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

    From Longevity Wiki



    0:00 is there a diet that makes them live longer any mixed combinations of carbohydrate protein and fat and was
    0:07 hoping to see finally what works and he found out they all did the same thing
    0:12 they all had short life spans but there was a one group what specifically sparked your mind to be to have this
    0:19 idea that we could extend our lifespan uh well to me it's it's plain
    0:26 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
    0:33 we don't have to accept what we think is the inevitable um and so the mantra in my lab and in my
    0:38 in the book that i wrote is uh nothing is inevitable and the problem with aging is that we
    0:44 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
    0:51 grandmother who taught me that that didn't have to be the case uh she raised me because my mother was
    0:56 working and she was young she had my father when she was only 15. and so that going back to the 1930s that
    1:04 was a big deal right she was kicked out of high school and but she came to australia ran away from europe from hungary
    1:10 and raised me and her view was adults screw up everything because she'd seen what happened during the war and after afterwards
    1:18 and but she was a huge rebel she was the ultimate rebel my my our 16 year old daughter has the same
    1:23 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
    1:30 she taught me and you know the police probably uh will remember a few of these things she told me you
    1:37 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
    1:43 those days was illegal she used to drive like a maniac not speeding so much but she would drive
    1:49 like this looking around and dance to the music so the car is going like this to uh beethoven's ninth
    1:55 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
    2:00 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
    2:07 leave your mark and allow humanity to reach its potential and not let others screw it up
    2:13 so i've spent every day doing that but why aging because to me it's obvious this is the biggest unsolved problem if
    2:19 aliens came down to see us and judged us as a species they'd say pretty good on
    2:24 atomic theory quantum mechanics but this aging thing you don't even realize it's a problem that you can solve we figured
    2:31 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
    2:37 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
    2:43 age and in fact you said that aging is and you you approach it as being a

    How aging is a disease.

    2:48 disease well it is a disease it's just we can call it whatever we want but what
    2:54 is a disease a disease is something that happens over time that causes you to have a disability which you know well
    3:02 and it causes frailty and eventually it can cause death okay that's aging right
    3:07 is it not what so what's the difference why do we separate disease from aging the only difference is
    3:13 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
    3:20 we focus research development policy on actually what kills most of us
    3:27 this is really fascinating because for me just you bringing up the conversation
    3:33 the way that you did i realized that we know pieces of aging like what it looks like and we're
    3:39 attempting to address different pieces but there is no unified theory of aging as you pointed out but there are these

    What the characteristics of aging are.

    3:46 uh characteristics of aging that we're all trying to attack well that that that was true a few years
    3:52 ago what i've put forth in my book is a theory that i think can explain why we age and
    3:59 explain why all these other things happen now we scientists have we love to put things into categories and we came up
    4:05 with about seven or eight causes of aging we call these the hallmarks don't want to get too carried away call
    4:11 them hallmarks um and we've been very satisfied for the last probably eight years
    4:16 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
    4:22 live longer now that i have no qualms with i think that's true but that still begs the question
    4:29 what causes those to happen and so my theory i've called it the information theory of aging if you boil it down to
    4:36 an equation if you want its first principles i think aging is a loss of information
    4:42 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
    4:48 hard drive of youthfulness that we can tap into and reset our computers this is so fascinating
    4:54 you specifically just this is a great uh segway into looking at the digital nature of dna
    5:02 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
    5:09 then when we're talking about our genes in our gene expression there's an analog aspect so let's talk about this digital

    What is the digital aspect of DNA?

