2021-12-27 - Interview Dr. David Sinclair - Huberman Lab Podcast - The Biology of Slowing & Reversing Aging

• https://www.youtube.com/watch?v=n9IxomBusuw&ab_channel=AndrewHuberman
• Interviewer: Andrew Huberman
• Length: 2:10:42
• In this interview, we discuss the cellular and molecular mechanisms of aging and what we all can do to slow or reverse the aging process. We discuss fasting and supplementation with resveratrol, NAD, metformin, and NMN. We also discuss the use of caffeine, exercise, cold exposure, and why excessive iron load is bad for us. We discuss food choices for offsetting aging and promoting autophagy (clearance of dead cells). And we discuss the key blood markers everyone should monitor to determine your biological versus chronological age. We also discuss the future of longevity research and technology. This episode includes lots of basic science and specific, actionable protocols, right down to the details of what to do and when. By the end, you will have in-depth knowledge of the biology of aging and how to offset it.

Transcript

00:00:00 Dr. David Sinclair, Harvard Medical School

- Welcome to the Huberman Lab podcast,

where we discuss science

and science-based tools

for everyday life.

I'm Andrew Huberman,

and I'm a professor of

neurobiology and ophthalmology

at Stanford School of Medicine.

Today, my guest is Dr. David Sinclair,

professor of genetics at

Harvard Medical School

and co-director of the

Paul F. Glenn Center

for the Biology of Aging.

Dr. Sinclair's work is

focused on why we age

and how to slow or reverse

the effects of aging

by focusing on the cellular

and molecular pathways

that exist in all cells of

the body and that progress

those cells over time from

young cells to old cells.

By elucidating the biology of

cellular maturation and aging,

Dr. Sinclair's group has

figured out intervention points

by which any of us indeed, all of us,

can slow or reverse the effects of aging.

What is unique about his work

is that it focuses on

behavioral interventions,

nutritional interventions,

as well as supplementation

and prescription drug

interventions that can help us all

age more slowly and reverse

the effects of aging

in all tissues of the body.

Dr. Sinclair holds a unique

and revolutionary view

of the aging process, which is that aging

is not the normal and natural consequence

that we all will suffer.

But rather that aging is a disease

that can be slowed or halted.

Dr. Sinclair continually publishes

original research articles

in the most prestigious

and competitive scientific journals.

In addition to that, he's

published a popular book

that was a New York Times bestseller.

The title of that book, is 'Lifespan:

Why We Age And Why We Don't Have To.'

He is also very active

in public facing efforts

to educate people on the biology of aging

and slowing the aging process.

Dr. Sinclair, and I

share a mutual interest

and excitement in public

education about science.

And so I'm thrilled to share

with you that we've partnered.

And Dr. David Sinclair

is going to be launching

the lifespan podcast,

which is all about the

biology of aging and tools

to intervene in the aging process.

That podcast will launch

Wednesday, January 5th.

You can find it at the

link in the show notes

to this episode today as well.

You can subscribe to that

podcast on YouTube, Apple,

or Spotify, or anywhere

that you get your podcasts.

Again, the lifespan podcast

featuring Dr. David Sinclair,

Claire begins Wednesday,

January 5th, 2022,

be sure to check it out.

You're going to learn a

tremendous amount of information,

and you're going to learn

both the mechanistic science

behind aging, the

mechanistic science behind

reversing the aging

process and practical tools

that you can apply in your everyday life.

In today's episode, Dr. Sinclair

and I talk about the biology of aging

and tools to intervene in that process.

And so you might view today's episode

as a primer for the lifespan podcast,

because we delve deep

into the behavioral tools,

nutritional aspects,

supplementation aspects

of the biology of aging.

We also talk about David's

important discoveries

of the sirtuins, particular components

that influence what is

called the epigenome.

And if you don't know

what the epigenome is,

you will soon learn in today's episode.

Coming away from today's episode,

you will have in-depth knowledge

about the biology of aging

at the cellular, molecular,

and what we call the circuit level,

meaning how the different

organs and tissues of the bodies

age independently, and how they influence

the aging of each other.

Today's episode gets into discussion

about many aspects of aging

and tools to combat aging

that have not been discussed

on any other podcasts

or in the book lifespan.

00:03:30 ROKA, InsideTracker, Magic Spoon

Before we begin, I'd like to

emphasize that this podcast

is separate from my teaching

and research roles at Stanford.

It is however part of my desire and effort

to bring zero cost to consumer

information about science

and science related tools

to the general public.

In keeping with that theme,

I'd like to thank the sponsors

of today's podcast.

Our first sponsor is ROKA.

ROKA makes eyeglasses and sunglasses

that are the absolute highest quality.

I've spent a lifetime

working on the visual system.

And I can tell you that the visual system

has to contend with a number

of different challenges,

such as when you move

from a bright area outside

to an area where there are shadows,

you have to adjust a number of

things in your visual system

so that you can still see things clearly.

One problem with a lot of

eyeglasses and sunglasses

is they don't take that

biological feature into account.

And you have to take off your

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depending on how bright or

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I wear readers at night and when I drive

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Today's episode is also

brought to us by InsideTracker.

InsideTracker is a

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that analyzes data from your blood and DNA

to help you better understand your body

and help you reach your health goals.

I've long been a believer in

getting regular blood work done

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that many of the factors

that impact your immediate

and long-term health

can only be assessed from

a quality blood test.

And now with the advent

of modern DNA tests,

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and compare that to

your chronological age.

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Today's episode is also

brought to us by Magic Spoon.

Magic Spoon is a zero sugar, grain-free,

keto friendly cereal.

Now I don't follow a

strictly ketogenic diet.

What works best for me is to eat according

to my desire to be alert

at certain times of day

and to be sleepy at other times of day.

So for me, that means

fasting until about 11:00 AM

or 12 noon most days.

And then my lunch is typically

a low carb, ketoish lunch,

maybe a small piece of grass-fed meat,

some salad, something of that sort.

And then in the afternoon,

I might have a snack

that's also ketoish.

And then at night is when

I eat my carbohydrates,

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the transition to sleep

and allows me to get great deep sleep.

That's what works for me.

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and use the code Huberman to get $5 off.

And now my conversation

with Dr. David Sinclair.

00:07:45 “Aging as a Disease” vs. Longevity & Anti-Aging

Thank you for coming.

- Thanks for having me here.

It's good to see you.

- This is mate by the way, that

we're toasting at 11:00 AM.

Unlike other podcasts, we,

well, I don't drink alcohol,

so I'm boring that way.

But truly, thanks for being here,

I have a ton of questions for you.

We go way back in some sense,

but that doesn't mean that I don't have

many, many questions about

aging, longevity, lifespan,

actionable protocols to increase

how long we live, et cetera.

And I just want to start off

with a very simple question.

I'm not even sure there's an answer to,

but what is the difference

between longevity,

anti-aging and aging as a disease?

Because I associate

you with the statement,

aging is a disease.

- Right?

Well, so longevity is

the more academic way

we describe what we research.

Anti-aging is kind of the same thing,

but it's got a bad rap

because it's been used

by a whole bunch of people that don't know

what they're talking about.

So I really don't like

that term anti-aging,

but aging is a disease and longevity

are perfectly valid ways

to talk about this subject.

So let's talk about aging as a disease.

When I started my research,

disease here at Harvard Medical School,

it was considered,

if there's something

that's wrong with you.

and it's a rare thing,

it has to be less than

50% of the population,

that's definitely a disease,

and then people work their whole lives

to try and cure that condition.

And so I looked up,

what's the definition of aging

and it says, well, it's

a deterioration in health

and sickness and you can die

from it, typically you do.

Something that sounds

pretty much like a disease,

but the caveat is that if

more than half the population

gets this condition, aging,

it's put in a different bucket.

Which is first of all, that's outrageous,

'cause it's just a

totally arbitrary cutoff.

But think about this,

that we're ignoring the major

'cause of all these diseases.

Aging is 80 to 90% the cause

of heart disease, Alzheimer's.

If we didn't get old and

our bodies stayed youthful,

we would not get those diseases.

And actually what we're

showing in my lab is,

if you turn the clock back, in tissues,

those diseases go away.

So aging is the problem

and instead through,

most of the last 200 years,

we've been sticking band-aids on diseases

that have already

occurred because of aging

and then it's too late.

So there are a couple of things.

One is we want to slow aging down

so we don't get those diseases

and when they do occur,

don't just take a bandaid on,

reverse the age of the body

and then the diseases will go away.

- That clarifies a lot for me, thank you.

00:10:23 What Causes Aging? The Epigenome

Can we point to one specific

general phenomenon in the body

that underlies aging?

- Yeah, well, that's contentious

because scientists like to

come up with new hypothesis.

It's how they build their careers.

But fortunately during the two thousands,

we settled on eight or

nine major causes of aging.

We call them hallmarks

'cause causes was a little bit too strong,

but these eight or nine causes,

at least for the first time

allowed us to come around

and talk together.

And we put them on a pizza

so everyone got an equal

weighting, equal slices.

But before that, by the way,

we were trying to kill

each other in the field,

that was horrible.

- Interesting that you guys work on aging

and you're trying to kill each other.

- Yeah, isn't it?

Well kill each other's careers.

Well I like to think

I was fairly generous,

but I was one of the kids

and the old guard really

didn't like the new guard.

We just came along in the 1990s

and said, free radicals don't do much.

They're actually genes

called longevity genes.

And that caused a whole ruckus.

And there was this competition

for what never happened,

which was a Nobel prize for this.

And it just led to a lot of competition.

I would go to meetings and

people would shout at each other

and backstab, it was horrible.

But then unfortunately

in the two thousands,

we rallied around this new map of aging

with these causes of hallmarks.

But I think that there's

one slice of the pizza

that is way larger than the others.

And we can get to that,

but that's the information in the cell

that we call the epigenome.

- Well tell us a little bit

more about the epigenome,

frame it for us if you will,

and then we'll get into ways

that one can adjust the

epigenome in positive ways.

- Yeah, so in science, what I like to do,

a reductionist is to boil it down

and I actually ended up boiling,

aging down to an equation,

which is the loss of

information due to entropy.

It's a hard thing to overcome,

second law of thermodynamics.

That's fair, but this

equation really represents

the fact that I think aging

is a loss of information

in the same way that

when you xerox something,

a thousand times you'll

lose that information

or you try to copy a cassette tape.

Or even if you send information

across the internet,

some of it will get lost.

That's what I think is aging.

And there were two types

of information in the body.

There is the genetic

information, which is digital.

ATCG the chemical letters of DNA,

but there's this other part of

the information in the body.

that's just as important,

it's essential, in fact,

and that's the systems

that control which genes

are switched on and off

in what cell at what time

in response to what we eat, et cetera.

And it turns out that 80% of

our future longevity and health

is controlled by the second part,

the epigenetic information,

the control systems.

I liken the DNA to the

music that's on a DVD

or a compact disc for the younger people.

We used to use these things.

- I recall.

- Yeah, and then the epigenome

is the reader that says,

okay, in this cell we need

to play that set of songs

and in this other cell,

we have to play a different set of songs.

But over time, aging is the

equivalent of scratching,

the CD and the DVD so that you,

you're not playing the

right songs and cells

when they don't hear the right songs,

they get messed up and

they don't function well.

And that is what I'm saying

is the main driver of aging.

And these other hallmarks

are largely manifestations

of that process.

- Can we go a little deeper

into what that these scratches are.

Is it the way that the DNA

are packed into a cell?

Is it the way that they're spaced?

What are the scratches

that you're referring to?

- So DNA is six foot long.

So if you join your chromosomes together,

you get a six foot post-sale.

So there's enough to go to

the moon and back eight times

in your body.

And it has to be wrapped

up to exist inside us,

but it's not just wrapped up willy-nilly.

It's not just a bundle of string,

it's wrapped up very carefully in ways

that dictates which genes

are switched on and off.

And when we're developing in the embryo,

the cell marks the DNA

with chemicals that says,

okay, this gene is for a nerve cell.

Your cell will stay a nerve cell

for the next a hundred

years, if you're lucky.

Don't turn into a skin

cell that would be bad.

And those chemicals,

there are many different

types of chemicals,

but one's called methylation.

Those little menthols will

mark which songs get played

for the rest of your life.

And there are other that change daily.

But in total, what we're

saying is that the body

controls the genome through

the ability to mark the DNA

and then compact some parts

of it, silence those genes,

don't read those genes and

open others, keep others open

that should stay open.

And that pattern of genes

that are silent and open,

silent, open, is what

dictates the cells type

the cells function.

And then the scratches are

the disruption of that.

So genes that were once

silent and you could say,

it's a gene that is involved in skin.

It's starting to come on in

the brain, shouldn't be there,

but we see this happen and vice versa,

the gene might get shut

off over time during aging.

Cells over time, lose these structures,

lose their identity,

they forget what they're supposed to do

and we get diseases.

We call that aging and

we can measure that.

In fact, we can measure it in such a way

that we can predict when

somebody is going to die

based on the changes in those chemicals.

00:15:53 Cosmetic Aging

- Are these changes, the

same sorts of changes

that underlie the outward

body surface manifestations

of aging, that most of

us are familiar with,

graying of the hair,

wrinkling of the skin,

drooping of the face.

Walking around New York lately,

it's amazing to me,

there are certain people

that seem to walk looking

down at the sidewalk

because their spine is

essentially in a C shape, right?

A hallmark, if you will, of aging,

that most of us are familiar with.

Are the same sorts of DNA

scratches associated with that?

