for the first time we could take an old

brain and we could give factors from a

young organism and ask is that going to

change the age of the brain and that's

indeed what it did. So we saw that uh

there stem cells in the brain of these

mice that they got reactivated there was

less inflammation more activity um that

we can measure in the brain and then

most importantly we actually saw that

their memory function improved. Welcome

to the Huberman Lab podcast where we

discuss science [music] and

science-based tools for everyday life.

[music]

I'm Andrew Huberman and I'm a professor

of neurobiology and opthalmology at

Stamford School of Medicine. My guest

today is Dr. Tony Weiss Corey. Dr. Tony

Weiss Corey is a professor of neurology

at Stamford School of Medicine and an

expert in identifying factors that can

help prevent and reverse organ.

Today we discuss the factors that are

present in young blood. Yes, you heard

that right. And the factors that are

present in blood after exercise that

have been shown to rejuvenate the brain

and other tissues in older individuals.

Dr. Dr. Tony Weiss Cory's lab has

discovered several proteins that are

present in high amounts when we are

young and that circulate in the blood

and that diminish with age and if these

are supplied to the aged body and brain

can reverse key features of aging

including improved cognition, tissue

recovery from stress, damage and more.

We also discussed how aging is

nonlinear. It does not progress

uniformly across the lifespan. And we

discussed the fact that there are

certain phases such as puberty, your

early 40s and your early 60s when aging

is accelerated and then slows again. We

also discuss how different organs in

your body age at different rates and how

you can measure that. Today's discussion

is a very important one because so often

these days we hear about anti-aging and

longevity. But today you're going to

hear about the real science of organ

rejuvenation. We also are going to talk

about the role of sunlight, fasting,

hormones, and the use of specific

molecular approaches to improve your

vitality and health. We also of course

discuss exercise and social

interactions, but in the context of the

specific molecules they release into

your blood to promote and enhance health

and how you can leverage that

information. Tony Weiss Corey is a

celebrated pioneer in the science of

these topics because of the rigor he

applies to the work. He's not just

talking about some molecule that someday

there'll be a drug or some activity that

we already know promotes health. He's an

avid tool developer for measuring and

reversing aging. So today we discuss all

of that and you're sure to come away

from the discussion with both tools to

improve your immediate and long-term

health as well as a deeper understanding

of the biology. 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,

today's episode does include sponsors.

And now for my discussion with Dr. Tony

Weiss Corey. Dr. Tony Weiss Corey.

Welcome.

>> Thank you.

>> Great to see another Stanford colleague

here.

>> You're a true pioneer. Your work is the

first work that I heard of where

somebody did a serious experiment taking

blood from a younger organism, putting

it into an older organism and observing

very interesting things. If you would,

could you tell us about that experiment

and what if anything has been done in

humans to examine whether young blood,

such a loaded term, but young blood can

be a rejuvenation factor for the more

mature body or brain?

>> Yeah. So we were actually not the first

ones. Um

>> okay

>> but we collaborated with um the person

who in sort of in more modern times uh

used this model again. It's called

parabiosis where um you have a surgical

model where an old and a young mouse are

paired and their circulation allows for

exchange of blood from the young to the

old animal. And my my colleague who uh

recruited me actually to Stanford Tom

Rando used this model to study aging of

stem cells in the muscle. So he

discovered that with old age the muscle

sort of deteriorates and and doesn't

regenerate. And when he used the mouse,

an old mouse and paired it with a young

mouse and then now this young

circulation

um infusing if you will the old muscle,

he regenerated that muscle and u it

looked almost like a young muscle. uh

and at the same time we also observed

effects in other tissues including in

the brain and that's when we started to

collaborate

um and and explored uh what could the

effects of the brain uh of of young

factors on the brain uh be and in part

we were also intrigued by that because

we had separate studies in humans where

we tried to find blood signatures of

Alzheimer's disease and what we noticed

is that we could see proteins that were

correlated or even predictive of

Alzheimer's disease. But the most

striking difference was between younger

and older people. So we saw that the

concentration of their proteins was very

different in young people and old

people. And when you see something like

that in biology always ask is this cause

or effect? So do the proteins in our

body change because they respond to the

aging of the brain for example or do

they actually drive the aging of the

brain? And here Tom had this model that

allowed him to ask that question or that

allowed us together to ask that question

because for the first time we could take

an old brain and we could give factors

from a young organism and ask is that

going to change the age of the brain and

that's indeed what it did. So we saw

that uh there's stem cells in the brain

of these mice that they got reactivated.

There was less inflammation, more

activity um that we can measure in the

brain with um electrical activity of

neurons. And then most importantly, we

actually saw that their memory function

improved. And so to your question, is

that relevant for humans? So we actually

try to translate that and we can talk

more about this where that the stage of

that field is right now to see whether

that can be translated. Yeah, I would

love to hear more about that. I um

realize in your description that most of

us think about blood of course

delivering oxygen and red blood cells

etc etc but of blood that's drawn as a

good

not the only but a good window into the

health status the age status of a of an

organism including us but what I'm

hearing is that it's also delivering

nutrients or proteins of some kind that

can

reverse some sort of clock and we'll get

into later whether or not it's an organ

specific clock or a bodywide clock. But

I think um bloodborne factors generally

I think of as a readout not um as a

medicine but you're talking about

bloodborne factors as medicine.

>> Yeah. I think that's really the

fascinating aspect of of of of this work

that over the past few years people

started to look at that many of these uh

proteins and probably other molecules in

the blood, they're not just reflecting

the status of the of the body, if you

will, but they're actively influencing

how it works. And the composition

changes dramatically from young to old.

We have this picture that I always like

to show when I give a a talk about our

work where we have um several thousand

individuals and we measure 3,000

proteins in them and then we use collars

to show low levels or high levels of

proteins and you see this dramatic

change from young people to old people

in a way that you can pick one sample

and you can say this person must be

about that old. And we can talk more

about what people call clocks. But to

your question, yes, there are factors in

the blood that clearly can change the

function of cells and organs. And what

the field is trying to figure out is

what are the key ones, which ones could

we use to slow down aging or to keep the

body healthy as long as you live. So

what has been done in humans in terms of

an equivalent or pseudoe equivalent

experiment to the parabios experiment

you described?

>> To try to translate that um we started a

company alkaist. Um to to see whether

factors from the blood of individuals

could influence first of all aging of a

mouse brain. So we took blood from young

people or old people and injected into

mouse brain. we could show that young

blood um could in fact mimic the effects

of young mouse blood. So there were the

similar factors in humans as in mice.