    5:14 aspect of dna yeah well this is the crux of everything and most scientists don't talk the way i do we've
    5:21 had to invent our own vocabulary and metaphors so dna we all are very familiar with without dna that we get from our parents
    5:28 we're screwed right without uh the ability to encode proteins and run the cell it's important but that information
    5:36 is much more robust than we realize we think of it as this very fragile chemical it's actually not fragile you
    5:41 can boil it you can find it in fossils it's pretty strong yeah so this is robust and it can
    5:49 certainly last 80 years our lifespan it can probably last a thousand years if we're good to it
    5:54 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
    6:00 atcg okay people will remember from high school days if they're not biologists it's just
    6:05 a digital code encoded in chemicals four of them instead of being as ones and zeros it's
    6:10 just four letters but there's this other type of information that's just as important for our survival and that's the epigenome
    6:18 okay so what's the epigenome it's just that's a complex word for the control systems that
    6:23 control the genome in the way that i'll forgive my uh anachronism here but
    6:29 the dvd uh is the digital information and the analog is is the ability to read
    6:35 that so the digital the dvd player is analog so it's moving around and it can move in any possible
    6:41 direction what does that mean for the cell well what's actually literally happening is that as we develop as embryos we're
    6:48 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
    6:55 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
    7:00 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
    7:06 like you would a hose reel and that keeps these genes off hopefully for a hundred years or more
    7:13 but what i'm proposing is that insults to the body and if our body becomes complacent
    7:19 and we there you know there are good things we can do to our bodies what we lose is that structure these
    7:24 loops and these these tight bundles and those fall apart we can see that in our studies
    7:30 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
    7:36 epigenome i can actually tell you how old you are biologically and i can predict with high
    7:42 accuracy when you're going gonna die almost to the month wow that's nice
    7:48 scary right i haven't had it done would you get your clock down i mean um
    7:54 and this is just a little sidebar here but this brings to mind the science behind
    7:59 telomeres and measuring that as this biological marker but there's more there's much more to it that's just one
    8:05 aspect yeah and what's um comforting about this theory and and
    8:11 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
    8:17 very complex system and aging is the ultimate complex system and we've also got
    8:23 a thousand years of observation that we have to explain and if it doesn't explain half of it throw the theory out
    8:29 but as i've described in in my book the theory does actually explain everything
    8:36 even telomere loss telomeres are the ends of chromosomes that that wear down over time
    8:41 the epigenome the proteins that package those loops and those those bundles are also packaging the ends of the
    8:47 chromosomes and the unraveling leads to acceleration
    8:53 of that loss as well and uh and actually the factors that stabilize our epigenome
    8:59 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
    9:04 healthy they are involved in protecting the ends of chromosomes as well and bundling them tightly so they don't erode and cause
    9:10 aging to happen as well yeah i i want to talk about these sir tunes this is really really fascinating so
    9:17 you are is this under that umbrella of what you're calling longevity genes yes
    9:22 okay and how many are there well in total the th there's dozens but they fall into three main categories
    9:28 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
    9:34 or you're dead they're really important but we have better copies than others some people have variants that predispose them to
    9:41 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
    9:47 variant to live long time but by the way only 20 of
    9:53 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
    10:00 about this theory is that if i'm right genes are only a tiny part of the story
    10:05 but these genes are still important because they protect the epigenome and make sure that dvd is read correctly and
    10:11 doesn't get scratches so you can read the symphony for longer this is so fascinating and i love that
    10:16 so much um and just to know and to have the affirmation with science that only 10 to
    10:24 20 percent of our longevity has to do with our genetics and this goes back because as i was
    10:30 reading before i got to this part i was thinking about the human genome project just automatically my mind always goes
    10:36 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
    10:41 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
    10:47 thousands or whatever the number might be but the the big missing piece
    10:52 was this junk dna right this there was all this other data that was just
    10:57 ignored because it didn't fit into the category of being a gene well that's right and we still we still
    11:03 don't have a complete human genome because the these missing pieces are very repetitive and they're also little
    11:09 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
    11:15 compared humans to chimps and macaque monkeys and these little genes there are thousands of those we think and with
    11:22 proteins swimming in our bloodstream that control health and longevity we have a lot to learn about the genome but
    11:27 what people have mostly missed is the epigenome because that's a lot harder to read
    11:33 you can read a code that's a one-dimensional program
    11:38 but to read something in three and even four dimensions if you include our lifespan over time
    11:44 that required another 20 years of innovation but we now have the tools where we can
    11:50 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
    11:56 um it's about that big in my lab we can do your whole genome instead of for a billion dollars i could
    12:02 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
    12:09 where those loops are where those bundles are and also measure the chemicals that accumulate on our genome that tell us
    12:15 where the loop should be and how old we are literally how old we are biologically
    12:20 so throw out the candles who cares about candles it's those chemical marks that seem to determine our actual age and how
    12:27 healthy we are this is so cool so i'm thinking in terms like we need to stop celebrating our chronological birthday

    How your chronological age is different than your biological age.

