“Age Reversal Is Coming.” Inside The First Human Trials - Dr David Sinclair - #1141

Transcript from https://podmenti.com/t/03f25bc4b2ab4883

The first ever
Podcast episode that I recorded in America.
It was with you.
In twenty nineteen.
Yeah. Harvard Medical School in your office with what looked like the
Illustration of a snail.
On the whiteboard.
And it was filmed on two iPhones, one of which I'd had to borrow from a friend, and a single white
USB microphone.
And that was over seven years ago. Yeah. And um here we are. Remember it well.
Uh when you were twelve, right?
I was twelve. Yeah, correct. Yeah. Uh it was very clear in from those days that you were gonna be a
Big success.
Smart driven, came prepared.
Uh and look.
This is beautiful now.
Full circle. Yeah, I had I didn't realise uh
Starbucks Venty.
has way more
Caffeine in.
than the British equivalent and it took my fucking face off sat opposite each other to think about Yamanaka factors and how important NAD and Rest Veratrol in in yogurt is, meanwhile I'm my whole body was vibrating.
But
You know you've done
Maybe more than almost anyone to make the biology of reversing aging a part of mainstream conversation.
So I want to talk about
kind of everything that's happened since we first sat down, the Yamanaka factors, what's happening with NAD and Rest Viratrol, news discoveries, I
Before we get into that though.
What
discoveries have excited you most?
Since twenty nineteen.
Gee.
Uh
A lot. I I'm very lucky to have a lab where there's
Up to forty people.
Running around making
Discoveries. I go back there to recharge. It's a it's like a willy wonko. You've been there, so you know what it's like.
It's unparalleled, I wish ever wish everyone could come visit.
Um
The highlights would be so in twenty twenty we published on the cover of Nature
Magazine.
That
We could reverse aging.
Safely in an animal for the first time.
A mouse.
We could.
It's blindness.
That was pretty big.
Cover of nature, it's what most scientists dream of in their lifetime. So that was pretty big high.
Since then uh it's been rewarding to see that
It's been repeated.
Not just by other labs, but
In
Different animals.
Monkeys.
It's been
working in different tissues. So it's not just the eye anymore, where we first tested it.
It's pretty much working in in every

Animal's body.
And then the big thing is we've now gone into people. So there are people getting
They're
hopefully their age reversed in their eye to cure their blindness, or at least improve their vision, at the very least.
Why start in the eye?
Yeah.
Yeah, good question. Um
This is a gene therapy, so we're introducing genes that
Are very powerful.
They're called Yamanaka factors, you mentioned them. And but we use a a subset of them that don't cause any trouble. If you just use what Professor Yamanaka used, it's not gonna

So we use a subset of those and we deliver them.
with a little virus like particle.
And the safest way
to deliver a virus like particle into a human is to go into a space that's enclosed, it's not gonna spread.
Um
And uh
The eye is where it's most been tested. And so we're
We did it for safety reasons, not because it would work better in the eye, in fact.
I told my student at the time, Won Cheng, that he was crazy to try to cure blindness. Why not do something easier like the liver? But he said, you know, the eye is is probably the best
Place to start.
For safety reasons, and he was right.
Mm.
I remember that though.
W we were talking about that in twenty nineteen when I was in your lab.
What has
Th there's been this recent
Release.
That came out last month.
What's that? Why's that so special?
The one about that we've gone into humans. Mm-hmm.
Oh
Well, I think p most people thought the aging field was a lot w lot further behind.
Age reversal you see online. Oh, we've done this in human cells.
We've done it in a mouse, but suddenly
There are people now getting

So for us it was old news. We we'd been
doing this and expecting it for a while.
In fact, we made the discovery back uh
Two thousand
sixteen, seventeen. So it's for us it wasn't
So
So amazing, but for the world I think it was a shock.
To hear that people are actually getting this
Potentially age reversal drug for the first time. What would be the issue that somebody has in their eye which would be reversed? What's the the sort of patient that this would fix?
The thing that
makes me super excited is that
Every
Piece of
or type of damage and disease that's that's been tested in animals.
Mm.
Not just mice, but larger animals.
It's work to
improve the vision of
either a disease or damage. So for instance, if you pinch the nerve.
uh you laser it or
You give a mouse glaucoma pressure in the eye.
Uh we can
Treat that effectively.
And nothing reverses blindness currently except for this treatment in animals even. And so that's what's
Exciting. Even Macula degeneration.
Uh glaucoma.
the two leading causes of blindness in the world, both of them are really
really easily treated by this uh new
uh mechanism. We call the drug ER one hundred, which is epigenetic reversal one hundred.
Um
But yeah, pretty much any disease or injury could theoretically be
Fixed treated.
Uh
by this technology.
Any theoret theoretically any disease or injury could be treated by this. Well, in the eye, um
But even beyond that.
The liver.
Motor neuron, so ALS
Uh the brain has been reversed in aging.
Memory comes back.
uh even joints. There was a Chinese study that came out recently, looked very good.
Yeah.
They used our technology to rebuild bone and cartilage in
In uh osteoarthritis. So, you know, I don't know anything else that just rebuilds body parts like this. Can you explain how it works?
To uh simpleton.
Uh not you, but uh
I don't think anybody listening is a simpleton, but it it's actually quite simple, the the good news.
We take three genes that are
normally turned on.
Early in life.
And these three genes make
factors that turn on a cascade of

The cell uses to reboot itself.
The simple way to think of it is that
I hypothesise that the body has
Software.
that gets corrupted as we get older. So an old person
Still has
information there, it's just that it's been corrupted.
The software.
We call that the epigenome.
It's separate from the genome, which is the DNA. The epigenome sits on top of that and
controls the DNA.
So
in in my book Lifespan, it's a little dated now, but you might remember
I chose a C D as the analogy, the epigenome.
is the reader of the music and the DNA is the music itself. And aging is a scratch CD. So for those
Listeners and viewers who don't
really know what a C D is. They were really cool things we could put twenty songs on.
But a better analogy now would be
Your phone has software.
You know, a really old phone is slow. It can be corrupted.
can get o you know over
Overused.
Um
And so we can reboot that.
And we we found that these three genes that we put in, which we call O S and K for short, these Yamanaka genes.
trigger a program that embryos normally use to reset their age.
Or something very similar to that program.
Mm.
Um something you might not know. Most people don't know this.
Is that when we're
Fertilized.
And we've all been fertilised, we wouldn't exist.
And then we need to reset this epigenome, the software needs to reset.
To go back to being young again.
And that has no way.
It's it's a fact. It's shocking but true.
Young very young embryos are old and then they get reset. So the the software is really it's not software, it's the way the DNA is folded in the cell and every cell has to compact the DNA.
'Cause it's six feet long, has to fit into a microscopic little little ball.
And uh
How that's compacted depends on
what kind of cell you're gonna get. So if you want to make a nerve cell
You compact different genes.
And when you compact them they switch off. But
You need to read nerves that make nerve cells, so you open those up.
And this
This bundling and opening of DNA.
is what the epigenome does.
And my theory called the information theory of aging said that
This pattern pattern of bundle loop, bundle loop.
Which is different for every cell type.
gets corrupted, gets eroded.
During aging.
And that literally is aging.
Mm-hmm.
And we tested this and
Published it in twenty twenty three.
and we created a mouse where we could disrupt those loops and bundles.
And the mouse's cells lost their function, they lost their identity, the nerve cells forgot how to be nerve cells.
And the mouse literally got old. We could speed up that process by corrupting that software, the epigenetic software. And then when we did that, which took us thirteen years,
uh we started working on reversing that process, which is how we

Yeah, people see aging as a certainty.
But
You call it a disease.
Is it truly a disease or is that just a useful metaphor?
Well, it's just a word, really. So we can call aging whatever we want, but I prefer to think of
Aging is a disease because otherwise
We're not really
Trading it.
Most doctors don't
Think of old age as something that is
Preventable or treatable.
Even though now we we believe we understand that it is very
Treatable, uh or at least slowable.
Um, so I think it's a useful way to look at
aging as something that we should address.
um even starting early in life to try to slow it down at least.
Um we all need to stick around for longer because the technology that's coming is incredible. Um
And I propose this
In my book.
And uh even put it on the back cover and I it was
A lot of people were telling me that that's crazy. Don't say that, David. It's gonna be scandalous. People are gonna not take you seriously as a scientist.
Um
But I'm glad uh Matt my co author at Matt Laplant
Convinced me we should go for it.
Actually that was his own.
main role besides writing was to say David.
Go for it. Just do it.'Cause don't worry what your colleagues will say,'cause some of them can be pretty brutal.
So we put it in there and uh
And it's
Seemingly
been embraced by a lot of people and now you hear it quite often.
What's the technology that's coming?
If that's what we've done so far.
What did the next few years have in store for us?
Well
There's a fork in the road. I don't know when it's coming, but
It's similar to the singularity with AI or or AGI.
We
When we show
And it's a matter of when, not if.
that aging is reversible in humans.
'Cause it works in all these other animals. It'll work in us. We're basically just
Slightly more intelligent monkeys.
And it works fine in in the monkeys.
That's gonna be a turning point, I believe, for humanity. There'll be a lot of people who say all right
Now let's get on board.
Let's invest. Let's blow this out of the water. There's already a lot of
billions of dollars put into this, but it's gonna
Can it be big like AI.
when that happens.
But these technologies, let's say it it works in the eye and now we can treat
Perhaps cure.
Most types of blindness.
Then we're gonna
We're already doing this. I should
You know, I can't talk about too much, but we're already looking at other tissues. The liver, for example.
And maybe there's joints and hearing that we can also repair.
Ultimately where this is going, obviously.
Is whole body.
Reset.
Um and we can do this in mice easily in my lab now. W and others have done this and every cell in a single organism.
Oh well, we don't have the technology
with the viruses and the genes to reset every cell. And that's a limitation of getting the genes into every cell. You can't do that. You can we
Can
Basically at best get it into half of the cells, but still a lot of them.
Um
We've taken a
Path that's a little different now.
You know, saying we've been doing this for a while.
And the world doesn't really know what we're up to in my lab.
Um, I can reveal that over the last five years we've made breakthroughs in turning it into a pill.
That's the next big thing.
that'll come out of my lab is revealing that we can
give a mouse, an old mouse
something orally, so we they don't chew on the pill, we give it down their throat for
Three days a week for a month?
Uh and we see that they are uh
uh rejuvenated in many ways.
Including um
Not just their memory, but things like even their skin quality.
What is what what's happening?
What what's the pill doing to them?
Well, that's a lot of work. Uh we're still trying to figure that out, but we But so you know it works. But you don't necessarily know why or how it works. Well we we actually literally
don't know how the genes that are in the eye of humans now work, really. That's a big question in
In my lab, uh he's trying to answer.
Where is this back up copy of software?
Um
But we do know it works. That's the hard part.
And then figuring out how it works will be important to make these drugs even better and more powerful and more potent and longer lasting. But what we do know is that.
The epigenome is involved.
In the pill.
uh not just in the gene therapy, because we can disrupt
that uh polishing of the C D or the reset of the software. Um
There are genes called tets.
Uh which make proteins that strip
uh away chemicals off DNA.
These are key to the epigenome reset.
In embryos as well as
In our bodies.
And we can
Get rid of them or inhibit them with a chemical.
Um
And we can feed those to the mice or give it to the cells, and we have some good evidence
Um, I hope my students don't kill me for saying this publicly. But we do have good evidence that
The pill, let's call it, the cocktail.
Does work through
This epigenetic
It's not just all the cells.
are getting stressed out by the chemicals and they fight back and they live longer. It's it's not that. It's truly through this reset mechanism and we can show that by getting rid of these TE enzymes that strip chemicals off the DNA. And without that mechanism
the cells don't get younger, even with the chemicals.
Do you think there's gonna be a realistic upper bound to human life?
Uh well the question is when. Uh I think that ultimately there is no upper limit to human life. There are
I just visited a bonsai garden in Japan where the trees are a thousand years old and that's they're not even halfway through their life, so
Biology doesn't have limits. It's just a question of what our genome encodes and our epigenome but
You know, we have control this century over our own biology. We don't have to just
Be it the whim of the
What evolution and the Serengeti gave us.
And I see
And no upper limit.
Doesn't mean I think
You and I will be immortals, that's
right now beyond uh imagination. Well
It's definitely imagination, but it's beyond technology that I can think of.
Uh but I do think that
some of us will have a chance to live decades longer and
Probably the first time.
person to live two hundred and fifty is already alive.
First person to live to one hundred and fifty is already alive. Yeah, I'm I'm not the only one in my field saying that. It's it's now
realistic. I mean, think about it this way. It's hard to imagine the future, right? But
The po a kid born today is gonna live into the twenty second century.
And we can't even imagine what the world's gonna be like ten years from now.
So the longer you live actually, the longer
You get to live.
Surely if someone took age reversal pills for long enough, they'd just become a baby.
Is that another way it works?
Well, we we made sure that wouldn't happen. That was one of the
the things that one Chang might be shut everybody into a
Yeah.
Well that was the trend. Okay, Yamanaka, um Professor Yamanaka won the Nobel Prize.
for making cells go back to H zero and making them into stem cells.
But that's not gonna help us. We don't wanna strip away.
the identity of all our cells, we die within it a couple of days. And and in fact if you do that to an animal, it's tra it tragically does die or gets gets cancer. So what took us the longest time from 2014 to two thousand
Seventeen was figuring out
How to reverse aging but not
So much that it loses
the identity of the cell erases it. And
My student one Chang uh
famously almost quit the project.
He was doing his PhD, he was in his last year.
And nothing was working.
He was
either having no effect on the human cells in the dish, or they would be
Becoming cancerous.
And he said, David, I I don't know how to stop it halfway.
And we came up with one last experiment that thank goodness it works,'cause we know
Wouldn't be talking about it now.
Uh we tried
A subset just three of the Yamanaka genes.
And leaving one of these
Gemanaka Genes out was the key.
Without that final
Jean?
It's called C Mic, we call it M. Without M, the M gene
Cells don't go back hundred percent. They go back about seventy five and stop.
And and that was the breakthrough. The stop was really hard to find.
Uh, but it's there and turn everything into stem cells. Yeah, yeah. Or cancer. It's even worse. Um
Well, maybe not not worse, but it's definitely bad. You're not gonna live longer or cure blindness. But that was a breakthrough and and Won Chang sent me the pictures of the cells that were younger and said, Eureka, I think we've done and it it was a remarkable
thing to witness.
What do you think most longevity experts secretly believe
But
Can't prove, I won't say publicly at the moment.
Gosh, that's a good question.
I was gonna say most of them secretly think that I hype this stuff way.
Way more than I should, which is
Again, a a not a fairer thing'cause my lab is eight years ahead of what we've published.
Um
But I think most su most aging researchers, I can say for a fact, behind the scenes
say this is gonna be much bigger and more powerful than we expected.
I've been told by some of my colleagues.
Don't say that number one hundred and fifty.
It makes us look bad.
You know, and I'll say, Well, do you believe in it? Yeah, but we can't say that'cause we're scientists and we'll lose credibility.
So yeah, I think a lot of the scient scientists are very cautious by nature, by the profession. I'm considered an outlier, speaking my mind and what I believe in.
But most scientists don't cause it uh
It's not something scientists typically do.
Mm.
Why is it that your
Seen as an outsider.
throwing more caution to the winds than other people? Is it that they're
criteria for
uh evidence is is different to yours. Is it that your lab has got access to information that other people don't?
Well, there's a few reasons. It's definitely that my lab has information that
Nobody else knows.
And that's been
Yeah.
Difficult my whole career knowing that something's true, but
It's not published yet, so in the minds of my colleagues it doesn't exist yet.
And in fact my book came out.
in some cases years before he published the work.
So the public knew my lab's work before other colleagues had seen it.
Um that's also rare.
Another why uh
I'm a bit of an outsider is
Um I'm not doing this.
to be a scientist. I'm doing this because I'm on a mission and my life
Is irrelevant?
Um I would literally die to achieve this mission. And so, you know, if I get criticized or if I speak my mind.
I real really don't care.
What is the mission?
Uh to impact in a positive way as many lives as possible.
Um, this was since I was uh uh four years old. My grandmother
Gave that.
mission to me'cause she lived through World War Two and the aftermath in Europe.
And uh she told me the horrific
Things that humans.
Did it.
And can do.
And
She was always saying
We can do better as a species and
I feel like
Uh I wanna die knowing that I
Done the most for humanity that I could possibly do.
And and if it upsets a few people, I don't care.
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Fashion
Modern wisdom. Longevity is a huge field, right? Includes
Everything.
when you think about all of the different types of interventions that people can do
How do you chunk them into groups? Sort of what are the buckets that people should be thinking about is contributing to their lifespan? Yeah. So I talk about this on on my YouTube as well. So there's a lot of detail on there now when I've relaunched it. Welcome back into the fray. I'm glad that you've stopped doing the wasteful work in your lab and
Yeah, I was uh working on uh
solving and now now that the clinical trials have started, I'm
Like more important. More important things. Mm-hmm.
Uh but yeah, so what we talk about on the podcast is
What are the the major things that people can do to slow down aging?
And even reverse aspects of it. But if we've got this technology coming soon, you're eight years ahead, everybody is doing the longevity escape velocity bet, right, for every day that I live, there's more days that I can hopefully live. So in the interim
Those are the buckets, right? That's the stuff that people need to focus on now. For sure. I think anyone that doesn't
Focus on their longevity.
Uh might miss the boat.
Um
It'd be tragic if you'd you died a few days before.

