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2022-01-14 - Interview Dr. David Sinclair - Reverse Your Age: What To Eat & When To Eat For LONGEVITY

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Transcript

is there a diet that makes them live

longer any mixed combinations of

carbohydrate protein and fat and was

hoping to see finally what works and he

found out they all did the same thing

they all had short life spans but there

was a one group what specifically

sparked your mind to be to have this

idea

that we could extend our lifespan

uh well to me it's it's plain

it's obvious it's in plain sight um and

what i'm trying to do with my life is to

shake the world up to realize that

we don't have to accept what we think is

the inevitable

um and so the mantra in my lab and in my

in the book that i wrote is uh nothing

is inevitable

and the problem with aging is that we

accept it because it's so common we see

everything around us get old and we say

well maybe there's

we just have to accept it and it was my

grandmother who taught me that that

didn't have to be the case

uh she raised me because my mother was

working and she was young she had my

father when she was only 15.

and so that going back to the 1930s that

was a big deal right she was kicked out

of high school and but she came to

australia ran away from europe from

hungary

and raised me and her view was adults

screw up everything

because she'd seen what happened during

the war and after afterwards

and but she was a huge rebel she was the

ultimate rebel my my our 16 year old

daughter has the same

genes so it's it's tough raising her but

the attitude when i was young was rules

are meant to be broken so she would

she taught me and you know

the police probably uh will remember a

few of these things she told me you

don't have to wear what people say you

have to wear so she was kicked off bondi

beach for wearing a bikini which in in

those days was illegal

she used to drive like a maniac not

speeding so much but she would drive

like this looking around and dance to

the music so the car is going like this

to uh beethoven's ninth

and that kind of thing so i i've grown

up saying we don't have to accept the

way the world is adopts adults grew up

everything but she also was a humanist

and she wasn't religious but she said

david you have to do the best you can to

leave your mark

and allow humanity to reach its

potential and not let others screw it up

so i've spent every day doing that but

why aging because to me it's obvious

this is the biggest unsolved problem if

aliens came down to see us and judged us

as a species they'd say

pretty good on

atomic theory quantum mechanics but this

aging thing you don't even realize it's

a problem that you can solve we figured

that out 50 000 years ago what are you

doing and that's what i'm trying to do

here with the time that i have yeah and

you said in the book and it was very

jarring to see you know you said that

there is no biological reason for us to

age and in fact you said that aging is

and you you approach it as being a

disease well it is a disease it's just

we can call it whatever we want but what

is a disease a disease is something that

happens over time that causes you to

have a disability which you know well

and it causes frailty and eventually it

can cause death okay

that's aging right

is it not

what so what's the difference why do we

separate disease

from aging the only difference is

because aging happens to more than 50 of

us

and that's a crazy distinction i would

say that that's even more important that

we focus research development

policy on actually what kills most of us

this is really fascinating because

for me

just you bringing up the conversation

the way that you did

i realized that we know pieces of aging

like what it looks like and we're

attempting to address different pieces

but there is no unified theory of aging

as you pointed out but there are these

uh characteristics of aging that we're

all trying to attack

well that that that was true a few years

ago what i've put forth in my book

is a theory that

i think can explain why we age and

explain why all these other things

happen

now we scientists have we love to put

things into categories and we came up

with about seven or eight causes of

aging we call these the hallmarks

don't want to get too carried away call

them hallmarks

um and we've been very satisfied for the

last probably eight years

uh that this is the the road map to

extending lifespan if you can solve or

treat each one of these eight then we'll

live longer now that

i have no

qualms with i think that's true

but that still begs the question

what causes those to happen and so my

theory i've called it the information

theory of aging if you boil it down to

an equation if you want its first

principles

i think aging is a loss of information

and that's what's causing the problem so

what we need to do is a preserve the

information and see if there's a backup

hard drive of youthfulness that we can

tap into and reset

our computers

this is so fascinating

you specifically just this is a great uh

segway into

looking at the digital nature of dna

and i like when i read this in your book

it really just flipped a switch for me

because there's a a digital aspect and

then when we're talking about our genes

in our gene expression there's an analog

aspect so let's talk about this digital

aspect of dna

yeah well

this is the crux of everything and most

scientists don't talk the way i do we've

had to invent our own vocabulary and

metaphors

so dna we all are very familiar with

without dna that we get from our parents

we're screwed right without uh the

ability to encode proteins and run the

cell it's important but that information

is much more robust than we realize we

think of it as this very fragile

chemical it's actually not fragile you

can boil it you can find it in fossils

it's pretty strong

yeah so this is robust and it can

certainly last 80 years our lifespan it

can probably last a thousand years if

we're good to it

so what's the other problem so that you

said that's the digital part of the the

genome or the the information so there's

atcg okay

people will remember from high school

days if they're not biologists it's just

a digital code encoded in chemicals four

of them

instead of being as ones and zeros it's

just four letters

but there's this other type of

information that's just as important for

our survival and that's the epigenome

okay so what's the epigenome it's just

