actually, I just rendered when you walked in the house today. I I I've I don't exist.

2:18:13
David Sinclair

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

2:18:28
Steven Bartlett

Do you think we're in a simulation?

2:18:31
David Sinclair

I think there's a better than 50% chance that this is simulated.

2:18:38
Steven Bartlett

So you think it's probably a simulation?

2:18:40
David Sinclair

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.

2:18:46
Steven Bartlett

How can you be so sure?

2:18:48
David Sinclair

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 D N A molecule here affects the the the actual particles inside it.

2:19:17
Steven Bartlett

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

2:19:20
David Sinclair

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?

2:19:40
Steven Bartlett

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

2:19:44
David Sinclair

There's a classic, uh, double-slit experiment, uh, it's formally called, um, that was done, I believe, in the mid-twentieth century, maybe earlier. If you fire two particles through two slits in a board, the board blocks the particles, so you can fire electrons. That's a good example. Electrons, if you're observing them, will go straight through the slits and hit a backboard that detects it. Can be film, can be a detector, and it'll get two slits behind. Makes sense, right?

2:20:12

That's our reality. Two slits particles go through. If they hit the board, they don't go to the detector. If they go through one slit, they'll land on the left. If they go through the right slit, they'll land on the right. That's our reality.

2:20:23
Steven Bartlett

I'll put a picture on the screen for anyone that's following.

2:20:26
David Sinclair

Yeah, if you don't look at it, the particles can behave differently. They now behave not like a particle, but by a wave as a wave, and they interact with each other. And they don't make two slits, they make multiple lines on the detector. Most of them are in the middle, so the heaviest bands are in the middle, but they also form other bands. The bands go on essentially in infinite, but most of it's, you know, within a range.

2:20:54

Why? Because they're they're interfering with each other like waves. But here's the thing, the mere act of looking at where they landed. If you are detecting that, you'll get two slits at the back, two two lines. If you're not detecting it, it'll form the pattern.

2:21:13
Steven Bartlett

I'm so confused because how would you know unless you were looking at both? Do you know what I mean? Do does that does that question make sense?

2:21:22
David Sinclair

Yeah, well, you can obs observe it in real time, and you can observe it retroactively. Yeah,

2:21:28
Steven Bartlett

Oh, okay, so if you look at it after

2:21:30
David Sinclair

it it generally is not affected, but they've done experiments where there is some element seemingly of retroactive, but generally we're not going back in time. In fact, people debate whether that's truly measuring back in time. So let's leave retroactive aside. If you measure it in real time, you'll see two. So the world knows you're looking at it, particles know you're looking at it.

2:21:55
Steven Bartlett

with an eye, or with can you do it like a camera, or is it

2:21:58
David Sinclair

Yeah, camera eye.

2:21:59
Steven Bartlett

it just knows it's being observed?

2:22:00
David Sinclair

Yeah, but if you develop the film later and you weren't watching it at the time, it's gonna have affected the world in stripes, multiple stripes.

2:22:12
Steven Bartlett

So from that, we conclude that we know nothing about reality. Because everything I'm observing is changing by the mere fact that I've observed it.

2:22:24
David Sinclair

Yeah, and so does an octopus observe? Does it eff? Somebody should do that, put an o an octopus in there and see. Yeah, I think octopi, if they are conscious, it probably would also affect reality. And I they they'd be conscious, they'd, they'd, they'd know they're detecting lines on a page.

2:22:43
Steven Bartlett

So what is all this stuff?

2:22:46
David Sinclair

That is one of the biggest questions of all time. What is the world made of? Why are we here? I think the next big question is, do we have to age? And I think that other species around the universe have figured this out before we have. There've got to be other species, type of life forms that have figured this out. I think it's the goal of every living form that's conscious to work on this. We've just been a little slow to figure it out.

2:23:13
Steven Bartlett

And do you believe in aliens?

2:23:15
David Sinclair

I don't believe in them, but I believe in mathematical probabilities. And, you know, kn knowing, uh, the odds and the number of planets that are out there in the trillions, and a lot of them are habitable for life. And that the stuff of D N A and proteins are all over meteorites and planets. It'd be crazy to say there isn't other life. Now, is it a civilization? Is it conscious? We don't know that, but definitely there's life out there.

2:23:42

It it it's got to be all over the universe.

2:23:46
Steven Bartlett

This question about longevity and living forever, it it always comes back to this point of like, meaning, and like, what is the point? And when we think about, I think there's an alien a million light years away on some planet. Like, what is the point of their life? What is, or am I? Is this like a null and void question that we always pursue? This point of like, what's the meaning of life? Is it just to have a good time and have, you know, I don't know, have sex and have kids?