And this is I'm not worried about you killing over any time soon, you're very fit.
Um
But you know, your parents, your grandparents think about them. So try to encourage them to live the healthy lifestyle that we're we're gonna discuss now.
The buckets are
uh lifestyle. So within that there's
the obvious things that we can talk about, which is
What you eat, how you move.
how you rest, your stress, these kind of things. That's what you can do and you should do on a daily basis. It's what I do.
And there's uh
Drugs.
Which some of which may work. So that's metformin, repercin, some senolytics.
And
Probably GLP one.
Receptor Agonus would fall into that bucket.
Um and then there's supplements, which is the Wild West. There's a lot of things said about them.
Um
I believe in a few of them based on a lot of animal research and some human data.
Uh those are the three main things uh that you should do in your daily life to maximize your chance of getting these
Medicines. Okay. Lifestyle stuff. Yeah.
Last time that we were talking.
It was all about calorie restriction and primarily fasting as a
root toward calorie restriction.
How should people eat if they want to live as long as possible now with twenty twenty six data?
Well actually what I've been saying uh
Actually I'm on my podcast for
now what four years. Uh it hasn't changed. And my book, Lifespan, which came out
We were talking about when we first met in twenty nineteen. It
Nothing in that book.
I've had to revise.
It's all considered. So there's no retractions from the book in twenty nineteen. No. No and my labs never retracted anything and
at this point never been proven wrong, which is a blessing and I
Knock on touch on wood.
But
That's good news, which means that the things that I've said before
People can go back and learn still.
Um, if this is the first time you're seeing me, uh, you know, let's let's start.
So the the main things
About fasting are
We know from animals.
Um and some human data, but mostly from animals that if you restrict how often you eat
Um and to some extent how much you eat.
You get longevity benefits.
Um
And we can talk about it.
protein ratio to carbs, to fats, that's also a whole big debate, as you know.
But generally I I like to eat one meal a day.
maybe two if I'm being social.
But not three. I think three meals a day plus snacks is marketing.
Um
Breakfast being the most important meal of the day was
General Mills, I believe. Uh one of those companies, Kellogg's perhaps.
But uh this is you know, it's all marketing. Humans are not built
To eat.
That consistently.
I don't think

eating their big breakfast saying, What are we gonna eat for lunch? I think
You know, maybe if they just killed a mammoth, but generally they were pretty hungry.
Mm.
And our bodies have adapted to that. We're not meant
To always be satisfied.
Um and so I try to be hungry. And if I gain a little bit of weight, sometimes I travel and I eat well and
Serena and I uh we do uh sometimes
Love to eat.
I'll come home from travel and
Just I won't eat for three days. Sometimes
Two weeks I can go without food. It's not a bill. Two weeks without food.
Yeah.
Okay.
I might munch on a on a piece of celery or something, but that's not really nutrition.
I will drink a lot.
I'll drink a lot of low calorie
zero calorie drinks, a lot of tea, that kind of stuff. But I can go without food for two weeks. It feels great after the first
three days I'm over the hunger feeling.
Um I can see on my monitor, which
I've got one on here. CGM.
Are the CGM? Yep.
Uh I can see the great impact it's had.
having on my body.
I can monitor it on my rings. I do blood tests, which is important. You don't want to just guess what's working, what isn't.
But yeah, I know two weeks sounds like a lot.
It is a lot.
I'm a regular guy. I I s I'm not
Like some people that spend millions of dollars on their body and and measure everything.
I'm kinda lazy. I
I don't like being hungry. I like food.
I like to snack.
I I like to stay up late. I'm a typical
Hedonist, if you let me go.
Um and actually up until a year ago
I actually hadn't fasted more than twenty four hours.
I just couldn't do it. Like this is
Painful.
Um and I'm stressed. So if I'm stressed, I'm gonna eat.
Um
But what I've learned over this past year is I can go beyond twenty four hours and once I'm over three days.
something kicks in. Actually, we know molecularly there's something called chaperone mediated autophagy or CMA, which is the deep cleanse of these misfolded
And modified proteins that you want to get rid of for aging?
Or slowing aging. And uh
After those three days.
you know, I I start to feel amazing, my mind clears.
Um I don't feel bloated at all.
Um
I don't even have to go to the toilet that often, except for all the tea. But you know what I mean.
And uh
Yeah, I feel energized.
And I I'm measuring myself, so I'm making sure I'm not overdoing it. This is not for everybody. If you're skinny and you've got
Billy.
Any fat.
or your elderly. It's not for you. But for me, I gain weight and muscle pretty easily. I can fluctuate.
And so I watch my weight come down. I've got
uh a scale that measures my weight.
Um it's
I don't know if I can measure uh say the name or if it it's forbidden, but
Um, I do like the withdings scale because it's smart scale links to the phone. Yeah. It would get your composition as well if you hold the handle. Yeah, and and I've had one since two thousand thirteen. So I've got all this data on my body weight and composition, which is awesome. And I'm trying to maintain that at the optimal level over these last thirteen. I'm this two weeks thing is blowing my mind. What are you running on?
after ten days. Are you supplementing with with vitamins and stuff so that you don't get scurvy? Like why are you dropping dead? I am. I'm glad you said that, Chris, because it's important to say it.
I'm a scientist about this, I'm not just willy nilly giving up everything.
Yeah. Well no, I'm not doing that. I uh
the reason I'm using my hands is I travel and at home I have a little carry pack.
with vitamin supplements.
um and medicines that I've been using
And know very well what I need. I
Every morning it's a symphony of supplements and medicines, actually.
I know what my body needs, I know what what works. Uh so I do that. So that's not
Not anybody can do that. So it's really important if you do fast for long periods, make sure you
Enough hydration, very important.
We know that. But also I'm making sure that I'm not deficient in any
minerals or vitamins and so I'm I'm taking in things like vitamin B
uh vitamin C as well, and some nutrients that I know
I can become deficient in.
What do you think's happening inside of your body after
From day four.
Until
in the day fourteen. What's what's going on?
Well, we we know, actually. Um
Not from measuring me, but
We know from
many years of study what happens to the human body.
Uh the first twenty four hours you you're gonna
uh use up a lot of
the the sugar and then the glycogen in your liver.
What I like to think is
My liver knows
Had her.
Steady my glucose and give me the right amount of glucose far more than my mouth does.
My live is smarter than my eyes and my mouth.
And anyone that's fasted knows that
your blood sugar if you're eating is like this and you go, Oh, energy, oh brain fog, energy, brain fog. Oh I'm sleepy in the afternoon.
That's our normal life. If you're fasting, your liver just puts out just the right amount of ketones for your brain.
Um or you can drink some some ketone drinks. Um or
Uh it's making glucose.
Or both. Your brain is
loves ketones and uh if you do it too long
you will start to lose muscle. So I'm working out more than I do.
Normally.
to make sure I don't lose any weight. And so that scale will tell me if I'm losing lean mass, which I don't want to do. And I make sure that I don't lose it.
Is there not a concern to do with
Your gut?
Is there not is that does there not need to be transit through
the digestive tract. I don't know what happens if nothing passes through your stomach for two weeks. Yeah.
Well I can tell you your stool changes, but there's very much it turns fucking invisible. Yeah, right. Phantom Poo is a little a bunch of gas coming out. Um so yeah.
That's what I meant. I'm not on the in the bathroom as often. It's actually much more productive.
Um unless you're productive on the other. I do find that the biggest um obstacle to my productivity is the bathroom, actually.
Are you sure you're not you're not tweeting away down there?
Uh but yeah.
Your microbiome, I think.
And and this is not proven. Um
By any means, but I feel like
Just like your body.
It helps to give your microbiome a shake up.
a bit of hormesis, which is a little bit of stress that's good for you.
And uh
I would love to do an experiment on myself as well, measure before
during and after and see what happens to my microbiome.
Positive effects for GLPs.
includes slowing mortality through the gut, which actually helps with things like SIBO or Candida or H. Py Lori, because
the pace this is why everybody, every bro lifter that's listening to this
Yeah.
you at some point in your life have glanced off the bottom of SIBO or maybe have it right now, because just the sheer volume of food that you're putting through yourself all the time, grazing high protein, high starch, like
that's one of the proposed mechanisms I think that helps from GLPs. And I didn't know that's why what I was interested, maybe creating this very
I was gonna say sterile environment. It's not it's barren, this completely vacant environment for two weeks.
I have no idea what that does it d w if you had uh overgrowth, does it kill it all because it's not being fed? Does it allow it to
create castles and cathedrals and uh you know, armor itself.
Yeah.
Yeah. Well
I don't know the answer to that. I I do know that there's
Some really interesting things in bile.
that uh comes out more when you're fasted.
Uh one of the components um
Is a
A type of
Which is