that's a complex

word for the control systems that

control the genome

in the way that

i'll forgive my uh anachronism here but

the dvd

uh is the digital information

and the analog is is the ability to read

that so the digital

the dvd player is analog so it's moving

around and it can move in any possible

direction

what does that mean for the cell well

what's actually literally happening is

that as we develop as embryos we're

spooling out parts of dna in every cell

differently in every cell so if you're a

nerve cell at this part of the brain

that's developing you'll have this big

loop of dna and those genes will stay on

for most of your life if not all but

there are parts that you don't want on

you don't want a liver gene on in the

brain so it spools out uh very tightly

like you would a

hose reel

and that keeps these genes off

hopefully for a hundred years or more

but what i'm proposing is that insults

to the body and if our body becomes

complacent

and we there you know there are good

things we can do to our bodies

what we lose is that structure these

loops and these these tight bundles and

those fall apart we can see that in our

studies

and we can actually measure that and

it's a clock

it's a clock of aging if we measure

those loops and the changes to this

epigenome

i can actually tell you how old you are

biologically and i can predict with high

accuracy when you're going gonna die

almost to the month wow

that's nice

scary right i haven't had it done would

you get your clock down

i mean um

and this is just a little sidebar here

but

this brings to mind the science behind

telomeres and measuring that as this

biological marker but there's more

there's much more to it that's just one

aspect yeah and what's

um comforting about this theory and and

it's the mark of any decent theory is

that it should be able to explain not

just one aspect but all aspects of a

very complex system and aging is the

ultimate

complex system and we've also got

a thousand years of observation that we

have to explain and if it doesn't

explain half of it throw the theory out

but as i've described in in my book the

theory does actually

explain everything

even telomere loss telomeres are the

ends of chromosomes that that wear down

over time

the epigenome the proteins that package

those loops and those those bundles are

also packaging the ends of the

chromosomes

and the unraveling leads to acceleration

of that loss as well

and uh and actually the factors that

stabilize our epigenome

and we work on some of these they're

called sertons we've worked on them for

20 years we can activate them by being

healthy

they are involved in protecting the ends

of chromosomes as well and bundling them

tightly so they don't erode and cause

aging to happen as well yeah i i want to

talk about these sir tunes this is

really really fascinating so

you are is this under that umbrella of

what you're calling longevity genes yes

okay and how many are there

well in total the th there's dozens but

they fall into three main categories

that we know of the sertuan's there are

seven of them you know we all have some

of them well you better have all of them

or you're dead

they're really important but we have

better copies than others some people

have variants that predispose them to

long life there's one called 3t6 and

if you have your genome we can have a

look to see if you've got the right

variant to live long time

but by the way only 20 of

longevity is genetic so the good news is

that a lot of it's in our hands because

it's epigenetic that's what's great

about this theory is that if i'm right

genes are only a tiny part of the story

but these genes are still important

because they protect the epigenome and

make sure that dvd is read correctly and

doesn't get scratches so you can read

the symphony for longer

this is so fascinating and i love that

so much um

and just to know and to have the

affirmation with science that only 10 to

20 percent

of our longevity has to do with our

genetics

and this goes back because as i was

reading before i got to this part i was

thinking about the human genome project

just automatically my mind always goes

there when i hear about genes and all

the work that went into it i think it

was like at least a billion dollars to

try to map the human genome when we get

back like it's like 20 000 genes and

we're thinking we'll have hundreds of

thousands or whatever the number might

be

but the the big missing piece

was this junk dna right this there was

all this other data that was just

ignored because it didn't fit into the

category of being a gene

well that's right and we still we still

don't have a complete human genome

because the these missing pieces are

very repetitive and they're also little

genes that were missed by the computer

algorithms in the 2000s which we in my

lab and others we've gone back and we've

compared humans to chimps and macaque

monkeys and these little genes there are

thousands of those we think and with

proteins swimming in our bloodstream

that control health and longevity we

have a lot to learn about the genome but

what people have mostly missed is the

epigenome because that's a lot harder to

read

you can read a code that's a

one-dimensional

program

but to read something in three and even

four dimensions if you include our

lifespan over time

that

required another 20 years of innovation

but we now have the tools

where we can

this is really amazing for for something

that costs i think it's a few thousand

dollars but it's the size of a candy bar

um

it's about that big

in my lab we can do your whole genome

instead of for a billion dollars i could

do it for maybe a couple hundred bucks

now take me a couple of days but we can

also now read the epigenome and tell us

where those loops are where those

bundles are

and also measure the chemicals that

accumulate on our genome that tell us

where the loop should be

and how old we are literally how old we

are biologically

so throw out the candles who cares about

candles it's those chemical marks that

seem to determine our actual age and how

healthy we are this is so cool so i'm

thinking in terms like we need to stop

celebrating our chronological birthday

and celebrate these biological birthdays

because they're different well they are

but the good news is you can't really

turn back your chronological age you

can't release well you can lie about

your age but it's not going to help

but you can what we've discovered is we

can now dial up aging speed it up

