A Harvard Geneticist Is Extending Human Lifespan: David Sinclair, PhD | Rich Roll Podcast

[Music] good to see you thank you for coming out Thanks wish things had me out I'm excited to talk to you again I want to preface this by saying if you have not listened to our first conversation definitely maybe even hit pause now and go back and listen to that I never go back and listen to old episodes but in the case of you probably mostly because I'm intimidated by you I did go back and like wrap my head around what we talked about last time I was like well how we covered a lot in that right like we went and we kind of went through the whole thing and I don't want to replicate too much of that but I'm excited to kind of extrapolate on what we spoke about last time so welcome thanks sounds good you were with you were over doing let's work out this morning right I was it was brutal so walk me through it oh well first of all how'd that come together um it was through mutual friends was such a bunch of us that have known about this for a while the mythic Laird Hamilton morning pool workout uh right so I I remember hearing what it was like and thinking I really hope I never have to do that and and actually I was right it was it was brutal but but I do feel really good now I'm actually uh they say it's it's good for your mind as well and I can see why I'm now just grateful to be alive yeah so what that's like is if if listeners don't know is you you start out in a really hot sauna and I'm not just saying a hot sauna it's like this temperature of the surface of the Sun yeah so I normally do a hundred sixty degrees at my own gym this thing was cranked up beyond 250 it was most high I knew I knew he said it around 200 I didn't realize it was that hot Wow yeah it's at the point where I was getting pretty dizzy so you do that and then you jump into the you have a shower jumping in the pool and you grab well first of all you swim underwater and tell you basically out of breath and you want to pass out then they give you weights and then you've got you go into the deep end you're underwater below the top of your head by you know maybe a foot and then have to jump up and down and you think okay I can do that there are two problems one is if you don't make it you're gonna take in a mouthful of water which is what I did of course the first thing and then the other problem is you go into this panic mode I don't know if anyone who's ever experienced what it's like to drown but now I know what it's like to drown it is not pleasant you you always let go of the weight and surface there is that but but there's only one think there's Laird standing there and try judgment of Laird yeah I would rather drown than embarrass and give up so you know I looked like a stupid fish well a land animal in water for a while I actually found out that I probably shouldn't have gone so far into the deep end mmm that was my first mistake but then what do we do we also warmed up again in the sauna and then we jumped into a big bathtub with ice with about a couple of inches of ice on the top and that wasn't so bad you know I've talked about cryotherapy before and saunas and hypoxia but I've never done it so extreme you know I know where offers is the guide of beat but I usually go to my gym which is just 4 degrees Celsius I don't know what that isn't in Fahrenheit but it's not that cold as far your frigid temperature and I found that brutal but actually going into that ice water I was I was fine I mean the initial shock like I can't breathe I'm gonna yeah and then but maybe 15 seconds later with Gabby Reece telling me breathe slowly breathe slowly feel the heat rather than the cold you can convince yourself that you're warm in this freezing cold temperature it actually was great and I got to three minutes as she was gonna do two minutes because she thought I was a bit of a a wimp got to three minutes and thought I could just keep going this isn't so bad no pouring ice on my head at that point were you up to your neck oh yeah I actually went on to a couple of times Oh huh that's great and then you get out and you feel great you feel refreshed grateful to be alive and yeah I would do it again in a second uh-huh how many how many people were there this morning there were about ten of us yeah I've got I have friends that go to that workout and I've had it I've had a kind of a you know sort of an open invite to drop I mean I kind of do my own that my own workout and it's a bit of a drive for me so I haven't made it over there but also in frankness like I'm scared to like you know I mean like but what I've what I've heard was Darren Eileen there this morning he's a sort of a layered look-alike like yeah Darren been on the podcast I'm very good friend of mine Darren has said that the people who fare well or the best are generally the people that that go into it with a healthy dose of humility it's the problems arise when you get these super alpha guys who think they're you know basically invincible like whether they're MMA fighters or Navy SEALs or whatever and think that they can do anything and kind of attack it from a perspective of you know some kind of dick measuring contest of like I'm gonna do this better than Laird or whatever and they're the ones who get crushed and humiliated yeah there's a bit of that today yeah yes it down and I talked about he's interesting guy right he's saucing yeah you guys they talk forever we we know we will meet up again good and yeah the Justin Ren was there well you know our friend Justin Rin that was his first time doing it too yeah and he was my buddy Sam I'm a fighter exactly so Justin was a fight foot of garden that's his charity wonderful wonderful guy check him out he was my buddy and first thing I asked him when I was teamed up with him was do you know CPR and especially need to rescue me yeah that's cool well you did you do I have this right like you have some scientific background in thermogenesis don't you did you do you know ray Crowe nice did you work with him on some of the studies that that he did on that or papers to get right that's what I thought yeah so right ray and I interesting story he was a former NASA scientist not even thinking about metabolism or right or health at the time he was overweight by his own admission and I met him at a TEDMED talk 2008 it was and after my talk about aging and longevity we were there with quincy jones of all people and he said David I've never heard a talk that's convinced when he you know to change my life I'm gonna do what you do and I'm gonna be a disciple now we thought okay you know ray will you know see you later uh-huh he did it and so now what is that you know over 10 years later he has changed his life he's he's a guru for for health and particularly cold therapy and we've published a couple of papers one is on the metabolic winter hypothesis the idea that you know these days we always look for comfort and one of the problems is we never experience temperature variation in our lives we will bundle up at night and we'll put on a jacket to go outside and this is one of the reasons we think that we all have tendency to get metabolic defects as we get older right Ray's now kind of pivoted more into the nutrition landscape she's got this new book out with Juliana haver yeah hell span I think it's called right helpful book yeah I gave it to my wife for for the holidays it cool yeah it's really great I really liked those guys both of them they make a good combination mmm because Juliana is the the cook and yeah brain yeah exactly it is it is a good mix they live like right up the street here what do they yeah they've been on the podcast cool well I think it's interesting that you you did the Laird and Gabi workout this morning with this combination of like sauna and ice baths so maybe a good you know first thing to explore is the relationship of those types of therapies on aging and longevity right well the bottom line is you've got to get out of your comfort zone and get your body out of its comfort zone hormesis is what we call it right and the problem with today's world is marketing branding our own just our own primeval brain we just want to be relaxed we want to be fed we don't want to feel discomfort and that's leading to a whole bunch of problems and if we're not always telling our body things that could be problematic our bodies don't care they don't fight against disease that aren't fight against aging so these treatments and these crazy things that I did today are all about turning on the the genes that we work on we could talk about those in a minute but this is the revolution that's happening and there's a whole bunch of people your listeners for example are realizing that one of the biggest problems in our lives is that we've just been you know handled with kid gloves and the food we eat is also not stressed out and that combination just turns us into mush it's interesting when you say the food that we eat is not stressed out so that's that's about kind of taking in stressed foods to prompt this hormesis type effect through our nutrition or you know explain what you mean by that right well we were working on resveratrol the residual stories what I first was known for in science world and we discovered there a whole bunch of different plant molecules one of them is resveratrol from found in red wine but there are a lot of others there's quercetin from onions for example and they all activate these longevity enzymes