black stuff that goes into your microbiome and your microbiome converts that
into a molecule that goes back into your bloodstream and turns on a longevity gene that we've been working on.
uh it actually binds to the protein and makes the protein more active. It's called Cert One. If anyone's read my book, they know what CERT one is.
Sort one regulates the epigenome, slows down the changes to the software.
And
So long story short, it's
It's
At least
plausible, and there's a nature paper on this from another group that I reviewed, that when you're fasting, your microbiome
Is more actively converting bile into healthy molecules, as well as short chain fatty acids. There's a lot of literature on that. And these molecules go into your body.
And they signal.
Adversity?
And you know that I like adversity. Adversity is good for your health.
Um, there's abundance and adversity mode. They're both good, but you don't want to stay in one or the other.
you'll you'll
Excelerate.
You're aging and you'll you'll die.
So you want to cycle between adversity and abundance and your microbes
help you get through that.

What
Would you say let's say that someone
Finds this quite a bit.
Seductive.
What would be a good
Start.
A one day fast, a three day fast? And what what should they do? What would be a a rough protocol to follow without having to be a
Conductor of supplements. Yeah.

Well if if you're
If you've never fasted and you just wake up and you eat a normal breakfast, lunch, dinner
Either you're a you're a beast or you exercise a lot.'Cause
That's gonna put on weight. Um
But if you
Uh
willing to try, I would suggest skipping
one meal and replacing it with a lot of liquids.
So for me, I I don't mind skipping breakfast.
Not everybody wants to do that because they work out and they feel like they need some food.
Um so you can instead you can skip dinner.
I would just have a very early dinner.
Um
What I was doing for many years, probably thirty years of my life was
Trying not to eat anything until late lunch.
Um, and you you will initially feel hungry. This is the thing. Don't give up.
Because it takes a few days for your body to get used to not having the food. It'll be screaming at your brain.
I'm so hungry I'm gonna die if I don't eat this
Bacon and eggs.
Uh but you get
Get through it.
And actually after two weeks it'll become
Really.
weird to eat food in the morning or at night. Your body gets used to it, your brain gets used to it, but it does take a while. And the cheat code is
Fill your stomach with lots of liquids.
Not sugary drinks, not a lot of uh
Of calories.
Zero if you can, or just a little bit.
Um I do have a little bit of calories in the morning because it's good with my supplements, but
Um
Lot of water. So
A low calorie drink like this, or water or tea.
Um
Black tea.
Coffee is very good. They're both good. Actually tea and coffee are both very good for you because they contain other molecules like polyphenols that
again can activate these enzymes that protect us.
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Have we seen
Any data.
That shows calorie restriction.
increases lifespan in humans. I know that this exists in
Rodents. Yes.
A study that was done, was it macaques or something, and that didn't actually
Work because
It was a two decade study.
And the first version of the study it turned out that they hadn't fed them the same diet and split it in half. They'd fed one of them a junk food diet and the other one and been given a healthy one. Then they ran it back and it seemed like the data was mixed there. What's the evidence about calorie restriction for longevity in humans? Is there any?
Uh no.
Uh, there's a lot of anecdotal and historical evidence that fasting is good for you. And there have been some short term studies over a couple of years. There was the calorie.
That
showed that you could improve a lot of health biomarkers in humans over that time that had lasting effects, including on the epigenome, but nobody's really done a prospective study
Uh with
placebo, it's very hard to do that or even controls. So we there's no proof, and I don't think anytime soon there'll be proof.
But who wants to wait another hundred years to let happen? You can't.
You've got to
at least go based on the evidence. And in animals it's incontrovertible that
that if you do it with nutrition, not just starving.
It's very good for you.
Um
And
That's why I do it.

I would say
with the monkey study, I know it very well because
The two labs that disagreed about this.
One uh
is one of my best friends and the other one is my trainee.
And
They were Oh well you're like Switzerland in between the two of them.
Yeah.
I didn't really get involved.
Um
But I did bring them together and they
They came to a the conclusion that
Yes, it did extend lifespan.
Um it depended on
the the veterinare and other other environmental things.
The University of Wisconsin where
The other lab is uh Rosalyn Anderson is the professor that I
Originally trained.
What is it?
twenty years ago.
Uh she runs the study now and her monkeys lived longer and they also
Definitely incontrovertible.
Uh
evidence that they had less cancer and I think heart disease, but definitely overall disease burden in these monkeys was lower.
And they lived slightly longer.
But even if they didn't live longer, I would say still
Look at the data on the diseases. I mean, who wants to get cancer and heart disease in their sixties and seventies?
Why would
high calorie turnover increase your likelihood of cancer and heart disease.
Yeah.
Well there's a few different
The theories, the one that I like the best, that's the simplest, is that when your body is in a state of perceived adversity,
And running.
Building muscle lifting weights.
and hunger are signs of adversity.
Um, also eating plants that are stressed is a sign to your body that your food might run out. This has put your body in adversity mode. And this enzyme that I mentioned earlier called SOT1, which protects the epigenome, it responds to hunger and exercise.
Um there's a molecule called N A D that a lot of your listeners and viewers would know about.
This enzyme responds to NAD levels.
Uh but long story short is
When you're in adversity mode, your body switches from growth and reproduction into survival mode.
And at least if you do that for some of your
day or some of your week.
You'll get
Some protection against the ravages of aging.
epigenetic changes.
um DNA damage, all of these things that we know contribute to aging.
Do you think that there would be a marked difference between somebody who restricted their calories by thirty percent over
A year, let's say.
And somebody who restricted their calories by thirty percent with big breaks in food.
Calorie restriction versus
calorie restriction through fasting. Do you think that those two people would have different kinds of outcomes?
Mm.
So are the
one is eating more than the other? No. They're both eating the same amount of calories.
A hundred calories an hour.
For eighteen hours of the day.
And another person has one meal that's eighteen hundred calories per day.
Um
There's a lot of evidence that
Eating within the time window.
Is the one that's much healthier.
Um the friend that I mentioned earlier, Rafa Rafael DeCabo, down at the NIH here in the US.
What he did.
Again in mice, but
I think there's a lot of evidence that it would translate to humans.
He gave mice.
Roughly the same amount of calories.
But he gave it to them all day.
And they had to gobble it all down quickly.
It didn't matter.
What they were eating was different amounts of protein.
Uh carbohydrate fat.
He was hoping to find the optimal diet, but he found that the group that ate within that window
lived substantially longer than the ones that ate continuously.
I saw you quote tweet something about
Protein being overhyped.
Yeah.
Protein maxing movement.
What's your position on that?
Yeah.
Protein is good.
Um, I'm not against protein at all. I eat a lot of protein myself, actually, mostly from plants for reasons that I'll get to. Uh but the this die hard, be a carnivore
Forget about the green stuff.
Is is definitely not.
not consistent with the science of longevity.
It's consistent with the scientist of bodybuilding.
And
Which of course as we know is a superior science.
Yeah. Yeah.
Well
Yeah I
As much as it doesn't look like it, I really like bodybuilding over other exercise.
Um, I'm just busy. I used to work out a lot.
Um, I love bodybuilding and
Protein is essential for building muscle, no question. Okay, and you can get a lot of protein from
Protein supplements and meat.

Where I think
It's been overhyped.
Is
We know that plants are essential for providing polyphenols and
having l a lack of
branch chain amino acids specifically is also very good for health.
A lot of data on that, especially in animals, but some in humans.
So branch chain amino acids, some people listening will know what they are.
Valine, isoleucine, leuine. These are three of the twenty amino acids that are found in
more abundance in animals than in plants.
And when you give animals a lot of these brain chain amino acids
Uh they live shorter than if you give them less.
And this has been shown in short term studies in humans. If you restrict protein
um that has a lot of brainstrained amino acids in humans, they get better metabolically. But I'm not saying
you can't eat meat or you can't eat protein. What I'm saying is
Just doing one or the other.
Uh not
really the best way to live. Mm-hmm.
I think the best way is
To pulse it.
Okay, so if you're working out, you want to build muscle.
Yeah, you can eat.
You can eat meat. I eat meat occasionally, it's not a problem.
But you want to have a period of your life or your
Let's say your day or your week.
Where
You're not eating meat or you're just not eating.
Um and that puts your body at least
part of the time in this adversity mode. Should you be doing both? Let's say that somebody's doing OMAD or 168 or some sort of fasting protocol. Would you still be looking to pulse protein intake as well separately to that?

Yeah, I yes. Yeah, the answer is.
Well, without protein
I don't think you'll live, right? Uh you need some protein, but you're you mean huge amounts of protein or you mean meat.
time for you to focus on protein and then there's time not to. You should be fasting. I'm wondering whether you should be fasting from protein from a micronutrient standpoint as well, in your opinion.
I don't
Think so. I don't try to fast from protein. I try to fast from
a lot of calories and I also try to fast from
a lot of animal protein, which has these branch chain amino acids. And we know the molecular mechanisms. There's mTOR, which anyone who follows longevity will know about this MTOR. And if you're eating a ton of meat every meal,
Or e every day.
uh your mTOR is gonna be active.
And MTOR's role is to
Help cell divide.
Grow?
Build muscle.
Great. That's what you want to do. When you're young, you want to build muscle, you want to look good, you want to be strong. Even if you're older and you have sarcopenia, mTOR is good.
But we know that animals that have active mTOR live shorter than those that have
Let's activate M Tor.
So how do you get the
benefits of both, well, that's what I'm saying is

Switch down.
Plant protein mainly, don't eat a lot.
MTO will
Help you.
When it switched off.
But you can rev it up when you want to build muscle or or uh run a marathon or something like that. You don't always have to be in one state or the other. Okay, talking about exercise, has your exercise philosophy changed?
What
is the best exercise protocol for longevity in your opinion? No, it hasn't changed a lot. It
Wh I just keep seeing studies that that say the same thing over and over again, and then people argue about the latest one.
We know that
the best health is a combination of weightlifting.
Uh muscle is good for hormones. It's good for not breaking bones when you get older.
Um
Balance is important. And then the other one is aerobic.
VO two Max. We know VO two max is correlated with very long life.
Um and so
You do need to lose your breath.
Minimum three times a week.
Ten minutes.
Um it's rare that people
Talk about sex as a a way to exercise.
I see your eyes bulging.
Um
I'm just waiting to see where you're gonna go.

Well I I was looking at a at a
at a tweet the other day, uh at an X, whatever we call'em now.
And it was saying Oh I think
I won't say who who it was, but they said, Oh, you can lose your breath ten times.
Oh, for ten minutes three times a week by doing XYZ.
And I thought well
No one ever mentioned sex, so
If you have an active sex life, count that as part of
Your daily longevity routine or your weekly longevity routine. Okay.
But also sex.
Can be
If you can go for ten minutes vigorously, that's
A good start for longevity. Uh there's sometimes restrictors for that, um that uh aren't simply cardiovascular, but go on.
Yeah.
Well, you can supplement it with um
Yeah, just running on a treadmill, going outside, rowing, sport, all of this stuff. Just as long as the the way to know if you're exercising enough to build up your VO2 max is you shouldn't be able to carry out a conversation easily like this. You're panting.
Um that's my judge.
I need to do a lot more of it. I these days I tend to do a lot of my exercise aerobically running to catch a plane.
Um
I admit that I'm not
the perfect role model for exercise.
Um
But I do know what the science says.
And that is the combination of
The the weights, the balance uh and the aerobics. Uhhuh.
What about zone two?
You haven't mentioned low and slow.