in animals and now that we know how

aging we think we know how aging works

we can also reverse it yeah

so that that's the what i wanted to tell

the world about because that's that

changes how you think about your life

absolutely i mean i couldn't help but

think about myself

um in my experience when i was 20 years

old i was diagnosed with

a condition that's usually attributed to

people who are much older i had

degenerative spinal disease degenerative

disc disease and my physician said i had

the spine of an eight-year-old man not a

healthy 80 year old either

and to get that bill of goods when

you're just 20 of course it could do a

big number on your psyche but he also

said this was incurable right i've

created this situation and there's

nothing i can do about it

and

we can get into the nocebo effect and

all that stuff but the bottom line is it

took about two years before i decided

let me try to do something about this

and i got a scan done it's probably been

about

a year ago now and my spine looks

younger than the age i'm at now right

how is that even possible you know and

this is what you're talking about in the

book well that's the power of the

epigenome you're not changing your

genome you get that from your parents

but you can change your lifestyle you

can change it tomorrow and you did

you're in a back brace as well you can

through that grace yep yeah it's

impressive but it doesn't surprise you

yeah really

and that's what i want everybody to know

and you're doing a great job telling the

world is that you can change your life

you can change your health just by how

you live your life even with without

medicines

and it's it's pretty easy to do right

but it's super powerful and the message

that i'm bringing is

thanks to work in my lab and dozens

around the world we've also figured out

we think why

these things that you're doing and

people who are healthy

why they work

because they're turning on these

defensive genes these longevity genes

that are in our bodies but they don't

get activated unless we do the right

things eat the right things eat the

right time of day we get enough sleep

um we exercise and the right way then

these genes come on and they protect us

and they don't just slow aging we see

that they reverse many aspects of aging

as well yeah and i want to talk about

some of these things specifically but

before we do i really want to give

people i think it's a brilliant analogy

of our genes

functioning sort of like keys on a piano

so can you share that analogy yeah sure

so the the genes are like a

piano with 20 000 keys

and imagine there's a pianist that's

perfectly

young and

skillful when we're young

and this is our cells are able to read

the right genes at the right time and

place so that's why when we get a cut we

get a cold we recover very quickly but

what's happening is the pianist in each

of our cells

starts to

lose her eyesight starts to become a

little bit demented and initially plays

a few of the wrong keys but if you're

listening not too intentively it still

sounds great but over time what's

happening is then she's losing her

eyesight she can't see the music and

she's banging the wrong keys eventually

it sounds like

crap and it's a cacophony and everyone's

walking out of the symphony

or or the performance that's what aging

is our cells are losing our ability to

read the right genes at the right time

because these loops and these structures

that we think we can now reset so we can

actually we think go in give the pianist

or even get a new pianist or give that

pianist glasses and new music

and within just a matter of weeks now

you get the symphony back again and

cells work like they did when they were

young again um wow

so cool

um

and can we talk a little bit about so

how how does the epi epigenetics play

into that whole equation

oh so the epigenetics are it's brand new

so this is science that you will will

not really read about anywhere else

the epigenetics are

laid down during development so is where

embryos i mean one of the miracles of

what what exists on this planet is you

can take a fertilized single cell and

make a baby that comes out with 26

billion cells that all know

what they are and how to work and work

together

but over time those instructions in each

of those cells

not the genes but the ability to read

the right genes is lost and that gets

accelerated in part by not activating

our longevity genes well when we're

young we have a lot of activity we don't

need to exercise as much right but as we

get older they become complacent if

we're obese if we sit around all day

you've written a book i've written a

book we know what happens to our bodies

they lose activity it's brutal

and eventually the pianist

is has lost her ability to play it

but what's great about what we've

discovered is that you can

make sure that those keys the pianist

stays young she doesn't need glasses for

much longer

uh and then what i didn't know until

about a year ago

and it is described in the book because

i was writing it as we were making these

discoveries

is that there's a backup pianist in our

cells every one of them that tells those

loops and those bundles

what they were like when we were babies

and we can access those just by turning

on a set of three genes out of those 20

000 that sets in motion a program to

reset the entire cell

wow this is so cool so cool

so would the the pianist be

function function sort of like the the

epigenetics yeah the pianist is the

epigenome and the piano is the gene so

it's determining which keys are getting

played which genes are getting expressed

and which ones aren't that's right and

every cell has to do that because the

nerve cell in your brain has been there

since we were young

and it's got to stay a nerve cell

if it starts behaving like a skin cell

we're in trouble but that's what i think

aging is if we take an old mouse two

years old and we look at its skin its

skin is going to look look more like a

nerve cell

and we have to remind it

go back to being a skin cell you you

fool but we can now do that we have

these reprogramming factors

reprogramming genes

that tells the epigenome

how to restructure itself and read the

genes as though

it was young and

cells remember what they should be doing

but but old people we see or at least in

old mice we see that there are a

cacophony a mess a melange of different

cell types instead of being

rigorously urinary cell get back to

being a nerve cell and one of the

amazing things that we did by resetting