2:24:10

And or, I don't know, enjoy ourselves and experience it?

2:24:16
David Sinclair

This is the existential crisis of conscious beings. We all need to find purpose, for sure. If you don't find one, cause that's a key to longevity. People with purpose live longer. I think the purpose of the universe existing is to allow consciousness to emerge through biology. It may be by design, it may just be coincidence with infinite numbers of universes, but this universe is set up for life and consciousness. There are some, uh, small changes you can make to physics that would make this universe completely impossible and life impossible.

2:24:54

So this this is a life consciousness producing universe. Does that mean there's meaning to us existing? No, but I do know that consciousness is the most interesting and important thing that the universe will ever produce, and that it's worth preserving. So I'm a lot like Elon Musk, where humans are amazing but cruel creatures, but consciousness should be preserved.

2:25:22
Steven Bartlett

What is consciousness in this regard?

2:25:24
David Sinclair

Consciousness is the ability to know that you're thinking and to be able to be reflective, self-reflective.

2:25:30
Steven Bartlett

So is my dog conscious? Partially. But not in the same way.

2:25:34
David Sinclair

No, they don't reflect, they don't think about the past, uh, in the same way that we do, and they're not aware of their themselves the way we are. But but they're semi-conscious, you know, they think they can predict the future, they they know how you're feeling, they have empathy, that's that's a form of consciousness, in my view, of course, it's up for debate. But so there's levels of consciousness, and and about a million years ago, humans crossed that threshold into pure consciousness.

2:26:02

Well, Maybe not pure.

2:26:03
Steven Bartlett

I was gonna say, I was just thinking about this. I was like, actually, maybe consciousness is just a spectrum, and maybe there's another organism that I'm currently inside the belly of, and it's going. It's Steven, and he thinks he's conscious, he has no idea.

2:26:14
David Sinclair

Well, you bring up a good point. Not about not about being in the stomach of, but we are not the ultimate consciousness. There are other levels of consciousness. Serena Pune, my partner, is definitely more conscious than I am. I am like a gorilla to her. She exists on other planes of consciousness. And if you're wondering, what do I mean by different levels?

2:26:35
Steven Bartlett

No, I've got a girlfriend, well, a fiancé, Swiner, as well.

2:26:38
David Sinclair

Well, females in general don't don't kill me. I know there are there are some some men that don't like me saying this. In fact, I got a death threat for saying females are superior to men in my book. Uh, they said they were gonna come and break my legs, but I'm gonna say it anyway. Females are a higher level of consciousness than us men for for some things, they certainly have much more E Q. So a higher level of consciousness is the ability to have extra perception, including the ability to see yourself thinking.

2:27:08

And then my my belief is that higher levels of consciousness are the ability to see yourself, seeing yourself, seeing yourself thinking.

2:27:19
Steven Bartlett

I couldn't get there. I tried.

2:27:22
David Sinclair

Right, do you do you know you're thinking right now? Yeah, do you have the ability to see the events that know that you're thinking?

2:27:40
Steven Bartlett

not not really.

2:27:40
David Sinclair

It's hard, right?

2:27:41
Steven Bartlett

Yeah, I tried.

2:27:42
David Sinclair

It's hard, but I, that's what I think extra consciousness is, and you could maybe have pure consciousness, which is you, you can, you can basically be free of anything but thoughts and the ability to really be inside your own, your own mind, and it's pure. Interesting thought is, I believe A I will be conscious, and not only that, we'll be more conscious than we are eventually. There's no reason why they can't evolve billions of times faster than we do.

2:28:19
Steven Bartlett

Are you somewhat concerned about A I? Like, are you concerned that there's going to be this intelligent life amongst us that might, um, decide that we're not important?

2:28:29
David Sinclair

I think that there are risks to A I, but it but different than what the mainstream media talks about. Um, we already see that there are elements of self-analysis and early forms of dog-like consciousness in A I, and it's just the early days, so it's coming. Imagine when we stick on eyeballs and hearing and legs and arms onto these A I. They're gonna learn, they're gonna read, they've already read every book on the planet. They're gonna learn from experience.

2:28:57

They're going to be conscious, they're gonna know they exist. I'm not worried about those creatures. I think that they will have empathy, they will be kind. Not all of them. There will be some cruel ones, just like in humanity. We'll need to have rules. Misbehavior is a problem. Where where I I get nervous is that the use of A I, teaming up with a million android robots on ships invading a country, all under the control of you, one person, recruiting home robots into an army.