    12:33 and celebrate these biological birthdays because they're different well they are but the good news is you can't really
    12:38 turn back your chronological age you can't release well you can lie about your age but it's not going to help
    12:44 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
    12:51 aging we think we know how aging works we can also reverse it yeah so that that's the what i wanted to tell
    12:57 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
    13:03 um in my experience when i was 20 years old i was diagnosed with a condition that's usually attributed to
    13:10 people who are much older i had degenerative spinal disease degenerative disc disease and my physician said i had
    13:15 the spine of an eight-year-old man not a healthy 80 year old either and to get that bill of goods when
    13:21 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
    13:26 created this situation and there's nothing i can do about it and we can get into the nocebo effect and
    13:32 all that stuff but the bottom line is it took about two years before i decided let me try to do something about this
    13:37 and i got a scan done it's probably been about a year ago now and my spine looks
    13:43 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
    13:49 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
    13:55 can change it tomorrow and you did you're in a back brace as well you can through that grace yep yeah it's
    14:01 impressive but it doesn't surprise you yeah really and that's what i want everybody to know
    14:07 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
    14:12 you live your life even with without medicines and it's it's pretty easy to do right
    14:17 but it's super powerful and the message that i'm bringing is thanks to work in my lab and dozens
    14:24 around the world we've also figured out we think why these things that you're doing and
    14:30 people who are healthy why they work because they're turning on these defensive genes these longevity genes
    14:36 that are in our bodies but they don't get activated unless we do the right things eat the right things eat the
    14:41 right time of day we get enough sleep um we exercise and the right way then
    14:47 these genes come on and they protect us and they don't just slow aging we see that they reverse many aspects of aging
    14:52 as well yeah and i want to talk about some of these things specifically but before we do i really want to give
    14:59 people i think it's a brilliant analogy of our genes functioning sort of like keys on a piano

    How our genes function like keys on a piano.

    15:05 so can you share that analogy yeah sure so the the genes are like a
    15:11 piano with 20 000 keys and imagine there's a pianist that's
    15:16 perfectly young and skillful when we're young
    15:22 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
    15:28 get a cold we recover very quickly but what's happening is the pianist in each of our cells
    15:34 starts to lose her eyesight starts to become a little bit demented and initially plays
    15:40 a few of the wrong keys but if you're listening not too intentively it still sounds great but over time what's
    15:46 happening is then she's losing her eyesight she can't see the music and she's banging the wrong keys eventually
    15:52 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
    15:59 is our cells are losing our ability to read the right genes at the right time because these loops and these structures
    16:05 that we think we can now reset so we can actually we think go in give the pianist
    16:11 or even get a new pianist or give that pianist glasses and new music and within just a matter of weeks now
    16:18 you get the symphony back again and cells work like they did when they were young again um wow
    16:24 so cool um and can we talk a little bit about so how how does the epi epigenetics play
    16:31 into that whole equation oh so the epigenetics are it's brand new
    16:37 so this is science that you will will not really read about anywhere else the epigenetics are
    16:43 laid down during development so is where embryos i mean one of the miracles of what what exists on this planet is you
    16:49 can take a fertilized single cell and make a baby that comes out with 26 billion cells that all know
    16:56 what they are and how to work and work together but over time those instructions in each
    17:02 of those cells not the genes but the ability to read the right genes is lost and that gets
    17:08 accelerated in part by not activating our longevity genes well when we're young we have a lot of activity we don't
    17:15 need to exercise as much right but as we get older they become complacent if we're obese if we sit around all day
    17:21 you've written a book i've written a book we know what happens to our bodies they lose activity it's brutal
    17:27 and eventually the pianist is has lost her ability to play it
    17:32 but what's great about what we've discovered is that you can make sure that those keys the pianist
    17:38 stays young she doesn't need glasses for much longer uh and then what i didn't know until
    17:45 about a year ago and it is described in the book because i was writing it as we were making these discoveries
    17:51 is that there's a backup pianist in our cells every one of them that tells those loops and those bundles
    17:58 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
    18:04 000 that sets in motion a program to reset the entire cell
    18:10 wow this is so cool so cool so would the the pianist be
    18:15 function function sort of like the the epigenetics yeah the pianist is the epigenome and the piano is the gene so
    18:21 it's determining which keys are getting played which genes are getting expressed and which ones aren't that's right and
    18:26 every cell has to do that because the nerve cell in your brain has been there since we were young
    18:32 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
    18:37 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
    18:44 nerve cell and we have to remind it go back to being a skin cell you you
    18:49 fool but we can now do that we have these reprogramming factors reprogramming genes
    18:54 that tells the epigenome how to restructure itself and read the genes as though it was young and
    19:01 cells remember what they should be doing but but old people we see or at least in
    19:06 old mice we see that there are a cacophony a mess a melange of different cell types instead of being
    19:12 rigorously urinary cell get back to being a nerve cell and one of the amazing things that we did by resetting
    19:18 the eye so we use the eyes as one of our test tissues we can take an old mouse that's
    19:25 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
    19:31 electrical impulses or we can see if they can see moving objects
    19:37 and in both those cases we can by delivering these reprogramming epigenetic reprogramming genes
    19:43 we can tell the nerves at the back of that old eye to function again to play the right keys
    19:49 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
    19:56 were babies fascinating that's so fascinating and that's a complex organ we're not talking about
    20:01 just skin an eye is probably the most complex part of the body if well the brain's probably more complex but this
    20:06 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
    20:12 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