Or are we talking about people

that are potentially

are going to look older,

but simply live longer?

- Well, it's actually, you

are as old as you look,

if you want to generalize.

So let's start with centenarian families.

These are families that

tend to live over a hundred.

When they're 70, they

still look 50 or less.

So it is a good indicator.

It's not perfect

because you can like me

growing up in Australia

and accelerate the aging of your skin.

But in general, how you look,

and no one's ever died from gray hair,

but overall you can get a sense

just from the ability of

skin to hold itself up,

how thin it is, the number of wrinkles.

A great paper just came out that said

that an AI System looking at the face

could very accurately

predict someone's age.

- Very interesting.

00:17:15 Development Never Stops, Horvath Clock

So I started off in

developmental neurobiology.

So one of the things

that I learned early on

that I still believe wholeheartedly

is that development doesn't

stop at age 12 or 15 or even 25

that your entire life is

one long developmental arc.

So in thinking about different portions

of that developmental arc,

the early portion of infancy,

and especially puberty, seem

like especially rapid stages

of aging.

And I know we normally

look at babies and children

and kids in puberty, and we

think, oh, they're so vital,

they're so young.

And yet the way you describe

these changes in the epigenome

and the way you have

framed aging as a disease

leads me to ask are periods

of immense vitality,

the same periods when we're aging faster.

- Yes, yes.

And this is something

I've never talked about,

at least not publicly.

So this is a really good question.

So those chemicals we can measure,

it's also known as the Horvath's clock.

It's the biological clock,

it's separate from your chronological age.

So actually what I didn't mention

is that when the AI looked

at the faces of those people,

they could predict their

biological age, their internal age.

So your skin represents the

age of your organs as well.

And the people that look after themselves,

we can talk about how to do that later.

But there are some people

that are 10, 20 years younger

than other people biologically

and it turns out if you

measure that clock from birth

or even before birth,

if you look at animals,

there's a massive increase

in age, based on that clock,

early in life.

So you're right, so that's

a really important point,

that you have accelerated aging

during the first few years of life,

and then it goes linear

towards the rest of your life.

But there's another interesting

thing that you brought up,

which is that we're finding that the genes

that get messed up, that get scratched

that are leading to aging

are those early developmental genes.

They come on late in life

and just mess up the system

and they seem to be

particularly susceptible

to those scratches.

So what's causing the scratches?

Well, we know of a couple

of things in my lab,

we figured out.

One is broken chromosomes, DNA damage,

particularly cuts to the DNA breaks.

So if you have an x-ray or a cosmic ray,

or even if you go out in the sun

and you'll get your broken chromosomes

that accelerates the unwinding

of those beautiful DNA loops

that I mentioned.

We can actually do this to a mouse.

We can accelerate that process

and we get an old mouse,

50% older, and it has

this bent spine kyphosis.

it has gray hair, it's organs are old.

So we now can control aging,

the forwards direction.

The other thing that accelerates aging

is massive cell damage or stress.

So we pinched nerves and we

saw that their aging process

was accelerated as well.

00:20:12 Puberty Rate as a Determinant of Aging Rate

- Incredible, this is more

of an anecdotal phenomenon.

It is an anecdotal phenomenon,

but at this experience

of in junior high school,

going home for a summer and you come back

and then high school in the US

usually starts eighth or ninth grade,

or grade eight or grade

nine for you Canadians.

And then some of the kids,

like they grew beards over the summer,

or they completely matured

quickly over the summer.

Do you think there's any reason to believe

that rates of entry

into and through puberty

can predict overall rates of aging?

In other words, if a kid

is a slow burner, right?

They basically acquire

the traits of puberty

slowly over many years.

Can we make some course prediction

that they are going to live a long time

versus a kid that goes home for the summer

and comes back a completely

different organism

or appearing to be a

completely different organism.

Like they basically age

very quickly in the summer.

Does that mean they're

aging very quickly overall?

- Well, yeah, I don't

want to scare anybody.

- Sure.

- That there are studies that show

that the slower you take to

develop it also is predictive

of having a longer, healthier life.

And it may have something

to do with growth hormone.

We know that growth hormone is pro-aging.

Anyone who's taking growth

hormone, pay attention.

- Just look at someone

who's taking growth hormone.

- Yeah.

- They often will acquire these

characteristics of vitality,

like improved a smoothness of skin,

but their whole body shape changes often.

- Yeah, I mean you'll feel better

for a short amount of time.

You'll build up muscle, you feel great,

but it's like burning

your candle at both ends.

Ultimately, if you want to live longer,

you want less of that.

And the animals that have been generated

and mutants that have low growth hormone,

or sometimes these are dwarfs,

they live the longest by far.

A guy in my lab, Michael Bankowski,

he had the longest lived mouse,

a mouse typically lives

about two and a bit years.

He had a mouse that lived five years

and he gave it chloric

restriction, so fasting,

combined with one of

these dwarf mutations,

low growth hormone, I

think he called it Yoda.

You look at who lives the longest,

it's the really small people.

This is a bit anecdotal,

but it sounds like it might be true,

is that the people who

played the munchkins

in the Wizard of Oz, many

of them went on to live

into their nineties and beyond.

- Really?

- Yeah.

- Huh, amazing.

- And are there are some

Lauren dwarfs as well?

There are dwarf mutations in South America

and they seem to be protected

against many of the diseases of aging.

You barely ever see heart disease

or cancer in these families.

00:20:12 Puberty Rate as a Determinant of Aging Rate

- So I having owned a

very large dog breed,

a bulldog Mastiff who lived

a long life for a bulldog,

11 years, but there are

many dogs that will live

12, 16 years that are smaller dogs.

Can we say that there's

a direct relationship

between body size and

longevity or duration of life?

- Well, there is, but that

doesn't mean that you're a slave

to your early epigenome

nor have to your genome.

The good news is that

the epigenome can change.

Those loops and structures can be modified

by how you live your life.

And so if you're born tall and I wasn't,

and I wished at the time I did grow,

but no matter what size you are,

you can have a bigger impact on your life

than anything your genes give you.

80% is epigenetic not genetic.

- So let's talk about some of

the things that people can do.

And I've kind of batch

these into categories

rather than just diving right

into actionable protocols.

So the first one relates to

food, blood sugar, insulin.

This is something I hear a lot about,

that fasting is good for us,

but rarely do I hear why it's good for us.

One of the reasons I'm

excited to talk to you today

is because I want to drill

into the details of this

because I think

understanding the mechanism

will allow people to make better choices

and not simply to just

decide whether or not

they're going to fast or not fast,

or how long they're going to fast,

I think should be dictated

by someone understanding

of the mechanism.

So why is it that having

elevated blood sugar,

glucose and insulin ages us more quickly

and or why is it that having

periods of time each day

or perhaps longer can extend our lifespan?

- Well, let's start with what

I think was a big mistake

was the idea that people

should never be hungry.

We live in a world now

where there's at least three meals a day,

and then we've got companies

selling bars and snacks

in between.

So the feeling of hunger,

some people never experienced

hunger in their whole lives.

It's really, really bad for them.

It was based, I believe

on the 20th century view

that you don't want to

stress out the pancreas

and you try to keep insulin

levels pretty steady

and not have this fluctuation.

What we actually found,

my colleagues and I,

across this field of longevity

is that when you look

at first of all animals,

whether it's a dog or a mouse or a monkey,

the ones that live the

longest by far 30% longer

and stay healthy are the ones

that don't eat all the time

actually was first discovered back

in the early 20th century,

but people ignored it.

And then it was rediscovered in the 1930s,

Claude McKay did Clark restriction.

He put cellulose in the food of rats,

so they couldn't get as many

calories even though they ate.

And those rats lived 30% longer,

but then it went away

and then it came back

in the 2000's in a big way,

when a couple of things happened,

one is that my lab and others showed

that there were longevity

genes in the body

that come on and protect

us from aging and disease.

The group of genes that I

work on are called sirtuins

there's seven of them.

And we show it in 2005 in a science paper,

that if you have low levels of insulin

and another molecule called

insulin like growth factor,

those low levels turn

on the longevity genes.

One of them that's really

important is called SIRT1.

But by having high levels

of insulin all day,

being fed, means your longevity

genes are not switched on.

So you're falling apart, your

epigenome, your information,

that keeps your cells

functioning over time,

just degrades quick.

Your clock is ticking

faster by always being fed.

Okay.

The other thing that I

think might be happening

by always having food around

is that it's not allowing the

cell to have periods of rest

and re-establish the epigenome.

And so it also is accelerating

in that direction.

There's plenty of other reasons as well,

that are not as profound,

such as having low levels

of glucose in your body

will trigger your major

muscles in your brain

to become more sensitive to insulin

and suck the glucose

out of your bloodstream,

which is very good.

You don't want to have glucose

flowing around too much,

and that will ward off type two diabetes.

- So hunger of course is

associated with low blood glucose

and low insulin.

Do you think there's anything

about the subjective

experience of hunger itself

that could be beneficial for longevity?

- Yeah, I do,

though you get used to

the feeling of not eating,

so I'm kind of screwed that way.

- It's like cold water,

you eventually adapt.

- You get used to it, unfortunately,

but there are some studies

that are being done

at the National Institutes of Health

that are able to simulate

the effect of hunger,

but still provide the calories.

And it's looking like

there's a small component

that's due to hunger, but most of it,

actually, is because

you've got these periods

of not being fed and then the body

turns on these defensive genes.

There's a really interesting experiment

that was published maybe

a couple of years ago

by Rafael de Cabo down at the NIH.

What he did was he took over 10,000 mice

and gave them different combinations

of fat, carbohydrate, protein.

And he was trying to figure out

what was the best combination.

And then you also cleverly had a group.

Well, two groups, one

that was fed all the time

or ate as much as they wanted

and the other group was only

given food for an hour a day.

And it turns out they ate

roughly the same amount of calories,

'cause of course in an hour

they're stuffing their faces.

It turns out it didn't matter

what diet he gave them,

it was only the group that

ate within that window

that lived longer and dramatically longer.

So my conclusion is,

and mice are very similar

to us, metabolically,

I think that tells us that

it's not as important,

what you eat, it's when

you eat during the day.

- What is the protocol

that people can extrapolate from that?

Or maybe I should just ask you,

what is your protocol for when to eat

and when to avoid food?

Do you fast, do you ever

fast, longer than 24 hours?

What do you do?

And what do you think is

a good jumping off place

if people want to explore

this as a protocol?

- Well, if there's one thing I could say,

I would say definitely

try to skip a meal a day,

that's the best thing.

- Does it matter which meal

or they're essentially equivalent?

- Well, as long as it's at the end

or the beginning of the day,

because then you add

that to the sleep period

where you're hopefully not eating.

- I think that that's an excellent point.

I realized it's a simple one,

but I think it's an excellent one

'cause I think one of

the things that people

struggle with the most

is knowing when and how

to initiate this so-called

intermittent and fasting.

And the middle of the day

obviously is not tacked

to the sleep cycle in the same way.

So it's much harder as

well for many people.

- Yeah, well, I'll tell you what I do.

I skip breakfast, I have a

tiny bit of yogurt or olive oil

because the supplements I have

need to be dissolved in it.

And then I go throughout the whole day,

as I'm doing right now, here

with this glass of water here,

I'm just keeping myself

filled with liquids.

And so I don't feel hungry,

be aware that the first

two to three weeks,

when you try that you will feel hungry

and you also have a habit of wanting

just to chew on something

that there's a lot of

physical parts to it,

but try to make it through

the first three weeks

and do without breakfast

or do without dinner

and you'll get through it.

And I did that most for

most of my life, actually,

mainly because I wasn't

hungry in the morning.

Some people are very hungry in the morning

and they may want to consider

skipping dinner instead,

but I will go throughout the whole day.

I don't get the crashes

of the high glucose

and the low glucose that anyone who goes,

oh man, it's three O'clock,

I'm going to need a sleep.

If you do what I do,

you will not experience that anymore

because what my body does

is it regulates blood

sugar levels naturally.

My liver is putting out

glucose when it needs to,

and it's very steady

and gives me pure focus

throughout the day.

And I don't have to even

have to think about lunch,

I'm just powering through.

At dinner, I mean, I love

food as much as anybody.

So I will eat a regular,

pretty healthy meal.

I'll try to eat mostly

vegetables, I can eat some fish,

some shrimp, I rarely will eat a steak.

In fact, my microbiome is

so adapted to my diet now,

if I eat a steak, it will

not get digested very well.

I'll feel terrible.

- If I don't eat a steak, I feel terrible.

[David laughs]

- Argentine lineage, but

we can talk about that

some other time.

- Well, everybody's different,

that's the other thing.

What works for me may

not be perfect for you

and we do have to measure

things to know what's working.

I rarely eat dessert, I

gave up dessert and sugar

when I turned 40 and occasionally

I'll steal a bit of dessert

'cause it doesn't hurt

if you steal it, right.?

But other than that I avoid sugar,

which includes simple carbohydrates,

bread, I try to avoid,

I've actually noticed,

this is just a side note.

I used to get buildup

of plaque pretty easily

and every time I went to the dentist,

they'd have to scrape it off.

And I even bought tools to scrape it off.

'cause it was driving me nuts.

I don't get pluck anymore

and I think it's because of my diet.

I don't have those sugars in my mouth

that the bacteria feed on

and then form the biofilm on the teeth.

Much better breath, by the way.

- That's a benefit.

Should you ever fast longer than this.

It sounds if you go to bed,

well, you used to tend to stay up late.

I know because I get texts from you

at like two in the morning my time,

which means you're out very

late and up early as well.