that we have in our bodies and they're found in plants as well and we were trying to figure out why would it be that these so-called polyphenolic compounds like resveratrol and quercetin why would our bodies benefit or why would a mouse benefit by eating these molecules and what we came up with was the concept of Zeno hormesis Zeno means between species and hormesis is what doesn't kill you makes you stronger and it's even though it's a mouthful what what it explains so much is that when our plants are stressed that we eat we've probably evolved to sense when the environment and our food supply is running out or potentially running out so if you're picking olives off a dry you know hill or you're eating fruit that's just had a massive drought you're gonna have molecules in that food that'll tell your body hey these plants may not be around for the next known month mm-hm and that was our explanation and it really does make a lot of sense and is fitting with a whole bunch of of data we've had over the last couple of centuries that's like different species communicating with each other through some you know unheard language it is it is and actually what it means is a couple of things one is donate foods that are grown on to perfect conditions that works well for the growers because they get food much more quickly think of the lettuce that you buy that's in the greenhouse that's never been stressed is just watery white and watery right avoid white and watery what you want is denser colored food the color is actually an indicator that you've got these polyphenolic beneficial molecules so I like to buy foods that are locally grown organic and typically grown in in conditions that are not perfect so what is it about it being locally grown or being organic that enhances the hormesis impact or the stress response in the plants like we couldn't you could you figure out a conventional way of growing food we're at the last minute you stress them before you pick them or something like that so you're getting an enhancement of those polyphenols or whatever it is that you're looking for that's exactly right that's what I think we should be doing and there's a business idea okay any facts Laird was telling me just an hour ago that that I didn't know this that people who grow oranges and know what they're doing drive a nail into the tree I think was a day or so before they picked the fruit and then gives it these extra well that's that's interesting yeah so we got to harm the plants just a little bit but doesn't need to be all the time it can be just before you pick them and think about grapes all right what we do when we want to have great wine is we pick them just as their stress that we you try to pick them when there hasn't been rainfall for a little bit hmm and then they fill up with these great tasting molecules but also these xeno hormetic molecules as well so how does that I mean when when when we're told like listen you should eat organic food it's really about trying to avoid the pesticides and everything else that gets packed into conventionally grown foods but what is what is it about Organic that relates well you know there's organic and there's real organic I'm talking about the plants that you know may have had a grub eat it or are exposed to too much sunlight that kind of thing being out in rougher conditions yeah I'm hyper organic right right all right not Natsu that's the name of a new company let's do it yeah that's cool well when you look at Laird I mean he's sort of a an experiment in motion right like what is he fifty-five now yeah thank doesn't look a day older than he did you know ten fifteen years ago and he's still killing it and I would say that he's probably a pretty good example of somebody who's practicing a lot of the things that you talk about I mean I don't know what his you know supplement routine is with respect to you know some of the research that you're doing but in terms of his daily exercise regimen and lifestyle habits it seems to be you know to comport with the things that you talk about often yeah right he's the orange tree with the name on it every day but I totally believe it and you don't just do it with hot and cold and you don't just do it with what you eat there are other things you can do like when you eat you can also you need to have plenty of exercise which is another thing and one of the breakthroughs that we've had in the longevity field is that we used to think you know let's go back 20 years ago that exercise was something that made your blood flow better and make you healthier that eating less food was healthy because it lowered inflammation somehow what we've realized is that all of these things are working through the same mechanisms and it goes back to work that we did in my lab in yeast cells you know a little fungi that we grow that we use for bread and beer what we showed and this is go back to 2003 now is that there's one gene that controls longevity it's got a name called PN C one it makes this molecule called nad which is very healthy turns on defenses we found that these yeast cells live longer when you gave them a bit of stress so if you turn up the incubator to 37 degrees Celsius and serve 30 they live longer or you starve them a little bit of or take away a little bit of the amino acids in their food or what else could we do we could restrict the amount of sugar that they are eating that'll made them live longer but it all worked through this one genetic pathway and that was a breakthrough at the time because you know even today most people don't realize that all of these things that we do are converging on this master regular regulatory pathway for our health mm-hmm is that part and parcel of this you know kind of singular information theory of aging that is you know the sort of the foundation of your work yeah it all connects it's all slowly coming together it's taken 30 years of work but we're getting there I can see the end of the tunnel and what what is interesting is that so this nad molecule is the fuel for a class of enzymes that acts like the traffic cops in the cell they they send out the troops to repair and fix things and one of the main things they do we found is they control the expression or the control information in the cell not not the genetic information but in how the genetic information is controlled mmm and these genes are called sirtuins Saussure to ins you can think of as the pianist that plays the genetic piano mm-hmm and when they're not active the penis becomes complacent makes a lot of mistakes and ends up becoming demented and that is what I believe is a large driver of the aging process hmm but if you're always activating your sirtuins the pianist keeps playing the controller for much longer and you we stay younger right we talked about this last time the analogy we use wasn't the pianist I know that's like the title of I think the second chapter on the book Yunus where you explain all of this the the metaphor that we used was was you know highway traffic right and and getting dispatched you know away from their their true role to kind of deal with crises potholes in the roadway and whatnot and then the signaling you know getting screwed up and then basically all of the kind of traffic copying going haywire and these these you know the NAD isn't going where it's supposed to go be going and the sirtuins aren't where they're supposed to be in the whole kind of system breaks down that's right and we first discovered this I was at MIT as a postdoc originally moved to Harvard in 1999 those years were were affirmative what we discovered in yeast cells it's incredible right you can learn from a little fungus these big concepts these sore tunes in the yeast cells were maintaining the identity of those yeast cells and making them stay young and healthy for longer by keeping the gene piano working for longer now what we also realized was that you can distract them from their main job the pianist can get distracted you know imagine you know you you start trying to you know whistle or get in get in the face of your pianist it's essentially the same and what is a major distraction for these sirtuins in a normal job is broken chromosomes broken DNA DNA damage and we know that DNA damage can accelerate aging anyone who's lived in California or Australia like we have knows that DNA damage from the Sun will accelerate aging but no one has ever fully understood why and it's been a mystery and mutations don't seem to be the main driver unless as the old theory so what I think is going on is that these breaks in the chromosome is DNA damage is distracting these sirtuins from maintaining the symphony perfectly they get distracted they go off and do stuff fix the chromosome and then most of them come back and keep playing the piano but some of them never make it back to where they should and over time that's cumulative and you end up with a cacophony so the goal the job the mission is to maximize the efficiency to really optimize this or two in functionality right and the way to do that is to make the body think that it's it could run out of food or has to run away from a saber-toothed tiger and that all relates back to the activity of these search because then they're not distracted by these sort of frivolous situations and they're they're focused on the the most important job that they're kind of created to deal with yes and the other way to think of it is without enough fuel in a is there fuel this