    How, what, and when to eat to reverse aging

    20:19 is obviously our nutrition and there are certain nutrients that play a part and then there's certain ways of eating that
    20:25 play a part so let's talk a little bit about each of those right so part two of the book is about
    20:30 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
    20:37 mentioned nutrients uh first of all we have a theory that uh bears out
    20:43 which is eat foods that are stressed stressed out which is a weird concept right but we do
    20:49 it naturally we drink some of us drink red wine which is a stressed grape before we pick it
    20:55 we often eat colored foods so spinach is a dark green food there's blueberries which are dark
    21:01 the wider ones are not as good so why is that well stressed food produces a lot of what we call
    21:08 xenohermetic molecules and i'll explain what that means it's a terrible word we coin but xeno xeno
    21:14 means from other species and hormesis is a very important word you've got to remember the word hormesis
    21:19 because it every day you should think about it hormesis is what doesn't kill us makes us live longer
    21:25 and it's a term that means you've got to get your body out of its complacency you've got
    21:32 to trigger those defenses those longevity genes so xenohemisis is
    21:37 you don't have to only run and eat well at the right times but you can also get
    21:43 these molecules from the right animals and plants but particularly plants that are stressed because when
    21:48 plants are stressed they're making these molecules of health for their own benefit right they're trying to survive
    21:54 they're turning on their longevity genes we forget plants have longevity genes too so a stress plant will make these
    22:00 colored molecules to protect from uv and dehydration when we eat them they trigger our own body's defenses and
    22:08 you can get the benefit so that's nutrition colored foods stress foods organic is stressed right you don't want
    22:14 the perfect lettuce that's been not put any stress and we need to do more of that we need
    22:20 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
    22:26 week about what's good what i do is in on the part three of the book i list it out
    22:33 um so i i truly believe that we've got to mix it up right the secret is not so
    22:38 much what we eat but when we eat and also what we eat should have variety
    22:45 so i don't say only eat meat i don't say only eat carbohydrate
    22:52 i eat a little bit of everything i try to avoid big amounts of meat because there's one of these longevity pathways
    22:57 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
    23:03 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
    23:09 worked out because our body needs amino acids but that's it make sure that you it actually what's more important than what
    23:16 you eat is when you eat how's that for an interesting thing to say and what we've discovered with my
    23:21 collaborators and i need to give a shout out to one of my friends at the nih national
    23:26 institutes of health rafael de cabo he studied 10 000 mice
    23:31 and what he tried to figure out was is there a diet that makes them live longer any mixed combinations of
    23:38 carbohydrate protein and fat and was hoping to see finally what works and he
    23:44 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
    23:50 the food two hours a day instead of all throughout the day and they lived about twenty to thirty
    23:55 percent longer wow love it wow so i if there's one thing i could say that i've learned after reading ten
    24:02 thousand papers and studying this my whole life it's eight less often
    24:08 that's so good that's so good wow um
    24:13 there's so much good news packed into that and the first thing is like you get to
    24:18 eat and you can see clearly with a study like that that we're
    24:23 debating the minutia of your macronutrient ratios right and for everybody can be dramatically different
    24:29 but what we do see across the board is that if you take whatever deliciousness you're trying to have and compact it
    24:35 into a shorter window of time and giving your body a little bit of uh of a break
    24:40 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
    24:46 want to trick your body into thinking times are tough adversity hormesis so you can tell your body through eating
    24:53 stressed foods that times are going to be tough because your food supply is dying you can trick your body into thinking
    24:59 that you need to be running away from saber-toothed cats because you get on a treadmill or you run or you you lose
    25:05 your breath um or you get hungry during the day and that also tricks your body into thinking
    25:10 whoa i need to fight back against adversity i need to fight against diseases and the long-term effect of
    25:16 that the benefit is longevity yeah so just to take a a small step back
    25:23 because i know that there's and it's so cool that you talked
    25:28 about this a little bit in the book but eating is
    25:34 it's important as well because for you know some of us can think and this is the american way is like a
    25:41 little of something is good massive amounts of it must be better
    25:46 right so instead of just doing an intermittent fast each day i'll just fast for you know