the eye so we use the eyes as one of our

test

tissues we can take an old mouse that's

a year old and it's doesn't see very

well

we can actually measure mouse eyesight

number of ways we can either measure the

electrical impulses or we can

see if they can see moving objects

and in both those cases we can

by delivering these reprogramming

epigenetic reprogramming genes

we can tell the nerves at the back of

that old eye

to function again to play the right keys

so turn on the right genes to be young

they do it

and just a few weeks later those mice

can see as well as they did when they

were babies fascinating that's so

fascinating and that's a complex organ

we're not talking about

just skin an eye is probably the most

complex part of the body if well the

brain's probably more complex but this

is a big deal um you go through certain

phases in the book and you start off

with some of the things that a lot of

folks are tuned to but you dive a little

bit deeper and make it make a little bit

more sense

and one of those things

is obviously our nutrition and there are

certain nutrients that play a part and

then there's certain ways of eating that

play a part so let's talk a little bit

about each of those

right so part two of the book is about

what we know and what we can do in our

daily lives and then we later on we have

a glimpse into the future but what we

can do right now is pretty simple so you

mentioned nutrients uh first of all we

have a theory that uh

bears out

which is eat foods that are stressed

stressed out

which is a weird concept right but we do

it naturally we drink some of us drink

red wine which is a stressed grape

before we pick it

we often eat colored foods so spinach is

a dark green food there's blueberries

which are dark

the wider ones are not as good so why is

that well stressed food

produces a lot of what we call

xenohermetic molecules

and i'll explain what that means it's a

terrible word we coin but xeno xeno

means from other species

and hormesis is a very important word

you've got to remember the word hormesis

because it every day you should think

about it hormesis is what doesn't kill

us makes us live longer

and

it's a

term that means you've got to get your

body out of its complacency you've got

to trigger those defenses those

longevity genes so xenohemisis is

you don't have to

only run and eat well

at the right times but you can also get

these molecules from the right

animals and plants but particularly

plants that are stressed because when

plants are stressed they're making these

molecules of health for their own

benefit right they're trying to survive

they're turning on their longevity genes

we forget plants have longevity genes

too

so a stress plant will make these

colored molecules to protect from uv and

dehydration

when we eat them

they trigger our own body's defenses and

you can get the benefit so that's

nutrition colored foods stress foods

organic is stressed right you don't want

the perfect lettuce that's been

not put any stress

and we need to do more of that we need

to let our plants stress a little bit

before we eat them

and then nutrition there's a lot of

nutrition now there's a debate every

week about what's good what i do is in

on

the part three of the book i list it out

um so i i truly believe that we've got

to mix it up right the secret is not so

much what we eat but when we eat

and also what we eat should have variety

so i don't say

only eat

meat i don't say only eat carbohydrate

i eat a little bit of everything i try

to avoid big amounts of meat because

there's one of these longevity pathways

remember i said there are three main

ones one of them senses how much meat we

eat and amino acids so you need to give

it time to rest and settle down so

that's important so often i'm not eating

a big steak but i will eat meat if i've

worked out because our body needs amino

acids

but that's it make sure that you it

actually what's more important than what

you eat is when you eat

how's that for an interesting thing to

say and what we've discovered with my

collaborators

and i need to give a shout out to one of

my friends at the nih national

institutes of health rafael de cabo he

studied 10 000 mice

and what he tried to figure out was

is there a diet that makes them live

longer any mixed combinations of

carbohydrate protein and fat and was

hoping to see finally what works and he

found out they all did the same thing

they all had short life spans but there

was a one group where he only gave them

the food two hours a day instead of all

throughout the day

and they lived about twenty to thirty

percent longer wow love it wow so i if

there's one thing i could say

that i've learned after reading ten

thousand papers and studying this my

whole life it's

eight less often

that's so good that's so good

wow um

there's so much good news packed into

that

and the first thing is like you get to

eat and you can see clearly with a study

like that that we're

debating the minutia of your

macronutrient ratios right and for

everybody can be dramatically different

but what we do see across the board is

that if you take whatever deliciousness

you're trying to have and compact it

into a shorter window of time and giving

your body a little bit of uh of a break

you can turn on some of these longevity

genes that's it so that that's the key

the the take-home message here is you

want to trick your body into thinking

times are tough

adversity hormesis

so you can tell your body through eating

stressed foods that times are going to

be tough because your food supply is

dying

you can trick your body into thinking

that you need to be running away from

saber-toothed cats because you get on a

treadmill or you run or you you lose

your breath

um or you get hungry during the day and

that also tricks your body into thinking

whoa i need to fight back against

adversity i need to fight against

diseases and the long-term effect of

that the benefit

is longevity

yeah

so just to take a a small step back

because i know that

there's and it's so cool that you talked

about this a little bit in the book but

eating

is

it's important as well because

for you know some of us can think and

this is the american way is like a

little of something

is good

massive amounts of it must be better

right so instead of just doing an

intermittent fast

each day i'll just fast for you know

two weeks or whatever you know what i'm

saying

and so but then there's this role of

something called mtor

that comes into play you know so and