00:32:44 Fasting Schedules, Long Fasts, (Macro)Autophagy

But assuming that people go to sleep

sometime around 1130 or

12, plus or minus an hour

and wake up sometime around 7:00 AM

plus or minus 90 minutes,

you're eating more or less on.

It sounds something like

a 20 hours of fasting,

four hours of eating

or 16 hours of fasting

and eight hours of food intake, et cetera.

But do you ever do longer fast,

like 48 hours or 72

hours a week long, fast?

- Occasionally I do.

So my typical day I would only

eat within a two hour window.

Just usually I'm either eating out or.

- 'Cause you're 22 too.

- Yeah, but I love well.

- And if you exercise,

do you feel like you,

then you just power through

and maintain that fasted state?

- Absolutely, I can exercise

and now I've already so used to it.

I don't feel like I need food

after exercising, I used to.

But have I gone longer?

Yes, but not very often.

I find it quite difficult

to go more than 24 hours.

But when I do it, maybe it's once a month,

I'll go for two days after

two and actually even better,

if you go for three days without eating,

it kicks in even greater

longevity benefits.

So there's a system called

the autophagy system,

which digests old and

misfolded proteins in the body.

And there's a natural cleansing

that happens when you're hungry.

Macroautophagy its name is

but a good friend of mine,

Ana Maria Cuervo at Albert

Einstein College of Medicine

discovered a deep cleanse

called the chaperone mediated autophagy,

which kicks in day two, day three,

which really gets rid

of the deep proteins.

And what excites me is you

just put out a big paper

that said, if you trigger

this process in an old mouse,

it lives 35% longer.

- [Andrew] Wow.

- Yeah, so it's a big deal.

If I could go longer, I would.

But I just find that with my lifestyle

and I'm going always

day, 110% I need to eat

at least once a day unfortunately.

00:34:50 Caffeine, Electrolytes

- One more practical question

then a mechanistic question

related to this, the practical question

is when you are fasting,

regardless of how long,

I know you're ingesting fluids like water

and presumably some caffeine

I heard you had several

or more espresso today,

which is impressive,

but are you also ingesting electrolytes?

Like I know some people get lightheaded,

they start to feel shaky when they fast.

And that the addition

of sodium to their water

or potassium magnesium is something

that's becoming a little more invoke now.

Is that something that you do

or that you see a need for people to do?

- Well, it makes sense, but I

haven't had a need to do it.

So I don't, I drink tea

during the day and coffee

when I'm first awake and

I don't get the shakes.

So I don't fix what's not broken.

And I do add things to my protocol

that I think will improve

me and avoid those things

of course that wont.

But yeah, because I

don't have a need for it,

I don't try it.

But it does make sense,

especially if you've had a

big night the night before,

you'd probably want to

supplement with that.

But I think there's fair

amount of good stuff

in tea and coffee as it is.

00:35:56 Blood Glucose & the Sirtuins; mTOR

- Okay, so then the

mechanistic question is,

you've told us that there's ample evidence

that keeping your blood sugar

low for a period of time

is 24 hours, can help

trigger some of these pro

longevity anti-aging mechanisms.

And that extending them

out two or three days

can trigger yet additional

mechanisms of gobbling up

of dead cells and things of that sort.

How is it that blood glucose

triggers these mechanisms?

Because we've said, okay, remove glucose

and things get better.

You've talked before maybe

we could talk more now

about some of the underlying

cellar and genetic mechanisms,

things like this are sirtuins,

but how our glucose in the sirtuins

actually tethered to one

another mechanistically.

- There's a really good question,

that proves you're a scientist

or a world-leading one.

So what we've now know is

that these longevity pathways,

we call them these longevity

genes, talk to each other.

And we used to say,

oh, my longevity genes is

more important than yours.

It was ridiculous.

'Cause they're all talking to each other,

you pull one lever and

the other one moves.

And the way to think of it is

that there are systems set up

to detect what you're eating.

So the sirtuins will mainly

respond to sugar and insulin.

And then there's this

other system called mTOR,

which is sensing how much

protein or amino acids

are coming into your body.

And they talk to each other,

we can pull one and affect

the other and vice versa.

But together when you're fasting,

you'll get the sirtuin

activation, which is good for you.

And you'll also through

lack of amino acids,

particularly three of them,

leucine, lysine and valine.

The body will down-regulate

mTOR and it's that up sirtuin,

down MTOR that is hugely beneficial

and turns on all of the body's defenses,

the pro chewing up the old proteins,

improving insulin sensitivity,

giving us more energy,

repairing cells, all of that.

And so these two pathways, I think,

are the most important for longevity.

00:37:55 Amino Acids: Leucine, “Pulsing”

- So interesting, you mentioned leucine,

within the resistance training

slash body building slash

fitness community.

Leucine gets a lot of attention

because there are long-standing debates

about how much protein one needs per day

and how much you want and

can assimilate at each meal.

It makes for many YouTube videos

and not much else, frankly.

However, it's clear that

because of leucine's effects

on the mTOR pathway, that

there are many people,

not just people in these

particular fitness communities

that are actively trying

to ingest more leucine

on a regular basis in order

to maximize their wellness

and fitness and in some

cases muscle growth

but also just wellness.

But what I interpret your

last statement to mean

is that leucine, because

it triggers seller growth

is actually pro aging in

some sense, is that right?

- Well, it could be that's

what the evidence suggests.

And again it goes back to the debate.

Should you supplement with

growth hormone or testosterone?

All of these activities will

give you immediate benefits.

You'll bulk up more.

You'll feel better immediately,

but based on the research,

it's at the expense of long-term health.

So my view of longevity,

the way I treat my body is

I don't burn both candles.

I have one end of the candle lit,

I'm very careful I don't blow on it,

but I also do enough exercise

that I'm building up my

muscle, but I'm not huge.

Anyone who's seen me,

knows that I'm not a

professional bodybuilder,

but I tried to actually, here's the key.

And I haven't said this

publicly, that I can remember.

I pulse things so that

I get periods of fasting

and then I eat, then I take a supplement,

then I fast, then I exercise

and I'm taking the supplements

and eating in the right timing

to allow me to build up muscle sometimes

because you can't just expect

to take something constantly

and do something

constantly for it to work.

And that's why it's

taken me about 15 years

to develop my protocol.

And there's a lot of subtlety to it.

- Yeah, it sounds like a

very rational protocol.

Does the name Ori Hofmekler

mean anything to you?

- No.

- Okay, just briefly, I

discovered Ori Hofmekler

about 15 years ago, he was

a in Israeli special forces.

He's now got to be close to 70.

Forgive me Ori, if that

number is inflated.

He wrote a book called 'The Warrior Diet',

which got very little

attention at the time.

But what he said was when he

was in Israeli special forces,

they rarely ate more than once per day.

And sometimes once every

second or third day.

And this is a guy who maintains

incredible physical stature,

he's very lean, very strong

and very vital at, I

wouldn't say an advanced age,

but he's getting up there

and he just seems to be

getting better and better.

Ori Hofmekler was the person

who essentially founded,

if you will, although

our ancestors founded,

to be completely fair,

the so-called intermittent fasting diet.

He called it the warrior diet

and this book didn't get much attention.

But one of the things that you just said

really reminded me of Ori.

I sat down with him, I

actually went to his home

and sat down with him and he

said, fasting is wonderful

but these pulses where

you nourish the body

or even slightly over nourish the body

provided they aren't too frequent,

have a tremendous effect on vitality.

And so I want to use

that as kind of a segue

to address this issue of

vitality versus longevity,

because here you're telling me

and certainly the evidence supports

that growth hormone will make

you feel better and younger

taking testosterone or estrogen,

we should probably say.

There are women who take

hormone therapies later in life

who take estrogen,

they experience a strong

increase in vitality

if it's done correctly, but

there is an effect of aging,

the body more rapidly,

it's sort of a second puberty if you will,

but this idea of restriction

and then pulsing,

not necessarily feast and famine,

but certainly famine and

feast in lowercase letters,

there really seems to

be something about that.

So at a cellular level,

we'd kind of go back to

mTOR and the sirtuins.

How do you think that the

cells might be reacting

to this kind of lowercased

feast and upper case famine

type protocol?

- Right, well, the pulsing, I

think is what you want to do

is to get the cells to

be perceiving adversity.

Okay, 'cause our modern

life we're sitting around,

we're eating too much,

we're not exercising.

Our cells respond.

They go, hey, everything's

cool, no problem.

And they become relaxed and their own turn

on their defenses and we age rapidly.

We can see it in the clock.

People who exercise and eat less,

have a slower ticking clock, it's a fact.

But my protocol is

different than most people's

because I am pulsing it.

Now, first of all, let's get to,

why did I even think

that might be possible?

'Cause I didn't read the warrior diet.

What I found in my research was that

if we gave resveratrol on

this red wine molecule,

that became well known in the 2000's.

If we gave it to mice,

their whole lifespan,

they were protected

against a high-fat diet,

which we call the Western diet.

They had lean organs.

They live slightly longer, but not a lot.

And if we gave them a high-fat

diet without resveratrol,

they actually lived a lot shorter.

So it resveratrol protected

them against the high-fat diet.

We gave it to them on a normal diet,

they just ate it when they wanted,

and there wasn't much effect.

This is what's not known though

it's in a supplemental data of the paper

that nobody ever reads.

The mice that were given

resveratrol every second day

on a normal diet live dramatically longer

than any other group.

- [Andrew] Interesting.

- So people out there, my

critics say, resveratrol

didn't extend the lifespan

of mice on a normal diet.

Therefore it's not aging,

it's just protecting

against a high-fat diet.

Well, look at the

supplemental data, please.

If you give it to the

mice every other day,

we had mice living over three years.

- Wow, that's a long time,

I have got many, many mice

in my owner ownership

at my lab at Stanford

and that's a very long life for a mouse.

- It was, by far.

And so it was a long life span extension.

And what that told me is that probably,

you don't want to be taking

a supplement every day.

You can take it either every other day

or give your body a rest.

And I do the same with my meals,

I rest during the day and then

I give a nutritious dinner

to my body and then give it

a rest, same with exercise.

And then I try to time it

because there are times

when I'm taking the drug

Metformin, which mimics low energy.

00:44:35 Metformin, Berberine

For those of you who don't know,

Metformin is a drug given

to type two diabetics

to bring down their blood sugar levels.

But it's been found that

looking at tens of thousands

of veterans and all those,

that those two type two diabetics

live longer than people

that don't even get type two diabetes.

So it's a longevity drug,

right now you have to get it

from your doctor in the US,

in most of the countries

you can just get it

over the counter and you protected.

It looks like, based on

epidemiological data, cancer,

heart disease for LT.

What else?

Dementia.

So I take Metformin.

- In addition,

you take Metformin end

fast fasting each day.

So when do you take it

relative to the fasting?

- Yeah, I always take

Metformin in the morning,

along with the resveratrol,

because for a number of reasons,

but mainly because my body responds better

and I've been measuring

my body for 12, 13 years.

But here's the thing, if I'm

going to exercise that day,

I will skip the Metformin.

And a lot of people who do pay attention

to this kind of thing,

think that they should

stop taking Metformin

'cause they're never going to get muscle,

or it's going to affect their

ability to build up muscle.

But that's not true, what

Metformin does to you,

it actually just reduces

your ability to have stamina

because it's inhibiting your

body's ability to make energy.

And so what happens is

when you're on Metformin,

you do fewer reps.

But guess what?

Those muscles that you

do build up on Metformin,

have the same strength and

have much lower inflammation

and other markers of aging.

You just won't have that

extra 5% size of muscles.

So if you want large muscles,

don't take Metformin and you'll be fine

during your exercise.

But for me, I'm not trying to get giant.

I want strong muscles

and I want to live longer

and healthier.

So I just try to time it

so that I get the most reps

out of my exercise regime,

but sometimes in scientific literature,

it's worth bringing this up.

If there's a 5% difference in a graph,

then either the press release

or some reporter will say,

oh my goodness, big difference,

5% contact Metformin during exercise.

That's the headline.

And then you go in and

it's barely significant.

And the graph is distorted

because they've changed

the axes to make it look bigger.

And now it's become a myth

that Metformin greatly inhibits

our ability to exercise,

which is not true, but in

an abundance of caution,

I skipped my Metformin on

days I'm going exercise.

And not only that,

I'm one of the 20% of people

that has a stomach sensitivity to it.

So if I'm not feeling great that day,

I don't take it either.

- You mentioned Metformin is available

only by prescription from a

doctor, at least in the US.

Berberine is a substance

that comes from Tree Barco.

I also learned about

many years ago from Ori.

He said, if ever, I'm going to overeat

like a Thanksgiving meal or something,

I take berberine, those were his words.

And I tried it and what's

remarkable about berberine

is that you can eat

enormous quantities of food

and not feel as if you've eaten

enormous quantities of food.

I'm not necessarily

recommending people do this.

But what I noticed was

if I took berberine,

which my understanding is

it works very similarly

to Metformin where some

of the AMPK pathway

and the mTOR pathway, et cetera,

that if I didn't ingest food

in particular carbohydrates,

I would feel a little dizzy

and kind of get a headache,

like almost hypoglycemic.

What are your thoughts on berberine

as an alternative to Metformin?

And are there any cautionary notes?

Obviously people should

talk to their doctor

before adding or subtracting

anything from their life,

including breath order,

anything that comes up,

but with all of that set aside,

what are your thoughts about berberine

and timing of low blood sugar

and these sorts of things?

- Right, well, before I

had access to Metformin,

I was taking berberine.