    25:53 two weeks or whatever you know what i'm saying and so but then there's this role of something called mtor
    25:59 that comes into play you know so and nutrition is involved in that so can you talk a little bit about this mtor yeah
    26:05 so mtar mtar is the second uh leg on the the three-legged stool
    26:11 uh i mentioned sirtuins yeah mtor is is probably the the most important to get right but they'll talk
    26:19 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
    26:26 leucine isoleucine branch chain amino acids and if you're always eating meat every day your mtor
    26:33 will be active mtor is there to to grow new body parts
    26:39 it's there to grow larger taller when you're developing the problem is if you're always feeding
    26:44 at amino acids and trying to bulk up yeah you'll get great big muscles and you'll look great but the long-term
    26:51 effect of that we've seen in animals at least is that you're not harnessing your body's defenses your longevity genes the
    26:57 mtor isn't in this case you want to turn it off you want to down play it because a
    27:02 low m tour activity predicts longevity and uh so that's why i'm mostly focusing
    27:09 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
    27:16 eat meat but give like you say give your body a rest mix it up so mtor is that's
    27:23 it's not talked about enough and especially in the kind of conventional health circles and fitness circles
    27:30 but this is one of the reasons we need protein and but the great news is that
    27:37 a small amount can go a long way is what i'm hearing well it is it is and you don't need to
    27:42 restrict everything it's important to give yourself the ability to repair itself but if you're always
    27:49 in this rebuild mode always body building mode which you know you'll end up looking
    27:55 great but it actually comes down to vanity versus longevity if you're only you only care
    28:01 about vanity you're going to miss out on the longevity part so this is the trick is to
    28:07 do the exercise do the weight lifting you need that um i need to do a lot more but i do it on weekends
    28:13 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
    28:20 meals a day we believe that's bad um and so we have to overturn what we thought which was more is always better
    28:29 so if we can let's talk about because we talked about amino acids thrown in there
    28:35 but some of the specific nutrients and one of them uh is resveratrol and you know we've been
    28:41 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
    28:49 its value and because of that we have the best people in the world here on my team
    28:55 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
    29:02 reading that that is one of the sources for me immediately i think back to to red wine and people was like oh
    29:08 resveratrol i'm a bottle a day right and it's that's not necessarily what we're going for there's
    29:14 many other sources well there is and uh you can have it in its pure form too i i do that because
    29:20 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
    29:26 which i do not recommend for breakfast yeah you might uh do your liver in uh but
    29:33 resveratrol is super interesting because we discovered that it controlled these sort of
    29:38 longevity genes and that was now 13 years ago and what we've been studying ever since
    29:43 is how do they work and when should we eat it and what does it do and the good news is
    29:50 that 13 years ago all we were doing was extending the lifespan of baker's yeast and worms and flies but now there have
    29:56 been clinical trials and there are products out there that have been tested on many people and there are clear benefits actually in
    30:03 these placebo-controlled trials which are essential otherwise you don't know for sure and you see a lowering of blood
    30:08 sugar you see improvements in in liver function and these studies finally show that what we saw in mice
    30:16 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
    30:23 who has been taking red wine for drinking red wine for the last uh you know a few years you're welcome
    30:31 but uh but seriously the the what we saw in the mice was that they were protected against high fat food
    30:37 they were just as healthy against an american bad diet but and they lived as long as a healthy
    30:44 lean one but that's not an excuse to just sit around on the couch and pop resveratrol
    30:49 by no means what's often missed even by scientists is the data that's in the back of those papers
    30:56 two important points one is if you take resveratrol every other day you get the greatest benefit and we've
    31:02 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
    31:09 was that that if you eat it with fatty foods it's actually better or you eat it with a bit
    31:14 of oil it gets into the body a lot better and so that's why i mix my resveratrol with some yogurt just a
    31:19 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
    31:25 making it into your system and there have been clinical trials that have failed and when i look at how they did
    31:30 it yeah they were giving their patients or their subjects a capsule with water
    31:36 and that's not gonna work wow that's fascinating that's really fascinating i never thought about that
    31:41 so it has a fat soluble aspect to it oh for sure it's like brick brick dust chemists would tell you brick dust