nutrition is involved in that so can you

talk a little bit about this mtor yeah

so mtar mtar is the second uh leg on the

the three-legged stool

uh i mentioned sirtuins yeah

mtor is is probably the the most

important to get right but they'll talk

to each other but this is a really key

one

uh mtor is sensing how many amino acids

are in your body particular amino acids

leucine isoleucine

branch chain amino acids and if you're

always eating meat every day your mtor

will be

active

mtor is there to to grow new body parts

it's there to grow larger taller when

you're developing

the problem is if you're always feeding

at amino acids and trying to bulk up

yeah you'll get great big muscles and

you'll look great but the long-term

effect of that we've seen in animals at

least is that you're not harnessing your

body's defenses your longevity genes the

mtor

isn't in this case you want to turn it

off you want to down play it because a

low m tour activity predicts longevity

and uh so that's why i'm mostly focusing

on plant-based foods as much as i can

but when i need to bulk up and if i work

out typically every sunday then i will

eat meat but give like you say give your

body a rest mix it up

so mtor is that's

it's not talked about enough and

especially in the kind of conventional

health circles and fitness circles

but this is one of the reasons we need

protein and

but the great news is that

a small amount can go a long way is what

i'm hearing

well it is it is and you don't need to

restrict everything it's important to

give yourself the ability to repair

itself but if you're always

in this

rebuild mode always body building mode

which you know you'll end up looking

great but

it actually comes down to vanity versus

longevity if you're only you only care

about vanity you're going to miss out on

the longevity part so

this is the trick is to

do the exercise do the weight lifting

you need that um i need to do a lot more

but i do it on weekends

but

then give your body a break you don't

want to work out hard every day we know

that yeah you don't want to eat three

meals a day we believe that's bad

um and so we have to overturn what we

thought which was more is always better

so if we can let's talk about because we

talked about amino acids thrown in there

but some of the specific nutrients and

one of them

uh

is resveratrol and you know we've been

hearing this connected with longevity

for a while and but for you to say it it

gave me a lot more mental credence as to

its value and because of that

we have the best people in the world

here on my team

somebody who read the book

and they brought in some chocolate for

you that we have sitting here uh some

high quality dark chocolate because of

reading that that is one of the sources

for me immediately i think back to to

red wine and people was like oh

resveratrol i'm

a bottle a day right and it's that's not

necessarily what we're going for there's

many other sources

well there is and uh you can have it in

its pure form too i i do that because

the amount that i'm taking and i've done

so for the last 13 years is the

equivalent of 500 bottles of red wine

which i do not recommend for breakfast

yeah

you might uh do your liver in uh but

resveratrol is super interesting because

we discovered that it controlled these

sort of

longevity genes and that was now 13

years ago

and what we've been studying ever since

is

how do they work and when should we eat

it

and what does it do and the good news is

that 13 years ago all we were doing was

extending the lifespan of baker's yeast

and worms and flies but now there have

been clinical trials and there are

products out there that have been tested

on many people

and there are clear benefits actually in

these placebo-controlled trials which

are essential otherwise you don't know

for sure and you see a lowering of blood

sugar you see improvements in in liver

function and these studies

finally show that what we saw in mice

initially in 2006 which by the way those

that study we put out sent red wine

sales up 30 and they stayed up so anyone

who has been taking red wine for

drinking red wine for the last uh you

know a few years you're welcome

but uh but seriously the the what we saw

in the mice was that they were protected

against high fat food

they were just as healthy

against an american bad diet

but and they lived as long as a healthy

lean one

but that's not an excuse to just sit

around on the couch and pop resveratrol

by no means what's often missed even by

scientists is the data that's in the

back of those papers

two important points one is

if you take resveratrol every other day

you get the greatest benefit and we've

had mice living over three years which

is a long time for a mouse they

typically die a bit over two

and the second thing um that we learned

was that

that if you eat it with fatty foods it's

actually better or you eat it with a bit

of oil it gets into the body a lot

better and so that's why i mix my

resveratrol with some yogurt just a

couple of spoons in the morning i don't

want to eat a big breakfast but without

that you're a lot of it's not even

making it into your system and there

have been clinical trials that have

failed and when i look at how they did

it yeah they were giving their patients

or their subjects a capsule with water

and that's not gonna work

wow that's fascinating that's really

fascinating i never thought about that

so it has a fat soluble aspect to it

oh for sure it's like brick brick dust

chemists would tell you brick dust

and if unless it's dissolved yeah it

just

pretty much won't get absorbed by the

gut

and so we know red wine's a source what

else do we have

missiles also supplements for sure

i take the supplement because you'd have

to eat a lot of chocolate as well

um

but you know

let me let me just make it clear that i

don't know

if it's going to make me live any longer

but i can tell you my cardiovascular

system looks like it's a 20 year old so

that's good so so far so good

but what else can we do we could peanuts

have a little bit

but unlike a lot of things we can do in

our diet

resveratrol isn't found in huge

quantities there's only a milligram or

two in red wine even yeah and i'm taking

between 500 and a thousand milligrams

i love the fact that you mentioned the

cycling aspect and this is true with so

much because again we have that some is

good more is better let me just do this

every day

and i love the the the concept and also

just the

the the