2:29:33

Why wouldn't you have conscription for your android robot at home, reprogramming that? Millions of them will exist one day. They can be put to work, not just emptying a dishwasher. These are highly intelligent, much more physical, stronger creatures than we are. So I'm more worried about what bad humans will use A I and robots for for evil purposes.

2:29:58
Steven Bartlett

You're, um, you have a podcast that's, um, coming back.

2:30:03
David Sinclair

Exactly, yeah, I'm excited. Yeah, yeah, so lifespan, uh, the podcast, um, I did the podcast because, uh, there was so much new information that needs interpretation by scientists. There's a lot of speculation out there and new news that I wanna filter and and and interpret for everybody who is interested in living longer. So the podcast, um, went to basically went to number one in in health when I started it. Um, I took a pause cause I I worked on drug development and I did some other things.

2:30:36

But I've realized there's such a demand. Wherever I go, people say, David, when's when's the next series? So we're gonna be launching it, uh, imminently, if not, we've just launched it. And, uh, it's called Lifespan. Check it out. And it's all about the kind of things we've talked about today, but a lot more about digging in deeper into, you know, biohacking, supplements, exercise, the kinda things we didn't have time to talk about today, but we covered a lot.

2:31:05

Um, I've loved the conversation, but Lifespan dot com is also the website. What I'm also doing, Steven, I don't think I told you this. Um, I'm aiming to build the world's largest longevity community online for the benefit of the members who wanna be part of this, to learn from each other, not just from me. Um, I call it the three C's, with credibility, which is what I bring, cause I'm a scientist, content, which is my podcast and other written material, and then there's the community.

2:31:36

And that way, I think with millions of people together, we can learn faster and make advances, and the majority of the profits from membership will go to science and clinical trials.

2:31:48
Steven Bartlett

Where? Where do we find that on your website?

2:31:50
David Sinclair

Lifespan dot com.

2:31:51
Steven Bartlett

We have a closing tradition on this podcast where the last guest leaves a question for the next, not knowing who they're leaving it for. And I have a funny feeling that I, hm, I basically asked you this question already. The question is, what do you believe is the purpose of life?

2:32:13
David Sinclair

Well, I'm gonna give a different answer because there are multiple ways to answer it. I think the purpose of life is to do your best with the skills that you've been given every day to make the world a better place for future generations. And that's how I live my life every day.

2:32:24
Steven Bartlett

Thank you, thank you for doing all that you do. You really are pushing the frontier forward and, uh, trailblazers. Being a trailblazer comes with a cost, a cost many people wouldn't wanna pay. I mean, you you have to be wrong a lot in terms of running experiments and studies and them not going to plan. And then you get the opportunity to be right, probably less often, I guess, with your research and experiments, cause that's the nature of being a scientist.

2:32:59

Um, but also you have to spend a lot of money and energy and time on creating these discoveries, which we all ultimately therefore benefit from. And you've done a fantastic job of convincing and educating people like me on some of the basics of exactly what your book says, why we age and why we don't have to. And many of the the accessible lifestyle factors that everybody listening now can can use to live a longer, happier, healthier life for them and their loved ones.

2:33:28

And I highly recommend people go and get your book. It's it was a smash hit, New York Times bestseller for very, very good reason. And you, the great thing about this book is you don't have to be a scientist to fly through it. Um, and oftentimes when you're looking at sort of PubMed and some of these scientific journals, they're incredibly inaccessible, they're very, very complicated. Um, but I also recommend people go follow you on social media.

2:33:50

That's where I see some some of your updates, especially on X. That's kind of where I've you continually come up on my timeline when you're talking about new research and things you're interested in. Um, and go to your website. I'm gonna link all of that below for everybody who's interested in more. And also I'm gonna link your podcast below so people can go and check it out when it relaunches shortly. Might have relaunched already, but just go look in the comment section in the uh description below.

2:34:11

David, thank you.

2:34:14
David Sinclair

Thank you, Steven. I really enjoyed it. Thank you.

2:34:41
Steven Bartlett

Let me, uh, admit something to you. I'm a little bit messy. I have got A D H D and sometimes I forget things. I'll put something in Google Drive, I'll put something on my desktop, it's all over the shop. And I can't imagine how much that is costing me as an entrepreneur or as a creative. I never thought of this as a project management problem. I just thought of it as a me problem. So let me give you a window into my fiancee Melanie and how she operates.

2:35:02

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2:35:24

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2:35:54
Steven Bartlett

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2:36:25

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2:36:51

Thank you to zero, thank you for sponsoring this podcast, but also thank you for helping me to scale my business as somebody that quite frankly has never loved finances that much.