little molecule called nad if you don't have enough nad they are very slow at doing their job they kind of they get detached from what they should be doing and then they drift off through the liquid in cell and they don't have enough energy to to fully fix the DNA quickly and they don't have enough energy we think to come back to where they came from but if you do have all the energy and they're in their prime still the youthful soar tunes they can fly off and come back mm-hmm but it's without the fuel lien ad or you know where is virtual is also an activator that's one of the things we figured out in mm so the combination of the fuel and the activator is virtual in the NAD is a fantastic combination we think for maintaining that that epigenetic Symphony as we call it right so what is the State of the Union when it comes to to the scientific research on sauna therapy you know cold therapy and its impact on nad and sirtuins and thus aging anti aging that's a really you just got a big smile yeah I can I can see why you're so good at what you do I'm just trying to follow my curiosity here I'm trying to keep up and and I really want to like understand this so anyway go ahead well so the connection is that the sirtuins are actually waiting for more nad production and remember that old yeast cell that the story that I told you about those one gene that was turned on by temperature and by low amino acids that gene it makes nad okay in our bodies we have the same equivalent gene it it's it's called an MP TNA MPT and we discovered is now 2007 that when you stress human cells in the dish and in in in the body as well that you turn it on so the MPT comes on and it makes more nad for the body and these so tunes can do a better job sewn MPT is really interesting we most people don't know about it or talk about it so I'm glad you brought it up that's why I'm so yeah we definitely didn't talk about this last time right so now I haven't talked about it publicly nem PT is is the master regulator of nad production it's the what we call rate limiting step in making an ad from precursors like vitamin b3 and so we took human cells we put them in the dish and we stress them out so we gave them not enough sugar we gave them too much temperature we call heat shock them and on came this an MPT and they made made by nad hmm so what I think could be going on is that the stress on the body when I'm you know 200 and whatever Fahrenheit and then jump plunging into basically zero degree Celsius that is making my body make more nad essentially mimicking the effects of exercise and hunger mm-hmm just a different way and making my sirtuins work optimally and that is something that I think is underappreciated that this one gene is the probably the main cause of the benefits of all of the things that we have figured out over the last two thousand years of being healthy and is there an understanding of the relationship between the hot and cold is it that combination that makes it effective could you just do this on or just do the cold therapy or like how does it you know has that been explored not well yeah no no and I'm asked all the time what's the best combo of diet right exercise we've to figure that out and then you know you you the keys of the kingdom arrived yeah but you have Rhonda Patrick talking about sauna and then you have the Iceman wim HOF talking about the cold therapy and now you have people like Laird who are combining these two I'm just trying to get a sense of like what is the ultimate stress or you know hormesis inducing protocol that's going to activate this nad producing signaling mechanism right so we need to figure that out but I have a philosophy that drives what I do and what I talk about and that is that you don't want to do the same thing over and over again mix it up right cuz you you acclimate to that right and that's no longer it's no longer creating the stress response exactly so I don't exercise every day not that I could but I don't it's a convenient excuse yeah really true you gonna pulse it uh-huh all right because as soon as the body gets used to what you know I mean this ice bath and after three minutes I'm like what's the big deal right you gotta you know switch it up and that's why I think that the best thing that we know right now is that you want to do some some exercise then you want to do the sauna then you do the ice bath that's what I do and until I know more I'm gonna keep doing that right similarly I would imagine you know when you look at Valter Longo and his fasting mimicking diet and all the science that's emerging around intermittent fasting I mean the the benefits of that are kind of boiled down a hormesis right you're trying to create a stress response that activates certain you know pathways in your in your system that that relate to aging or anti-aging but I would imagine that you could you could develop a set point with that as well kind of acclimate to that and get used to it and then you're no longer experiencing that benefit do we is that is that it does it work that same way with the e well it's it's complicated because the there are two experiments that have been done one is to consistently just give mice low-grade food and basically mix their food with cardboard cellulose and that works so if my son nibbling all day on low-calorie food that still works so you don't have to do intermittent fasting for this to work you never get used to not eating yeah yeah your body will still respond but at least we understand what's going on and again it's this an MPT gene in large part that's turned on when your body doesn't have enough glucose and insulin is being produced but also this intermittent fasting the reason I like it and I you know volt has been an old friend we used to by the way we used to study yeast cells together yeah well we both came from the intermittent fasting for me is is better because it means you can eat instead of 70 percent normal calories you can eat 95 percent or 100 percent calories you just have to squeeze it into a window of a few hours to be optimal and that's just easier to do right and in the mouse world if we do calorie restriction which is this low quality diet or low calorie diet of course versus intermittent fasting they both work about the same that you know you can argue about my new [ __ ] but basically they all extend lifespan but the Meister on intermittent fasting can eat a lot more in their lifetime yeah and you know if you're not eating food and enjoying life you know it's not worth it probably but I need to get hormesis hormesis I'm gonna starve myself well yeah I I'm skipping one to two meals a day and it's changed my life I feel great and a lot of people say it makes me feel queasy or my stomach's burning I found I get used to it and if you if you find that it's too hard try cup of hot water I think coffee is great tea and that gets me through the morning mm-hmm yeah I've been playing around with it and experimenting with it for a while and and I found that that you know it's so much of this psychological and mental like I'm now in a place where you know there's plenty of days where I won't eat until dinner and it's not because I'm trying to provoke suffering like it's just I'm not even really thinking about it where you really realize realize it and I know you posted about this on Instagram the other day is when you fly when you get when you get on a long plane and I use those generally as opportunities to to play around with this thing because I'm not gonna eat the food that they're serving on an airplane and it's hard to get healthy food in airports and the like but for the most part most flights are you know four to six hours unless you're going to Australia which we're gonna talk about it's not that big of a deal right and then when the when the flight attendant kind of repeatedly drops by and says they're sure you don't want anything and they're the look on their face they're just like amazed that you're not eating and you're like it's not that big of a deal right they're saying but but you've paid for this it's free you have to eat it do you want some ice cream and cookies no it'd go away the more you say no the more they come back yeah but I I agree with you it's a moment to really test yourself because you're sitting there and all you've got to think about is the food and the person next to you is eating right and then then you really test your mental will and actually I use that as a way to test myself and one of the things I do is I think you know it's fine to eat now what do I want to look like feel like a day a week from now 30 years from now and that allows me to help my future self yeah well you don't look a day older than the last time we spoke which was at least a year ago I think yes sorry 50 51 50 no I'm still I'm still 50 but uh yeah no gray hair I'll let you know no yeah definitely not a gray hair on your head yet and what maybe this is a good place to talk a little bit about the difference between the biological clock and what you call horvath clock right the [ __ ] the Horvath measure of Aging yeah can we talk about that yeah that's really important it's a massive breakthrough in the field of aging for many many reasons one of the big things that's held us back in studying aging is we didn't have a real measure of what aging was you could look at a mouse or a human and say okay they look younger they look old big deal but we needed a mathematical and a a non subjective measure