Well
If you can't do fast and quick and hit
Uh
Low and slow is fine. Walk, move, get up.
Uh, I'm I'm always walking around my office. I have a standing desk. I rarely sit down. So that kind of exercise is very good, certainly for balance, um, overall metabolism. So yeah, I
I try not to sit at all.
Um
I'm sitting now, but I rarely sit during the day. Um it's one of the things people find weird about me. They come to my office and I'm
I'm I'm pacing, I'm twitching, I'm I'm t often chewing gum.
That's not the same as zone two, though, right? No, no. You need to do a little bit more than that.
Um
What I like to do as a sport.
Um
Yeah, it's
tennis could get you there. I do a lot of gardening, so I'm
Carrying stuff. Gardening as a sport.
Yeah, that's my sport actually. It's my big hobby. Interesting.
lifting a lot of heavy plants and building walls and
hammering and drilling and all that stuff. Um yeah, a little bit
You know, k kayaking is something that I like.
I'm not out of breath, but I'm out
Yeah, I'm getting a good workout.
Sleep.
And recovery.
And rest.
What is the
Most up to date data saying around that.
It's still the same.
Um
It's
You do
Need to watch your sleep if you're not getting quality sleep or sleeping for that long.
it's gonna affect your metabolism. Figure out how much sleep your body needs at a minimum. You can do that using some of these rings. It's very good for that.
Some people need
Eight hours, some people need seven hours. Typically if you're younger, you need more.
The good thing about getting older is you need less typically.
But it's also about quality.
Um I can get away with five hours sleep.
and my HR V is still in the eighties, nineties.
Um because I'm getting deep sleep.
I'm not drinking caffeine late in the afternoon.
Um I practice
as best I can, relaxation, meditation, practices, breathing. And that
gets me to sleep and into
Rem and deep sleep pretty quickly. I also take a supplement.
That uh my partner Serena makes.
And um it's got L theanine and some other stuff.
That also I know from
My own experiments gets me into deep sleep quickly.
And so my efficiency is typically according to these rings.
Uh in the nineties, ninety percent sometimes.
Close to a hundred. And then I can get away with less.
Um which is nice,'cause I travel a lot.
I think that's the big learning that
Everybody who starts using a wearable takes away from it, which is you're sleeping way less than you think you are.
Like, well, you know, I I was in bed for eight hours. It's like no
You thought that you went to bed at eleven, but it was
Actually sort of eleven thirty and you were
reading or watching TV until nearly twelve and
Then
your actual efficiency was maybe eighty five percent. So that seven hours has turned into five forty five or six or something. And yeah, it's stuck. I've got
Maybe
fifteen hundred, maybe two thousand nights on Woop tracked, right, over the years. And
It it's you're just always sleeping less than you think you are.
That if you don't have money to buy a wearable.
Just the rule is you're sleeping less than you think you are.
That's it.
Yeah, I agree. And especially if you're
You were eating late.
Drink.
Coffee or tea late.
Uh or matcha.
Caffeine and and alcohol are big ones for bad sleep.
Um not just stress.
Having a hot room.
Or too many blankets is another.
Mistake that a lot of people make.
Um you can get those beds that cool. Eight sleep. Eight sleepers. Anyone that's not using an eight sleep, it's medieval. I understand they're expensive, but
There's no one that I've got
to do yeah, they're a partner on the show or whatever, but like this has got nothing to do with it. Every single person that I've got to try it.
can't believe that what life was like before they had a a
cooled. And there's other cheaper versions out there, I'm sure eight sleep's the best, but there's there's there's other ones that you can get. Trying to cool your bed
from outside of your bed, when the job of your bed is to keep the temperature in the bed the same, is kind of a little bit like fighting against the tide.
Yeah.
Oh, exactly. And you should wake up every morning feeling totally rested, excited.
about the day. If you're waking up and like oh I need a coffee, oh I need a shower
You're probably not getting the sleep that you need. Mm-hmm.
You mentioned stress as well as kind of the fourth pillar when it comes to lifestyle. What is that?
Look like how do you how do you come to think about stress as a longevity, doctor?
Yeah, well you can measure cortisol, for example. Um
or D H E A caught as all the levels.
We're all stressed. You know.
Sure.
The old days of sitting around.
A campfire.
Not really.
there anymore. We're driving to work. We're worried about
Income.
And so what we wanna do is uh
Learn to
To deal with the daily stress.
No, the world is changing faster than ever.
So what what I've learnt personally is
Really not to let
Warriors of life.
Get me down.
Um I try not to
Focus on them.
I have a happy place which is
an orchard uh on Cape Cod
And my mind
When it's stressing out and I feel my
Body tense up.
I take myself there.
I breathe.
I'm amongst the trees.
Um if it gets really bad I I go there physic and do some work. But yeah, it's it's all about
Learning not
Two
Ruminate.
Um and a lot of us A types, I'm sure you in your success are like that. What did I do wrong? I could do that better. I'm worried about tomorrow, worry about next week, I'm worried about ten years.
Um
Don't do that.
It took me
Fifty years of my life to figure out.
Don't do that and how not to do that.
And a little bit. How do you s how do you stop worrying?
You have to train yourself. It's like don't be an idiot. Stop thinking about it. Um, it's not gonna
Kill you if you're
Distract yourself with something else.
Overthinking something is is a real uh
Uh issue.
For modern life.
And uh so I don't do that anymore. If I uh find myself overthinking, I'll just say I'll think about it later, put it off to the side. And I used to be the kind of guy that I had to text back immediately and email back immediately.
Put it aside. I'll get to it.
I think a lot of people are riven by
The overthinking
intrusions that they just can't get their brain to focus on what's in front of them. There's always this concern. There's always this situation that could be a little bit worse. This thing that could make life a little bit harder that's coming down next.
And yeah, you're you're
uh kind of being puppeted by these ghosts of the future that haven't yet come about.
Yeah, that's the thing.
What you realise
when you get to my age, I'm now fifty seven, is that
It's never as bad as you think.
And w what I do now is I depend on myself. I know
But
these big problems in my life and I've had
Big ones, deaths and
Issues. Um
You get through it.
You trust yourself, you know. You know, maybe when you're a teenager and you're in your twenties you don't
know that you can get through these things.
I'm at an age where I know
I'm not gonna die. I'm gonna get through it. It's gonna be okay.
Um, if I have a problem, I'll solve it.
Um
The sooner you can realize that
that you are capable of anything if you put your mind to it.
Mm.
Then you shouldn't stress about problems that come up. Tell me if this sounds familiar. You train regularly, you eat reasonably well, you feel fine, but you're just kind of going off
Vibes.
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That's functionhealth.com slash
Bottom wisdom. Okay, let's talk about your current drugs stack.
What are you taking? How's your
Daily stack changed.
versus what you were doing when you wrote the book.
It hasn't changed. That's the amazing thing. Uh, I thought I'd have to change things depending on the science, but the science has held up.
So in the morning?
And if you go to page uh what is it, three hundred and four of lifespan, it's still in still there.
Uh and I still do that.
Uh Ris Virtual.
It's been
Back and forth, controversial. It's not controversial in scientific circles.
There's a few naysayers, but they make a living out of it.
Uh, resveratrol is from plants that are stressed and they activate certain one this
resetter of and slower of the epigenome.
Uh noise.
So I've been taking about
A teaspoon, call it a gram of reservatrol every morning.
Uh almost every morning for the last G probably
Twenty years old.
Doing all right. Um, it seems to help in clinical trials.
It's been tested in a number of clinical trials.
I mix it with a either a little bit of olive oil.
That's my calories. Um or uh
Greek yogurt or
Vegan yogurt.
And uh
It's been good to me.
Um
I also
Take that with uh.
NMN, which is an NAD supplement. It's a precursor. We studied both in my lab.
And uh we just resubmitted a paper.
This is something I can
Reveal.
We just resubmitted a paper uh

That showed that NMN
Is very good for the health of old mice.
and can extend the lifespan of mice, particularly females.
And uh so that'll come out probably. Resubmitted.

Yeah.
We we had
Reviewers' comments, criticisms, spent another year working on it to please them and send it back. We'll see what they say.
Hm. What what was the
Controversy'cause I know
Since the last time we spoke there's been
Some fuel around Rest Veratrol, some more fuel around N A D, maybe N M. Yeah. Can you explain what happened? Yeah, sure. These are all
Typhoons and a teacup or whatever it is.

I can't stop drinking a drink, it's very good.
Good.
That's all I needed.
The uh
So let's start with Reserve Troll
I try not to bore everybody.
Um sort one is an enzyme.
I'll use my hands. It's an enzyme that carries out
Reactions that stabilizes
the epigenome so it doesn't decay.
So think of it as stopping the corruption of the software.
More sort one is better.
So there are two ways to activate sort one.
Um
with with a pill rather than exercise and dieting.
Um and if you do all of them, I think it's the best.
So you can either take resveratrol.
And that
We showed in two thousand three.
Long time ago, I'm old.
uh activate sort one directly. So the enzyme
Is
Removing
Chemicals from the epigenome.
And making it stable.
And it can do it slowly.
You know what a Pac Man is?
You're old enough.
Uh so it's chewing away uh
Chemicals stabilizing things. Faster the better. Whereas virtual, we know binds.
physically to the enzyme.
And now makes it chom faster, okay.
The controversy that came up was that Pfizer, a team at Pfizer
Not the whole company, just a group in the company.


Doesn't do this.

It must be an artifact is doing something else that makes it look like this.
Um so with we then spent three years testing that.
And found.
Exactly how it works to the atomic level.
We could even block it by changing an amino acid in this protein.
And we actually have a study now that we've made a mouse that
has this block.
And resertal doesn't make the mouse healthier anymore, it doesn't live longer. So that's
as good as evidence that you could get that we were right in the first place and Pfizer was wrong.
Um and
We've put out papers since and others have shown that we were right. So
No controversy. Going head to head with Pfizer's no small task.
It was brutal. Uh that was one of the hardest things in my life because
I remember try to def trying to defend myself in public.
Mm.
It was on NBC.
And I said,
I'm not sure what Pfizer is doing, but
Our chemicals don't kill mice and they
activate the enzyme.
And the comments were brutal.
Sinclair thinks better than Pfizer or Pfizer.
Knows what they're doing.
Um
I will say that
I don't have ill will towards those scientists because it's a the job of scientists
To challenge theories.
Um
What I do have a problem with is the
the people who still say it's wrong and are trying, you know, just
What's the remnant if you've put something out which pushes back against Pfizer, what is the remnant argument?
There isn't one. The the problem is that the the m what I've gotten to see in my career over thirty years is the media
Loves the negative story.
But the redemption story.
Isn't as popular.
So it's never come out in
These journals like Nature.
They put out the negative story.
But they never did the oh.
We were
that was wrong. So it's just a matter of reporting. Um, but in scientific circles, everyone's read our science paper uh from 2013 and
It's not debate. That's put into rest that the evidence is put to rest, in your opinion.
Yeah.
Yeah, it's at the atomic level unless you want to
complain about atomic theory, you know, we're we're done here.
Okay. And what happened with N A D
And Amen.

Uh so yeah the
Let's bring everyone up to speed on what N A D is. So Cert one also
Can be activated by giving it fuel.
which is N A D sort one chomps with N A D.
Um
And in fact
This is not often known. The chemical that it takes off the epigenome
Structures.

Donated to NAD.
So without NAD you can't take the chemicals off.
And
more levels of N A D make it work faster and better and
If you give it to cells.
uh you see more stable and healthier cells.
Um
There was dogma that
NAD levels went down with aging.
And that boosting it back up.
was healthy.
So the second part is true. We have shown
In cells in animals.
And even in humans for the last
And by we I mean the field, not just my lab.
that raising N A D levels above
normal baseline is very good.
For humans.
Okay, I can give you examples.
Um
Shelley Basin, you could look up uh in PubMed. He's got a couple of really good papers giving
uh NMN which is the precursor to N A D to people that are either obese
uh or diabet pre diabetes or even super fit ones.
Um
Maybe the Superfit isn't published yet, but he's done the work.