It's often known as the

poor man's Metformin.

- He just called me poor.

- Women can take it too.

So the thing with berberine

and we started it in my lab,

it is effective at boosting

energetics in the body,

just like AMPK and Metformin does.

And we've actually given

it to rats and mice

and seen that they are very healthy,

especially on a high-fat diet.

So I think it's likely to be good.

There are some human studies that exist,

clinical trials showing

that it increases insulin sensitivity.

You have to take high doses.

- Which is a good thing, right?

I think when people hear

insulin sensitivity,

sometimes people think,

oh, well that's bad, right?

No, but you want your cells

to be insulin sensitive.

You don't want a lot of

blood sugar floating around

that can't be sequestered into cells.

- Exactly, so this is

anti type two diabetes.

And so that this berberine

does have wonderful effects

on the metabolism of animals

and in some clinical trials

on dozens of people that's being tested.

Now, there's one cautionary

tale, which just came up,

Caenorhabditis lab

published that berberine

reduced the lifespan of worms,

but I'm not sure worms

trump human clinical trials

at this point.

- Not in my opinion,

no disrespect to my C. elegans colleagues

or rather my colleagues that work on C.

- Yeah, well, what I like to do

is to give all the information,

people can decide what they want,

but I would say based on the worm data,

I wouldn't panic just yet.

And I think berberine has been shown

to be really safe in humans.

00:50:29 Resveratrol, Wine

- You mentioned resveratrol,

think now would be a great time

to talk a little bit about,

protocols for resveratrol,

great seed extract, et cetera.

Let's start with the obvious

one that I know you get a lot,

but for the record, can't

I just drink red wine

and get enough resveratrol, David.

- You can try, you need to

drink about 200 glasses a day.

- I'm sure it's been tried.

- There are some, and I drink

a glass of red wine a day

if I get the chance,

but any more than that,

it's a lot of calories and

your liver will get fatty

and it's all bad.

So, I mean, realistically,

you can only get the thousand milligrams

that I take a day from a

supplement that's pure.

Now there are a lot of

people selling resveratrol.

If it's not light gray or

white in color, throw it away.

The brown stuff has gone

bad or is contaminated.

And the contaminated stuff

beware it'll cause diarrhea.

But regular resveratrol

should not do that.

- So a thousand milligrams

per day is what you do.

- Yeah and I had for about 15 years now.

And you ingest that with

some fatty substance,

like olive oil or yogurt, is that right?

- Yeah, you have to, and other supplements

of course it's in curcumin.

These are crunchy things,

that is not going to get through your gut.

And I'm not just making this up.

I always base my statements

on human studies.

So we've done a lot of

studies on resveratrol

as have others since,

and we know that from,

we found out early, I was

one of the first people

to take a high dose for resveratrol.

And when we included it with food,

the levels in my blood went up five fold.

And so you want to have

something in there.

If you just drink it with water,

it's not going to get through.

And unfortunately, some people

have done clinical trials

without even thinking that they might need

to dissolve it in something.

- So are you taking this

all at once in the morning

and chasing it with some olive oil

or are you dissolving it in yogurt?

What's the specific protocol?

- Yeah, I've been improving perfecting

what I do for about 10 years

I would take some Greek yogurt,

a couple of spoonfuls, put

the resveratrol on there,

mix it around, make sure it's dissolved

and put that in my mouth and swallow that,

these days, what I like to do,

because I've realized that olive oil

and particularly oleic acid,

one of the mono unsaturated,

fatty acids is also an activator

of the sirtuin defenses.

So I'm trying to ingest

more of oleic acid.

So I switched to olive oil.

What I do is I put a couple

of teaspoons of olive oil

in a glass mix around the resveratrol,

and maybe some Coresatin

a similar molecule.

Make sure it's dissolved.

I put a little bit of vinegar

and if I have a basil

leaf, I'll put that in.

And it's like drinking

some salad dressing.

And it's very Delicious

00:53:20 What Breaks a Fast?

That raises a

question that I want to ask

before we get to NMN

and NR and vitamin B3,

which is by doing that,

do you think that it breaks your fast?

And I want to just frame this

question of breaking the fast

in a more general scientific theme.

And I'd love your thoughts on this.

One of the questions I

get asked all the time

is does ingesting blank break the fast,

does eating this or drinking this, coffee?

If I walk in the room and

someone else is eating a cracker,

does it break my fast?

People get pretty extreme with this,

my sense and please tell me if I'm wrong,

but my sense is that it

depends on the context

of what you did the night before,

whether or not you're

diabetic, lots of things.

So for instance, if I eat an

enormous meal at midnight,

go to sleep, wake up at 6:00 AM.

I could imagine that black coffee

or coffee with a little bit

of cream might quote unquote,

break my fast, but the body

doesn't have a breaking the fast switch.

The body only speaks in the

language of glucose, AMPK,

mTOR, et cetera.

So do you worry that

ingesting these calories

is going to quote unquote break your fast?

And more generally,

how do you think about the

issue of whether or not

you're fasting enough to

get these positive effects?

Because not everybody can manage

on just water or just tea,

or we should say not

everybody is willing to manage

on just water or just tea for

a certain part of the day.

- Well, my first answer is not scientific,

it's philosophical.

If you don't enjoy life, what's the point.

And so I'd like a cup of

coffee in the morning,

a little bit of milk, spoonful of yogurt,

it's not going to kill me.

Olive oil doesn't have protein

or carbs in it, not many.

And so I'm probably not affecting

those longevity pathways

negatively, but without that,

first of all, I wouldn't

enjoy my life as much.

Second, well, the olive

oil isn't is not as great

as the yogurt, but I'm trying to optimize

and there's no perfect

solution to what we're doing.

And we're still learning.

We don't know what's optimal for me,

let alone everybody else.

But I'm with you,

I don't believe that taking a couple

of spoonfuls of something,

unless it's high fructose corn

syrup is going to hurt you

because I've now got the rest of the day

till about eight, 9:00 PM

of not eating anything.

And that I forgive myself for that.

And that there's a really good point here.

You and I were discussing this earlier.

The point about doing this is

that you try to do your best.

If you go from regular living

to donate the whole day,

you're going to fail.

It's like quitting smoking, cold turkey.

It's easy to chew gum

and stick the patch on

because your body has to get

used to all sorts of habits.

And it's social, it's physical,

putting stuff in your mouth,

chewing, not just the

low blood sugar levels

and your brain will fight it.

Your limbic system is going to go,

hey, do it, do it, do it.

And you're going to have to fight it

but once you get through

it, you'll be better,

but you do it in stages.

Do breakfast first, then do small lunch

and then eventually cut lunch out.

Don't go cold turkey

because everyone knows.

It's a fact that if you

try to do a strict diet

right out of the gates,

they'll almost always fail.

- Now, I think that captures the essence

of the fasting rationally

and irrational approach

to supplementation very well,

along the lines of supplementation.

00:56:45 Resveratrol, NAD, NMN, NR; Dosage, Timing

What about NMN, NR and B3, niacin?

How does one, I want to know what you do.

I also want to know what I should do,

and I think most people want

to know what they should do.

These are molecules that

impact the sirtuin pathway

impact the pathways that control aging

or rates of aging in the epigenome.

How do they do that?

And how does one incorporate that

into a supplementation protocol?

Should they choose to do that?

All right.

- Well, disclaimer is I

don't recommend anything,

but I talk about what I do.

So a bit of scientific background,

these are two in genes that we discovered

first in yeast cells when I was at MIT

and then in animals as I

moved to Harvard in the 2000's

one of my first post-docs,

actually literally my

first postdoc Haim Cohen,

published a great paper

just a couple of months ago

and found that turning

on the sirtuin six gene,

middle of the seven, number

six gene is very potent.

It extended the lifespan

dramatically of mice

that he engineered both males

and females, which is great.

So what you want to do

is so naturally boost

the activity of these sirtuins.

They are genes, but

they also make proteins.

That's what genes

typically make or encode.

And then those proteins

take care of the body

in many different ways as we've discussed.

So how do you turn on these

genes and make the proteins

they make even more active?

You want to rev up that system.

So exercise will do

it, fasting will do it.

What about supplementation?

Well, the first activator of

the sirtuins that we discovered

that acts on the enzyme

to make it do a better job

of cleaning up the body

and protecting resveratrol

We looked at thousands

of different molecules,

eventually tens of thousands.

And the one that was the best

was resveratrol in the dish.

And then we gave it to

little organisms, worms,

and then flies and

mice, eventually humans.

And we saw that it activated that enzyme.

So resveratrol is one way to activate it.

And you can think of it as the

accelerator pedal on a car.

It revs it up, but there's

something else that the sirtuins

need to work and that's NAD

and is a really small molecule,

little chemical in the

body that we need for life.

It's used by the body

for chemical reactions,

for a hundred different

reactions in the body.

And without it, you're dead

within seconds, you need NAD.

The problem that we've

seen is that NAD levels

decline as you become

obese, as you get older,

if you don't ever get hungry and the body

not only doesn't make enough of it,

it's chewing it up as well.

There's an enzyme called

CD38 that Eric Verdin

over at UCSF showed choose up.

Now he's now at the Buck

Institute in California,

choose up NAD as you get older.

So it's a double whammy.

You don't make as much and chew it up,

which is really bad because

what we've shown in my lab

and so have others is that NAD levels

are really important for keeping

those sirtuins and defenses

at a useful level.

And you can give a lot of resveratrol

but if you don't have the fuel,

you're basically accelerating a car

that doesn't have enough gas.

So you want to do both.

And that's what I do.

I take a precursor to NAD called

NMN and the body uses that

to make the NAD molecule in one step.

And so I know from measuring

dozens of human beings,

that if you take NMN for

the time period that I do,

I've been taking it for years.

But if you take it for about two weeks,

you'll double on average,

double your NAD levels in the blood.

Okay, that's not public information.

That's from clinical trials

that are not yet published

over the last two years.

There are other ways

to increase NAD levels

in someone like me, who's

getting older, I'm 52 now.

You can take NR, which

is used to make an amend,

which is used to make

NAD, and both NMN and NR

are sold by companies in the US.

NR is laxter phosphate,

the phosphate is a small

chemical the body needs.

You've probably heard

of the atom, phosphorus.

Let's go back one step.

How do you make NR?

NR gets made from vitamin B3, often.

You can also find it in

milk and other foods,

but sometimes people ask me,

why don't you just take vitamin B3?

And won't that just force

the body to make NAD?

And the answer is no, it

doesn't work very well.

We know this just by doing the experiment,

but the reason I think is is that NAD,

I said, it's a small molecule,

but relative to vitamin B3, it's big.

It's got those phosphates

on there, it's got a sugar,

it's got the vitamin B attached.

So you've got all these

components that come together

to make this very complicated

little molecule called NAD.

When you give NMN, it

contains all three components

that the body needs to make NAD.

If you give NR or just vitamin B3,

which is an even smaller molecule,

the body has to find

these other components

from somewhere else.

So where do you get phosphate,

well, the body needs it for

DNA, it needs it for bones.

So high doses of something

that requires additional phosphate

makes me a little concerned.

And we have compared to

NMN and NR head-to-head

in mouse studies, for instance in NMN,

we've shown in a cell

paper a few years ago,

makes mice run further, old

mice can run 50% further

'cause they had better

blood flow, better energy.

NR are at the same dose, did not do that.

In fact, it had no effect.

- I see, dosage wise, if

I were elect to take NMN

in supplement form to

increase my NAD levels

and presumably slow my aging,

how much NMN should I take?

What's the protocol that you do?

And are the various

forms that are out there,

are some better or some worse?

- Well, I'm always happy

to tell you what I do

and what my father does,

my 82-year-old father,

we take a gram of NMN every day.

- So it's a gram resveratrol

and a gram of NMN.

- Right.

- Okay a thousand milligrams.

- Now another important point,

which is, I'm not the

same as everybody else.

I have a different

microbiome, age, sex, right?

And so I've been measuring myself

and so I know if something's,

or I think I know if

something's making me better

or worse based on measuring

45 different things.

So I just want people to be aware

that what I do may not perfectly

or work at all for others,

but I have studied, as I said,

dozens of people who take NMN, at a gram,

sometimes two grams.

And I know by looking at all those people

that without any exceptions,

that if you do what I do,

your NAD levels go up by

about two fold or more.

And so I do that every day,

the thousand milligrams.

Now people sell it.

Now I never get into brands and all that.

First of all, I don't have

the time to measure products.

I don't know, though I should say,

I do want to say I'm working on a solution

for people to know what works

and what's real and what

isn't, but I'm not there yet.

And in the meantime, I would say,

if you do want to buy this,

let's say you want to buy NMN,

look for a company that

is well-established

that has high levels of quality control.

Look for three letters, GMP,

which is good manufacturing practices.

And so that means they make

it under a certain level

of quality control.

You're not going to find

iron filings in there

and it probably has the stuff

in it that they say it does.

But so that's all I can say right now.

I'm working on something that's

going to be much more helpful,

but overall, make sure it's

white, crystalline NMN,

and that to me, it tastes

like burnt popcorn.

- You crack open the capsules,

and you'll take a little sample

to make sure it tastes like burnt popcorn.

- Well, when I'm making

my capsules, I'll taste it

and I do a lot of quality

control on the stuff that I take.

- Do you take that gram all at once

with the resveratrol

or do you take it spread

throughout the day?

- It's all in the

morning for those things.

So if I take Metformin, it's NMN

and the resveratrol altogether.

And there's a good reason for that.

It's all scientific, I try to be.