and we finally had that finally until recently all we had was some blood tests that tell you you're looking okay you're looking healthy you're on the right track but the clock changes everything because it's a mathematical clock and actually Horvath who's Steve Howe that's one of my very good friends great guy he's a mathematician by training and somebody got their clock measured by him I'll tell you in a minute about how the clock works but someone said I got a really bad result on my clock I'm biologically 10 years older are you sure the clock is right and he said as intrude German for me said I think Austrian actually he said there's a greater chance that the earth will be hit by a meteorite tomorrow so that's how good this is and it's not so hard of a bedside manner though no no if it's got a great dry sense of humor so what we've got actually is and the beautiful thing about it is it's not just helpful to be able to say this is how old an animal or a human is biologically but also it comes back to this information theory of aging the epigenetic information is what I think is lost during aging the most important thing that basically the penis not the piano the clock is measuring the pianist's of state of mind right and when so what Steve's doing with his clock he's measuring how demented the pianist is so that that's of course a metaphor what's actually happening in real life is that our DNA has chemicals on it that tell which gene to be on and off that's basically that the notes are for a symphony the the Ray score but it when you're born you have a certain pattern of these what are called methyls these are little chemicals just carbon and three hydrogen's that bond to the C letter you know on DNA there's a CT gene right so the C's get this methylation it's called just a chemical that sticks there and doesn't come off unless the body takes it off it's a permanent mark and that's what says that gene needs to be switched off that gene in your brain only comes on in the liver so keep that off for the rest of your life and I think that that pattern that changes over time is what drives aging now what Steve found independently from me is that if you can read the pattern of those methyls it'll change over time and if you use machine learning and say okay this is the pattern of a 50 year old 20 year old even a five year old you can draw a straight line mm-hmm and then once you've got that straight line he can hear I can take your blood map your methylation pattern as we call it and place you exactly within a few percent error of where you are on that curve or on that straight line and then we can say you're likely to die in July 2050 oh wow I would imagine that gets more and more accurate every day right as the data set grows it is we're learning a lot we've got now clocks for human skin the blood in my lab we've got mouse liver and kidney but also here's the amazing thing we didn't know this until just a couple of years ago that you can take a dog's clock and use it to predict the age of a human or a sheep or a bat what is you know that that sounds fanciful but what that's telling me Steve is that there's a universal underlying clock of aging in mammals at least and I think it probably goes all the way back to jellyfish we're gonna do a jellyfish clock because jellyfish can be immortal so we want to figure that out how that works but what we basically have converged on we think is that I'm saying I think we understand what drives aging mainly is the loss of that perfect pattern of which genes are on and off when we're young and that Steve has a figured out has figured out a way it's actually quantify that mmm so what is your what is your age according to the Horvath math I don't know yet and when are you gonna die what do you mean here you don't know no no I've been too busy but no I've done just the the old-fashioned blood tests and uh-huh but I'm gonna do it I'm not avoiding it I tell you what we are doing that I haven't told anybody it's a little bit of a secret but why not right now the test costs a lot of money mmm I think a really good deep test would cost him at least 300 sometimes a thousand bucks to do so it's not cheap and he can't do it every week he can't do it every month but we're working in my lab when he just had a breakthrough we think him we can bring it down to five or ten dollars and then you could do it at home right if you if you brave enough there's another business for you yeah well that that will be hopefully a business that's one of the reasons we're doing it but also right now it's too expensive to measure the age of a million people but without technology we could do that right and then things get interesting then we can say people who drink this coffee that I'm holding in my hand how do they do does their clock go backwards or not mmm and finally we can figure out within a short period of time what things work for slowing or reversing aging and there was a study that Steve was on recently last year that at least suggested with a small number of people that a treatment in humans could actually reverse the age of those people by at least a couple of years Wow yeah then the data becomes unbelievably valuable right it's it's less about what the consumer finds out about his or her life and more about the value of that data set and what you can straw plate from a lot of people are scared to measure their age because I don't want to know that you know even myself I will admit I'm kind of scared to look yeah what would happen if it said you know here here you are the the anti-aging longevity guy you're gonna die in two years yeah that would not be good for a bad day for business yeah well you know I don't live perfectly that's for sure I don't every day I jump up and down in a swimming pool like I probably should be and I'm on planes a lot which is not good I'm sitting down a lot I'm typing so there's I might actually be older they're not than I look who knows I will I will tell everybody when I get that data but here's the really important point rich which is that data is important right I'm data-driven as a scientist but everybody with their bodies should be cognizant of how they're doing just ignoring aging is not gonna make it go away or slow down so what happens if you find out that you're a bit older than you actually are based on your birthday candles what does that mean is that do you just go to bed and get it have depression no this is enabling what it means is that you can actually alter the trajectory of your life that trajectory that you're on it's not fixed just because I say you're gonna die the beginning of 2050 that's if you don't change anything but you can bend the needle and the things we're talking about today the hormesis effects we already know can actually change the slope right since we last spoke has there been any interesting breakthroughs or new studies or science that has kind of shifted or or expanded your perspective on any other things we talked about last time I yeah a lot you know every day I before I get out of bed I'm actually reading scientific papers can you believe it pretty much every day I'm excited by something new there was something a couple of weeks ago that came up but but I'd been hoping to see for at least 12 years and that was to find out why does whereas Verret role activate the sirtuin enzyme why is that so one idea is that we're sensing the stress in and verse adversity of our food but we also have hypothesized since we first discovered virtual and its role in aging anti-aging is that it's probably mimicking something that our bodies make mm-hmm we call it the endogenous activator the elusive endogenous activator and what this paper showed was that the byproducts of that at the what we call lipolysis the breakdown of fat when you when you're hungry produces monounsaturated fatty acids the kind that you can get from olive oil right those molecules circulating in the blood are about a thousand times more potent than resveratrol and activating this longevity enzyme so what does that tell us first of all resveratrol is pretty cool you can mimic your body's fasting state by by ingesting it but also it means that we kind of been vindicated because we got a lot of crap for his role yeah if you google your name and resveratrol there's a there's a lot of [ __ ] talking coming in your direction yeah earlier stuff from years ago well yeah and it's been it's been a brutal part of my career but we've always gone back to the bench and done better science because of those challenges and one of the big challenges in my career was that resveratrol we said it activates this enzyme by actually literally sticking to and binding to it physically and making it more active like a Pac Man would move faster and then a couple of companies came out big big pharma companies and their scientists said literally that is bull right and that's Bruin that happens and everyone almost everybody except close friends said are we gonna believe with companies and David's wrong and that that's a tough time in anyone's career in my lab shrank down to about fifth of its size and couldn't get great money but we fought back we went back to the bench I got out of bed eventually and I had a student called basil Hubbard who's now professor in Canada he didn't give up everyone else in my lab was kind of like oh we're screwed let's get out of here a sinking ship he said know what you know what I'm gonna test this and he he worked really hard