Um
You see improvements from lipids, whole bunch of lipids.
uh cholesterol, blood pressure.
So raising an A D
I think most people would
What
say that it's good feet for humans and animals. Okay. And again we're gonna publish that it's good for longevity too.
Where
The debate that came up I think it
Talking about the one that was maybe a few months ago.
Um
somebody showed that human blood levels in white blood cells
The white blood cells don't have less N A D as you get older.
So some people who love to make a living of being naysayers, especially towards my career, uh jumped on that and said, The whole theory's wrong.
If
white blood cell N A D levels don't go down with aging
Then the whole theory must be incorrect. Which is as you can tell is complete.
BS
In fact we we've known for
Probably a decade that that was true.
And it it doesn't affect the theory. We know that raising NAD levels in humans either by exercise
uh or by supplementation.
So
It was crazy to say the whole theory fell apart. It was just a way to get clicks, I think. Mm.
What's the
Status I'd looked at
Something to do with it was a pharmaceutical
Then it was a supplement and now I don't know what the level of access is with N A D and stuff at the moment. How what's how's that classified? Yeah.
Um or just a final thought.
There is a really good study that showed that people who have lower levels of NAD in their muscle
Um
I think it was a not as metabolically active as those that have higher levels. And
or they had metabolic syndrome.
Anyway, we could check it out, but
But there is some good correlations between N A D levels and and
Age related.
Conditions.
Wanna be accurate.
All right, so the FDA thing, um
Basically it was that there's a rule
in the US that if
Any molecule, whether it's natural or synthetic, goes into a human clinical trial.
Before it's on the market.
People can't put it on the market'cause then it
negates the reason to do clinical trial.
And we need clinical trials to know if things work.
Makes sense. The law makes sense. Where things got crazy was
Uh
a company that I started called Metrobiotech started a clinical trial with NMN
And
A little later people started putting NMN on the market.
And I've always said publicly
You can read it.
Fine, let's do both. Let's do the clinical trials, make a drug.
It's gonna be pure, it's gonna be tested.
And there'll be supplements that are less rigorously produced.
For people that are not sick.
But for the sick ones who have diabetes or need a drug
We'll have that.
Happy world.
Um
the legal team at Metrobiotech made a decision without
My approval.
Actually, with my disapproval.
to um
write a letter to the FDA pointing out that it it
That there was this law
that they shouldn't have simultaneously sales
And clinical trials.
Uh I objected.
Um
The FDA uh initially said
You shouldn't be selling
Uh NMN.
on the market in the US according to that law.
Though they didn't enforce it.
And then it was
recently reversed.

So now it is enforced?
No
I mean the opposite.
The FDA s I believe says it's okay to have NMN on sale now. Interesting. Okay. There was a court case uh that
Uh I think resolve that.
Are you still taking the baby aspirin?
Yeah.
I am that's controversial too.
One baby aspirin a day. Yeah, eight eight the eighty one milligrams, though eighty one is
is only because a trial did eighty one, it's not magical. Brilliant.
But yeah, you could take a hundred probably. Um, but talk to your doctor.
Do you want to talk about aspirin in detail? Sure.
The reason for the controversy is if you dig into it.
And
You know, I do this because it it's my living. Most people don't have time.
The American Medical Association weighed the risk.
Of
having stomach bleeding.
and other complications versus
uh lowering the amount of uh
Risk of cardiovascular.
Events
And came to the conclusion that looking across
Everybody
It doesn't make sense.
I'm totally against the word everybody when it comes to health.
Everybody's different. So I I believe in precision medicine. And there's a group of people, for example, that were
It does make sense to take
baby aspirin. It's been shown that there can be benefits. And it's those people
Just as an example, who have high levels.
Of lipoprotein.
A or L P Little A. Mm.
Um I'm one of them.
So I continue to take baby aspirin, but these are decisions to make with your physician.
What else?
I I I can't work out whether
we call breast virotrol a supplement or a drug or pharmaceutical. I'm sure you can get it in pharma grade, but it's
What else from the
Not foods consumption stack.
You take'cause aspirin would definitely be in the sort of meds.
Category, I suppose. What have we missed off?
Well, there's whole websites devoted to what people think I take every morning. Okay.

Set.
Well,
That will I'll have to come back for another show or or people can listen to my podcast. Yes. Because it's a whole it's a whole box of things and I'm not taking them all the same day. Um but I still like um
Um
Alphalopoic Acid.
for mitochondrial health. So I've been taking that.
Uh, for over a decade now. I did a PhD on it, so I know a little bit.
About its benefits.
Uh but that was a long time ago.

Um, let's see. CoQ ten, of course, because I'm I'm actually on a statin. I might switch to a PCS K nine inhibitor because it's more effective, but my family is very high cost. I'm on I'm on Rapatha.
Great.
Yeah. You like it?
Uh I've actually stopped taking Rapatha because
I want to see if it's causing some brain fog.
Oh.
That is
Sometimes associated to anecdotal.
Uh but I noticed
Apo B went through the floor.
Fucking brilliant, brought everything back in line, isn't that lovely?
Yeah, brain s stopped working quite in the way that I wanted it to.
Okay, well let's see what happens if I take a little bit of a break and let's see and brain comes back in line with where I want. But I found Rapha largely it's every
I've got the every two weeks one rather than the monthly.
And that's been good, but I've also been taking Telmasaden as well.
Because
Uh
I've got I didn't realise this until
I guess I've done a lot of health
discovery since the last time that we sat down.
Um
I have every polymorphism under the sun for somebody that's gonna have
high cholesterol and high blood pressure.
Like just um
really perfect suite of
Hyperabsorber, hyper retainer, all of the dispositions that you want. Are you on Z?
No.
What's that?
Uh the draw that's the common name. Um I thought I'd use it.
Uh
it is the drug that blocks uptake of cholesterol. So the combination of
A statin and um
The Z EO has been shown to be very effective at Lowrench Draw. The supplement industry is full of products making claims that they can't back, which is why I'm such a massive fan of Mementus. Their co-founder, Jeff Byers, played in the NFL and saw firsthand just how wildly the quality of supplements can vary, so he built Mementus around a higher standard. Every
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I did.
Carnivore toward the back end of twenty twenty four.
Uh meat and fruit, technically, for
six, nine months or so when I was recovering from living in a house with toxic mold. It was really brutal, but I actually felt phenomenal. Looked great.
Shredded, jacked in the gym, energy was good, little
on edge, like a little adrenaline-y all the time, but that's maybe to be expected, right? Without any sarch or carbs to sort of really bring you into land. Uh
And I managed to get my cholesterol up into the four hundreds. Which four hundreds? Yep. Yeah, it was really impressive. It was kind of like a personal only briefly. Um and then had creamy blood. And then brought it back down. Um but
It's kind of what I've come to you you're right to say that
Uh
Everybody is different.
Everybody has a different system. And the fascinating thing when you do these sorts of
playing around with ex self experimentation and intervention is you find out there's something that can make you feel amazing.
Make you look amazing. Take in all of the subjective metrics that I care about. Right.
Shit's going great.
Except for the one that might kill me pretty quick.
And then I went and did a clearly scan, which is
Talking unbelievable technology, by the way. The basically
This
Special type of
uh contrast scan is able to look inside of the uh arteries of your heart
And look at plaque builder.
without having to do anything invasive. It's
magic. And and had a small, very small, but mild amount of plaque progression. And okay, I need to put the kibosh on this regardless of how Jacked and
alert I feel I need to eat a much more sort of Mediterranean
Low fat, low protein diet. Yeah. Yeah.
Um
And I know it's not proven, but uh I do like the idea of uh
Pluck reversal. So there's two ways that we know of
that might do it. One is reducing your LDL so low that it reverses.
So repath, that kind of drug.
Um there's an oral.
Um
PCS K nine inhibitor just come on has come on the market, which I've
Got a prescription for I'll try it out.
That's one way.
Uh and then the second one uh was
Based on a study that had a thousand
People in China.
I know it's not the perfect study, but
But to me it looks like it might be true.
And given that
This substance is so safe.
The downside is cost me a few bucks.
Uh Nato Kines.
Do you know about Netokines? No, what's this?
Uh, so do you know what NATO is?
Natural. No, you're lucky.
Yeah.
Anyone
Who's been to Japan?
probably has seen at breakfast.
In the hotels they serve this goopy
bean sticky substance that if you lift lift it up it looks like cobwebs. Okay. And it smells like vomit.
Okay.
Serena eats this stuff. I don't know how she does it. I have to hold my nose.
That stuff, it's Bacillus subtlis and some other bacteria eating soybeans.
they found that there's an enzyme in that stuff.
that if you swallow it, it can remove
Well at least it looks like it can remove Ploque.
Hence.
Nato kinase. Kinase is the enzyme. Nato is the the food.
And so I I swallow
Uh
Depending on the day, about 10,000 units of this stuff.
Every morning.
And I'm gonna get some sort of capsule.
Yes, just a capsule, you swallow it. Right.
In the morning.
And I'm gonna measure it. Um I typically do an ultrasound on my carata every year.
Um similar it's like the clearly it's just uh
on your neck and uh
You can actually do your um
intermediate thickness, which is important. Tell your doctor if they do that. Tell me my I am
T.
And that is a number that will tell you
Very similarly how you're doing cardiovascularly for your whole body. Mm-hmm.
And I'm gonna see if nato kinase makes a difference. Fascinating.
What's all this hype around erectile dysfunction medication?
Yeah.
Yeah.
That's a lead in question. Um
Well, yes, it's
Recently come.
into social media because it was found that the
That uh these E D drugs are also good.
For some types of cancer.
And can change the immune system so that
It goes from protecting the cancer to killing it.
Uh
And I tweeted out what's not to love and it
Millions of people saw that.
Um
But I'm serious. I I take uh
Oh what is it?
Um
Sialis is the common name.
Um to download Phil.
Um
Every morning. That's a low dose.
It's just uh
A little bit
bit. And I I do that because
In twenty twelve we published a paper that showed
That
One of the the most
pernicious causes of aging.
is low blood flow. And then we could reverse that.
with NMN
Through sort one.
More blood flow.
And
It's really underappreciated how much
A lack of blood flow leads to diseases. Your
Especially your your muscles and your brain.
And so I take this low dose.
in the hopes and expectation that I will
If I get dementia, it will be
A decade later.
And now
Add on that.
Cancer killing.
It's an amazing drug. And it was actually not even developed initially.
For these angina medication, exactly. Do you know the story of why they realized it had that side effect?
Um
Was it?
Was it pulmonary?
When when they were doing the the trial, typically you do a a a meds trial and
patients come back into the lab and you ask them to give the drugs back and nobody has an issue. But none of the guys wanted to give the drugs back anymore. And the nurses noticed that the
uh patients when they were doing their interviews
Was sitting cross legged.
And they had this strange
The contorting of the posture to try and hide the fact that they all had hard ons. Yeah. And uh it they said, Hey, we we need the angina thing we're not so sure about, but we've done some wonderful stuff to the penis. Uh well I I can say taking a low dose
The good news is it doesn't
make your your penis get erect without warning. That that isn't a problem. Yep. But the low dose really um
I've
Let's put it this way, I haven't had any downsides yet. Fantastic. Uh there's a there's one other thing, Chris, I want to say, which it before I forget in my old age.
and my lack of blood flow is um so there's a there's a study in mice at least that hints that
Lack of blood flow to hair follicles is a reason that you lose hair.
And so my
Hope, scientifically, is
That uh continuing to get blood flow in my hair follicles will
Keep my hair. More hard ons, less balding. That's the equation.
Yeah.
I don't I don't know which one I'd choose if I had one, but I guess a l a lot of guys don't have that choice.
Uh Hubman had said something to do with the uh perfusion of the prostate as well.
uh that opening up blood flow i is especially given how close you are to
Ground zero. Might be a like a useful
side of it. I don't know, man. I I I said
My favorite conspiracy theory about this. I I hope that it's working. I hope that it's a a
Like
pretty much all gains intervention that everybody can use. But my favorite conspiracy theory about why
erectile dysfunction medication is being pushed so hard is that it
reduces any of the stigma of any one guy having to take it. It's like, darling, I've got to take it. It's important for my hair. Dr David Sinclair told me that it would stop me from going bald. And also, you know uh great grandma, she had she had Alzheimer's is very important for my neurodegeneration. I'm you don't want the prostate you know, granddad, he had the prostate thing. So it's the the E D you don't need to worry about that. It's normalizing E D'
But I think you're a hundred percent right. And uh
I'm sure there have been some wives like
H honey, why are you eating ten of them?
Yeah.
Yeah.
Um, what about omega 3s? You know, omega 3s commonly touted as something that's very important for people's longevity. Why do you come into land on
Omega three levels and supplementation.
Uh I take an Omega three. Um
The the data looks really
Pretty good that uh if you have some of that it's anti inflammatory. Whether or not it
totally prevents heart disease. It it's controversial now.
But
Have you got a brand that you prefer?