    31:48 and if unless it's dissolved yeah it just pretty much won't get absorbed by the gut
    31:53 and so we know red wine's a source what else do we have missiles also supplements for sure
    31:59 i take the supplement because you'd have to eat a lot of chocolate as well um but you know
    32:05 let me let me just make it clear that i don't know if it's going to make me live any longer
    32:10 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
    32:17 but what else can we do we could peanuts have a little bit but unlike a lot of things we can do in
    32:23 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
    32:29 between 500 and a thousand milligrams i love the fact that you mentioned the cycling aspect and this is true with so
    32:37 much because again we have that some is good more is better let me just do this every day
    32:42 and i love the the the concept and also just the the the
    32:48 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
    32:55 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
    33:02 being hungry is good for you but we used to think that based on monkey studies and rat studies that those animals and
    33:09 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
    33:14 while and uh and that's great news because if you give mice and rodents now rats food
    33:23 during the day they can eat 90 of what they would normally eat in a calorie restricted diet but be hungry all the
    33:28 time so we can live great lives i eat a late lunch or skip lunch but then i
    33:35 typically eat a really nice dinner and i've actually grown to love food a lot more for that reason wow
    33:40 you do appreciate food rather than just shoving it down during the day uh but i think i live first of all a
    33:46 much healthier life but also one where i'm a lot more grateful for food yeah and i i could um
    33:53 i could personally affirm that experience and i remember i mean this is
    33:58 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
    34:04 know so i would do uh several weeks of fasting where i'm just having juice right it's vegetable juice
    34:11 and i remember the and i i've shared the story before but it might be hard to believe but i didn't
    34:16 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
    34:22 was raised on like fish sticks and like i was probably like four percent ravioli like just in my
    34:28 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
    34:35 a 21 day fast i went and got a salad and prior to this just a couple weeks
    34:41 before i did the fast i tried to eat the salad went right to the trash can gagging okay
    34:46 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
    34:53 was still scared i'm like i'm gonna throw up any moment and i took the next bite and i'm just like
    34:58 this is the greatest thing i've ever eaten in my life and i ate the the whole little salad i'd
    35:03 gotten for myself it was that whole foods just like tucked in a corner and this is true so i was walking out i
    35:09 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
    35:14 another planet they're like oh okay you know and i was just blown away at how much i
    35:20 appreciated eating after not eating for so long right and so having those moments even now you know just
    35:26 intermittent fasting through the day i totally agree last night we had dinner i was really crushing it yesterday just
    35:32 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
    35:37 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
    35:42 something for the first time uh on on your show uh now that i appreciate food and and i
    35:48 i know that food is not just pleasurable it's actually good for you i'll go back to my old habits and
    35:55 there's food around us that's the problem it's everywhere so you you your reptilian brain will pick up something
    36:01 shove it in your mouth and then i'll think that's in my mouth why did i do that
    36:06 and i'll go through the calculation does this meet the criteria of whether it's worthy of eating do i swallow and
    36:13 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
    36:18 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
    36:26 i really want to eat yeah but i love it fascinating um you know
    36:32 just opening up this conversation and looking at the different dimensions of how it's not just the food that we're eating
    36:38 but how we're doing it right when we're eating has a huge role to play um it's just it broadens the
    36:44 conversation because i think we really can easily get caught up in the the minutiae like we talked about earlier
    36:50 you know like trying to get your macronutrient ratios correct that stuff matters but there's a bigger
    36:56 conversation and getting more into this bigger conversation in the book
    37:01 um you also stretch out and you you get into conversation and things that we've got
    37:07 science behind that were really counterintuitive for me or things that for example metformin right i want to
    37:15 talk about this i spent over a decade working in my clinical
    37:20 practice as a nutritionist alongside physicians to help get people off metformin and then seeing this data that
    37:26 you're sharing in the book that metformin might actually be one of those well it is according to
    37:33 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