and figured out that the experiment that we originally did too show that resveratrol was activating the enzyme in the test tube was not an artifact and it was actually real so we published that in the journal Science in 2013 and so that the scientific ha Bob went down mm-hmm basically we were you know largely accepted that we were correct but out in the media you know no one no one cares about correction of a scientific idea it's all about the controversy that's interesting and so that's still out there in the world so anyone listening who who knows that this was controversial we've actually scientifically resolved the controversy whether it's true or not it is true but it still left open the question is there something in the body that we make that activates the enzyme like resveratrol does mm-hmm so this new study then basically kind of you know what I infer from that is that we should be eating monounsaturated fats or that we should somehow be truck be trying to trigger this lipolysis you know situations so that we are you know creating this impact that we're trying to have I mean what do we do with this information yeah well I think the the lipolysis were going to be doing with intermittent fasting anyway oh it's up and down but I think that the most exciting thing about the paper is that they found that oleic acid from olive oil is also a very potent nano molar for the aficionados activator of sirt1 so what does that mean that means that when you eat olive oil you're actually activating your sirtuins quite potently because it's also just like where's virtual mimicking this lipolysis effect and maybe the I and the authors of that paper have written that this could explain why the Mediterranean diet is so healthy mm-hmm or alternatively in in lieu of olive oil you can get the same result via resveratrol well yeah so one thing that occurred to me was so I've been taking resveratrol for over 10 years now and I'm glad I have maybe I should have been taking a little bit of olive oil as well but resveratrol has no calories so I basically been drinking olive oil for the last decade with calories right that's a good thing what is we talk a little bit about this last time I think it's worth exploring a little bit more what is the difference between taking in resveratrol via you know red wine versus a supplement in terms of bioavailability and your body's ability to kind of metabolize it yeah so resveratrol is unfortunately a pretty insoluble molecule now in the plant what they the plants do is they put a sugar on on it and it's quite soluble for the plant but for some reason we we like to purify it away from the sugars well not for some reason because if you don't it's a sticky horrible mess so we isolate resveratrol that's free and clear of all these other bells and whistles that the plants like to stick on them but what we're left with is basically a crusty dry powder that doesn't get absorbed by the body very very much and even if it does it gets basically gotten rid of by the liver so what we had to learn early on even for worm studies when we were showing or as virtual extends the worms is you have to dissolve resveratrol in some sort of solvent so for worms we use a thing called DMS so in humans we found in the early 2000s that you if you mix it with a fatty meal and that's true for mice as well you get about five to ten fold the levels and so I always mix my reservatrol with something that's got a little bit of fat in it like a homemade yogurt every morning and what I what I've noticed is that the studies in people that have not showing the benefits other ones the way they've just given a dry capsule to the patients or the subjects and those that work are those typically that are giving it with a meal or something that the resveratrol would dissolve in right so there is some sense that that that definitely increases the no question we did these clinical trials a long time ago as we were working our way to making a drug and but we actually we ended up making synthetic molecules that were a thousand times more effective than resveratrol we didn't know at the time we were making the equivalent of olive oil alig acid but i guess now we do know that those molecules actually went into clinical studies with with humans that's also not very well known and there's a the skin condition psoriasis it worked really well they that popped a pill of these activators and one of these activators and the patients did better now I'm still hoping by the time I die I'll have one of these medicines on the market we're not there yet yeah and that's actually one of the brutal take-home messages actually is um I don't want to complain because I've been very lucky in my life it's it saddens me that that in science you can be derailed by a decade for a decade by you know by your your naysayers and I'm hoping to get things back on the rails seems like so far so good well the last time we spoke you know this book has not come out yet now it's been out you've been doing the you did the book tour thing and you know I kind of canvassed some of the press around that and it's interesting because it's my sense is that on the one hand kind of in popular culture you're being feted and and celebrated for this book and your work breakthroughs you know this bold you know taking this very bold position that that aging is reversible that we're on the precipice of new science and breakthroughs that are gonna revolutionize how humans live their lives and and think about their lives and on the other hand you know some pushback from the conventional scientific community and some grumbling amongst you know the old guard saying not so fast you know what I mean thank you like fast yeah you're you you've got your your foot on the accelerator and and they seem to be saying you know slow down you're you're you're kind of out over your skis here yeah that's true but that's you know so be it we have a certain amount of time on this planet and I'm going as fast as I can the other thing that most scientists don't realize is sometimes it takes us a decade to publish our work so we know I know a lot more about what we're working on than other people and when they say to me Oh David or say behind my back David's out over his skis they they only think that I know what's published but we've got all these other stuff so when we were challenged by these companies even though it was sad I had a whole body of data from my lab that said uh I'm not don't be so sure of yourself but yeah it's tough as a scientist especially one at a conservative university like Harvard you know I often get my knuckles right because I'm out there right but but I do it not because I'm seeking fame or anything I'm pretty shy guy but I do want to see technologies adopted within our lifetime you know it's fine future generations will do well but I really do think that it would be a real shame if our generation was the last to live a normal lifespan you would think that Harvard would celebrate this I mean don't they want people that are sort of breaking paradigms and pushing the envelope I mean what is the purpose of a lab if not to test the limits of our of our understanding and the kind of you know dream boldly yeah well so in Havas defense what what gets them riled up is when I get misinterpreted by mainstream media so I rarely now talk to that never happens yeah it's tough as a scientist because you you you say here are the facts here the facts and the headlines out for me typically is Harvard scientist says we're all gonna live 250 right which I'd never have said but then the University says David what the heck are you saying it's like so you know it's easier for me to not now talk to sensationalist media and I've now I'm much more comfortable doing this kind of thing where I can talk directly to the public right and I appreciate your not getting misquoted yeah and and and how's the lab doing like how and how are the colleagues like in the wake of the books success New York Times bestseller like you know books everywhere everywhere you look I see it you know how are they kind of you know acting towards you now good yeah I've had no backlash about the book which surprised me because I've it's a bold thing to say you know we figured this out it upsets a lot of people right but as far as I know they're not upset in fact I've had a lot of praise from colleagues it's cool the book is I mean congratulations I think it's a it's I really think that it is a paradigm breaking master work and what's what's really interesting and unique about it and and I suspect unsuspected for somebody's gonna pick this up is that is that it's not just this hardcore scientific tome it's sort of you weave in a little mem memoir aspect to it you tell these stories there are incredible illustrations throughout I know you want like an award for the illustrations or the artist did and you tell these amazing stories and you have these kind of poetic you know chapter titles so it's a different experience than then I was expecting looking into it like it's it's it's kind of general john rebending in that regard well thanks I appreciate it you know anyone who knows me I'm not not really a scientist I'm doing science and because I have a goal in life I in high school I was an artist and some of the illustrations at the back of the book I drew myself moon for headshots so I'm an artist masquerading as a scientist but I think they go well together actually I'm I think in terms of shapes