Yeah.
But I won't say it. Okay, I'll tell you why I use Nordic Naturals two X are the best.
Um
I do like I do like them.
Um, their products are really pure and distilled, so you want to avoid the cadmium and lead products.
The what what? The ones that have heavy metals.
Okay, so I I I mean I remember this. My mum would tell me this twenty five years ago when I was a kid and she would be taking h and
There would always be this line of
low quality
Cod liver oil back in the day, low quality omega three supplements.
on really
That good for you. So this is like
You know, mythological
Fucking ancient wisdom.
It it really is. And actually while we're on the topic of um
Contamination.
I uh and other labs have measured uh supplements.
And they're often contaminated with things.
And I even got sucked into a lawsuit because I said
I tested this product on it.
This type of product and it had contamination. But I I do want to say
At the risk of
Yeah.
Against me that
NM
And these N A D
Precourses.
Can have
Contaminants in them. Now I don't sell, I don't
market anything. I don't get any money despite people using my name and even video across the internet.
So I've nothing to do.
To gain all loop.
really lose by this, well I've got a lot to lose, but nothing to gain.
NMN can have things like
Well, first of all, I think the study that was published, it's worth looking at by Andrea Meyer.
Um
She's out of Singapore.
She found that a lot of the NMN supplements didn't have NMN in it.
And if they did it was a low amount. And we found in my lab, which I don't think is in Andrew's paper,
Is that there is endotoxin.
In NMN.
bulk and supplements.
Endotoxin comes from bacteria, causes inflammation. It's part of the
purification process, but they don't get rid of it. And we found out the hard way we were feeding it to mice to make them live longer.
Which is not gonna work if it's contaminated.
NMN that you were using in your lab that you thought was pure.
was so contaminated that it was infecting the
Study participants.
Hundred percent.
Wow. So we've had to really work hard with manufacturers to get
It really pure. How hard do people need to work? If they're somebody's taking an NMN supplement now.
Is there anywhere that a normal person can go that's not
Gonna risk being contaminated?
Mm-hmm.
Well,
If I ever mention a brand it's gonna be it'll blow up the internet, might I bring it down, but
Um I will say that
To help the viewers. Um
the and the listeners of this show, I would go for a company that
has a strong reputation.

that provides the analytics. So sometimes
They give the sh spec sheet and you can see the purity.
And um you know, some companies they've got such a big reputation they're not gonna risk
adulterating it or putting something else in it or giving you less
Um GMP is important always. Any supplement should be
uh good manufacturing practices, um, USB label. Look for those badges of
Purity.
Um and if your company that you like doesn't share the analytics online, you can write to them and say, Can you please share that batch?
Right. They're not cheap.
Interventions for people. And if you're spending a lot of money on something, you want to make sure that it's actually I the worst thing is I'm taking this thing that I think is going to make me more healthy and it's actually making me sick.

That's the real problem.
Um
Um and I'm gonna do a shameless plug if that's okay. Um

I'm launching a
community.
A a website community for us to figure this stuff out together.
I'll be testing products, we'll learn what works together.
Um and
I hope that it becomes the world's largest longevity community.
What does the what what's the community build around? What is it? Yeah, it's called lifespan.com. So my show is Lifespan. This is the website version.
Um
My goal ultimately is to
Fix health care.
Across the planet.
We've done a top down government big
industry, HMO.
Um we know that doesn't work.
The US especially is spending close to twenty percent of GDP on the healthcare and
got some of the worst healthcare. So got to do something. So
Grassroots movement, Lifespan.com
will be a community that comes together to learn what works, what doesn't.
Um and eventually
Where I want to take this is that we
Wait.

And with AI
with knowledge, with
Yeah, we're also funding medical research.
And testing a brand. So
We know what's pure.
And we'll find new medicines together.
I wanna share.
in the profits of that with all of the members. So that's being launched soon.
Um it probably launched by now.
Um there's
For members, so that there's an unpaid version you can do show notes and you can see
Some uh some stuff.
But if you
Um
Pay the eight dollars a month.
Um
We've pulled together something really interesting. We've got this community that we've built, but also
There's information w that will basically complement what we've been talking about today.
There's a magazine, World's first magazine written
Well written by people who are doing the research.
So you don't have to rely on some
uh newspaper or reporter who doesn't know anything, who also wants clickbait.
Um I actually brought a copy of this magazine. I had it
Printed in hard copy just for you.
Oh, let's get it. I wanna see. You haven't seen it. This is this is
Being hidden here.
This is Lifespan Magazine first.
One I've given out to anyone.
And this is a gorgeous magazine that every member gets.
Online.
What if aging isn't damaged?
But lost information, a radical
idea now entering human trials.
Oh.
That's that's the paper from Nature that I thought I'd give you as well in twenty twenty.
They changed everything. This is so cool. Thank you.
Have a look inside. I'm so proud of how it looks now. Um
This is going to be coming out every month.
And it's got
About a hundred pages of
The real science, the real stories of what it's like.
And what we're learning before it even comes out in
journals and in the media.
Oh, this is cool. But it's very beautifully put together.
Beyond your birthday, Steve Horvath on the science of epigenetic aging.
I know Steve Hover. Yeah. Yeah, Steve discovered the epigenetic cloud. Can a simp simple multivitamin mineral supplements slow down aging?
This is awesome.
Congratulations.
Thank you. That we really we're really driven by mission. We want to change the world and we want everyone to join us in it. Unreal. Uh okay.
Interventions, other stuff that's happened.
The world of
Longevity, biohacking has really sort of
It's not exploded. I think it's I think it's become more sophisticated. You may say otherwise. The evidence may say otherwise. But at least from the
Like self experimentation.
Uh you know
Twenty seventeen, eighteen, nineteen
It was a lot
of the Biohackers Handbook. It was, you know, Ben Greenfield's uh friend of the show sticking ultrasound things on his penis to see if he can improve his his erection quality and his orgasm length and stuff. And then it seems like it's really
Come on.
data backed, a lot more um
Mm.
evidence based crowd stepping into this.
Well, thank you to to you.
Yeah.
For example, uh guys like you are bringing
Scientists like me and people who know what they're talking about.
So that people can hear it from the horse's mouth. Whereas before it was just somebody hyping and selling stuff which you couldn't trust.
It's true. I mean what's been interesting has been to see
At least in in Greenfield's case, like how right he was about tons of stuff super early on. Yeah, though I
didn't mean to imply Ben was one of those people. But there's so many pe even uh uh uh Timu Timu Arena was it that wrote the Biohackers Handbook? It's his coffee table book, I've still got my house in Newcastle. Now look at some of that and
It's the same as the bodybuil thing. So many bodybuilders stumbled onto a particular way
to look at health or dieting or whatever that
A decade later, science then comes back around and says, Oh yeah, that's the way But then also there are a lot of people that throw shit at the wall and much of it doesn't stick.
One of the most
uh popular interventions that people are talking about, contrast therapy, sauna and ice baths.
What does the evidence say around
Cold and heat exposure for longevity.
Um
Increasingly we're learning. Um in two thousand nineteen, when you and I first met, there was very little evidence, actually. Um and you're right, bi hacking was
something that was looked down upon especially by doctors, um and the public didn't know what was going on.
Uh
Then came the pandemic and
Most people saw their mortality and it's like what are we gonna do? And
It's amazing to see what's happened since that it's become mainstream and even doctors have had to
learn about this because
But their patients are coming to them with more knowledge than they have, especially with AI now.
Um but we are we are in a world now where
the individual can know more about a certain topic than their own physician, which is incredible.
Um
That does include sauna and colts when we met twenty nineteen.
There was a little bit of data in saunas and nothing on Cold Dodds except a mouse.
dunked in the cold. Um now there's much better evidence. Um I put it in my book Lifespan because
Uh
I was told by the editor that that would be interesting, but I was hesitant because there was such little data on saunas and and nothing on ice bugs really.
That's different now. I can now say
As a scientist, scouts on our
I I was a scout.
Forget how we do it.
Um that
Definitely sauna. There's a lot of evidence. Mostly
uh Nordic men have been studied.
Uh less women.
But
If you do regular
what they call sauna bathing in Finland.
A few times a week.
Your rate of heart disease can
And and that
is reproducible. So that I think saunas are great.
Um I try to do some of that myself.
Um as hot as I can bear.
Ice bodies.
Contrast.
It makes sense scientifically, hasn't really been studied.
But uh
Cold therapy.
We do know it can activate brown fat, which is very good.
What does that mean?
Well, so we we actually
Going back in history, thirty years ago we didn't know that
We adults.
Humans had uh brown fat.
Babies have brown fat.
It's a highly metabolically active type of fat.
in babies that keeps them warm because they can't shiver initially.
Um and then using PET scanning.
People at Harvard, some friends of mine discovered
That
adults can have brown fat on their own bodies as adults.
Um
Often in
They're in the back.
You can get it.
More brown fat by by doing cold belt?
Cold plungers and being cold.
Um Do you want more brown fat?
Yes.
Gonna say the
The brown fat's full of mitochondria, which are healthy.
Tast.
Brown fat seems to secrete factors that are good for health.
Um
But yes, people that have more brown fat
tend to have better metabolism in general.
And they also burn more energy.
Which is good in today's world where this
Yeah.
So yeah, in general, yes, brown fat is considered very healthy.
Um, but the older you get, the harder it is to
To make?
And convert from white to brown or beige. And uh so
My view on that is
And that's true for mice. I'm not sure it's true for people, but
Let's say it is
I still believe that the earlier you start to build up your brown fat reserves, the better.
Because by the time you're in your eighties it's hard.
Cold exposure is a good way to do that.
Exactly.
Right.
Um
I don't know if it's true, but I like
to experiment with sleeping a little cooler and
As I wrote and have said a few times.
Turn down the temperature.
Don't sleep with a lot of blankets, we've already talked about
Eight sleep beds. Mm-hmm.
that is a way probably to burn more heat, more more energy, but it it might help
If you're feeling cold during the night.
Uh build up brown fat.
That is a mite. You will get more brown fat.
If you
cold plunge, um and do those kind of things roll around in the the snow. It is controversial though. I did see
A little bit of pushback against Wim Hoff and what he was saying.
It may not be as spectacular as what he's claiming. Yeah. And I it's strange because
The
Immediacy of the reward if anyone's had a
cold shower or used a cold plunge, you feel
really good as long as you stay in for a little bit. You feel so good afterwards.
But
I'm
I like to do it, it's fun or whatever, but I would probably take a sauna twenty times over taking
A cold plunge. I if I'm gonna try and do something for my health. I'm the same. I'm the same. I I do a hot every every day, including a
Yeah.
But uh I call plunge probably once every
Two weeks.
At best by it by turning on the cold tap.
What do you make of Brian Johnson's approach to longevity?
Well it's totally different. Um
putting the two of us side by side, some people do, it's it's not the same animal.
Uh I'm doing science, I'm doing the research, I'm figuring out the molecular mechanisms.
Um he's a compliment.
to that. He is self experimenting. It's not a clinical trial, obviously, he will admit that. But where I think Brian shines
Um
Is in a couple of areas. He's very courageous.
I like that he stuck his neck out.
I I have a lot of uh
admiration for those people who are brave that way.
Um he's also been um helpful
bringing a spotlight to the field of longevity.