practicality of cycling nutrients

because even if you just think about the

way that we evolved you know we're not

having the same thing every day

yeah and here's the great news we used

to think that calorie restriction was

the way to go and

we've known for thousands of years that

being hungry is good for you but we used

to think that based on monkey studies

and rat studies that those animals and

we would always have to be hungry

but you've got to pulse it you're

allowed to eat and be full once in a

while

and uh and that's great news because if

you

give

mice and rodents now rats food

during the day they can eat 90 of what

they would normally eat in a calorie

restricted diet but be hungry all the

time

so we can live great lives i eat

a late lunch or skip lunch but then i

typically eat a really nice dinner and

i've actually grown to love food a lot

more for that reason wow

you do appreciate food rather than just

shoving it down during the day

uh but i think i live first of all a

much healthier life but also

one where i'm a lot more grateful for

food yeah and i i could um

i could personally affirm that

experience and i remember i mean this is

over a decade ago but i would go this is

one of the things that makes me good at

what i do is that experimentation you

know so i would do uh several weeks of

fasting where i'm just having juice

right it's vegetable juice

and i remember the and i

i've shared the story before but it

might be hard to believe but i didn't

eat a salad like an actual salad until i

was about 25 years old that was the

first time i ever had one in my life i

was raised on like

fish sticks and like i was probably like

four percent ravioli like just in my

blood right and so eating a salad just

was out of my paradigm it's just like

why would i do that and i remember after

a 21 day fast i went and got a salad

and prior to this just a couple weeks

before i did the fast i tried to eat the

salad went right to the trash can

gagging okay

i got the salad and i took the first

bite and my brain is just like lighting

just like this is so good i can't but i

was still scared i'm like i'm gonna

throw up any moment and i took the next

bite and i'm just like

this is the greatest thing i've ever

eaten in my life

and i ate the the whole little salad i'd

gotten for myself it was that whole

foods just like tucked in a corner and

this is true so i was walking out i

threw the box away and i told a random

person i was like i just ate a salad and

they looked at me like i was from

another planet they're like oh okay you

know

and i was just blown away at how much i

appreciated eating after not eating for

so long right and so having those

moments even now you know just

intermittent fasting through the day i

totally agree last night we had dinner i

was

really crushing it yesterday just

working doing some stuff behind the

scenes we had dinner it was the it was

like the best meal i've ever had in my

life you know and i've had that same

food before but it's just i appreciate

it so much more well i'll confess

something for the first time uh on on

your show

uh now that i appreciate food and and i

i know that food is

not just pleasurable it's actually good

for you

i'll go back to my old habits and

there's food around us that's the

problem it's everywhere so you you your

reptilian brain will pick up something

shove it in your mouth and then i'll

think

that's in my mouth why did i do that

and i'll go through the calculation does

this meet the criteria of whether it's

worthy of eating do i swallow and

occasionally i'll say no it's not worth

swallowing this crap what i don't even

enjoy this and if i'm not enjoying it

it's not worth it so you know i know

there's eating disorders this is not one

of those but

i really i only put in my mouth now what

i really want to eat yeah but i love it

fascinating um you know

just opening up this conversation and

looking at the different dimensions of

how

it's not just the food that we're eating

but how we're doing it right when we're

eating has a huge role to play

um it's just it broadens the

conversation because i think we really

can easily get caught up in the the

minutiae like we talked about earlier

you know like trying to get your

macronutrient ratios correct that stuff

matters but there's a bigger

conversation and

getting more into this bigger

conversation

in the book

um you also stretch out and you you get

into

conversation and things that we've got

science behind that were really

counterintuitive for me or things that

for example metformin right i want to

talk about this i spent

over a decade working in my clinical

practice as a nutritionist alongside

physicians to help get people off

metformin and then seeing this data that

you're

sharing in the book that metformin might

actually

be one of those well it is according to

your data

those things that can help to switch on

those longevity genes so let's talk a

little bit about that so just for if you

can for everybody share what is

metformin and why is this something that

folks are now who don't have diabetes

are taking

yeah so metformin is one of those gifts

to humanity it's on the list

so the world world health organization

has called it an essential medicine for

humanity because it it's so safe

it's not perfectly safe but it's so safe

and the benefits are are really clear

especially for diabetics

so there are these three legs to the

stool the three pillars sirtuins we

talked about we talked about mtor and

amino acids the third one

is called ampk or amp kinase and this

protein senses how much energy we have

in the body

and if we have low amounts of energy

then it'll try to make more and that's

actually healthy so you want to also

trick your body into thinking it has low

energy you don't want low energy but you

can trick your body so how do you do

that one is to be hungry

one is to exercise and the other is to

take a medicine

that inhibits mitochondria and lowers

the amount of energy that the cells

producing so the body goes holy crap

we're running out of energy and it'll

make try to make more

and that's good for you now the side

effect of that

is having better blood sugar levels so

your body becomes

what's called insulin sensitive you know

this that when you're type 2 diabetic

your body doesn't register the insulin

that's your pancreas is putting out and

it just makes more and more insulin and

eventually your pancreas can give out

but the problem with that is you have

high amounts of sugar glucose in your