The levels of NAD go up in the morning

in our bodies naturally.

Our bodies actually have a

cycle of NAD, it's not steady.

- It's Arcadian?

- It's Acadian.

In fact, NAD controls your clock.

This was shown by Shin Imai and colleagues

in this nice science

paper about a decade ago,

that if you disrupt the NAD cycle,

which is controlled by the

sirtuin gene that we worked on,

that is what's telling your

body, oh, it's time to eat,

it's time to go to sleep.

And if you take these, the NMN

late at night, for example,

you can disrupt your circadian rhythms.

- Interesting.

- Conversely, when I travel

and I want to reset my clock

to the time zone, I will take

a boost of NMN in the morning

and I feel great.

- Does this protocol for you,

does it produce any immediate effects

of increased energy, et cetera?

You mentioned that one would,

if it's right for them,

would have to take it

for at least two weeks

to start to see the NAD levels increase.

At that point, when NAD levels increase,

could one possibly expect an increase

in overall energy, focus, et cetera?

I realize we're not making promises here,

but I'm just wondering whether

or not the only measure

of whether or not this protocol is working

is whether or not you die at

age blank or blank plus 20.

And of course, once you're dead,

you can't really know if

you would've lived longer

if you'd done something

differently and vice versa.

- Sure, well, there was a

study again by Shin Imai

my good friend at Washington

University in St. Louis

that showed that improves,

remember this insulin sensitivity,

which is a good thing.

But you can't know your

insulin sensitivity

unless you're measuring glucose,

have a glucose monitor on your arm.

- Do you have one on right now?

- No, no, I used to, I learned a lot.

- Yeah, last time I

saw you had this thing,

it looks like a small leach,

not a large leach and it was

measuring your blood glucose.

- They're very informative

because you learn

what your body reacts to

and grapes were really bad.

Rhonda Patrick agrees with

that, but the issue was,

was what, where were we, Andrew?

- The issue is whether

or not you can expect

any immediate effects on

energy, vitality, focus,

just even subject.

- So what do you feel, is the question.

And anecdotally,

'cause I've been taking

this for a long time,

if I don't take it, I

start to feel 50 years old,

it's horrible.

I can't think straight.

It may be placebo, but who knows?

But what we're doing now are

very careful clinical trials.

We've done the safety for two years,

and we're now treating elderly patients

at Harvard Medical School with

some wonderful colleagues.

And those people are actually going

to be an currently in MRIs.

So you can measure the

energetics and the NAD levels

in their legs as they

exercise in real time.

And that will tell us if

what we see in the mice

is increased endurance actually works.

In the meantime, it's fun

to talk about anecdotes.

I have a number of athlete friends,

some of which have increased their load,

their time in marathons, for example.

There's a good friend

of ours in our circle

that is winning marathons at age 50 now.

And he attributes that to

the protocol that he's on.

- Interesting, I haven't

started taking NMN,

but I'm planning to do that

when my next birthday arrives,

which is in a couple months.

But I do experiments on my

sister and have for years,

I have a sister who's three

years older than I am,

who is very enthusiastic

about these protocols.

And I'll tell you that

after reading your book,

I started purchasing

for her and giving her

an NMN supplement and she

claims and I believe her.

She has a quite sensitive system

and she's very tuned into it.

She feels far and away

better when she takes it,

as opposed to when she doesn't

and I've done the control

experiment of removing her supply,

and then giving it back to

her in this kind of thing.

So that's my other laboratory.

This is what younger brothers

do to their older sisters.

01:09:10 Are Artificial Sweeteners Bad for Us?

I have a question about something

that if it has no relevance,

we can just treat it as a speed

bump and then move right on.

And the artificial sweeteners,

these things that we

should say non-glucose,

increasing sweetener.

So you've got Stevia,

which is a plant basically.

And then you've got

sucralose and aspartame

and all these things.

There is some evidence that

I know we're both aware of,

they've been publishing

quite reputable journals,

showing that they can

disrupt the gut microbiome

in certain cases in particular saccharin,

the one that basically

nobody uses anymore.

And it's questionable as

to whether or not Stevia

has the same negative effects, et cetera.

That's not what this is about,

but in terms of the sensation of,

or the perception of sweet taste,

is that itself a possible detriment

to these pro-longevity,

forgive me for using the term,

the pathways.

If I were to drink a

diet coke during a fast,

am I somehow disrupting this?

And I'm asking this question,

because I get asked this question a lot.

- Well, there may be small effects.

I don't think they're

worth worrying about.

Joe Rogan laughed at me 'cause

I was drinking a diet coke

during the first

interview I did with them.

I will drink diet coke, I've

read the scientific literature.

And again, it's this 5% thing

that I think is blowing out of proportion.

If I was to put a number

on it, I would say,

if eating a high sugary meal

or drinking a sugar-filled soda,

what is that, 30 grams of sugar?

Let's say that's a 10

out of 10 bad for you.

A diet coke might be a one.

And if I'm, which am I going to do?

I could have a 10 or a one

or go without in my life.

I'll do the one on occasion.

I try to avoid them because I

don't like the ones as much.

But you can't say that sucralose

is equivalent to drinking a sugary soda.

There's just no comparison.

And I think suc, what is it?

Stevia, I do use Stevia whenever I can,

because it's a naturally sourced product.

And I haven't seen any good evidence yet

that it's bad for you.

But I think a lot of this is overblown,

and a lot of it's the media trying

to give equal weight to stories

as you know as a scientist.

It can be frustrating

when something's a 10

and something's a one,

and they're equated.

- How do I say this respectfully?

I think if science

journalists were required

to post their credentials

alongside their name, [chuckles]

then people would take the articles into,

with additional grain of salt, right?

I mean, in other words,

that I think that the science media

is mainly generated

around two specific goals.

One is to make people very, very afraid

or get people very, very excited,

and oftentimes the get people excited part

is sponsored content,

and I think that's overlooked in any case.

Thank you for that.

01:12:04 Iron Load & Aging

I want to talk about iron and iron load.

We were talking earlier about ferritin.

And of course, women menstruate.

And so their iron needs

are greater than people,

men that don't menstruate

or women that don't menstruate.

I don't think we can get right down

into how much iron somebody needs

because it'll vary person to person.

But I was surprised to learn that iron

is actually going to accelerate

the aging process in various contexts.

- Well, this is a new

finding out of Spain.

Manuel Serrano's lab has

found that excess iron

will increase the number of

senescent cells in the body.

And senescent cells are these zombie cells

that accumulate as you get

older and they sit there

and they cause inflammation mainly

and also can cause cancer.

And it's found that if

you get rid of these cells

or never accumulate

them, you stay younger.

In animals, and there's some

really interesting studies

out of Mayo Clinic in humans as well.

So iron is a pro-senescent metal.

And so what I think

is that if you're taking

excess iron as a supplement,

you're probably accelerating

your aging process.

The other thing that I

found really interesting

is I've looked at hundreds of thousands

of people's metabolism and

their blood biomarkers.

I was one of the first people

in InsideTracker as a board member,

and I'm still their scientific lead guy.

So I can look anonymously

at hundreds of thousands

of people's blood work.

And we also know how fit

they are, how old they are.

Some of them are marathon runners,

some of them are CrossFit.

And there's a signature of health

that actually is different

than your average person.

Now, I'm not going to

say bad things about MDs

'cause a lot of my best friends are MDs

and I work with them at

Harvard Medical School.

The issue though, is

that with MD training,

there's a scale of what's normal,

and if you're out of that normal range,

something must be wrong,

that's the paradigm that they work under.

But first of all, everybody's different,

and you want to know their baseline

and track people over years to

know what's normal for them.

And what I find for example,

is people who are really

healthy and live the way I do

and have a diet that's fairly

vegetarian, but not strict,

still have slightly low hemoglobin levels,

slightly low iron, slightly low ferritin,

but we have super amounts

of energy, we're not anemic.

And we're getting along great in life.

But a doctor who just

looks at that might say,

oh, we need to give you more iron.

All right, so what I'm

getting at is an example of,

we need to personalize medicine

and look at people over the long run

to know what works for them

and what's healthy for them,

and not just work towards

the average human,

but work towards what's optimal for human.

- I love that answer.

01:15:05 Blood Work Analysis

You mentioned tracking

and tracking over time.

And this is a really interesting area

that I know you have been

focused on for a long time.

I've been getting blood worked

on about every six months

frankly, since I was in college.

I just got, I like data

and I got interested in

supplementation and exercise

'cause it made me feel better,

but I also want to know what

was going on under the hood.

So you get numbers back, you

get this hormone, that hormone,

this blood glucose measure, et cetera.

How do you make sense of the data?

I mean, what InsideTracker is doing aside,

how do you personally

make sense of the data

in ways that might differ from the way

that a standard MD might

look at one of these charts?

Because the standard practice is to say,

is it red, yellow, or green, right?

Is it basically too high or too low?

Is it somewhere close to

the margins or are you okay?

Are you in these ranges?

Are there any things

that you pay attention to

that you think are

particularly interesting

for people to just take note of?

I mean, we're not asking you

to go against anybody's physician.

But what sorts of things

should people start

to educate themselves about

in terms of what these

molecules are on their charts

if they choose to get them,

and what do you look at?

- Yeah, well, there's a lot there.

The first is that you

should be tracking things,

because one measurement isn't enough.

These things vary and over time.

And if you can have a

decade or more of data,

it's super important, informative,

as you know, well know, as you know.

So the physician, interestingly,

my physician, let's

take him as an example.

So he sees me, he says,

"How are you feeling?"

"I'm feeling great."

"Okay, see you next

year," that's craziness.

Anyway, so I say, okay, stop.

Let's talk a little bit about.

- Let me educate you, that's

what David tells his physician.

I imagine that the

12-year-old David Sinclair

says to a physician,

"Listen, let's have a

different discussion."

Is that how it works?

- It is.

He finds me pretty annoying

as does my dentist.

But so I say, so hang

on, I've got this data.

I've got the InsideTracker data.

So I pull that up on the screen,

and I'm showing him the

changes in my cholesterol

and my CRP, which is

inflammatory marker as you know.

And we're going through it,

and you can see things change over time,

and I've corrected them

as they go slightly out of

the optimal range for me,

which is different than

what he would do, of course.

But what was funny is that he says,

this is great, I love this data.

But I'm not allowed to get

this because of course,

the insurance companies won't pay for it.

So again, you can pay out of pocket.

It's not super expensive.

I would say, if you save a

bit of money on a coffee,

you can afford this kind of stuff.

But the main point is that

doctors do like this data.

It's just that they're

unable to spend the money

on every one of their patients to get it.

- Is there a code word

that someone can use with their physician

that will trigger a

comprehensive blood test?

I keep trying to figure

out what's the code

that one needs to ask

or tell their doctor,

I'm feeling blank so that

they get a full blood panel.

- Well.

- Do you have to be hemorrhaging

from the gut or something?

- Well, I usually use the WTH method,

which is what the hell?

And then he says, "Okay, we'll do it."

- 'Cause I think a lot of

people out there are thinking,

look, I'd love to have blood

work repeatedly over time,

but that's hard to get

for financial reasons,

but also a lot of people

just don't know how

to approach the conversation.

And this is one of the things

that I hope that we can educate people on,

that they deserve to know what's

going on inside their body,

and that it makes a

doctor's visit worthwhile,

and that you don't have to

feign illness in order to do it.

- Right, yeah, and a lot of people do.

So I would say, if you

can't afford these tests,

there are increasing number of companies

that offer these tests,

InsideTracker is one of them.

And you just do it a couple

of times a year at a minimum.

And then you can share

that with your doctor.

If you can't afford that, then

I would say to your doctor,

here are the main ones

that Andrew and David do.

- Yep, and we must.

And there's an email

that is something like 555,

or a phone number, rather, it's 555-5555.

I think if they have any complaints,

they can just call that number.

David will pick up on the

east coast business hours

and I'll pick up outside of those hours.

- But there was the

main ones, I would say.

Your blood sugar levels,

you want to do your HbA1c,

which is your average glucose

levels over the month.

There's CRP, which I

mentioned for inflammation.

01:19:37 C-Reactive Protein, Cholesterol: Serum & Dietary

- Yeah, let's talk about

C-reactive protein for a second.

'Cause I think it's been shown

to be an early marker

of macular degeneration

of heart disease, of a

variety of different things.

CRP is something

that we don't hear enough about, I think.

Maybe, what do you know

about CRP that I don't,

I'm guessing a lot, but.

- Oh, it was originally picked up

as something that was

associated with heart disease

in the Framingham study, I believe.

It is the best marker for

cardiovascular inflammation

and is also, we use it as

a predictor of longevity,

and its levels go up with mortality.

And so this is an association,

but there's enough data that I would say,

if you have high levels of CRP,

you need to get your levels down quickly.

And the levels usually go up with age

and with levels of inflammation.

So the ways to get it down

would be to switch the diet,

eat less, try to eat more vegetables.

You'll find it will come down,

and there are also drugs that can do it.

Anti-inflammatories can do it as well.

But CRP is, it's actually, hCRP,

there's a high sensitive

hCRP, your doctor will know.

Get one of those readings.

'Cause if you've got

normal blood sugar levels,

your doctor, or fasting

blood sugar levels,

your doctor might say you're fine.

But a lot of people

have normal blood sugar,

but have high CRP, which is

just as bad for you longterm,

and can predict a future heart attack.

- On the lines of heart attack.

I want your thoughts on cholesterol

and serum cholesterol

and dietary cholesterol.