And then we went a step further and

worked uh collaborated very closely with

a company um called Griffles who is

producing clinical medicines

um for for hospitals based on plasma

donation. So they have centers where

volunteers donate plasma and then they

pull this and they isolate uh for

example antibodies. So if you're immuno

deficient or you had cancer therapy and

you you are uh immunosuppressed

you will get regular infusions of

antibodies that are sourced from healthy

people from these volunteers. Also if

you lose a lot of blood you may get

albamine which is the main protein in

our blood. So this company had this

manufacturing process where they collect

thousands of donations and they process

it into different medicines and this

allowed us to test these different

fractions and see which ones have an

effect in the mice. And again we could

find some of them that really were more

powerful than others. And so we started

some clinical trials in patients with

Alzheimer's disease and Parkinson's

disease and infused them with these

fractions that we've shown uh have uh

effects in mice and these were small

trials but they looked promising and

they're related to what people have been

observing

previously that if you get a blood

transfusions often people have sort of

feel invigorated it or their mind they

say their mind got cleared or they they

improved and this company actually

Griffles had also run a clinical study

that was blinded placebo controlled in

patients with Alzheimer's disease where

they first removed their plasma this is

called therapeutic plasma exchange and

then infused them back with um a major

blood component this albamine which also

contains other factors and they saw for

clear significant benefits and this was

in 500 patients. So the field is trying

to figure out next steps and hopefully

do really one of these large clinical

studies where you can then say this

actually works and could get FDA

approval. Have you done one of these?

>> I haven't. I haven't.

>> Are you close with anyone who who has?

>> I know people who have done it. Yes. And

I know people who as a response actually

then supported the research that we have

to been doing in this field. Um there

are companies now that offer this what

is called therapeutic plasma exchange

and there was a small trial that was

again placebo controlled in 40

individuals

uh from a company called circulate

therapeutics and they then looked in

these individuals. These are healthy

older people and they use some of these

measures that allow us to assess how old

an organ how old the body is or how old

an organ is called epigenetic clocks.

Um, and they could indeed see that some

of the uh organs looked younger or the

body overall looked younger. There's

some improvements in function. Not

dramatic but suggesting that there might

be something there.

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to claim a free sample pack. I can

imagine a situation where there are

factors in blood that can damage tissues

that arise when there's some sort of

injury. Let's say a heart attack or even

a a hip fracture um you know pick pick

an injury. I can also imagine a

situation where the blood of very

healthy vigorous

younger organisms is devoid of all of

that.

So, when I'm thinking about what could

be in young blood that could be

rejuvenating, I can imagine that there's

sort of a possible double dissociation

there. That as we get older, we're

having little, let's just call them

micro injuries that we're not aware of

all the time. And that infusing young

blood into that person um would make

them feel better. So, you're

counteracting the bad stuff. But there's

another picture where you're supplying

something that's pro- youthful. Do you

know whether or not the proteins that

are contained in young blood are

inhibiting the damage induced bad stuff

or it's supplying something that is

really a kind of a youthful factor? Two

different things.

>> Yeah. Yeah.

>> Right. And and you could see where they

would interact. But the reason I'm

getting granular here is because I think

ultimately for a therapeutic you'd want

to be able to um dissociate between

these two.

>> Yeah. Yeah. Yeah. No, it totally makes

sense. And in a short I answer it. It's

all of the above.

>> Um, so what we see is with age there's

an increase in many what we call

inflammatory proteins and we actually

identified some and in mice if we knock

them out or if we neutralize them then

cognition improves in the mice in old

mice. So there you have examples of uh

factors and actually natural factors

that can inhibit some of these

detrimental factors. But then you have

also um active progrowth factors, growth

factors that um stimulate the activity

of cells and might you know maintain

stem cells better. So they're they're

truly beneficial factors, right? The

challenge in this field has been to

figure out which ones are the most

important ones and is there a a smallest

possible number of factors that you

would need to have an effect, right?

Sort of a cocktail.

>> Now, you could say our blood is nature's

cocktail, right? It's the the alexia of

youth. It just sort of or it's the

fountain of youth that lives in us, but

it dries out as we get older. But it

also accumulates. There's also an

accumulation of bad stuff. So it's not

just a loss of that fountain. We have

now tools where we can in mice again we

can look at every cell in the body of a

mouse and we can ask how does to the

cells in an old mouse respond to young

blood. And what you see is that almost

every cell changes their behavior when

we measure their transcript. So their

gene expression in these cells but they

respond in different ways and it's

expected because they have different

what we call receptors. So one cell may

respond to one factor and another cell

to another one. And what's also

interesting we see a lot of stem cells

seem to be targets of these young

factors which sort of proves what what

we originally described but now in an

unbiased way. We look at everything and

we ask what are the major effects and

then you what you also see that some

organels such as mitochondria these are

the energy producer units in in inside

cells they are key targets of these

rejuvenating effects. So it all makes

sense based on what we know from the

aging field, what we know from stem

cells and maintenance of stem cells. But

pinpointing

which factor you would need to have this

rejuvenating effect or which one you

have to block has been extremely

challenging because you almost have to

go into the organism and then we call

this crisper tools where you can knock

out one gene after another and ask which

one is the important one. We can't

really do this easily in vivo yet, but

that's almost what we need to do. So,

unfortunately, in the past 10 years, you

know, there's individual factors that

people keep describing, but I think we

have not really come up with a good

method to integrate multiple different

factors that could provide or sort of an

amplified benefit and mimic what what

nature is doing.

>> Should I be banking my blood? You don't

have to um because what we find even

though there's differences clear

differences from one person to another

overall

if you have the blood of a young person

that blood has overall the similar

concentrations from another young person

and it would still be beneficial to you.

So all the blood that we ever used in

our studies was always a pool from

multiple individuals and that still has

the beneficial effect. So for for these

type of studies, you would not have to

bank your own blood.

>> Is the lore around Dracula based on this

general logic? And if so, how do you

think that lore arose? Meaning, I don't

think somebody sat back and thought,

"Oh, I can make up this story about this

Count Dracula who, you know, drank

youthful blood." And um I mean, does

that mean that

>> experiments were being done long ago?

I'm not trying to get gruesome here, but

we know for instance blood letting and a

bunch of other um you know

scientifically dubious uh uh things have

been used throughout history. But then

again to reduce iron load in the blood,

some people will give blood. Um it's

also a nice thing to do for your blood

bank. They need blood in hospitals and

too much iron load isn't good. We know

that. So what's known about the origins

of the Dracula story visa v the science

that we are now aware of?