And I remember a lot of my colleagues, uh my highbrow colleagues in longevity
really said he's the worst thing that's that's happened to our
to this field, he brings a bad name to longevity.
But I I disagree. I think that
He
The
We
as a field of scientists.
had a marketing problem.
As much as we talked about longevity, it wasn't getting through up until
twenty twenty.
Almost nobody had used this word even.
Brian came along.
Um
I came along, but definitely Brian got a lot of attention.
And I think it's been helpful to
Wake people up from

They're stupid.
Uh not everybody, but
A lot of people just live their lives and eat whatever they want.
Um do a little bit of exercise.
Brian said we can be
much better about this. We can
Science the heck out of this.
And I love that approach.
And so I think the
It's complimentary. I'm saying
Let's do real science, clinical trials, molecular.
Uh but also
With an N of one?
doing pre-treatment, post-treatment, see what happens under doctor supervision, we can learn some things too.
Um
Yeah, it's
I I think Brian deserves a lot of credit for for that, for bringing attention to you've got a highly unsexy field.
I'm not saying Brian Johnson's sexiest guy on the planet, but he's definitely made uh an existingly unsexy field at least a little bit more sexy.
What uh knowing what you know about his approach
To
Um
the fundamentals for longevity. Have you got any
smell test or sort of lick your finger to work out where the wind is coming from, where you think, Oh, he might really be onto something there. Is there something that he might be out ahead of where the the data or the research or the science is at the moment?
Um
Not really. I I
I don't pay as much attention to him as I probably uh
Should.
Or could
Yeah. Um
I do look at
Some of the
the blood work that he posts and uh there's a particular test
Um that's called the Dunedin Pace of Aging, which is a measurement of your epigenome changing. So we
Steve in the magazine, Steve Horvath discovered the epigenetic lock. For those of you who don't know what that is, it's chemicals on the DNA.
that change with time. These are like the scratches on the CD.
Or the c software corruption.
You can measure that.
You can do it before
And after that.
Will you take it?
every you know, three months or every year.
And Brian has published
publicly his results.
And you can determine what
is representative of your pace of aging.
And his was, I recall
Something like point four something.
Thus and one would be you're aging one year for every year. Yep.
And you know, if you're two then you you're doubling your rate of aging, so you're gonna die early.
According to that, that's one of the lowest
pieces of aging I've ever seen for a human. So that's pretty impressive. If that's
Maintained.
He could live decades longer than
He's supposed to.
Than he would if he didn't take care of himself.
Is that
Taking into account telomeres or no?
No, it's not.
No, I d I don't believe so. It's uh
Just uh looking at the
What's called DNA methylation pattern on the DNA.
What do you think are the biggest wastes of money that people spend on longevity?
Yeah.
Oh well.
the overdosing of vitamins, particularly B vitamins, um
I think that if you're on a vegan diet, yeah, you should
Make sure you're not deficient in any
B vitamins.
Um
Generally if you're taking
A lot of multi
uh what do you call it? Multivitamins.
Uh it's excessive
And it can actually be toxic if you have too much. So vitamin C.
Uh can be pro
oxidation, not antioxidant, if you take a lot.
Continuously.
So overall I'm not I'm not for multivitamins.
Um I do believe you should measure your vitamin.
Uh in your blood?
And if you're deficient, you should make sure you're not deficient. But overdosing on
Vitamins.
Especially B, you know, you could do I V, some people do that. I think yeah, you'll get a short term hit.
But
I
I nibble on my B vitamins. I don't
Take the whole.
I tried again the self experimentation over the last couple of years recovering from this this
Mold complex illness stuff has been
Interesting to say the least. And the start of last year
one of the potential culprits for why I was feeling so shitty was methylation. So it did a
bunch of genetic testing, came back up got four different polymorphisms that make me suck at B vitamins, like one in the blood, one in the brain, one in the methylation, and one in the something else. One of the
Potential put forwards.
uh explanations was well your meme collicular volume, your M C V
is high. It's like just at like 101 or whatever, which is just above the upper range. Oh, well, maybe this is something to do with bees. I was like, okay, well I'll try
Some uh intramuscular
Methylated.
B twelve, like five hundred micrograms. It's almost like gotta put a huge needle in your leg to put this teeny tiny amount of B vitamins in. I didn't realize that you can get something if you push it too far, but
Called
B twelve induced confusion.
So you can actually just make yourself confused and your brain gets very slippery, given that this was the thing that I was trying to push back against.
What I'm saying is I know what happens when you push B vitamins too far. Um and I actually did that the week
It was the biggest week of the show last year where I had Rogan I was on Rogan on the Thursday and then recorded the Naval Ravacant on the Saturday. And I went into it going
I've like
poison myself with f fucking B vitamins and now I can't think straight. It was fine. It was it it all ended up being great in any case, but uh
Yeah, okay, so um spending too much money on
Uh vitamins, multivitamins is one of the biggest wastes. What else? Well at the risk of being sued. Um
I would say.
I'm not sure about
Again, I'm not saying it's wrong. I'm just not sure about
Uh certain laser therapy.
Um Serena, my
Partner loves shooting
lasers at her body.
But I'd skincare?
Uh
Internal as well.
How do you shoot a laser internally?
Well Which which hole does it go in?
Yeah, well it it
Shines on your skin back and forth. So I don't know if that
Is doing anything. I'd like to see some data on that. Is that like red light stuff? It's red light, but it's different colours and wavelengths. Oh yes. Yeah, I've seen those things. Those huge big panels that people can stand in front of.
Well the red light
Is not
Crazy. So certain infrared I've got
near infrared panels. I'd have that actually I'd shine that in the shower sometimes. Okay.
And that
the science is coming around to confirming some benefits there. So
I think that's fine. And the red light saunas, um I'm gonna get one and see how that goes. But the yellow lights and the other things it looks like. It's uh fourth of July. Uh
in in the house.
But
I'm not sure about that one.
Um
But you know.
You've gotta be careful what
You say is BS now turns out to be true.
This is where the biohackers get it right, dude this is where the biohackers get it right.
We're seeing a lot of them are actually really
Helpful. Talk to me about GLPs.
'Cause you know, this has been
This wouldn't have even been a discussion.
Right. Three letters that I'd never have even heard put together the last time that we
Sat down two thousand twenty one and certainly not in twenty nineteen. Yeah.
What's your opinion on GLPs?

Uh, in general I'm very favorable. The
The number of
Studies are
that come out as showing that they're actually quite useful, especially microdosing for healthy people.
If you're obese, it it's it's almost a must. Go talk to your doctor, I think.
If you can't lose weight.
Alone, please.
consider using these. I I think obesity is the fastest way to
to an early grave, it certainly ages you faster.
But if you're if you're like you and you're already already close to optimal
Are they useful?
I think so.
There are
Of
Target.
Things besides obesity and metabolism that seem to be
Important.
Brain health.
Um immune system.
New things are cropping up all the time. It's as close to a longevity drug as
We probably have right now, given what we're seeing. Yeah.
It's still early days'cause we we need to do long term.
And there are some downsides. There is increased risk of
but low uh risk of kidney issues and even blindness. Um
Don't panic. It's not.
It doesn't happen very often. So it's still really rare.
But they're it's not.
perfectly safe. So I just wanna make sure people know that it's not like going out
injecting uh candy into you or anything.
Um
But I do think that
And I have taken chilpy ones. Um
Small doses to see.
how I would feel, what would happen. I definitely didn't have hunger at that
Was
obviously what would happen and I lost weight more easily.
Um I didn't take it long enough.

We're benefited. It looks like uh there's protection against
uh dementia.
From those who are
On
And this is from
A mechanism other than just calorie restriction.
It's hard to tell.
Right,'cause most of the people on them are
Already overweight.
But yeah, I saw a study recently.
Um, I don't remember the journal.
Um but I'll look it up and
And post it online.
on my social uh but I did see one that
had really good evidence that it was not due to weight.
Lost. It's just uh I would say in general
Whenever I go to a longevity conference and there's a company
uh like Novo Nordisk or Lily, like you should see this latest study, we've shown that it o it does this thing that we didn't expect at all as a side effect. Um and it's funny these companies are now calling themselves also longevity.
companies it's become that
Fashionable.
Well I suppose anything that
Anything that reduces morbidity technically in one point.
Mm.
People that make helmet bike helmets are longevity companies, you know?
You're right, and it's it's a word that's unfortunately getting overused like anti aging was.
Mm. Thirty years ago.
And we'll have to come up with something else to decision. Huberman says he thinks retruti will be a trillion dollar drug.
Do you reckon about that?
Um
I think it's possible.
Uh if the oral ones really look good, th th they may actually be uh
Even more interesting.
But yeah
What is it? Something like ten percent of Americans?
Have either tried it or been on these drugs?
of Americans say that they would. Jerry, can you uh chat GPT whatever the
The numbers are of
GLP uses and desired
Uh uses in
B USA.
Find that out.
Uh but yeah, I mean
What is it?
Obesity is twice as big of an issue as malnutri as uh uh starvation now globally. It's a billion people that are obese and half a billion people that are starving. It's like the number one leading cause of malnutrition globally is obesity.
Currently around about eleven percent of US adults, twenty nine million
Americans
ever used a GLP fifteen percent. So that means that only
What's that about?

Two thirds of people who have used one.
are currently using one.
And
Ninety one percent of Americans are aware of them.
Uh twenty percent of US households. Can you say uh how many people
Want to
Uh I'm sure that this was from
Uh the
most recent book that Johan Harry brought out saying that it's like forty five percent of Americans would either have tried or want to try them.
About forty percent of US adults have obesity fo we'll say that my number's correct. That sounds great. Um
Yeah, I
I mean the off
Target effects of this. Oh, it seems like people
Don't want to drink alcohol so much. Though it seems their cravings for
Video games and porn.
get curtailed sometimes. I mean I
We're getting into
And not just
Like neurobiology, but
the framing
Of your own
sense of self. What is your mission? I am the sort of person that is disciplined. I'm the sort of person that can do hard things. I don't need to eat that food. I'm not going to have that junk. What is the snowball effect that turns everyone into kind of a micro David Goggins because
They're working hard in one area of their life and diet is
usually the first frontier that people get stuck into when it comes to discipline, right? I uh on both sides of it, whether it's good or bad. And okay, well, maybe I'm gonna get up on time. You know, I didn't eat the junk food last night. I'm on a bit of a roll. Yeah, maybe it was pharmacolog pharmacologically uh assisted with what I did with my discipline around food.
But I'm getting a part Oh maybe there is some
No super magic wizardry that's going on inside of the brain. I don't know. But it's it's definitely interesting and
Fuck like
It does feel the one the one problem is it feels like an artificial solution to an artificial issue.
Which is we shouldn't have a food environment which is so hyper palatable and calorie dense and attractive that we now need to medicate our way out of this Yeah. It is dystopian for sure. Yeah.
Um
But it's a blessing that
that obesity was declared a disease and then companies worked on it.
And now we have these meds. Mm-hmm.
I want aging to be the same. Aging should be declared a disease.
We work on drugs and then we treat it. And in the same way that GLP Ones now are saving the world.
The same will be true, I believe, twenty, thirty years that
People say, Why didn't we treat aging earlier?
What
common health advice today do you think people will laugh at in fifty years' time?

Uh
Yeah, I think the
Uh
Eating three meals and snacking the this
You go to the you go to the supermarket and there's health bars down the hollow aisle aisle that you're supposed to never be hungry.
That's gonna be sane as
extremely toxic. You you your body needs to feel
Hungry sometimes.
Uh have a break from food. So this
This
trend of
You're a bad parent, if your child feels hunger, is gonna be looked at like oh, what were we doing to our kids? Mm-hmm. Mm-hmm.
Do you think AI is going to
Make
bigger inroads into longevity research. I don't know why I mean again
you know, seven years ago when we sat down AI w n you with your snail, you're drawing of a
Fucking snail on the whiteboard. There was no AI to be found. I don't remember what the snail was, too. I asked you about it at the time and it was something to do w it was explaining s it was some nerd stuff. Oh I remember it.
We we we said, Chris is coming, let's draw a snail through. Draw a fucking snail. What's AI doing to longevity research? Yeah, well you asked me, Do I think I know it's having a big impact already on research. My lab
Is thriving on it.
It's going way faster.
We just did something in a few months that would have taken us a hundred and sixty years.
That was
That's using old technology.
These days we can do
Oh I'll tell you a story that's funny.
On Friday, I had a meeting with a student that just came to my lab over the summer.
And he's been here maybe three weeks.
And he's nineteen years old.
And
I gave him a task. I said, According to the information theory of aging,
If you look at all this data
that's out there that nobody's looked at in a certain way.
It should have this signature.
And uh if it has that signature.
We might be right, we might have found the backup copy to the software.
And I said okay.
That that's your task. Go go do that thinking.
You know how that'll take it. Exactly because
I've had about three people in my lab try to do that and they weren't not really successful.
And he came in on Friday, uh and
He's with his team and his mentors, and we sat in my office and they've all got this big grin on their face, and they threw up on the L C D screen in my office.
The results.
And this wasn't
Just the usual I wrote some code in R and ran it.
And and and we got some graphs.
This was truly using AI, he was using
one of the the the the leading AI models
And he presented it like it was already
published work with beautiful graphs and looking at terabytes of data that's out there in a new way.
And he found something that