I cannot, for the life of me,

get my arms around this literature.

And even if I ignore all

the essentially nonsense

that's out there in various

social media groups,

as saying cholesterol is the

worst thing in the world,

or cholesterol is not,

or dietary cholesterol has nothing to do

with serum cholesterol and

nothing to do with longevity.

I can't seem to sort

through the very basic data

that essentially ask,

is having high levels of LDL

going to kill me earlier?

Should I be striving to always

reduce LDL and increase HDL?

Is that a reasonable goal?

And if so,

is dietary cholesterol the

primary determinant of that?

And just as a final point about this,

I am aware of quite good data

that shows that anorexics,

people that essentially eat no food,

unless you force them to,

can often have very high LDL.

So their dietary cholesterol

is essentially zero,

and so they're manufacturing

a lot of their own.

So realize this isn't your

primary area of expertise,

but you're a smart guy

and you think about this

kind of stuff a lot.

What do you think is going on

with the cholesterol literature?

And will we ever get to the bottom of this

as a scientific and medical community?

Because to me, it is rather perplexing.

- It is, but you can get

through the politics.

I know a fair bit about cholesterol

'cause it's in my family history.

And I was headed for an early death,

my grandmother had a stroke 30,

that's how bad I am in

terms of my genetics.

So I went on a statin, and I

know there's a lot of people

who say that statins long-term are bad.

It's associated with Alzheimer's disease.

I've been taking a statins since I was 29.

And that's 'cause I forced my same doctor

to give me the statin,

the conversation was something like this.

You're too young to be on a statin.

And I said, what?

You want me to have a heart attack

before you give me

something, give it to me now.

So 29, I'd been on a satin,

and my cholesterol was

way up in beyond 300,

which is a massive mess up.

Basically my blood was creamy to look at.

So I've now got my cholesterol down

to low, low levels to what would it be.

You can check on my InsideTracker,

but so my ratio of HDL to LDL,

which you want to be less

than five, is now two,

and the LDL is below a

hundred, so it's all good.

And I've measured my

cardiovascular health with an MRI.

I've got a movie of my heart beating.

I've still got a heart of a

20-year old, so that's working,

I'm willing to forgo the risk

that the statin is causing problems later

because of my family history.

But other people, I would say,

be aware that statins

aren't perfect drugs.

There were some interesting new ones.

There's one called the PCSK9 inhibitor,

which is, I think fortnightly,

every two weeks injection,

that blocks the release

of LDL from the liver.

And then that seems to be

great for lowering cholesterol,

but also has other benefits

that might be prolongevity.

And there were some people

that I was just talking to

on the cutting edge of this,

and their doctors are

trying them on this drug

instead of the statin.

So you could talk to your doctor about.

- Do you avoid dietary

cholesterol for that reason also?

Red meat, butter.

I mean, I have been to love butter.

I love red meat.

I realized there's some people who don't.

My cholesterol is a little bit high,

but I'm working to bring that down a bit,

although not by altering

my food intake yet.

But what do you think is the relationship

between dietary cholesterol

and serum cholesterol,

and what's going on with the liver?

Why are anorexics?

Why is there a certain cholesterol so high

when they're eating nothing?

- Well, there've been in a

number of papers over the years

that have been ignored.

And our friend, Peter Attia,

brought to my attention recently,

a new study that I think definitively said

that dietary cholesterol

has almost zero impact

on blood cholesterol levels.

- Good.

- Yeah, so I'm annoyed

'cause I'd been avoiding eggs

and butter for most of my

life and I didn't have to.

So I have eggs-

- Plenty of time, or

at least in your case.

- Yeah, yeah.

So that's the thing.

You can eat these foods

that were ones banned

because it's very difficult

to take cholesterol up

into the body from the gut.

And most of it's being

synthesized in the body.

- Well, I'm just pausing

there for a second

because I think that it's

what we've been told.

Six meals a day, eat a

lot of grains and fruits

and this kind of thing, avoid cholesterol.

I mean, basically everything we learned

in the '80s and '90s and early 2000s

is getting flipped on its head now.

01:26:02 Amino Acids, Plants, Antioxidants

But, and I think this

is a very strong caveat

that's important to mention, amino acids.

In particular, the amino acids

that come from animal products, right?

Seem to have some pro aging

effect on them, right?

At least the way that I've

heard you describe your diet.

And I'm somebody who

enjoys meat, I like it.

But so I'm by no means, a vegan at all.

But I've heard you say

you eat mostly plants,

but a little bit of fish

or chicken or something

of that sort of eggs or.

But is that specifically

to avoid excessive amino acid intake?

Or is it something specific about plants

that excites you with

respect to? [chuckles]

I mean, vegetables are

delicious too, but what is it?

Is it something great about plants

or is it something bad

about when I think of meat,

I guess the biologist in me

thinks amino acids, right?

I don't think top sirloin,

I think amino acids.

And I think top sirloin as I'm eating it,

but really what they are, are amino acids,

including leucine.

- Yeah, well, there are two

good things about plants,

and neither of them is taste for me.

I would eat steak all the time if I could.

I did when I was a kid, I'm an Australian.

But plants have two benefits.

One is that they're highly nutritious,

and they'll give you a lot of the vitamins

and nutrients that I need.

I don't take multivitamin,

I don't want to have the

excess iron in my body.

So there's that high density nutrition.

So those dark leaves, if

it's a spinach salad, great.

The second is that there

is what's called xenohormetic

molecules in plants.

That term, xenohormesis is a term

that I came up with

with my friend, Conrad.

How it's, which means

stressed plants make molecules

that benefit your health.

I'll break it down.

Xeno means between species,

and hormesis is the term,

whatever doesn't kill

you makes you stronger

and live longer.

And the idea is that when

plants are stressed out,

think of a great vine that's dried out

and then starting to harvest the grapes,

which is typically how it's done.

They are full with resveratrol,

because resveratrol is

a plant defense molecule

that I think is made

to activate those

sirtuin genes in a plant.

So plants have sirtuins just like we do.

But by purifying or at least concentrating

in a light-proof bottle and

keeping it out of the air,

we stabilize the xenohormetic molecule,

or it's a cocktail, not just

one, there's others in wine.

We then ingest those and get the benefits

of activating our own defenses,

because our food was getting stressed out.

And by stressed, I don't mean

psychologically stressed.

I mean, biologically stressed.

And so I try to eat plants

that have gone through a bit of stress.

They might be brightly colored,

they've had too much sun

or got nibbled on by a caterpillar.

So you go to places where it's

organic or it's fresh, local,

and those are the plants

that aren't perfect,

and they probably have high concentrations

of these molecules.

And in addition, I also

buy the supplements

to make sure I'm getting

enough of those as well.

- Which supplements mimic that?

- So resveratrol will,

there's another one called quercetin,

or quercetin, some people call it,

what you find in trace

amounts in apples and onions.

And we also showed back in 2003

that it activates sirtuins as well.

But others have, 20 years later,

found that it kills senescent cells

or helps kill senescent cells.

So it's a double whammy

with that molecule.

- And are you actively

picking out the peaches

that look like they were

nibbled on by a caterpillar?

- No, but I don't worry if

they've been banged up a bit.

- What's the story with antioxidants?

Are they of any value whatsoever,

because the way that you

describe them at the beginning,

and what I've heard recently

is that they are not all

the rage for anti-aging.

What are they doing that's useful?

Should we be seeking

out antioxidants anyway

for other seller health purposes?

- Well, yeah, antioxidants

are not going to hurt you

unless you take mega doses.

We do need some oxidants

for our immune system.

And there's even, what's

called mitohormesis,

which is your mitochondria power packs,

need to have a little bit

of these free radicals

to be able to function.

So you don't want to overdose

on these antioxidants,

vitamin C, vitamin E, don't overdo it.

- You don't take a multivitamin, correct?

- Right.

- I think I'm going to stop

after this conversation

'cause I've always just taken one

for the kind of insurance purpose,

which is a stupid purpose.

Not actual insurance, but just thinking,

oh cap top off on my ACBD.

- Right, and I'll pee out what

I don't need, right, sure.

- But that never bothered me.

The whole expensive pee thing never got.

That argument never got

made because of that.

A good vitamin is not that expensive.

I just figured better safe than sorry,

but it may be that it's detrimental.

- Well, it can in the case of iron

as we discussed and the antioxidants.

So when I came into the aging

field in the early 1990s,

it was all about antioxidants.

And we thought that enzymes

by the name of catalyze

and superoxide dismutase, well,

they're going to be the key to longevity.

It turns out that it's

largely been a failure

that giving animals and

humans antioxidants,

haven't had the longevity

benefits that we dreamed of.

And the main reason is that

there's a lot more going on

than just free radical damage.

The epigenome gets disrupted,

we've got these proteins misfolding.

And so the problem really has

been that we didn't realize

that you need to turn on

the body's natural defenses against that

plus a whole host of other

things to get the true benefits.

But I'm not going to say

it's a problem taking it,

an antioxidant drink,

pomegranate juice for one

is full of good stuff,

including xenohormetic molecules.

But resveratrol is a good case in point,

which is when I worked on resveratrol

as a longevity molecule,

first we showed it in yeast

and worms and flies and mice.

Before that, it was

thought that resveratrol

was good for your heart in red

wine when you drink red wine,

because it's an antioxidant.

So then we showed that

it extended the lifespan

of yeast cells through this

genetic pathway, the sirtuins.

And we then tested whether resveratrol,

if we change one atom

to make it not an antioxidant, guess what?

It still worked fine.

So it wasn't its anti-oxidant activity

that was extending lifespan.

It was its ability to turn on

the yeast's defenses against aging.

Conversely, when we gave

the yeast antioxidants,

they lived shorter.

So yeah, that was the

beginning of my transformation

into thinking turn on the body's defenses,

don't give it the antioxidants.

- This is an opportunity

for me to say something

that I've been wanting

to say for a long time,

which is that, what's so

wonderful about science

is that because the goal is mechanism,

you can really start to understand

as you just described, what

actually mediates a process

is very different than

what modulates a process.

I mean, if a fire alarm goes

off in the building right now,

it's going to modulate our attention.

That doesn't mean that it

controls our attention,

it's not mechanistically relevant.

And so I think this

thing about antioxidants

is one of these cases,

it sounds like where it's

in the right ballpark,

but until one really unveils

the mechanism as you have,

you can be, one can or in a field,

can be badly wrong for a

very long period of time.

It sounds like the sirtuins

and really getting down to

the guts of the machinery

of what causes cells to age

is really what it's about.

01:33:45 Behaviors That Extend Lifespan, Testosterone, Estrogen

Zooming way out, what

are the behavioral tools

that one can start to think about

in terms of ways to modulate these?

Basically the way that DNA

is being expressed and functioning.

I've heard you talk before

about hormesis of other

sorts, cold exposure.

We talked about fasting.

We talked about exercise in broad terms,

but what about any evidence, if it exists,

as to whether or not aerobic training

versus weight training,

these sorts of things.

In other words, what

are the sorts of things

that people can do to improve

their sirtuin pathway?

And I realized that there are caveats.

We can't go directly from

a behavior dissertations,

but in the general theme,

what can people do, what do you do?

- Right, well, we know

that that aerobic exercise

in mice and rats raises their NAD levels

and their levels of sirt,

one of the genes goes up

two actually, number one and number three.

What we don't know yet

is what type of exercise

is optimal to get them to change.

We will learn, we're doing work.

Now it's revealed that we're doing work

with the military in the US,

to try and understand that kind of thing.

And I'll always tell you and the public,

when I don't know something

I'm not going to extrapolate.

But what do I do?

I base my exercise on the

scientific literature,

which has shown that

maintaining muscle mass

is very important for a number of reasons.

The two main ones are,

you want to maintain your hormone levels.

I'm an older male,

losing my testosterone

and muscle mass over time.

And by exercising, I will

maintain that and have,

in fact, I probably haven't

had a body like this

since I was 20.

So that's one of the benefits

of having this lifestyle.

- Sorry to interrupt you.

You do know we did an episode on hormones

and there are data in humans

that show that there are some

males in their '80s and '90s

where their testosterone is equivalent

to the average of 25 and 30-year-olds.

I can get you that information,

is really impressive studies.

Unfortunately, they didn't

include a lot of information

about the lifestyle factors, et cetera.

But this idea that testosterone

goes down with age,

it might be the trend,

but it's not necessarily a prerequisite.

- Right, I believe in naturally increasing

and maintaining these hormone levels

and I've been measuring

them for a long time.

And I could see for me,

my testosterone levels

were steadily, levels were going down.

- And then you got tenure

and they went back up again.

[both chuckle]

- No, I actually became complacent.

And it was the worst.

Actually my age changed in the

wrong direction after that,

'cause I was relaxed.

- Interesting.

- And not worried about the future.

But then I got serious.

And I actually, according to

the InsideTracker algorithm,

got my age down from 58 to

31 in a matter of months.

So that was a big drop.

And I've been getting steadily younger

over the last 10 years,

according to that

measurement, the blood test.

- What about estrogen?

Because women are different in the sense

that they do the number of eggs that they,

and the ovaries change over time, right?

Do you think that they can

maintain estrogen levels

in over longer periods of time

using some of these same protocols?

- Well, yeah, I get into trouble

from a certain university

when I talk about this too much.

- About estrogen?

- Just about fertility and long story.

I don't want to get too

much into the anecdotes,

but I'll tell you the science,

which is that if you take a

mouse and put it on fasting

or caloric restriction

for up until the point

where it should be in fertile,

so that's about at a year of age,

a mouse gets infertile, female mouse.