>> Yeah. sort of in retrospect, I think

where they came from is maybe more that

people realize that, you know, blood is

this essential fluid. If you get a cut

and you bleed too much, you're dead,

right?

>> Um but then maybe also associated it

with um with age or youthfulness. I

don't know exactly how we have not done

and you know this question came up many

times before. We have actually never fed

mice young blood. You could try that,

right? To because it would have to be

absorbed. The factors would have to be

absorbed into the body.

>> I wouldn't be surprised if some of them

wouldn't have beneficial effects and

survive sort of the the you know the the

the the stomach um acid environment of

the stomach, but uh nobody's ever done

it. I don't know where it comes from but

it's [gasps and laughter] yeah I mean

there's a lot of these questions and

blood letting too you know it's blood

thinning also right the

>> um these leeches release factors into

the blood

>> and they must have done something

otherwise people would probably not have

done it it's pretty wild I again not I'm

not trying to be gruesome or medieval

here it's just you know now and again

something from the historical text shows

up

>> in um modern science and we kind of go,

well, there's sort of a mapping of of

some of the past to to something that

is, you know, clearly of a scientific

validation. I'm not promoting drinking

blood. I'm interested in organ specific

rates of aging.

>> Um, and then I also want to circle back

to organ specific delivery of nutrients

because what you're talking about is

blood infusion goes everywhere. It goes

into the general circulation. you've

mainly focused on the brain, but um it's

possible that certain organs are more uh

receptive to these youthful factors than

others. I mean, even the brain has a

bloodb brain barrier. The gonads have a

blood gonad barrier for interesting

reasons. What is known about the rates

of aging in different organs?

>> Do they happen in parallel or no? And

how different organs respond to these

youthful factors?

>> Yeah. So it's really interesting that

you know intuitively you think an

organism just ages sort of as a whole in

synchrony we would say right but what uh

researchers have discovered and this was

first I think Monica Driscoll uh was the

first to show in worms that when she

looked at at the ultraructural level

that some of these organs in the worm

seem to look more aged than others and

over the years now we have molecular

tools where we can look at a single cell

level or within an organ. And what we

clearly see is that organs and cells

within uh an organism can have slightly

different rates of aging. And the way we

conclude that is if we look at all these

tissues in many different organism and

we every you know period of weeks or

months in mice for example we harvest

tissues from different animals. We can

see these trajectories that some of them

are relatively stable for a long time

and then they start to decline where

others continue decline from early

adulthood and and yet others you know

may maintain almost until the animal

expires. So

that allows you then on an individual

level to ask if you compare now one

individual to another, do their organs

age exactly in the same way or is maybe

there a person um whose heart ages a

little bit faster than their actual the

rest of their body and in another person

it would be the lung or the brain. And

that's indeed what we seem to be seeing.

And [clears throat]

the way we did this in humans and maybe

we can talk about this now is again we

look at these proteins and there's

company companies now that can look at

thousands of proteins in a drop of blood

and this is not Sranos. This is this

actually real um platforms real science

where uh in in just a drop of blood

there's companies that measure 11,000

proteins. Now the concentration of these

11,000 proteins and there's large

population based cohorts uh where people

follow healthy people over

two decades or even longer now and they

collected blood and so we can profile

this blood now and we can ask are

proteins in that blood related to what

diseases people develop or how they age.

And the way how we make this what people

call a clock for a specific organ is we

look in your blood for proteins for

example from the brain. So out of these

thousands of proteins that we can

measure in the blood. Some of them

originate from your brain. Some

originate from the lung, from the liver,

from the heart. And we've always used

that in clinical medicine, but we

measure only a handful of proteins. It's

usually a few liver proteins, a few

heart proteins and we use them to assess

injury or um uh loss of function. So if

your liver is damaged, that's what we

detect. But here we have now an

opportunity to look in thousands of

people at proteins that come for example

from the liver and ask how do they

change with age? And that allows us to

then estimate the age of the liver in an

individual. And what we find is that for

most people, the age of your organs is

pretty much in sync with your body. But

for some individuals, you have more or

less of a deviation. So your liver may

age faster

um than that of the rest of the

population and the rest of your body.

And what is really super exciting, we

call this an age gap. So the difference

between your actual age and the

estimated age of your organ. And that's

a very strong predictor of your future

risk to develop disease in that organ.

>> So in other words, if your heart shows

to age faster, you're more likely to get

heart disease or a heart attack. If your

kidney ages fast, you're going to get

kidney disease. If your brain ages

faster, you're more likely going to get

Alzheimer's disease.

>> Is this a test that anyone can now take?

Is it commercially available?

>> Yeah. So, that's a great question. We

started a company uh with Paul Ketta um

called Vero Biosciences. Vero Vero

Biosciences. And the mission is really

to profile the age of organs to

ideally eradicate chronic diseases and

to um maintain or to predict which organ

is going to age. Because what we find is

that if you have an organ that ages

faster, if you can detect that and you

can do an intervention, you can

potentially delay aging, right? And

extend health span. And this is really

the mission of uh of Vero. The Vero

Compass uses a combination of this

biological signature together with

clinical and wearable data to create a

platform that can predict how you

respond, which or first of all which

organ is the most sensitive, which

intervention you can use and then

whether your organ responds or not by

repeated testing and sort of creating a

continuous loop where

>> I tell you which organ is of concern.

You get medical advice based on other

data that uh we can obtain from you and

then you may get an intervention could

be a classic medical treatment

>> but it could also be a change in your

lifestyle exercise change of diet type

of exercise but have it tailored

>> to your specific needs and then we can

test does that intervention actually

change the age of your organ. It seems

spectacular. I realized in addition,

let's say I were going to start a new

medication. Um maybe uh taking a new

drug for ADHD. Not for me. I don't have

ADHD fortunately. But you know, people

are doing this all the time now, trying

different drugs for different things or

uh taking something to lower their APO

as it were. And then you could monitor

how that impacts for better or worse

>> the the age of a particular organ or or

set of organs.

>> Exactly. Absolutely. So in many

diseases, complex diseases, Alzheimer's

disease in particular, we know that

people have probably different forms of

Alzheimer's disease and we know there

are risk factors that predispose you to

have Alzheimer's disease, but most of

the trials now are done in all comers

with the disease who already have the

diagnosis. And so you could imagine that

if you have these predictors of change,

the predictors of risk and you get

actually more resolution and we can talk

about that in a minute. What the next

stages of this type of research, you may

get different profiles in people and say

okay let's test this new drug in this

type of Alzheimer's disease who has a

very particular risk profile

uh rather than in everyone. and then the

drug fails. I think we may have tested a

lot of drugs out there that might

actually be beneficial, but because we

apply them to everyone and we apply them

too late, they fail and we throw them

away.