and things moving around I'm not so much a mathematician mathematician but that that's why the book ended up being like that also have to give a big shout-out to my co-author Matt LaPlante who took a whole bunch of crazy ideas that I had and synthesized them and wove them into this narrative including some history which I really believe that the best way to predict the future is to look back over the last 200 years to see where we're going especially also when you look at society and a lot of things are said about the work that we're doing oh we're all gonna run out of jobs we're gonna have not enough food or we can do with all these people of population if you look back at history we've always been worried about that right and there are solutions I mean it's not perfect we can't have unlimited number of people on the planet but that's why I wove history in there because you forget that if people have gone through these kinds of things before and come out the other side much better I don't think you'd want to go back to the 1840s with cholera rampant now but we have our own particular set of problems now and I do want to explore the kind of ethical and philosophical implications of your work and I think a good kind of inroad into that is to start with Australia right your Australian last time you were on the show you told these amazing stories about your grandmother Vera wearing a bikini on Bondi Beach for the first time and just being this like you know I don't know like I just wish I had someone like her in my life she just sounded amazing and I can see how you know her influence on you has catalyzed this path that you've been on but I spent I just spent a month in Australia I was there for all of December I think you were probably there for part of that as well right yeah I think we probably overlapped yeah and and it was it was quite something being in in Sydney and amidst these fires and it's I know it's even worse right now in terms of air quality around that city but it was relatively dystopian on days people walking around with masks on you really you know couldn't breathe the air the sky was orange the entire you know Khosla I mean it's just the the the the sheer scope of what's happening there right now is hard to imagine I mean I saw a new story this morning that said the smoke from the fires has actually circumnavigated the entire globe and is now back to Australia after going all the way around the planet yeah yeah it definitely feels like Armageddon when you're there and even I'm live in Boston of course and a few days ago it was 70 degrees and you know you walk out there you go this is this is craziness you know I grew up in Sydney right on the bush as I described in the book I almost had my house burned down actually last week my brother's family lost a house it was all burnt down and there's nothing left excepting a bit of steel on the ground everything else just toasted it it really brings home the fact that we are living in in dangerous times and you can deny it you can deny that the world isn't changing and we've lived through these times before but let's just face it let's use Occam's razor the simplest explanation is that the world is [ __ ] up and we are cooked the cause of it it's not that hard to admit unless you've got some other agenda and Australia is a if you've never been to the Australian bush you got to realize this isn't like a forest with soil this is tinder this is the kind of leaves that if you put it in a fire they explode there full of oils eucalyptus oil mainly and it's not hard to start a fire you better than you know throw cigarette out or whatever once it's going this is basically a fire that you cannot put out because it's it's not just going from leaf to leaf it's going from tree to tree across the top it's creating its own weather patterns there was a couple of firemen were killed because the truck was caught in a tornado and blown on top of them right that's arm again kind of stuff and you go there and there's just this I think the Australians are in shock when I was a kid my house almost burnt down I know what it's like to feel that your house has been burned down the problem that I see now is that you know this is this is not a one-off fires in Australia normally starting around February and you know where we were in December or January and this could be the new normal in California right now it's it's fires all year round pretty much yeah and this fire in Australia has been going on for like four months at this point right right right and the safe are similar but it's a lot of different fires or it sort of meeting up with each other etc yeah yeah it's it's a scary world and we have to do something and so what so most people look at me and like Oh David you you study mice what would you know about climate change I have a conscience and I think about the impact of my research all the time and what I've written about is that we need to mobilize resources on the planet billions if not trillions of dollars to tackle this as well as other problems we have like energy resources consumption you got to take money from somewhere to solve these problems if they don't solve themselves we can take it from the military you could there's opposition to that you could take it from education you don't need to do that what about health care right now we waste billions of dollars taking care of the elderly who don't need to be old if if we're right and we do the kind of things that we talked about today as well as advances we could have a world by the time we're elderly where people in their 80s are just starting a new career like my dad did that's a world where you a glow bit word save trillions of dollars okay so now it's easy to say you save trillion dollars but that's money that can be poured into solving these problems I to think about old London a lot because old London in 1840 the cholera thing that I mentioned people in the 1840s they weren't solving the world's problems because they were too busy trying to figure out why everyone's dying in a world where people are not dying and you're not taking care of them then you've got the resources to solve these problems mm-hmm and I don't know any other way besides stopping the military spending of getting a few trillion dollars to spend yeah I mean the silver lining in what's happening in Australia is the opportunity that it will catalyze political will right and one of the things that was interesting when I was there is I didn't fully have have a sense of just how conservative the government is and you know everything that's going on with the PM and he goes to Hawaii in the middle of all this on vacation and you know the the impact of the coal industry on kind of you know the political perspective on what to do or not to do is all very interesting right so you're somebody who is incredibly optimistic about about human ingenuity and you know excited about the potential of our species to innovate our way out of any problem that we find ourselves in and I can see that perspective and to some extent I can agree with that but I think the limiters are are really you know the the government's and the politicians who are tied up in old systems that are holding us back and basically exacerbating the problems we're trying to solve yeah no doubt no doubt and just to hit the exclamation point old London when they figured out that it was actually cholera from the water well what snow did was he removed the handle of the pump and cholera went away but talk about politicians what's not really known is that the politicians were under pressure because people didn't want to admit that the fecal-oral route of infection was true they thought it was you in the air so they actually the politicians put the pump handle back on and for another couple of years there were still cholera plagues in London so you know you talk about politicians screwing things up I absolutely agree that if we can mobilize human engineer we can solve anything but we do a very bad job of that I think where we are here in California is a hot spot for innovation but most of the world doesn't really innovate yeah when we look at the state of healthcare in the United States I mean it's just it's it's horrific compared to where it could be in terms of what we could be doing for people and it's such a Byzantine mess I don't see our way through it or out of it without some really significant changes at the highest level well I agree with you and that's one of the things that we're doing in the aging field is to talk to politicians as well as the FDA to convince them that aging is something that is important right now if you talk to most doctors even geriatricians who treat older people aging is just the way it goes we've got to deal with it it's natural well you know when have we humans put up with what's natural if we didn't want to everything else we we work on Aging is one of these things let's all live with it but in at the political level I and my colleagues have talked to them it's slow you can't change the course the Titanic too quickly but we do see things bending and the FDA is actually agreed that if we do certain clinical trials for instance with metformin the diabetes drug that we think might slow aging if we can hit certain end points and show things are actually working they are well prepared to consider calling aging a treatable condition if not a disease that's right that we can prescribe medicines for right yeah I mean