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

- 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.

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.

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I've spent a lifetime

working on the visual system.

And I can tell you that the visual system

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you have to adjust a number of

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One problem with a lot of

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Today's episode is also

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Today's episode is also

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Magic Spoon is a zero sugar, grain-free,

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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

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And then at night is when

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And now my conversation

with Dr. David Sinclair.

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.

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.

- 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.

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.

- 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.

- 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.

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.

- 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.

- 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.

- 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.

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.

- 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, 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.

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.