>> Yeah. We had um David Fagenbomb, Dr. Dr.

David Fagenbomb, he's an MD uh

University of Pennsylvania professor of

medicine um who himself was diagnosed

with Castleman's disease and took it

upon himself to try essentially every

approved drug as a lastditch effort. He

was dying basically and he came up with

a combination a small kit of already

approved medications and he's now been

alive 11 years since his essentially

death diagnosis or excuse me death

prognosis. Um and he has a a a um not

for-p profofit called every cure where

people with um

diseases that have resisted all other

forms of treatment people can go there

and they use AI to come up with you know

reasonable candidates to try because as

he he said exactly what you said which

is that many of the solutions to

diseases that are common may already

exist but they've been swamped by the

variation in those diseases when when

looked at in clinical trials. So, uh,

the idea that we're that we're already

sitting on good treatments and cures

that wouldn't have to pass through all

the testing is very interesting. There's

also very little incentive for drug

companies to invest in those because

they've passed through their um, patent

window. So, there's not a lot of money

to be made.

>> Sometimes another problem.

>> I have a question that I promise I'm

just going to be I I've had this podcast

long enough to know that I don't tap

dance around things anymore. David

Sinclair has been very um I'm not trying

to attack David but I want to know David

has been very vocal about NAD and the

NMN pathway which is you know upstream

of of and NR others have talked about NR

there's you know true niogen I'm not

trying to go after any one person or

company but for a while there was a lot

of excitement mainly generated by David

that um

NAD which goes down across development

into adulthood uh might be a

prolongevity treatment. I confess I take

NMN

um powder. I don't get paid to say this.

I know I won't doesn't even matter what

company I get it from cuz I buy it like

everybody else. Um I don't have any

belief that it's going to increase my

lifespan, but it seems to have a pro

energy effect that I like. For some

reason, it makes my hair grow very fast

and my nails grow very thick, which is a

side effect I wasn't looking for.

>> Okay, maybe I should try it, too. My

sister experiences the same thing. But

you know, this is all anecdata, right?

Again, I make no money for saying this,

but

>> I've seen a lot of criticism of the NAD

hypothesis of longevity. And so, is

there any evidence

that increasing NAD levels either

through NMN or through NR or direct

infusion or injection of NAD, any of

those things can actually extend the

lifespan of humans and or experimental

models.

>> Yeah. Yeah, I mean this is not my area

of expertise but um just as a blank

statement there is no human intervention

that can extend lifespan that has been

tested or validated. There are many that

have shown beneficial effects in animal

models including NMN and you know all

these metabolites. Um there's actually a

clinical study that shows that if you

take these supplements they increase

your levels in the blood. That's a good

clinical study, but it doesn't show that

it has an effect on lifespan or even on

frailty or any other tangible outcome.

And this is the case with many other

medications that might be beneficial,

but they have simply not been tested in

a clinical trial. They have been tested

in disease sometimes and they are you

know very good drugs to treat a person

who is sick but they have not test been

tested in healthy

>> elder people and see whether they reduce

aging or increase health span. There's

really nothing out there except exercise

and diets. Um those have sort of proven

um effects. There's a very good study

from a researcher in in in Singapore who

tested 10 different preparations of of

NMN and she found that many of them

actually don't contain what is on the

label.

>> That doesn't surprise me

>> and that's the case for most supplements

for half the supplements. There's, you

know, many resources out there you can

check or you can just ask CHPT. Um

there's not in there what it says. And

with NMN apparently and according to

Chachi PT um is very unstable and so it

it degrades quite quickly. So you want

to make sure I think with any supplement

if you want to try it make sure it's

from a good source

>> um and that it has that it has been

third party tested. Yeah. And and and

you use it within the you know

>> time frame.

>> Yeah. No, I I appreciate you saying

that. I um like I said, I I don't expect

to live longer because of taking NAD. I

just sort of like the effect that it

appears to give me. I'd like to talk

about the relationship between things

that increase vitality that are abundant

in youth versus their possible role in

decreasing longevity. I've been

fascinated by this for a long time. So,

um bear with me here. Uh and I'll try

and set the stage and then I'll be

quiet.

Puberty is perhaps the fastest rate of

aging that we undergo in our entire

lifespan. Within two years, we transform

as an organism. Right? Some people

progress through puberty much faster.

Other people seem to have a more

protracted puberty. And here I'm

defining puberty as the acquisition of

secondary sex characteristics, facial

hair, etc. Uh uh reproductive uh

ability, etc. Okay. So um puberty is a

constellation of things that obviously

differs in males and females. It's

correlated with hormones like

testosterone, estrogen, gonadotropins,

etc. But really it's a brain thing that

switches on that then start initiates

all of this. So there have been many

attempts in the the kind of health and

wellness space to take the hormones

usually testosterone,

estrogen and growth hormone being the

three primary ones and then supply those

to people in adulthood. Pmenopausal

women taking estrogen and or

testosterone nowadays quite frequent

this happens a lot. Uh men taking

testosterone either because they need to

quote unquote replace it or they're just

trying to augment what they already

have. growth hormone. Certainly all of

these things dosed appropriately we know

will increase vitality, energy, libido,

recovery from exercise in some cases

maybe cognition etc. But it's also been

demonstrated that when you increase

growth hormone and IGF-1

that you decrease lifespan. This is seen

in large dogs versus small dogs. The

reason larger dogs live so much shorter

lives than small dogs

>> is because of the dosing of IGF-1. So,

how do you look at the balance between

vitality and longevity? And are there

factors that can increase both vitality

and longevity? Because to my knowledge,

the things that these hormones mainly

that increase vitality,

>> well, if they allow you to exercise more

and perhaps be leaner, then perhaps they

buy you some time, additional time in

life,

>> but they also decrease the amount of

time you have alive. So, it's a very

interesting interplay and most people um

conflate longevity and vitality.

>> That's an an excellent question and you

know short answer is we don't know. We

don't really know and in the aging field

this is called antagonistic pleotrophy.

So something that is good when you're

young can be bad when you're old, right?

It it relates to this to this concept.

And humans are of course you know

they're sort of exempt from evolution uh

if you will right so our natural

lifespan is probably around 30 to 40 if

you look back in history that's how long

people lived I mean there were always

individuals who had

>> you know exceptional lifespan but most

people would die much earlier and

>> infections

um and

it was probably mostly infectious

diseases Um, but you know, you could

could argue from an evolutionary

perspective, once you're sexually

mature, you reproduced, and you

guaranteed your offspring, which is

around 30 to 40 years,

>> nature doesn't care about you anymore.