- Due to fasting or

due to simply to aging?

- Due to aging, due to aging.

The fasting, it's not extreme fast,

it's just less calories.

Then you put them back on a regular food,

and they become fertile again

for many, many months afterwards.

So the effect on slowing down aging

is also on the reproductive system.

- Interesting.

- And so that, I wouldn't

say to any woman,

I wouldn't think that they

should become super skinny

to try and preserve fertility,

that's not what I'm saying.

But these pathways that we work on these,

sirtuins are known to delay

infertility in female animals.

Case in point, I'm one of the lead authors

on a paper where we used NMN.

Remember, this is the gas, the fuel,

the petrol for the sirtuins.

We gave old mice.

One group of mice was 16 months old.

Remember they became infertile

at 12, gave them NMN.

And I think it was only six weeks later,

they had offspring.

They became fertile again,

which goes against biology,

the textbook biology,

which is that female

mammals run out of eggs.

Turns out that's not true.

You can rejuvenate the

female reproductive system,

and even get them to

come out of mouseopause

as we call it.

So that's a whole new

paradigm in biology as well.

- That's super interesting.

Sorry to interrupt you,

but I'm reminded by a set of studies

that were done by your former colleagues

'cause they're no longer there,

David Hubel and Torsten Wiesel,

my scientific great grandparents.

Won the Nobel prize for discovering,

what are called critical periods,

this phase of early development

when the brain is extremely plastic.

And a big part of their work

was to show that after a certain point,

the critical period shuts down,

essentially the brain can't

change or not nearly as much.

And then people came

along later and showed

that you could open up these

critical periods again,

but very briefly,

and it takes a very specific

stimulus, essentially,

high degrees of focus, et cetera.

However, there's a well-known

phenomenon in this literature

where if you take an

animal and to some degree,

this has been shown in humans as well,

and you let them pass

through the critical period,

but then you essentially

sensory deprive them.

You take away experience,

you close both eyes.

You essentially reopen

the critical period.

So it seems like I couldn't

help but mention this,

that there's this parallel

between what we're talking

about here with fertility

and neuroplasticity, where yes,

there is a timer where

certain things are available

to the organism early in life,

and then they tend to taper off.

It's not an open and

shut, but they taper off.

But then a deprivation

can actually reactivate

the availability of that process.

Forgive me, I just couldn't

help him mention it,

but to me,

so both of those things

are associated with youth,

fertility and neuroplasticity.

And so I think that

it'd be so interesting.

01:40:35 Neuroplasticity & Neural Repair

I'd love to collaborate with you on this

to explore how neuroplasticity

might actually be regulated

by these things like the sirtuins.

- Right, and the sirtuins

do control memory

in neurons as well.

So what I think is really interesting

is that what we're learning from work

that you and your colleagues have done

and in my lab as well,

is that the body has

remarkable powers of healing

and recovering from illness and injury.

And what we once thought

was a one-way street

and you just can't repair,

or you can't get over these diseases,

you can reset the system,

and the body can really get rejuvenated

in ways that in the future will wonder,

why didn't we work on this earlier?

The future of humanity

is more like us walking

around like Deadpool.

We'll probably be cleaner,

and we won't smell as badly,

but Deadpool, if you don't know,

can get injured and just recover.

It's very hard to injure this guy,

and we're going to be the same.

There are many species

you cut off the limb,

the limb grows back.

- Salamanders or.

- Yeah.

We are now learning how

to tap into that system.

And in part, what we're doing

is reversing the age of those cells,

and telling them how to read

the genes correctly again,

reversing the age of that epigenome.

And when you do that, the cells,

the brain, for instance, the skin.

We did the optic nerve.

- Let's talk about those

results for a second.

Then I want to make sure that we return

to some of these behavioral protocols.

You have this amazing paper

at the end of last year,

cover article, full article in nature,

showing that essentially a small menu

of transcription factors,

which control gene expression, et cetera,

could essentially reverse

the age of neurons in the eye

and rescue those cells against damage.

Essentially allow blind mice to see again,

and offset degeneration

of these retinal cells,

incredible paper, and

such a boom to the field.

Where does that stand now in

terms of human clinical trials?

I mean, how do, what are you envisioning

in terms of the trajectory of those data

from mice into human someday?

- Right, well, to get to

the point immediately,

we're going to be testing

the treatment on monkeys,

just for safety reasons.

And then the first patient

should be done sometime in 2022,

early 2023, and we're going

to try to recover blindness.

- This involves making an injection

of a virus into the eye, right?

Right now, there's no

way that I am aware of

to manipulate these transcription factors

through a pill or some other?

- And that's why, we working on in my lab

at Harvard right now.

So it will be-

- It will base moderation of-

- Well you pop a pill in the whole body

gets rejuvenated by 20 years.

That's what we're aiming for.

Now we do it with gene therapy

in the eye and other places.

So in the IES, it's single injection,

the genes go into the retina

and we can turn it on,

with a drug called doxycycline.

And we do that in the mice

for four to eight weeks,

then the eye gets younger.

We can measure that' cause

you can measure the clock.

And then the vision

comes back in those mice.

And I don't see any reason,

why it shouldn't work in people

because it's the same structures

and mechanisms that are

on in the human as well.

Now these-

- And it's one injection.

- It's one.

- I should mention injections into the eye

obviously nobody should do this

outside of a ophthalmology clinic.

And there definitely by

an ophthalmologist but,

the injections into the eye

are painless if done correctly

by the right person.

It sounds dreadful, but it's actually,

I've seen it done hundreds of times.

I've done it, thousands of times

and it's not to myself,

but to other creatures.

And there's a way of doing this

as completely painless to the person-

- Oh you don't feel it.

It's a tiny, tiny needle too.

But the great thing about this is that

it's a one-time treatment.

Those genes go into the back

of the eye and stay there,

forever.

And you can just turn

them on whenever you want.

So what we found is you can

turn them on in the mice,

they get their vision back,

and then you turn it off again.

And so far, many months out,

the benefit has remained,

but if it does decline,

we'll just turn it back

on and reset the system,

rinse and repeat.

So one day what's exciting is that

we could potentially do

this across the entire body

and just take this antibiotic,

every five years and go

back time and time again.

- And thinking about the body

and what's going on under

the head I'm amazed,

still that there isn't a

simple, affordable technology

that would allow me to just

look into my body and see

whether or not there are

any tumors growing anywhere.

I mean, it's not that hard

to look into the body.

I mean that the technology exists.

why hasn't anybody created an at home

or pseudo at home solution,

like a clinic where you can go

and pay 50 bucks or a hundred bucks

and see if you have any

tumors growing anymore.

- Yeah, it's still expensive.

You can get your doctor

to try to get you in,

there's some companies

that offer blood tests

that look at circulating DNA,

that'll measure it.

We're getting there.

It's still probably five to 10 years away

from being really cheap.

You can do things like a

colon cancer test at home.

I think it's a hundred

and something dollars.

You ship off your shit,

excuse my language,

and they measure it.

And they tell you if

you've got colon cancer,

with high probability,

I did that during the pandemic

because I didn't want

to get a colonoscopy.

- Mhmh, is it more accurate or

as accurate as a colonoscopy?

- I believe it's close

to being as accurate.

The downside is that during a colonoscopy,

they can pinch off the polyps

that are looking dangerous,

whereas this obviously isn't that,

but it's certainly easier to do.

And my father who's

Australian tells me that

it's free for Australians.

They get this test routinely.

- Mhmh, interesting.

01:46:19 Ice Baths, Cold Showers, “Metabolic Winter”

I want to return to the topic

that I took us away from.

So I apologize, which

is behavioral protocols.

Do you regularly do the cold shower thing?

Ice baths, cold water swims,

are you into that whole biz?

[David chuckles]

- Well, you do know that

I've done it at least once

'cause we did it together.

- That's right.

Not the same bath, just to be very clear,

same sauna, different ice baths,

[David chuckles]

the idea of Sinclair

and Huberman taking an

ice bath together it's a,

it might warm some people's hearts,

but just to be very clear, different,

same ice bath, different, different times.

- Yeah, thank you for clarifying.

- [Andrew] Yeah.

I don't do them regularly.

I do try to sleep cool.

I sleep better anyway.

I try to dress without

a lot of warm clothes.

I'm here in a T-shirt and

it's middle of summer,

but in winter, I'll try

to wear a T-shirt too.

- So you're challenging your

system to thermoregulate?

- Right, right.

I've got this,

hypothesis with Ray Cronise.

We published what's called The

Metabolic Winter Hypothesis,

which is, few tens of

thousands of years ago,

we were either hungry or cold or both

and we really experience that now.

And so, we try to give

ourselves the metabolic winter

and part of the problem I

think with the obesity epidemic

is that we're never cold and cold,

when you're cold you have to burn energy.

It may be only slightly,

but over the whole night,

if you're a little bit cool,

you'll actually expend more energy.

So I try to do that,

but I'm not a big fan of cold showers.

The sauna, I don't have access

to my gym as much as I did.

So, but I do want to get back into it.

I used to do it regularly with my son

and I posted on Instagram once

that he could stay in there for 15 minutes

and I could only stay in for about three.

Anyway, long story short,

I try to compensate with

changes in my diet and exercise

until I get back into it.

01:48:07 Obesity & How It Accelerates Aging, GnRH

- You reminded me of something

that I meant to ask earlier

that obesity reduces NAD

levels and accelerates aging.

How?

I mean, okay.

So again, this is the,

the scientist in the us,

so someone's carrying a lot

of excess adipose tissues,

subcutaneous and,

visceral fat.

But why should that reduce NAD in any ways

that are independent of

effects on glucose and insulin?

If it, you know,

is there's something direct

about white adipose tissue.

And the reason I ask this,

is not simply to dig into mechanism alone,

but I think there are

really interesting data now

that fat actually gets neural innervation.

I mean,

it's not just a,

it's not just stored fuel.

It's stored fuel,

that's acting as an

endocrine organ, essentially.

So,

why would being fat

make people age faster?

- Yeah, that's a question that,

is so obvious, but so few people ask it,

that's what makes you a good scientist.

And so that we don't know,

but I'll give you my best

answer, which is that,

obesity comes along with

a lot of problems that,

include a lot of senescent cells in fat,

if you stain old fat for

senescent cells, it lights up.

- Mhmh.

And when you kill off those cells,

at least in mice, and maybe in humans,

it looks like the fat is

less toxic to the body.

'Cause those senescent cells

in their fat are secreting

these inflammatory molecules

that will accelerate aging as we now know.

We talk about the sirtuins in NAD.

So if we,

if we just look philosophically,

at why this would be the sirtuins only,

like to come on or get

activated when the body needs,

is on the right adversity.

And if a cell is surrounded by

fat or contains a lot of fat,

it's going to think times a good,

it doesn't need to switch on.

So that's the evolutionary argument.

Mechanistically, we don't know,

but it could have something to do with

the response to glucose,

which then responds to the sirtuin gene,

but that hasn't been worked out very well.

- And is there any evidence that leptin,

this hormone from fat can actually,

interact with the sirtuin pathway?

- I don't recall seeing that-

- Maybe I could do a

sabbatical in your lab

and that'd be a fun one.

- Definitely-

- Because leptin during

development is what triggers,

the permission for the hypothalamus

to enter puberty, right?

- Yeah.

- This is why kids that eat

a lot when they're young

and get overweight will also start to go

and undergo puberty more quickly,

although they have

reproductive issues later.

- Well yeah.

We should study the

hypothalamus together 'cause,

the hypothalamus is,

can control the aging of the body.

- The most interesting part of the brain.

[Andrew chuckles]

- For sure.

- Yeah, absolutely.

- If you turn on the SIRT1 gene,

the SIRT2 that we work

on, in the hypothalamus

that actually, will extend lifespan.

Also, it's been shown by Dongsheng Cai

at Albert Einstein College of Medicine,

that if you, inhibit

inflammation in the hypothalamus,

in a mouse, it will increase

or maintain the expression

of what's called GnRH,

which is the hormone that,

he found actually controls

longevity in the mouse in part.

And so keeping inflammation

down in the hypothalamus,

is sufficient to extend

the life span of animals.

And I reviewed that paper for nature

all about seven years ago.

And that was the first demonstration

that the hypothalamus is one

of the leading regulators

of the body's age.

- I find this fascinating GnRH,

for those of you that don't

know actually comes from neurons

in the hypothalamus that then,

literally reached down into the pituitary

and trigger the release of

all the things that control

fertility, luteinizing hormone,

follicle-stimulating hormone, et cetera.

It's such a powerful set of neurons,

and it's never really been clear,

what at a behavioral level

triggers the release of GnRH.

There's all the stories about pheromones

and timers and puberty, et cetera,

but environmental conditions

and dietary conditions

and behaviors that can

control GnRH release, I think,

is an incredible area for exploration.

I'd love to do that sabbatical by the way.

01:52:10 Methylation, Methylene Blue, Cigarettes

I have a couple, well

seemingly random questions,

but I can't help, but ask

because one thing I like to do

is forage the internet for

practices that at least more than

a few people are doing,

and then wonder whether or

not there's any basis for it.

You mentioned methylation

as a detrimental process,

the way it disrupts the

epigenome and the CD reader,

so to speak.

There are people out there who

are ingesting methylene blue.

And when I was a kid,

I used methylene blue

to clean my fish tank.

And I love fish tanks.

I know you're into aquaria also,

a different podcast episode,

we'll talk about aquaria,

but why in the world, would

people ingest methylene blue?

Meaning is their logic correct?

And or is that a dangerous practice?