the kind of underlying theme in the book and in your work is this idea that there is no biological law that we need to age like we just sort of accept that as a truism but in fact you know that's that doesn't necessarily hold water no no no nobody has any reason to say that that we have this clock that that cannot be changed in fact what we've learned going back to the horvath clock is that about 80% of our lifestyle 80% of our health in old age is due to a lifestyle how we live right and only 20% is genetic and actually that that's done by studying twins who you know some smokes I'm done I live different all this stuff your jeans are not your destiny that's the good news so that what that means is it's up to you and if you want to be frail or to be honest dead at 80 go for it we know how to do that do everything that the marketing people want you to do eat the cake sit on your fat ass and watch movies that'll get you there pretty quickly yeah but fortunately you know in part thanks to new media like this we can actually all talk about what we think of their ways to extend lifespan and and and not be frail in old age like my father I talk about him a lot I'm very proud of him as a beacon of hope at 80 he's still running around like he's 25 he's got no aches or pains very sharp minded using all sorts of high-tech lifting more weights than I can actually and our trainer who's currently training the two of us together he says you know what I think my dad was dead lifting what was it uh something like 180 pounds something a lot and he said the last 80 year old that I trained was was learning how to get out of a chair right yeah you uh you posted something on Instagram he's like you know in the in the squat machine or whatever like just killing it at 80 the guys in his second career he's had this kind of you know resurgence and vitality as a result of finding new purpose and meaning and he's also somebody who's been on your kind of protocol for a while at this point and to see him in the gym at 80 like crushing it it's it's very inspiring well I think most of us can achieve that in life know there will be unlucky people that of course diseases dual heroes but most of us are wasting our lives because we're basically not not you but most people don't think about their longevity they dif they think oh when I'm old I'll deal with that when it kinds but now in early and midlife is the time to invest because it'll pay off dividends later in life mm-hmm we've done such a good job with medicine and pharma and increasing I mean you would probably disagree but an increasing lifespan but not so good in terms of increasing health span right like we now have to dodge all these bullets of modern life just to basically you know counteract that genetic marker to extend our vitality right through the processed foods and the kind of you know luxury imperative that our culture you know reaffirms and enforces like all of these things we have to kind of opt out of the you know dominant paradigm in order to kind of thrive later in life yeah well the dominant paradigm that's that's existed now for about 300 years is that doctors treat diseases they don't treat lifestyle typically there are exceptions but mostly the doctors around where I work at these great hospitals you they only see patients after they get sick and so the the the aging process is already pretty advanced at that point and aging is let's not be be silly about it aging is what's driving cancer heart disease Alzheimer's it's the main cause of disease and disability on this planet it's not I mean do these diseases are real but they're the endpoint of this process that we're working on but most doctors don't think about aging they don't think about what got people to the cliff in the first place and I call it whack-a-mole medicine which is and this is all great I'm not criticizing my colleagues we are we do need medicines we need to treat diseases but it's a little too late for a lot of people and this whack-a-mole medicine leads to the the paradigm of coming with a disease we'll treat it hopefully fix it kick you out the door wait till you get sick again come back and repeat until failure mm-hmm let's talk a little bit about the ethics of your work so we were talking about Australia you know if we just look at what's happening there as as a symbol of you know climate change in action and I kind of you know degraded planet Earth in a certain trajectory that we're on and have been on for some time as somebody who you know by your own words said you know I'm concerned about the climate just like everybody else you have this mission to extend lifespan which inevitably is going to lead to population growth which is an exact servant to the climate change problem that we're trying to solve so let's kind of dig in to this and the implications of like let's say you're successful and your colleagues are successful and we get to a place where people can live to be 150 175 people are I would I would imagine more likely to have more kids there's more people on the planet suddenly we have to sustain a greater population and deal with these other problems that we so far today too haven't been so good at dealing with so everything you said was right except one thing hmm the healthier people are the less kids they have later in life so we can now extend the healthy period of life and we think based on some animal studies extend fertility so women in the future will be able to have kids much later in life and have fewer the fewer of them but let's look at the planet we do have any show on the planet of course we've been going on exponential growth for the last couple hundred years for our species but it's it's not the doomsday that we thought it was in the 1970s Malthus and the erlik's used to panic make all of us panic because they said don't slow population growth well about you're running out of resources if you extrapolate this curve vertically of course we're all gonna starve to death in the next thirty years actually they thought by now we'd all be starving to be fair but what's happening is that what they didn't realize would happen I think most of us didn't predict is that as populations across the globe become healthier they become wealthier when they're wealthier they become healthier and then you'd Li you have women who become educated mm-hmm and women don't want to have 15 kids they don't want to always be pregnant when you give them the choice they have you noticed a few and where we're seeing is particularly in Africa the rates of population growth are dramatically declining I was just in Uganda and late last year and I was talking to the locals and I said you know tell me how your family all my grandparents 15 kids or 13 kids I exaggerate I have five brothers and sisters what about you oh we only want to have two want to give them an education that's happening across the planet so well you know I'm drawing these curves anyone who's listening can't see this but basically we're tapering off this exponential growth we're going to max out according to the United Nations World Health Organization at about 11 billion now that that's still a lot of people of course max out on the resources no no the number of people on the planet so it's already tapering off and we're gonna hit a sustainable level and actually start to decline in population based on projections why wouldn't we just continue to populate until we blow through that ceiling well because it let's look at um even in the u.s. actually population is going down and is barely a replacement level in Western Europe its declining couples on average are having less than two kids and as plenty of people who choose not to have kids yeah I mean this is one of Paul Hawkens big things when he in his book draw down one of the most powerful tools in the war against climate change or the you know the the battle to to solve this problem is educating girls the more we can educate girls in the developing world they're less likely to you know have as many kids right exactly exactly so we're gonna help build some schools over in Kenya that if anyone who can see this risk brand this reminds me everyday first of all how lucky I am with my family here in the US but also that there are people on the other side of the planet that need our help but you're right being a woman in in the these countries is the worst they're if they don't have a well they have to walk you know thanks for - Justin Rainey's helping with the wells those things giving them water giving them education that's part of the solution to the problem of overpopulation and it doesn't initially make sense but what you just said rich is the most important thing give women the choice to decide how many kids they have right conversely as a thought experiment let's say you could live 200 years and and a you know a female's ability to reproduce extends way later into life you can have these you know now it's sort of like you mature you have kids and then you kind of you know gray into your older years but you could get like two cracks at this right like you could have kids and they grow up and you get older and then you get a new career and you know then you could just say hey let's do this again Yeah right you I'm sure there'll be people and we know people like that I won't name names but I know a 98 year old who has a kid who's in their 70s and also in their twenties anyway I'm proud of him he why I'm mentioning his name Martin Norman