bloodstream which will cross-link

proteins and accelerate aging

and all sorts of problems cardiovascular

disease wounds won't heal and this is

truly accelerating aging we've proven

that in our field

metformin

is shown to be very effective against

type 2 diabetes and if you have type 2

diabetes your doctor will typically put

you on that medicine now it comes from

the french lilac it's derived from a

plant so it's a xenohermetic molecule

actually

and but it's classified as a drug so it

falls into that category so in this

country at least but not all

you need to get a prescription for it

which actually puts it out of reach for

many people but it also makes a lot of

people wary that if it comes from a

doctor it might be a little bit fishy it

might be toxic but it really has been

shown in a study of over a hundred

thousand people now many studies

actually

that diabetics who take metformin in the

long run

aren't just better off for diabetes but

are actually

healthier and protected against cancer

heart disease alzheimer's and frailty

even more so than people who don't take

metformin and who don't have type 2

diabetes

that's it that's stunning yeah and when

i heard that i didn't believe it my

friend near brazil eye doctor neil

brazile's the world's expert he told me

that and i had to go and check on these

papers which i referenced in the book

it's true so i become a real convert and

about two or so years ago i started

taking metformin i don't have diabetes

yet but i was on my way up i actually

met my trajectory of the last

11 years and i could see i was headed

for diabetes it's in my family

so i stopped it in its tracks and

actually reversed

type 2 diabetes i wasn't

now i'm i'm at no risk of having

diabetes because i'm on metformin

because i've made these changes in my

life

now is it for everybody i think if

you're young and your blood glucose

levels are low

not not needed if you're exercising and

eating eating right

but if you're i'm 50 now and if your

blood glucose goes up every year

and you can't control that metformin i

think is a good thing to talk about with

your doctor yeah you know what and just

since you just mentioned that being 50

if folks aren't watching the video on

youtube you look like

maybe maybe 30s you know like 35 you

know um

you have this uh and your your energy is

high you're creating all these different

projects working on different papers

um so you have that aspect your physical

appearance like you're living you're

living proof of the stuff you talk about

and i can see you're just getting warmed

up as well you know and so just a little

shout out for those who are listening to

audio

the guys got it dialed in you know and

so but i wanted to bring this up because

i also with the model health show i want

to stretch our thinking

we do like i mentioned you know i was

looking at what can i do for these

patients to help them to normalize their

blood sugar naturally right and removing

the cause oftentimes was you know

mountain dew or whatever it was you know

just

but if we eliminate those things

and your body is already in a healthy

state

adding in these different medications

potentially again this is just a

conversation i want to get going there

might be some potential benefits

and this is still early but it really

got me thinking when i was reading the

book

and

one of the other aspects

i think this might go back to because

for me i think

that this competes metformin can compete

with some of the hermetic

benefits of other things potentially

right so can you talk a little bit about

that maybe like let's talk about

exercise in that context because it's a

hermitic stressor yeah so how does that

compete

yes so remember we're working with a

very complex machine our bodies and

there are these three legs of the stool

but we don't know exactly which ones to

tweak and when we're still figuring this

out as scientists

the good news is that we live in a world

now where scientists can talk directly

to the public and we put out newsletters

so you don't have to wait 10 years to

hear it from your doctor or 20 years

but we the honest truth is we don't know

exactly what the best combination is and

we're learning actually that sometimes

you don't want to combine them at the

same time you might want to do them on

off days and metformin and exercise

is a case in point

now what we've just discovered in a

couple of papers that came out this year

only

is that metformin because it it tricks

the body into having low energy by

inhibiting the mitochondrial energy

levels

if you give elderly patients metformin

and give them weight lift do

ask them to do weight lifting

they will bulk up both of them all right

both sets with me from without but the

ones that didn't get more metformin will

have bigger muscles

okay but not a lot not a lot bigger they

all got bigger muscles

so it is inhibiting the growth the

hypertrophy of muscle but here's what's

not talked about on social media or

appreciated by a lot of people

those people those elderly people were

all the same strength even though they

didn't have the same sized muscles

so it still gave them the benefits they

just didn't look as bulky so that's

where i go back to vanity versus

longevity right but i think there is a

way to optimize it we don't know for

sure and dr peter tia our friend uh he

argues this with me and he also agrees

at least on this point

that

we don't want to be taking metformin on

days where our muscles are growing

that's probably the best and that's what

i try to do i skip metformin when i go

to the gym

but we disagree on exactly

what the precise

combination is

uh but he also thinks that uh fasting

for a long time is good

and i i don't know if that's true i find

it extremely difficult to go for more

than one day

i start to lose

my blood sugar goes too low and i've

measured it with one of those uh

monitors that you can stick them on

right fascinating by the way have you

done that yeah the 24 hour i mean just

stays with you i haven't yeah yeah but

many of my friends have you learn a lot

um and actually i didn't have breakfast

i can feel it right now my blood sugar

levels are going low i should eat some

chocolate actually

um but yeah if i go for three days or a

week like peter does

he actually is turning on pathways that

i think are even more beneficial yeah

there's one called chaperone-mediated

autophagy which is basically super

recycling of the body's proteins and

that's something i think that

he's right about

and uh if you can go for three days