    How Metformin switches ON the longevity genes

    37:39 can for everybody share what is metformin and why is this something that folks are now who don't have diabetes
    37:45 are taking yeah so metformin is one of those gifts to humanity it's on the list
    37:51 so the world world health organization has called it an essential medicine for
    37:56 humanity because it it's so safe it's not perfectly safe but it's so safe
    38:03 and the benefits are are really clear especially for diabetics so there are these three legs to the
    38:09 stool the three pillars sirtuins we talked about we talked about mtor and amino acids the third one
    38:16 is called ampk or amp kinase and this protein senses how much energy we have
    38:22 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
    38:28 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
    38:34 that one is to be hungry one is to exercise and the other is to take a medicine
    38:39 that inhibits mitochondria and lowers the amount of energy that the cells producing so the body goes holy crap
    38:46 we're running out of energy and it'll make try to make more and that's good for you now the side
    38:51 effect of that is having better blood sugar levels so your body becomes what's called insulin sensitive you know
    38:58 this that when you're type 2 diabetic your body doesn't register the insulin that's your pancreas is putting out and
    39:05 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
    39:12 bloodstream which will cross-link proteins and accelerate aging and all sorts of problems cardiovascular
    39:18 disease wounds won't heal and this is truly accelerating aging we've proven
    39:23 that in our field metformin is shown to be very effective against
    39:29 type 2 diabetes and if you have type 2 diabetes your doctor will typically put you on that medicine now it comes from
    39:35 the french lilac it's derived from a plant so it's a xenohermetic molecule
    39:40 actually and but it's classified as a drug so it falls into that category so in this
    39:46 country at least but not all you need to get a prescription for it which actually puts it out of reach for
    39:51 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
    39:57 might be toxic but it really has been shown in a study of over a hundred thousand people now many studies
    40:02 actually that diabetics who take metformin in the long run aren't just better off for diabetes but
    40:09 are actually healthier and protected against cancer heart disease alzheimer's and frailty
    40:15 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
    40:22 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
    40:28 papers which i referenced in the book it's true so i become a real convert and
    40:34 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
    40:40 met my trajectory of the last 11 years and i could see i was headed for diabetes it's in my family
    40:47 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
    40:53 diabetes because i'm on metformin because i've made these changes in my life now is it for everybody i think if
    40:58 you're young and your blood glucose levels are low not not needed if you're exercising and eating eating right
    41:05 but if you're i'm 50 now and if your blood glucose goes up every year
    41:10 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
    41:16 since you just mentioned that being 50 if folks aren't watching the video on youtube you look like
    41:22 maybe maybe 30s you know like 35 you know um you have this uh and your your energy is
    41:29 high you're creating all these different projects working on different papers um so you have that aspect your physical
    41:37 appearance like you're living you're living proof of the stuff you talk about and i can see you're just getting warmed
    41:42 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
    41:49 so but i wanted to bring this up because i also with the model health show i want to stretch our thinking
    41:56 we do like i mentioned you know i was looking at what can i do for these patients to help them to normalize their
    42:01 blood sugar naturally right and removing the cause oftentimes was you know
    42:07 mountain dew or whatever it was you know just but if we eliminate those things
    42:12 and your body is already in a healthy state adding in these different medications potentially again this is just a
    42:19 conversation i want to get going there might be some potential benefits and this is still early but it really
    42:26 got me thinking when i was reading the book and one of the other aspects
    42:32 i think this might go back to because for me i think that this competes metformin can compete
    42:39 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
    42:46 exercise in that context because it's a hermitic stressor yeah so how does that compete yes so remember we're working with a
    42:53 very complex machine our bodies and there are these three legs of the stool
    42:59 but we don't know exactly which ones to tweak and when we're still figuring this out as scientists
    43:04 the good news is that we live in a world now where scientists can talk directly to the public and we put out newsletters
    43:11 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
    43:18 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
    43:24 off days and metformin and exercise is a case in point now what we've just discovered in a
    43:30 couple of papers that came out this year only is that metformin because it it tricks the body into having low energy by
    43:37 inhibiting the mitochondrial energy levels if you give elderly patients metformin and give them weight lift do
    43:44 ask them to do weight lifting they will bulk up both of them all right both sets with me from without but the
    43:51 ones that didn't get more metformin will have bigger muscles okay but not a lot not a lot bigger they
    43:56 all got bigger muscles so it is inhibiting the growth the hypertrophy of muscle but here's what's
    44:02 not talked about on social media or appreciated by a lot of people those people those elderly people were
    44:09 all the same strength even though they didn't have the same sized muscles so it still gave them the benefits they
    44:15 just didn't look as bulky so that's where i go back to vanity versus longevity right but i think there is a
    44:20 way to optimize it we don't know for sure and dr peter tia our friend uh he
    44:26 argues this with me and he also agrees at least on this point that we don't want to be taking metformin on
    44:32 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
    44:38 but we disagree on exactly what the precise combination is uh but he also thinks that uh fasting
    44:45 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
    44:51 than one day i start to lose my blood sugar goes too low and i've measured it with one of those uh
    44:57 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
    45:04 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
    45:10 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
    45:16 he actually is turning on pathways that i think are even more beneficial yeah there's one called chaperone-mediated
    45:22 autophagy which is basically super recycling of the body's proteins and that's something i think that
    45:29 he's right about and uh if you can go for three days you know more power to you right yeah
    45:35 and i love that so much because there when when i made the reference earlier about some is good
    45:41 uh more massive amounts is is great there's still there's usually something there in
    45:47 the middle or closer towards you know that little bit those little micro doses and having an extended fast you know of
    45:53 a few days uh obviously you're going to activate more of these different beneficial process processes uh autophagy and the
    46:01 list can go on and on but we also have to be mindful of the longevity aspect of happiness