the last ten years.
And it's right there. There's his signature goes, I've given it a new name'cause I didn't know what to call it.
This signature, I'm calling it the reverse tail. I said, What the heck is a reverse tail?
And he said, Uh well I called it this because of that and I said
Dumb name. We'll think of a new name for it.
But
It's a idea of ship branding. Yeah.
We'll work on branding later, but the fact that you found it.
is incredible. And that's a nineteen year old
Uh I think he just finished high school and with AI
He's gonna revolutionize biology, I believe. And that's just one kid.
Imagine when whole teams are doing this.
That's wild.
That's why so
Have you
Has there been anything as far as you're aware in the field of longevity
that's been uh generated or inspired by AI that has gotten itself to
Trials testing and
And fully
published as a a world changer or is are we still at the frontier of that?
not reading me meeting the real world yet.
Oh, we we're we're undergoing this revolution, so tomorrow's gonna be better than yesterday.
But we're now at a point.
Where
Almost.
Somebody on their phone.
Can you
Discover a drug candidate.
Whereas it would have taken a pharmaceutical company years
Uh and
hundreds of millions of dollars.
It's that world.
We can go from now that um
Uh Demus.
Hasavis has
And his team.
Not just him has cracked the code for protein folding.
We now know all the chess pieces. We were guessing and it took years to find out what one chess piece looked like.
And there's
Um
Over fifteen thousand of these pieces now.
These are all now modelled in three D. Now we know not just how they look in three D,'cause they used to be one dimensional.
based on the DNA. Now we've got three dimensional amino acid structures.
Now we're seeing how they fit together. Computer is actually smart enough to figure out which ones dock with each other and eventually we'll figure out how they're all working together.
Uh an artificial AI.
Version of a cell.
We can
do in silico experiments at the molecular level now.
And Doc.
Trillions.
Last year it was billions. Now this year it's trillions of chemicals.
Real drugs and
Imagine it's not.
Yeah.
Yeah. Are these accurate? So if I run the synthetic
Lab.
Is it
One to one with the real world. It's not one to one, but it it increases your odds.
Exponentially
Because you don't need to do test, test, test. Okay, maybe this. You can discount a lot and then the interesting ones get moved into the real world. Yeah.
Yeah and and
The old way of doing it, which felt really modern was
You have libraries of little plates.
hundreds of these little plates with ninety six or
Sometimes little wells.
And each one has a different chemical that's physically in a freezer somewhere. You have to pull it out, give it to the robot. The robot then does its work overnight, tests it on cells, take a picture of the cells.
This kind of work is is is slow.
compared to today, which is
We don't even need to have the fridge.
We can make up.
Trillions of
Potential drugs.
Test them.
Run it for a few weeks.
It'll tell us here's the top two hundred.
And probably
At least half of them are
Pretty good.
And now we can do that experiment with hundreds instead of
Trillions. And trillions is impossible, by the way. Um the most a pharmaceutical company would screen would be in the millions.
No we do trillions.
Uh and then you can even order them online. That's the thing that blows me away.
We got a set of two hundred that
we think can reverse aging using AI.
Um
And then I thought, oh, it's gonna take us a long time to synthesize these two hundred.
No, we just
Order them up, the company can make them for us.
in a matter of weeks. Now we've got them in the lab. We're testing them on human cells. We've developed an AI system that can tell us whether the
Ninety year old sells.
skin cells from a human are going back to being
twenty or anything in between, just by looking at them, we paint them with dyes, different colours.
And then
Where we're at is hopefully in the next uh month or so.
Jim Hunts.
We will have to do it.
a set of chemicals that can replace the current cocktail.
that reverses aging in the mouse that
If you are
paying attention earlier, not you, but listeners if you've just joined us.
I was talking about
We've got things that we can
Uh.
pill or a swallowing thing, uh a drink to a mouse.
Swallow thing.
Um to a mouse and it reverses its age. We've got that.
But it's a cocktail.
A very secret cocktail, but it's got
At least three things in it.
We wanna bring it down to one.
And turn it into either a supplement or drug or
Uh a patch.
Mm. Or a thermal.
Yeah, some kind of cream.
or all of the above.
But we're getting really close to
Being able to have
The
single molecule that can truly safely reverse aging.
In human cells.
We'll test it on the mice.
And uh we'll run from there.
How big of a role is expectation in how someone lives?
If somebody
thinks about aging as being associated with frailty and degeneration.
Can I actually make them live less long?
Oh, you mean mentally if they're Yeah.
That's well studied if you're optimistic and you're enjoying life and you don't just
Get retired.
Just retire and be bored.
Um yeah, mental attitude is huge.
Um, Robert Voldinger, a Harvard scientist, has found that the mental attitude and your social life is
as important as your blood pressure and cholesterol, if not it more important. And the one thing that was the best was have a reliable partner. I went through a divorce was horrific, uh during COVID.
And I believe that it took years of my life, so
It felt like it anyway.
But uh it was a it was a shock. I didn't know it was coming. But uh it's brutal.
Um anyone that
Is young getting married just
Anywhere.
Um
We all change over decades, so
That's a
Something to keep in mind.
But the point there is uh
the amount of stress and cortisol that runs through your body when you have
a really big life event.
Moving house.
Breakups.
Uh Death in the Family.
Your own illness.
These are age accelerators. And on the other hand, we've talked about today the kind of things that keep you healthy.
um the exercise, the diet, the social life, the sleep, the relaxation, these are all we know
Um
are likely to not just slow aging, but eventually
Keep your disease free.
And I do I do want to mention that a lot often people think, Oh, I don't want to live longer because I don't want to be old for longer. That's not what we're talking about.
We're talking about still being young and vigorous.
In your nineties. My father's almost nineties, eighty seven now.
He'll be here on Friday.
From Australia.
it'll be, I think, second or third time he's come to the US. He was just in Japan. This is not a typical eighty seven year old. He is living life
Probably better than he did in his forties. He's out every night.
With different
People.
Mostly uh
Uh women that he's
Excited about. Um
No, they're good friends. I won't I don't want to
Disparage my father.
He's not a dirty man, but um he
He is a very sociable guy.
And in his forties
He was raising me and I wasn't easy to to raise. I was a pain in the gut.
He will he will say he's never had
A better time in his life than now.
At eighty seven.
If you were
thirty five or forty again, and you could only do
Two or three things for longevity, what would they be?
Um definitely
Don't overeat.
Be lean.
What's your weight?
have a BMI of around
Let's say twenty two, twenty four.
Make sure you
You don't get overweight.
Um
Obviously.
Don't overdrink and don't smoke. These are
Clearly.
really the worst things you can do, having lost a mother to smoking.
Um so don't eat too much.
Right, try to skip meals. Uh work out, maintain a very good
Body mass.
um and exercise. Those are the fundamentals. Everyone will tell you that.
Um, what I didn't realise till I was in my fifties was how important food is.
I thought vegetables were a garnish for meat.
I love me.
Um they taste meat tastes great.
I've switched over to being more plant focused and I've seen a great improvement in my overall health and biomarkers.
So those are good, learn not to stress, we've talked about um that took me a long time to to learn that as well.
But I've never been healthier because I've
it's been slow, but I've learned how to do all these things really well.
I'm gonna do a lightning round. So in a sentence or two.
Give me your review on these interventions for longevity, okay?
Okay.
Create.
How we how we scoring?
Just uh however you want. Give me a review. Yes, no, like it, don't like it, useless, buy it, do whatever you think, whatever you don't. All right, so creatine, um
In favor of it.
And take it.
Stem cells.
Interesting and
If you have a
certain condition like a a joint that needs repair can be helpful, but it's not long term solution.
C Pap machine.
Really important.
Um for
folks that have anoxia like oxygen at night for the brain.
Um, though you could try other methods, which is lose weight.
Um
Don't drink.
Uh get a
Thin pillow, try to sleep on your stomach.
hyperbaric oxygen therapy.
Uh in favor, there's good evidence that certainly cycling uh up and down in pressure is good for the brain and blood flow.
And uh
Done it myself and uh

improvements in wound healing in others.
So yeah, in general.
It's it's a plus.
Blue light glasses.
Yeah.
Y you mean yellow uh blue light blocking glasses?
Um
I
prefer to turn down the brightness of the lights at night and have a T V that's not so bright. But yes, I think
They were much more fashionable five years ago.
But I still use them.
So yes, but definitely in general
Watch out for bright light at night.
But try to get
violet and blu light in the morning. It's very important. A friend of mine in Japan found that
If you don't see violet light.
Uh
And you're a mouse, you get uh short sightedness.
So early morning light can be
Um
Protective.
Yeah, yeah, and we live indoors and we we don't get enough of it from L E Ds.
Okay, glucose monitors.
Love'em.
They're really good. Yeah, I I I think that we should all be empowered by our own data.
Um anyone who says I don't want to know about
My biology, I think.
I don't know
Agree with that.
The CGMs have been very useful.
Personally?
I can see how I react to foods and I was surprised.
Um grapes send me through the roof. White rice through the roof. I remember the grape thing. Potato.
Yeah.
And it's still true. I'm wearing one right now. I wear them
Fairly regularly.
The other thing that surprised me about CGMs was
I gave one
To my son, who at the time was
Yeah.
And
We had a competition.
Who can uh
have the best blood glucose levels.
And he would eat.
A lot of bad stuff.
It changed his life. He is eating much healthier. He's now aware of what food does to his body.
Now I'm not saying go give it to children.
But I do think there's an education and a behavioral change that can come with CGMs that as I think you mentioned earlier today.
can really really make a difference.
Therapy.
You mean
Just general uh psychological psychotherapy.
Yeah.
Well, I think it it depends on the person and the therapist.
Um I think that
Talking about your problems can really help.
Um I think it can be overused.
Um
As a friend.
Um I
I've tried everything.
Um I didn't find
A lot of the therapists to be
that useful. I found it better to read books and listen to experts and
Uh but I do think therapy is very important. I've
Um had kids that
benefited from therapy, it's very hard being.
A teenager these days, uh, with the pressures. So yeah.
A thumbs up for therapy, though, make sure you have a therapist that is well qualified and
provides benefits rather than just listens to your complaints.
Grounding.
What do you mean? Grounding. Uh walking on grass negative electric discharge stuff. I don't
Think that's
scientifically based, but I do think getting out in nature and
Touching uh nature.
smelling nature, listening to nature is very valuable and

But he
will f turn out to respond in ways that we don't even understand yet.
Marriage.
Be careful who you marry.
Um
know that it's not always forever.
know that people change over decades?
Um
know that it's a long term investment.
Be loyal, never lie.
And if kids are involved.
Try to work it out.
Mouth taping.
And uh mouth taping. Uh so I
I do snore if I
Uh
Or eat.
Certain supplements at night.
I've found.
So I
Have
tried mouth taping and
Serena says I make even more noises.
Gasping.
So I don't use mouth tape. I
I
Do use those nose strips'cause she thinks they help. Yep.
But no I haven't
had success myself with mouth taping. Testosterone therapy.

Uh I prefer natural versions.
If you can't raise it naturally.
Yeah, for older people there's been a lot of benefits. Um I mentioned Shelley Basin as a scientist that's worked on N he's also done a lot of testosterone work, which shows benefits, but it doesn't extend lifespan. There was no evidence that it does that for longevity. How do you you talk to a lot today about
Supplements, lifestyle, interventions, rest, recovery, what the future's gonna look like, AI, GLPs.
Something that we never got to talk about when me and you first sat down were the perils of over optimization.
I think that
It was so frontiery.
in twenty nineteen, z everything was new and exciting and
You couldn't really be drowning in data in the same way as you can now.
Mm-hmm.
And
I wonder what
You've come to believe about
The negative health
Implications.
Of
Caring too much about your health.
Of over optimizing.
the neuroticism taking away not only your enjoyment from life, but the
effects of supposedly all of the interventions that you're actually trying to do? How do you come to think about over optimization?
Well, obsession about anything is possible and also deleterious to health. Uh so if you have
Those tenancies be careful.
Yeah, it's true for anything, social media use as well. Um
And I I can be u obsessed. What what I've
done myself, which I recommend is
Treat it like a hobby. It's fun. It's not too serious. You're not gonna die if you didn't sleep well last night.
Um
You know, everything's challenge.
Uh
My meals are
An experiment.
Um
Not always, sometimes.
It's a failed experiment. Um

But
Uh I live my life like it's a journey and it's fun and I'm
Testing things.
Um
And so don't

are not perfect when none of us are ever perfect and none of us are gonna live forever, in my opinion.
So enjoy the journey, do as best you can.
That's stressed.
Heck yeah. David Sinclair, ladies and gentlemen. David, you're awesome. I appreciate you seven years later. Why should people go to check out everything that you've got going on?
Uh well the big one is lifespan.com.
become a member, get the magazine, learn how to live longer.
And we'll learn together. We'll do some big things together.
Um and
I'm on social media, you can see what I do. Podcast season. Podcast is big. Uh so that's on YouTube and all all podcasts.
Uh that's called lifespan.
With Doctor David Sinclair, we have
We're about to
half a million followers not like you, but we'll get there.
You're doing good. We did take some time off to do the trials, but we're back and uh even better now.
So join us there too. Thank you, Chris.
Appreciate you, mate.
Like the next time. All right. Goodbye, my beauties.
Dude, yes.
So good.