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

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    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