And so, there's no longer, it's very

brutal to hear, but

>> as long as your kids are are sufficient

enough to raise, an infant can't raise

itself.

>> That's right. a seven-year-old maybe

could if they were very industrious, you

know, but but kids need us at least

until they're in their late teens,

>> right?

>> And then, you know, you you may have

some evolutionary pressure to maintain

individuals who have knowledge and

wisdom to help the, you know, the the

group to survive.

>> But that's probably a much weaker um

force of evolution to keep you alive,

right? And so that's why people

increasingly see now that there these

inflection points that you know

menopause but also in men around age 30

to 40 dramatic changes in the

composition again of the blood. We just

looked at this mentioned earlier. If you

look at the composition of the blood

across human lifespan from 20 to 90 we

call these waves of aging. The first

wave is around 35 years of age. dramatic

changes in concentrations of lots of

factors and not just in women in men as

well. 35. It's a degra degradation, any

improvement.

>> Some go up, some go down. And you know,

it's it's speculative, but does that

have something to do with this is how

long nature needs us and then it doesn't

care. And you know the the fact that we

live now 80 or even longer on average,

right, is really thanks to hygiene and

you know um certain medications that you

know blood pressure and and heart

disease that we have. I have a friend

who's called me over the weekend. He's

got some

>> antibiotics.

Brutal infection that that

>> could almost took out his vision in one

eye. Antibiotics infused. Boom. Done.

And I know some listeners don't like

antibiotics and they're concerned about

it. I'll tell you, if you have a brutal

infection that's aggressive and it's

near your brain or your eye and you get

on systemic antibiotics and they're the

right one,

>> you are one lucky individual. And if you

don't, you're you could be looking at

excavating one or both eyes. It's

brutal. Yeah. Yeah. Wonderful.

>> Many different infections. Antibiotics

are, you know, a lifesaver.

>> Absolutely. Yeah. So, um, it's a really

good point and actually my my my friend

Tom Rando uh mentioned earlier he always

makes that point that, you know, a lot

of the study look at lifespan as an

outcome in animal models, but they don't

really look at how active or, you know,

what what is sort of the the level of

that extended lifespan is are they just

hanging in there these organisms or are

they still strong and and and vital?

right? Is the vitality still there? And

and I think we don't we haven't found a

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I've been um somewhat surprised,

although not entirely, by some of the

data on um sunlight exposure and

lifespan. There's this really

interesting large-scale study out of

Sweden where people the more sunlight

exposure people got, the longer they

live. Even smokers who get more sunlight

appear to on average these are averages

folks seem to so overlapping

distributions but live longer than um

non-smokers who don't get sufficient

sunlight. Now getting a lot of sunlight

is also correlated with

>> outdoor activity, fresh air, a number of

things. So it's it's far from perfect

>> study but um

>> yeah the interplay between vitality and

I think of sunlight as provitality um

and

>> longevity is such an interesting one

because the dance that we seem to be

playing now with medications and

>> could be supplements but really

medication and lifestyle is what can we

do and take to get more life but also to

enjoy that life more. And there are

certain things like growth hormone which

will make people feel much more

youthful, much more youthful, skin,

hair, even cognition etc. Ability to

maintain or put on muscle, lose fat and

on and on. But

>> higher IGF-1 and growth hormone, broadly

speaking, means a shorter life.

>> Yeah. Maybe comes at a price. Yeah.

>> Yeah.

>> So I guess um I mean that can be

determined individually whether or not

somebody wants to make that tradeoff.

But what I'm excited about are the

things that are possibly in these uh

blood transfusions

that come from younger humans, maybe us,

but younger humans, you said pulled um

that are getting to cellular function in

a different way that are restoring

vitality and longevity. And maybe there

are a few candidates that you could

discuss with us and what pathways they

impinge on. I probably won't be familiar

with the specific molecules, but are

they impacting DNA, the the epiggenome,

are they impacting mitochondrial

function? If you would maybe pick your

two or three favorite candidates, if you

if you can, I know some of these are

still under study.

>> The factors often are growth factors.

Um, GDF11 is is one of them that has

been described. Growth and

differentiation factor. There is you

know IGF-1 actually also has been

described to be in young blood is is

higher. There are factors that have been

identified through an approach that is

similar to transferring young versus

old. So what one of my trainees did,

Saul Va when he was a graduate student

in my lab, he did these parabiosis

experiments and then his lab and my lab

independently

um did an experiment where we exercised

mice, young mice, we took their blood

and we injected it in nonex exercise

mice and we could show that the

beneficial effects of exercise on the

brain were transmitted again by blood.

>> Were you going young to young? So we

went young to young. Saul went young to

old and could show that he can has a

stronger effect on uh on these brains

than just uh young blood. If it's

exercise young blood, it's even better.

>> So surprising to me because um I think

of exercise as a purposeful stress

>> that induces inflammatory molecules that

then induce an adaptation. Are there

factors that are liberated during

exercise, brain derived neutrophic

factor, etc. that are that are prohealth

and vitality that are not designed to

get a an adaptation

>> that are just good stuff coming out of

the cells when we exercise? What both

actually he and my lab found is that

somehow this exercise seemed to trigger

the release of factors from the liver

that then go to the brain and make the

brain function better. In our case, we

described the protein that's called

clusterin.

>> It's has many different roles. It can

bind to lipids. It's also called

apoloprotein J. It's involved in

coagulation and complement pathway. very

complicated. We couldn't quite figure

out how does it have these uh effects

but we could show that if we rec if we

make re combinant synthetic uh clusterin

and injected into mice we could mimic

some of the effects.

>> This is clusterin.

>> Yeah,

>> it's in the compliment pathway. uh

compliment um initially identified as

part of the immune system uh coat cells

as a part of the eat me signal uh in the

immune system system or the eat me

system um but does many other things too

right involved in synapse formation and

remodeling and we know from Beth Stevens

work and others um wild

>> wild yeah

>> wild

>> and then uh Saul found another factor

that's called GLDH um that again uh he

can clearly show has an effect um But

how exactly does that is is not clear.

Most recently he does did another really

creative experiment where he um did

caloric restriction of mice and again

that's sort of a an accepted you know

beneficial effect and longevity

promoting potentially

um and takes the plasma from mice puts

it into other mice and again can isolate

factors that mimic this effect

>> because of of intermittent fasting.