you know more power to you right yeah

and i love that so much because there

when when i made the reference earlier

about some is good

uh

more massive amounts is is great there's

still there's usually something there in

the middle or closer towards you know

that little bit those little micro doses

and having an extended fast you know of

a few days

uh obviously you're going to activate

more of these different beneficial

process processes uh autophagy and the

list can go on and on but we also have

to be mindful of

the longevity aspect of happiness

you know um

i think that we don't talk enough about

this first of all and this is just

something consistent that i see you know

i'll read i don't know why i do this all

the time but whenever i can

something comes across my attention on

my phone or a friend or somebody that

that lives to be 100 years old or older

i interview them i read their stories i

read their articles and there's this

consistent thread of happiness there's

this consistent thread of like

meaning in their lives you know so

if you're gonna be pissed for three days

and just like

a krabby patty right just mad at

everybody really that that's it doesn't

equal out for me the benefit potential

benefit that you could be getting yeah

that's right so when we calorie restrict

these mice in my lab they also get

really crabby they fight with each other

especially the the boys so it's natural

but you need to overcome it yeah

but uh i totally agree that that if

you're not happy it's not worth it but

the the key to happiness is mission

and i just came from a conference where

we're talking about how to optimize

those three legs on the stool

and uh one of the speakers was dr cooper

he's the guy that coined the term

aerobics and you might wow

he must be 100 years old he's almost i

mean he's in his late 80s but he's had a

mission in life to make people live

longer and he's treated presidents the

first bush

um george bush

and he his mind is super quick he's

talking like this bam bam bam you think

you're not 80 you're more like a 20 year

old in the way you talk and think and

move now these are test cases these

aren't clinical trials but when you see

him

he's been doing aerobics for the last 40

50 years

i mean a guy like that you want to mimic

that and what he's shown in thousands of

patients that he's treated and tens of

thousands of kilometers or miles that

his patients have run

he can reduce the the rate of aging

clearly and through the trajectory of

his patients

instead of the average lifespan being 80

which is what it is at best for this

country he gets them out to near 90.

so it's clearly the case that if you do

what he's recommending you eat the right

way

starting at an earlier age you don't

have to live to 80 you can play tennis

and at 90 maybe live to 100. yeah but

wait till there's new technology is

coming yeah so exciting and that's why

people have to stay connected to you to

learn more about this

and

speaking of mission

i want to ask you personally um what is

the model that you're setting for other

people with how you live your life

personally right

the way that you are conducting yourself

your business your research what is your

bigger mission

that you're wanting to express or to

achieve

with your life right now

well i think it's the same as a lot of

successful people

i'd be surprised if you don't feel the

same way

we know we're going to die right

there'll be a day where

we know this is it we're done for uh

unless you get hit hit on prematurely

buy a bus or something

when that moment happens i want to be

able to say to myself

i did the most i could to leave the

world a better place than i found it and

it can be a little bit it can be a big

bit but you got to put everything into

it

and i think that humanity can do a lot

better there's far too much complacency

and giving up

and a lot of us just give up they say

the world can't be changed

but you know friends of ours

we all agree that if you have a mission

just pick something that you're good at

and you like and never give up that's

the secret it make you know life's tough

it's long if you're not driven every day

to get up and do something that you love

and you think that it's worthwhile

it's a tough life

yeah i love it

can you let everybody know where they

can pick up your book

and also connect with you online

well we have a website lifespanbook.com

so at lifespanbook.com we have a

newsletter for updates

uh things about lifestyle things about

the new science that we've read

um updates on my dad who's still going

strong at 80 uh climbing mountains and

all lifespanbook.com on social media i'm

on you can find me on twitter and

facebook and on instagram pretty easily

um but we sell books on barnes noble and

amazon um audiobook actually we recorded

the audio book book in this building

right here

and uh it's doing great it's a

bestseller new york times bestseller on

the audiobook and the hardback

um but the audiobook's special to me

because we did something different we

did in between the chapters we had chats

about what we were how we wrote the book

and how we thought about designing the

book so that's an extra free bonus for

people who get the audio book perfect

perfect thank you so much for sharing

your time with us today and thank you

for putting together such an epic trates

on longevity and i think that this is um

it's something that we just really

haven't seen before

uh you weren't afraid to get into the

science you did make it understandable

but this is a little bit more

science-heavy than what publishers would

typically allow

but the stories even like you

articulated with the the pianist example

like it really brings it to life and i

just really admire that so thank you man

well thanks you won't read it anywhere

else because it's it's science right on

the cutting edge but it also it'll

change the way people think about their

lives and what's possible

awesome and you're an inspiration sean i

appreciate it thank you thank you i

received that man thank you thank you

for coming to hang out with us any time

hey if you like this video make sure to

check out this video right here

to up level your health today other

things that were causing cancer that we

didn't know and didn't quite link to

that whole paradigm but we thought well

it must be just the genetic thing so

that's that's why that genetic paradigm

really took off and everybody was sort

of all in on it for so

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