I'm not sure I'd want to

ingest methylene blue,

sounds not like a bad thing to do.

- It stains your body if you've

seen, yeah methylene blue-

- Yeah, there was someone

in my lab as a postdoc

was using it to study a

completely different process

related to the blood-brain barrier

and used to inject into animals

and they would turn blue,

but then again, people

ingest colloid silver.

You know they'll put

in there, there's this,

please people don't do this

or if you do, just don't tell me,

'cause I won't like it.

They, people put it in their eyes

and some people actually stain their skin.

They actually become kind of

a silver purple brown color

if they do it excessively.

I mean, there's a lot of

crazy stuff out there.

But what do you think they're thinking

with this methylene blue thing

or should we just get them

to a good psychiatrist?

- I don't know, for sure.

I think methylene blue was found

to extend the lifespan

of some lower organism

and that's where it came from.

My recollection-

- With the emphasis on lower organisms.

- Yes smaller organisms.

I think doesn't, do you

remember Andrew does it,

interrupt or interfere

with mitochondrial activity

and that's-

- Maybe that's why the are doing it.

- Yeah.

- [Andrew] Okay.

- We need to look this up and post it.

- [Andrew] Okay.

- We'll get to the bottom

of this, but those methods,

let's talk about those.

- [Andrew] Yeah.

- Those methods have to

be placed on the right,

part of the genome.

They get attached to the right

genes in the wrong genes.

And if you have a lot of methylation,

it's going to mess up the epigenome.

Smoking will do that, lack of

exercise, all that good stuff.

So you, what you actually want

to do is you want to measure it

and make sure what you're

doing with your body,

is working.

How do you know that if you do this

or that is actually helping.

And so you can test your age.

I could take, a swab from your mouth

and tell you how old you are biologically.

And then we could work on

trying to bring that down

and actually there were anecdotes now,

that people are reversing

their age by a decade or more

just by doing some of the

things that we've talked about

and some other cutting edge stuff

that I'm going to write about.

But yet, but you have to measure stuff.

That's, I didn't want to

forget to bring that up.

I'm measuring stuff all the time.

I have blood tests like you,

I've got this monitor that

stuck to my chest right now

that's measuring myself

a thousand times a second

and I measure my biological age.

- What's it measuring a

thousand times a second?

A huge list of things.

- Yeah, yeah.

So this, this little device is stuck here

and it's for two weeks

that you just recharge it

or send it back and get a new one.

It's got a body temperature movement,

heart rate variability.

It's an FDA approved

device, it's not a toy.

It's not one of these recreational things.

It also listens to my voice,

eventually will me if

I need a psychiatrist

or if I'm depressed,

it will tell me how I sleep, obviously.

But when you put all that data together

and it's individualized and anonymized,

it can now tell my doctor in real time,

if I've got a cold that

needs an antibiotic,

or it's just a virus.

If I am suffering from COVID-19

or even if I'm going to have

a heart attack next week.

And so these little devices

are going to be with us

all the time, instead of going

to your doctor once a year,

which is ludicrous.

01:56:17 X-Rays

- I have to ask you about x-rays.

'Cause every time I go through

the scanner at the airport,

I think, "Sinclair would never do this."

And the argument I heard

you give about this before

was a really excellent one, which is that

it's a low level amount of radiation,

going through at the airport,

but the argument is always,

well, it's just as much as on the plane

and your argument, your

counter-argument I should say was,

"Well then why would I

want to do both, right?

Why would?"

So when you go to the airport,

assuming you're not running late

and you have to go

through the standard line,

what do you say to them?

And do you say, "I'm David Sinclair."

And then they shuttle

you to your own line.

What do you say?

You do say, "I don't like this thing."

Do you have to give them a reason?

- No, you don't.

You can say, "I don't want this."

And they'll get annoyed

'cause it's hard for them

to pat you down,

but you get a pat down and you you're done

as long as you're not

in a hurry, it's fine.

If you want to pay for

the TSA Pre in America

or the way to get around those

scanners, you can do that.

So I travel a lot, so

it's worth it anyway,

but I just go through the metal detector,

I don't get scanned.

- And the metal detector

doesn't have the same,

same problem.

And what about x-rays at the dentist?

Yeah.

- Well, you know one x-ray

is not going to kill you.

Two's not going to kill you, but I-

- Three will kill you.

No, I'm just kidding.

[Andrew chuckles]

- I try to limit it

because it's cumulative.

- Right.

- And I went for six years

without having a dental x-ray

and then my last visit, I just gave up.

I was tired of arguing with my dentist.

So they gave me one,

but they've got led coats on

and they put lead all over your body.

That's telling you something right there.

And funnily enough, my

teeth hadn't changed.

Now you can balance that by saying,

"Well, one x-ray, two x-ray,

three x-rays is worth

it if I have cavities."

And that's true,

you want to know what's in there,

but doing it regularly, for me,

I don't think it was worth it because it,

my teeth are in perfect

health and I've always been,

I don't have any cavities,

didn't have braces,

they're fine.

So stop scanning me.

I mean, I know you have

to pay for the machine,

but you know, do I have a choice?

Yes, so stop pressuring me.

- You know, who shared your

sentiments about x-rays

and the dentist in general?

My apologies to the dentists out there,

was the great physicist, Richard Feynman.

This is a story about him that's

not especially well-known,

but he had very serious

concerns, health concerns,

about x-rays because he

understood the physics

and he understood enough biology that,

he was actually quite vocal about his,

dislike of dental

technology and its dangers.

And he talked about some of that.

People can find that on

the internet, if they like.

01:59:00 Public Science Education, Personal Health

Speaking of people who,

are like Feynman,

who've been engaged in public

discourse about science.

One of the things that I

appreciate about you, in fact,

the way that you and I,

initially came to know one

another is through your

public health education efforts.

So, obviously we're doing this podcast,

you've done the Joe Rogan Podcast,

Lex Fridman's Podcast, excuse me Lex,

I'm still adjusting that.

Lex Fridman's Podcast

and many other podcasts,

you've written an amazing book.

What are you thinking these days

in terms of what the

world needs in terms of,

education from scientists,

education from MDs,

education in general as it

relates to these things because,

I think if nothing else

2020 revealed to us that

there's a gap,

there's a gap in understanding.

And that the scientists too are guilty of,

not knowing what to do

with all the information

that's out there on pub med or elsewhere.

I'm just, you know,

what are you thinking for

yourself and in general,

I'd like to just know,

what do you think the world needs there?

Maybe we can recruit some

more public educators.

- Yeah.

Well, we've gone from a

time, when you and I were,

in college and young

professors where the only way,

to get our voice out to

the public was either

through a newspaper or a

very short radio interview,

which for me was extremely

frustrating 'cause particularly

the newspapers and my topic,

every time was twisted into something that

was not just embarrassing,

but Harvard university

used to bring me into the back office and-

- Frankenstein.

- "How did you say such a thing?

We're all going to live to a 250."

I didn't say that.

So, we're now also in a world where

we're overwhelmed with information,

and most of it is wrong

and anyone can pretend to be an expert.

So we've gone from early

days to now the future,

and we're experiencing it right now

thanks to guys like you, people like you,

is that the experts, some experts,

a small number who are

brilliant and good communicators

are talking directly to the public.

This has never been able to be possible,

until this time, right now.

So another five years from

now, and certainly by 10 years,

I would hope that there are

trusted sources of information

of people who can not just

communicate, the ideas directly,

but are able to talk about

things that are going on that

aren't even published yet to say,

"Here's what's really going on.

And this is what the future looks like."

But this is somebody, like yourself

who spent their whole life

studying a particular topic

and knows what they're talking about.

And this,

this is also something

that I think most people

don't know that we

scientists, if we tell a lie,

we burst into flames,

we absolutely cannot tell

something, that's untrue.

And to the best of our

knowledge, we say it as it is,

because if we don't, we're beaten up,

and we, or we kicked

out of the university.

So the people who survive to our age,

and I'm a little older than you.

So I've survived a bit longer.

- But a lot younger inside.

[Andrew chuckles]

- Nah, but we have to measure you with-

- Yeah we need,

I probably need a little

help, hopefully not too much.

- We'll measure that,

and we'll work on your

eating, but this is really,

really important is that,

finally people like your are

allowed by our universities

to talk to the public.

I used to do it,

with a real threat to my survival.

People would look at me,

"Oh, he's a salesman, he's

promoting this and that."

It was seen as a real

negative, but finally,

I think we're in a world where,

it's not negative anymore.

And the pandemic showed that

we needed voices of reason,

voices of fact, that you could trust.

And you can see the

popularity of your podcast,

shows that the public,

they're desperate for

facts that they can trust,

'cause they don't know

what to believe anymore.

- Well,

I'm being completely honest

when I say this, that,

you know, I followed your lead.

I saw you on the Joe Rogan

Podcast and my jaw dropped.

I was like, "This is amazing, like this."

Because,

you get out other good

scientists on before but,

you're tenure Professor Harvard Genetics,

Department of Genetics.

And for those of you don't know,

there's the Harvard and of

course, Harvard Medical School

and they're both excellent, of course,

but these are the top,

top tiers of academia.

And I certainly understand

what it takes to get there

and survive there and to thrive there,

it's like a game of pinball.

You never win.

You just, you just get to,

if you're doing really well,

you get to keep playing.

And that's the truth in academia.

And if you're not, you

stop playing basically.

But when I saw you,

explain what you were doing

in a way that was accessible to people

and also talking about,

possible protocols that they

might explore for themselves

to see if those were, right for them.

I was just, I was just

dazzled and excited,

and I made every effort to

get in contact with you.

And, the rest is history,

but, I think what's really

exciting to me these days is

because of 2020 and with

everything that's happened

and it continues to happen.

There's a thirst for knowledge.

There's also this direct

to the public route

that you mentioned.

And, I think there's also an openness,

I'd love your thoughts on this,

but it seems to me that

there's an openness in,

from the general public,

about health practices,

that there are actually things

that people can do to control

their stress level, to control,

their sleep, to control their cholesterol

if that's what they to

do, maybe they don't

and to even control their lifespan,

which I think is remarkable.

And, I know I speak on

behalf of so many people,

when I just,

I want to say, thank you.

You've, truly changed

the course of my life.

I would not be sitting here doing this

were it not for your example.

And I always say Sinclair,

many people have written books,

many academics have

written books, as you have,

but in terms of doing podcasts

and really getting out there

with your message in a way that

I have to assume raised

your cortisol level

and heart rate just a little bit,

but you did it nonetheless.

You are truly first man in and that,

that deserves a nod.

And, I have a great debt of

gratitude to you for that.

So thank you so much.

- Oh thanks, Andrew.

You're a,

you've become a good friend

and I'm super proud of what

you've done and what you,

I know what you will do.

- So in addition to your book

and your presence on social

media, Instagram, and Twitter,

and appearances on podcasts,

02:05:40 The Sinclair Test You Can Take: www.doctorsinclair.com

recently I've noticed

that you've opened up,

a survey email/website

that people can, access,

excuse me,

to get some information

about their own health

and rates of aging.

Tell us about that and

what's being measured.

And what is this test that

you've been working on,

secretly and now soon, not so secretly.

- Yeah, well that,

what I want,

is a credit score for

the body to make it easy

for people to follow their health.

And there is a number,

there's a,

there's a biological age

that you can measure.

Unfortunately,

the test is many hundreds

of dollars right now,

but in my lab, we've been

able to bring that down a lot.

And so I want to democratize this test

so that everybody has access to a score

for their health that can predict their,

not just their future

health and time of death,

but to change it.

And I'm building a system

that will point people

in the right direction

and give them discounts for certain things

that will improve, not

just their health now,

but 10, 20, 30 years into the future.

And we can measure that,

and very cheaply, keep

measuring it to know

that you're on the right track,

'cause if you don't measure something,

you can't optimize it.

And so this is the biological age test,

we've developed it, it's

a simple mouth swab.

We're rolling it out.

We're building the system right now.

And there was a sign up sheet

'cause a lot of people

want to get in line,

go to doctorsinclair.com,

you can get on that

and you'll be one of the

first people in the world

to get this test and see what we're doing.

- Oh, fantastic.

Will people be celebrating their,

biological age birthdays?

In other words, if I'm

minus, like if I can imagine,

so I'm 45 right now, soon to be 46.

But if I,

if I were to be so lucky as

to get my biological age to 35

within 12 months, maybe

you can help me do that.

Do I get to celebrate,

a negative birthday?

- Absolutely.

And my plan is that those

people who take their age back

a year or more, we think we can

go back 20 years eventually,

they'll get a birthday card from me

and it's a negative birthday card.

[Andrew chuckles]

- I love it.

And probably very little,

actual birthday cake being ingested but,

who cares 'cause you're

living that much longer.

- That's full of stevia,* that'll be fine.

[Both chuckle]

And thank you for talking to us today.

I realized I took us down deep

into the guts of mechanism

and as well, talking

about global protocols,

everything from what one can

do and take if they choose,

that's right for them to,

how to think about this

whole process that,

that we talk about when

we talk about lifespan

as always an incredibly illuminating.

Thank you, David.

- Thanks Andrew.

02:08:13 Zero-Cost Support & Resources, Sponsors, Patreon, Supplements, Instagram

- Thank you for joining

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Also take note that the

lifespan podcast featuring

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launches Wednesday, January 5th,

you can find the first episode here

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They also have their

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You can find the link to that

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So please go there, subscribe on YouTube,

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I've seen these episodes,

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And last, but certainly not least,

thank you for your interest in science.

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