>> Yeah. What this tells us is that this is

physiology, right? We call this

physiology, but organs in our body

communicate with each other and there's

an orchestration of effects that leads

to factors that are

released into the blood and then they go

to different organs and have in this

case beneficial effects. So the exercise

effect is not just because you think

you're exercising, but they're actually

factors released that seem to benefit

your brain. So interesting. There's this

idea that was at least to me first put

forth in a book called Spark. Do you

know John Ry's book? It's some it's you

know came out some years ago. He's a a

physician I believe trained at Harvard

Med. um and he talked about the

essential requirements for movement and

brain plasticity. This was early days of

understanding neuroplasticity but uh he

talked about brain derived neutrophic

factor other things are liberated by by

exercise but he described some

interesting experiments in there of for

instance there's a a um a sea dwelling

creature that swims around and has a

fairly elaborate nervous system at least

for it but then at some point in its

life settles down on a rock and eats its

own nervous system um basically

>> and there's been some interesting

experiments looking at what happens when

you get that organism or other organisms

I believe I think it was that organism

but other organisms to continue moving

it seems like there's feedback from the

process of moving the musculature and it

could be neur neuromuscular in origin it

could be hormonal in origin I I don't

think we know that it comes from muscle

but there's something about the

requirement for movement that signals to

the brain that it needs to continue to

exist and not just the motor portions of

the brain and that it or the portions of

the brain controlling motor activity,

but that the body may supply chemical or

other types of feedback to the brain

that if if it's moving and continues to

move that the brain needs to continue to

be robust,

>> which I find very interesting because

few things to me explain how movement of

the body would signal vitality of the

brain aside from hormone factors. But it

kind of makes sense, right? Continuing

to move the body is essential for

keeping the brain healthy.

>> Yeah. And I mean exercise interventions,

you know, there's thousands of studies

that show that exercise is beneficial

cardiovascular, but also other exercise.

>> Yeah. Now it seems everyone's excited

about resistance training. I mean, I

think both is is clearly the answer. I

mean, you're you look good. What what's

uh I mean, you're you're not in your

80s, but um do

>> I might be

>> Do you exercise? Right. Right. Yeah,

that would be impressive. Um, what what

is your exercise regimen? People will

want to know.

>> Yeah, I I I run. I like running

outdoors. I like the sun. [laughter]

>> Um, I I try to get two runs, 5 to 10k

per week.

>> Yeah, that's the main exercise I do. I

do some Pilates in the morning.

>> I'm struck by how quickly the body

degrades after an injury, especially if

that injury occurs after age 60. When we

are injured as kids, we heal up

>> like it's amazing, right? I mean, kids

getting cuts and then just like what

happened? It just they heal right up.

>> Do we know why we heal more quickly as

kids than as adults?

>> We do know that the immune system ages

like everything and it has this bias

that it goes from a more specific

response to a non-specific response and

that is often associated with

inflammation.

So, it's it's possible that um part of

it is that if you have a wound, there's

too much of an inflammatory response and

less of a healing response.

>> But we also s know from from aging

organisms that if you have a cut, there

is more of um

um there's proteins in the extracellular

matrix like collagens and things like

that that are often overproduced. and

they may interfere with a quick healing

response. So I think everything is a

little bit out of tune and that might be

the reason uh but it's not really

something I would know the details. I've

always been fascinated by the fact that

if we get a cut on the surface of our

body um that it may or may not heal with

a scar, but if we get a cut on the

inside of our mouth,

>> which is loaded with bacteria and

>> warm and moist and in contact with the

outside world all day long, it tends to

heal

>> with either zero or much less of a scar.

>> There has to be something in the mouth.

>> Fascinating. healing and I believe

people are studying this but someone's

got to figure this out

>> and it could be saliva

>> wild right I mean the the rate of

healing I know there's a lot of blood

supply

>> but there's also a lot of blood supply

to the nose and and to the hands and

there's scars form on the hands and on

the nose

>> yeah there's also scarring in babies

right may not leave or a cut in a baby

may not leave any uh trace but the same

type of of wound in an older person may

may leave a um a scar for the rest of

their life. Yeah.

>> So, how do we move past correlation and

to really understand um causitive stuff?

So, we'll get back to lifestyle factors,

but I mean it's so very clear from the

animal studies and from the human

studies that you described that there's

something in young blood or things in

young blood

>> that are pro-rejuvenation for the brain

and other tissues. How do we get to a a

real prolongevity

molecule medication

treatment

>> or prohealth maybe more right? I think

most people in the field are not really

interested in extending lifespan which

would be longevity but health span. So,

>> and we talked about this before, right?

That you try to maintain the function of

your organs until you die. So that your

brain would still be functioning your

cognitively intact. All your organs

would still be functioned relatively

well and then you know you fall asleep

and and that's the end of your life. Um

and not necessarily extending lifespan

as you said. It could be that we extend

lifespan and you just have 10 more

miserable years. That's certainly nobody

would want that, right? But I think to

get to causation, we need these types of

experiments, physiological experiments

in animal models first to isolate

individual factors and then test them on

an individual basis with very rigorous

methods which we can do and say okay

this factor has the capacity to maintain

for example brain function in the mouse.

And then we have to test it in humans

and do it in a in a careful clinically

uh controlled trial where people are

blinded whether they got the treatment

or not and do a big enough study that we

can say okay this truly works and then

we have a drug.

>> How close are we to the clinical trial?

>> There are different molecules. Colossal

is actually another one. It's this um

protein that um has been described to

have beneficial effects on multiple

different organs. The biology again not

exactly clear but

>> K L O T H O clone

>> that's right. Yeah. Yeah.

>> Um

and you know there's there's companies

trying to move this into humans into

human trials.

um some of these other factors I think

their their companies are trying uh or

inhibiting detrimental factors and with

with you know individual clinical trials

you could get there um in the next 5 10

years there may be something that has an

effect I think we will not have a

[snorts] factor an individual factor

that just has you know this miracle

effect on everything this is very clear

from the studies of young blood. It's

many different factors

and they target different pathways,

different cell types in different

tissues. So you really need to you may

have to decide, you know, for this organ

we need this treatment, for this organ

we need that treatment to optimize its

function and keep it, you know, running

at full capacity until you're 100 years

old. I'm not suggesting anyone do this,

but I I do seem to hear now and again

that people are taking cloth already. Um

not surprising. People will, you know,

get ahead of the curve, so to speak.

>> Yeah, I've also read people taking this

GDF11. Um I don't know where to get it.