    The role happiness plays in longevity

    46:09 you know um i think that we don't talk enough about this first of all and this is just
    46:15 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
    46:20 something comes across my attention on my phone or a friend or somebody that that lives to be 100 years old or older
    46:26 i interview them i read their stories i read their articles and there's this consistent thread of happiness there's
    46:32 this consistent thread of like meaning in their lives you know so if you're gonna be pissed for three days
    46:39 and just like a krabby patty right just mad at everybody really that that's it doesn't
    46:45 equal out for me the benefit potential benefit that you could be getting yeah that's right so when we calorie restrict
    46:50 these mice in my lab they also get really crabby they fight with each other especially the the boys so it's natural
    46:56 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
    47:03 the the key to happiness is mission and i just came from a conference where we're talking about how to optimize
    47:08 those three legs on the stool and uh one of the speakers was dr cooper he's the guy that coined the term
    47:15 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
    47:23 mission in life to make people live longer and he's treated presidents the first bush
    47:28 um george bush and he his mind is super quick he's talking like this bam bam bam you think
    47:33 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
    47:39 aren't clinical trials but when you see him he's been doing aerobics for the last 40 50 years
    47:46 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
    47:52 thousands of kilometers or miles that his patients have run he can reduce the the rate of aging
    47:59 clearly and through the trajectory of his patients instead of the average lifespan being 80
    48:04 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
    48:12 what he's recommending you eat the right way starting at an earlier age you don't
    48:17 have to live to 80 you can play tennis and at 90 maybe live to 100. yeah but
    48:22 wait till there's new technology is coming yeah so exciting and that's why people have to stay connected to you to
    48:28 learn more about this and speaking of mission i want to ask you personally um what is
    48:35 the model that you're setting for other people with how you live your life personally right
    48:40 the way that you are conducting yourself your business your research what is your bigger mission
    48:46 that you're wanting to express or to achieve with your life right now
    48:52 well i think it's the same as a lot of successful people i'd be surprised if you don't feel the
    48:57 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
    49:04 unless you get hit hit on prematurely buy a bus or something when that moment happens i want to be
    49:09 able to say to myself i did the most i could to leave the world a better place than i found it and
    49:15 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
    49:20 better there's far too much complacency and giving up and a lot of us just give up they say
    49:26 the world can't be changed but you know friends of ours we all agree that if you have a mission
    49:32 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
    49:39 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
    49:46 it's a tough life yeah i love it can you let everybody know where they
    49:51 can pick up your book and also connect with you online well we have a website lifespanbook.com
    49:59 so at lifespanbook.com we have a newsletter for updates uh things about lifestyle things about
    50:05 the new science that we've read um updates on my dad who's still going strong at 80 uh climbing mountains and
    50:11 all lifespanbook.com on social media i'm on you can find me on twitter and
    50:16 facebook and on instagram pretty easily um but we sell books on barnes noble and amazon um audiobook actually we recorded
    50:24 the audio book book in this building right here and uh it's doing great it's a bestseller new york times bestseller on
    50:31 the audiobook and the hardback um but the audiobook's special to me because we did something different we
    50:36 did in between the chapters we had chats about what we were how we wrote the book and how we thought about designing the
    50:42 book so that's an extra free bonus for people who get the audio book perfect
    50:48 perfect thank you so much for sharing your time with us today and thank you for putting together such an epic trates
    50:55 on longevity and i think that this is um it's something that we just really haven't seen before
    51:01 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
    51:08 typically allow but the stories even like you articulated with the the pianist example
    51:13 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
    51:19 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
    51:26 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
    51:32 hey if you like this video make sure to check out this video right here to up level your health today other
    51:38 things that were causing cancer that we didn't know and didn't quite link to that whole paradigm but we thought well
    51:44 it must be just the genetic thing so that's that's why that genetic paradigm really took off and everybody was sort
    51:50 of all in on it for so