>> I'm guessing it's just Mexico and um

Central and South America. There there

are a lot of clinics that do this sort

of thing. I I will put out a a true

story. Um cautionary note a friend who

when whenever people say I have a friend

it's you know but this is a medical

doctor um who had a back pain that was

uh giving him a lot of issues and he

went to a stem cell clinic in Mexico got

an injection of stem cells into a spinal

disc which my neurosurgeon friends tell

me is a terrible idea. Turns out the

disc cannot accept cellular injections.

a neuros a ch a chair of neurosurgery

told me that. So

>> you can come at me if you want folks,

but he's the chair of neurosurgery at a

prominent medical school. So that the

disc cannot accept direct injections of

foreign cells. Anyway, this guy went a

different guy, different MD went uh and

got this injection and ended up with a

um an egg-sized infection that left him

paralyzed.

He was fortunate enough to be uh

airlifted to a certain clinic and uh in

the United States and uh told he was

that's it. You're done. We're going to

have to just sever your spinal cord. Uh

he was uh taken to another clinic where

fortunately they were able to excise

this um this infection and he's mobile

today. He will tell you and I'll tell

you that you have to be very very

careful getting injections of cells in

anywhere but the regulations out of

country often are are not as stringent

and I tell that story because a number

of people are excited about stem cells

they're excited about these technologies

but it it really can be quite dangerous

>> and again this you know is what we

discussed earlier the this

you know experience that we have in the

medical field that you really need to

test something in people in a very

controlled fashion very carefully with

the dose and and and then test it in a

blinded fashion ideally so that you know

it really works and it's safe and what

you mentioned earlier with stem cells

there are no such treatments that have

been tested rigorously

>> and for many of these other factors they

work in some animal models there are

some mouse studies that showed they

might have an effect. But you cannot

translate that to humans. It's just a

long road

>> and I would be extremely cautious to

take anything that is not really

prescribed to you from a from a

clinician that you trust.

>> Thank you. Uh by way of contrast, um

plateletri plasma PRP is approved by the

FDA. People who are undergoing fertility

treatments will get injected into their

ovary. People are getting PRP injected

into their shoulders, their knees, their

whatever. Uh I'm not trying to be

disparaging of this. It is FDA approved.

To my knowledge, plateletri plasma does

not contain stem cells.

>> That's correct.

>> But it seems to be beneficial enough and

safe enough that the FDA has approved

it. Uh what is the deal with plateletri

plasma? What has it been shown to be

actually useful for? Because just

because something is allowed for one

indication and is used broadly for a

bunch of things doesn't mean that

there's evidence that it works for all

those things.

>> That's right. That's right. So

plateletri plasma has these platelets in

there that are full of growth factors.

They have these granules that help in

wound healing is a primary function. And

um somehow that seems to be beneficial

in sports injuries. it's often given and

as far as I know I think it's from your

own blood you you you concentrate these

platelets and then they release these

factors so you may have a massive load

of growth factors that help you heal

these various tissues that you mentioned

yeah I haven't tried it but I know

people who have and and reported some

positive effect I've heard also a lot

about exoomes and [snorts] there are

some clinics I believe where I think

exoomes are FDA approved as a treatment

What are exoomes and what what have they

been shown to be useful for in studies

andor clinical?

>> I don't know in clinical studies how

they're used, but um so cells can

release sort of little packages of

material that is filled with proteins,

but there's also RNA molecules in there,

lipids, metabolites.

And some cells do this all the time.

cancer cells for example do it. But also

some immune cells have a very active

release of these little

um sort of like little packages,

vesicles we call them, that are filled

with um again all these different

molecules in the [snorts] blood. You

find large numbers of these exosomes and

that's where they're usually purified

from. Different cells have different

cargo in these in these vesicles and it

seems that they function to some extent

to deliver information from one cell to

another. It's still a very new field but

people explore you know whether they can

be used for for treatment purposes but

also for diagnostic purposes. Do they

tell you something about a specific

organ or a tumor that is developing? So

when we measure these proteins that we

talked about earlier in the blood

um we actually measure what's in the

exosomes also. So these exosomes they

float basically like immune cells they

float in the blood and uh we open them

up and we measure what's inside.

>> We should probably talk about some of

the things that damage vitality and

longevity.

accident and injury aside, we know that

smoking, especially nicotine, um damages

DNA, uh increases inflammation and will

shorten your life. I don't think there's

any debate about that, right?

>> But what about some of the other things

that might produce low-level DNA damage?

In particular, these days, I'm very

interested in EMFs. I I don't actually

believe that the low levels of EMFs that

are present in most technologies are

damaging in the acute uh way that you

know being near them is going to harm

you. But there is the idea that things

can be cumulative, right? I mean I get

one X-ray every few years when I go to

the dentist, but there's a reason the

clinic the the technician runs behind uh

the wall. Uh he or she doesn't want to

be exposed to that on a daily basis.

So how do we feel about things that at a

low dose don't damage DNA

um or mutate proteins either but that if

we are exposed to them over a lot of

time could very well do that. What are

your thoughts on this?

>> A very difficult question. I mean you

could ask the same question about any

chemical that we invent and we put into

food or we get exposed to right the you

know the plastic we you know we drink

out of cups hot stuff out of a cup that

is coated with plastic and you know

we're full of plastic. How is that going

to change our lifespan? It hasn't in a

in a measurable way so far, right? But

we don't know what's going to happen in

20 30 years or if people you know

synthesize a compound that is

detrimental that it doesn't look

detrimental. It has been tested and is

safe but as you said if it accumulates

maybe or in combination with other stuff

it may be detrimental.

>> I think about this from time to time and

and I wonder about what's in my

environment that I can easily control. I

try not to drink out of plastic. Um, uh,

you know, I try and drink out of cans

that don't have BPAs and things like

that if I can.

>> Yeah, if you if you go down that route,

you know, it drives you crazy and you

could, you know, sort of not do anything

anymore or not eat anything.

>> Well, it's getting harder nowadays to to

live a clean life. I mean, how long were

you in Switzerland before you came to

the States?

>> I was 26. Yeah.

>> You were weaned in a very clean

environment.

very you know uh that's not just a a uh

stereotype about about the Swiss being

things are yes very tidy and clean the

streets are remarkably clean you could

drink out of the lake in Zurich right

>> maybe not the lake but you know most

most there's still fountains with ground

water where you can drink in any village

basically yeah if you're lucky enough to

grow up in a place where the tap water

is clean

>> the food tends to be pretty devoid of

dyes and preservatives Um, and your home

is centered around eating mostly whole

foods,

>> foods that you cook, fresh fruits and

vegetables and freshly prepared, right?

Even desserts that are fresh that are

prepared, right? As opposed to a lot of

packaged foods.

>> It seems that that that's a far and away

different experience than most certainly

Americans get nowadays,

>> right? And you wonder what the effect of

that is going to be. We simply don't

know.

>> Yeah, we don't know. And I know now

there's a big, you know, kind of attack

on food dyes as the thing and there no

there's no smoking gun data on any of

those. But yeah, I think the cumulative

effects of things are are worth

considering. I think for most people,

>> I try not to think too much about it,

but I also I mean growing up in an

environment where, you know, we had a

big vegetable garden. I have a vegetable

garden, you know, I have lots of fruit

trees and

>> try to get, you know, stuff out of my

own garden. That's a luxury, of course,

for a lot of people. Um, but as you

said, you can, you know, you can also

buy uh fresh fruit. It's more work,

right? It's more work than just buying a

readymade food, but you know what you're

cooking and what's in there.

>> I'm fascinated these days by the um the

data on organic versus non-organic

fruits and vegetables. I I spend the

extra money on organic, but the more I

look into it, the more you find that the

differences aren't that great. Now taste

can be different and ideally you're

sourcing from local farms but I have a a

friend um actually I'll just he he'll be

okay with me saying this. We had uh he's

a physician Dr. Teaos Solommani. He's a

dermologist

um whose son ran an experiment for his

uh school project uh looking at uh the

differences between organic and

non-organic fruits and vegetables in

terms of what contaminants and and

things uh are on them, pesticides, etc.

and found this is one kids study but um

uh

essentially no significant differences

in that particular set uh set of batches

of fruits and vegetables and so that is

I would say reassuring on the one hand

because it means that people who can't

afford organic will um probably be doing

about as well as people who can but I

think if you can grow your own or or

access from local farms I mean surely

it's cleaner I mean the highest rates of

endocrine disruptors are found in rural

areas. I always thought that being in a

big city was the most dangerous for your

lungs and endocrine health. And we had

Sha uh Shauna Swan on the podcast.

Serious researcher in this area and she

said, "No, I mean if you live in an area

where they're um spraying crops,

>> cancer risk, endocrine disruption. It's

very serious."

>> Also association with Parkinson's

disease and Yeah.

>> Right. [clears throat]

>> I'd like to take a quick break and

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to get early access to Function. Well,

as long as we're talking about food, we

should talk about not eating. We should

talk about fasting.

So many studies now showing in worms, in

mice, in monkeys, and perhaps even in

humans that subcaloric intake or inter

uh for long periods of time or perhaps

intermittent fasting, we can talk about

how we define that um can extend life.

How is that thought to work? Is it the

reduction in this mTor malian target?

Is it um reduction inflammation? Is it

clearing of senocence cells? Give us the

the overview and and any specifics about

intermittent fasting and and perhaps

start by saying how you define

intermittent fasting. Is it daily or is

it 2 three days?

>> I think just to answer that there is no

definition.

>> Okay.

>> There is no definition and the whole

field is also MS. Um you know it's again

taking studies in mice for example um

and then translating them to humans you

know that the lifespan the their whole

rhythm um their environment is so

different from our environment right

that to translate these um is is always

a stretch and there's no clinical

studies that show a clear benefit of of

fasting in humans and some studies in

monkeys actually suggest that it's

detrimental

um for monkeys to fast for example they

had more um uh I think worse kidney

function and things like that um so

overall in from animal studies it's very

clear that you activate sort of

beneficial pathways they're very diverse

um again we can now use unbiased um

assessment of any different cell types

in an organism at you know gene

expression across thousands of genes and

we see that different cells respond in

different ways and you get functional

improvements but they're very broad.

They're in part reduced inflammation. Um

other cells um you get benefits on their

energy metabolism, protein turnover, how

they handle sort of what we call the

garbage that accumulates in cells. um

overall from these animal studies

clearly benefits from reducing calorie

intake. Uh also less what we call

oxidative damage. So it's like you you

burn a fire, right? And if if that fire

is really intense, you may cause more

damage. But how you translate this

really to tangible benefits in humans,

I'm not sure.

>> Do you practice intermittent fasting?

rarely

>> you like breakfast.

>> I I tried um you know Longo's uh diet uh

a few times where I reduce you reduce

calorie. Walter Longo,

>> I'm familiar with him. What's what's the

the contour of the diet?

>> So it's mostly you switch to a ketogenic

diet. So a fatrich diet. So your

metabolism changes basically from a

regular sort of glucosriven diet to

burning fat. Um, and you feel that when

you start to starve that somehow it's

almost like your body changes a little

bit in um you you get a bit more alert

almost. And in a way that makes sense,

right? If you think you're out there in

a wild in the wild, whether you're an

animal or a human being,

>> if you don't have enough food, the last

thing you want is that your brain

doesn't work well,

>> right? I imagine the catakolamines,

dopamine or epinephrine and epinephrine

increase.

>> Yeah. Yeah.

>> So you get more alert, right? A little

hangry.

>> Yeah. Hangry. Exactly. Got it.

>> But um I'm not sure how long that lasts

and how beneficial this is in the long

run. But yeah, I've done it a a few

times. You know, you do one week, you

you lower your calories, I think down to

a thousand per day. So it's pretty

pretty brutal, but only for 5 days and

then we go back to normal. Yeah. I know

of a few people who've done um long-term

fasts, so three or four days with just

water and electrolytes, maybe some

ketones, and they were very overweight,

carrying a lot of excess body fat, and

when they returned to eating, claimed

that their appetite was forever changed,

in particular, the types of foods they

were hungry for. And um that's thought

to be uh an effect on the gut

microbiome, which then impacts the

brain. So, there may be a place for

those longer fasts. um uh what do they

call the medically supervised fast?

>> I generally just like caffeine,

electrolytes, and water until about 10

or 11:00 a.m. Um and then I like to eat

>> no later than no later than nowadays at

700 p.m. because I go to bed a little

earlier. So is that intermittent fasting

or is that just um being a busy person

>> who wants to still sleep well and

exercise, you know?

>> Yeah, it is sort of a fast, right? Uh I

mean in English we call it a break fast.

Um um and and it is like you know 12

hours maybe where you have no food and I

think that that probably triggers some

metabolic activity that is different

than if you continue to eat. I think the

worst is probably for the body to eat

all the time like a lot of people snack

the whole day. That's not how we were um

how we evolved, right? That we evolved

being starved on a regular basis. But is

that a good thing or a bad thing? For

sure, our body is used to it. That's

that's

>> that's a fair statement. It can handle