Lear he's fantastic okay norms of one of those guys but but most people don't do that yeah but but but if what I'm saying is when you're not just extending the number of years of your run you're extending your vitality into those years right so if you if you remain vital later in life like the idea of having a child at age 70 if you're operating the way you were when you were 40 seems like not such a bad idea thank you for saying that because this isn't about science fiction living 170 and having you know a third of the world in wheelchairs what we're talking about is real life how much time do you want to spend with your parents before they get sick how or do you want them to spend another you know decade in a nursing home before they die this is really personal but it also we've got to throw away our preconceptions of what being old is right we talk about lead Hamilton in his 50s he's basically got the body and the looks of someone much much much younger being 50 is not old anymore suddenly 60 even 80 like my father that's not old anymore if you take care of yourself you extrapolate that into the future there'll be a day when being a hundred isn't old you know they'll still be people who don't take care of themselves and be sick at 60 that'll always happen but on average people will continue to live longer we've been on this trajectory of living healthier and being more youthful in our old age for the last few hundred years and a child born today if we stay on that trajectory here in the u.s. can expect not just hope but expect to live 104 okay that means that they'll still be healthy 80 and 90 mm which is great it's all about keeping people healthier for the longest period and then dying relatively quickly yeah when I was you know ten years old if there was a Laird Hamilton doing what he was doing it would just be it would it would have blown people's minds right I mean not that he doesn't blow people's minds now but that would just be the the craziest thing you'd ever heard of exactly so we live in a wonderful world where people can learn about things that typically they never read about or maybe they'd have to wait 20 years right my research I'm talking about it as it happens pretty much it's it's a crazy world we live in but it's wonderful and also young people now have access to information you go back to when we were kids how did we get information well there was the local library which was books that were basically old and musty or you could go to a World Book Encyclopedia or is Encyclopedia Britannica and look up you know a paragraph of something and this was all data and information that was old and not cutting-edge today you can learn about stuff that's happening and change your life based on things that we only dreamed about his kids right from a philosophical perspective and like kind of playing playing on this thought experiment like let's say you could live 200 300 years how does that impact the psychology of a young person's mind in terms of how they make decisions about their career path or what they want their life to look like and we did talk a little bit about this last time but I I'm interested in in how that impacts like risk assessment right like if you're if you're like hey man I'm I'm 18 and I'm gonna live to 300 you know barring me getting hit by a bus like you know I have a lot of life to live so am I really gonna go skydiving because then the risk of that seems so much more severe than it would if you're looking at well I'm gonna only lift it you know life short and I'm gonna die at 80 anyway like I'm gonna roll the dice and take these risks and then how does that play out on a macro level in terms of what culture and society looks like yeah well we're already on that path I don't think people in the 1840s and 50s were worried about bicycle helmets if they had bicycles you know what I mean that the long we live healthy we are the more protective we are of our bodies and our children and that'll continue right now that we're seeing a rubber banding with that with like Jonathan height and what he's doing in terms of like you know we need to rewilding want them go outside without a helmet on it's lost her in the street it's extreme I just got back from Shanghai where there are cameras that that shame you on Billboard's if you cross the street when the lights are really the red yeah and it's and it's got a shame you it like a photo of your face yeah right on the street you can see the lady that crossed the street this morning that uh disobeyed the rules and she apparently like as demerit points on her social sister social score oh that's just like that's black mirror stuff right there yeah scary stuff hopefully this world that we live in won't be like that anytime soon but yeah that the the risks will you don't want to take massive risk but you know what I think that we're we're exaggerating maybe if we live for a million years we're gonna be a little bit more cautious crossing the street but I think that if we live to 150 say there were those of us who like taking risks anyway I don't think somebody says I'm gonna wait till I'm 90 to jump out of an aeroplane Doreen you're 20 right so it's there are risk takers and most of us will still take risks in life you know people actually funny funny side is people think that I'm scared to die because I'm working on Aging but anyone who see me drive my car knows that that's not true I'm a big risk-taker ocean Allah on the road I'm not well not anymore I'm now bit sedated but oh I shouldn't say sedated but I'm more calm about my driving but I do drive a fast car I Drive it a Tesla for that but but I do like I do like the feeling of risk and it's the reason that I'm in this career in the first place cuz I took a lot of risks when I was young to get here point being you know maybe I'll live to 100 maybe 150 I don't know maybe I'll die tomorrow you know I don't care I like doing things that are novel I like doing things that are risky and I think that a lot of us will still do that no matter how long we're gonna live but I think the trend in in the world is that the longer we live the more scared we become of danger right fireworks are we gonna worry about fireworks yeah that kind of thing but I'm not so worried I think that these are small prices to pay for a world that is different from today as we are from 1840 London yeah I think in tandem with trying to elongate life's lifespan and health span you know we also have to solve these other kind of you know cultural dilemmas that we find ourselves in that are contributing to mental decline and emotional decline the disconnection the you know addiction to technology the you know lack of purpose that underscores most people's lives and we talked about this last time to like how does the how does like the work of Gambian or in the Blue Zones kind of intersect with your own work you know ultimately what's the point in living so long if you know our value system is is you know not in alignment with you know what's required to be fulfilled and to be happy and to have you know purpose for living that long yeah a hundred percent so there's the there's the world of molecules and genes that that I do for my day job but I'm also very passionate about finding mission and purpose and doing the best you can in life because that that's also what I what drives me and so I think you're right that if if you're someone who's prone to depression giving up giving up hope you've got to get out of that you've got to find what excites you what drives you I teach a lot of students at Harvard and there are some students who were very smart you know some of the best brightest in the world but they're there I'm not sure I can do that and you know whining around I'm a compass lapping around find a goal go for it this is your opportunity and don't come to me with an experiment that'll advance science by one step come to me with with an experiment or a question that'll advance us 20 years into the future now that's not easy right that's the hardest part of the rest is just manipulating chemicals it's finding something that you want to go for and change the world and that's that's what I think has been if I have a secret to success besides a lot of luck and hard work it's at age four having a goal and going for it yeah it is interesting that that it dates all the way back you know your whole life has been infused with this you know this drive this passion to you know solve this problem or you know yeah well no advance humanity in this way well you know makes a good story and of course we're looking back on it it looks pretty easy but there were there's still are plenty of times where I wonder you know do I really have to get out of bed today this is tough you know ups and downs and I say that because anyone who who experiences this and has adversity they have to know that that's part of the process you don't grow you don't learn you don't succeed unless you go through that and it never ends right I'm not riding high I still have massive ups and downs and obstacles even at my age but I've learned actually that if you have a goal that's what gets you through it so when it's all said and done like what is the what is the legacy that you're working to leave behind like what when you when when when you're complete what does it look like ideally uh well of course that's never gonna happen but you hold this great vision so what is that vision well I would love to have a time machine to go a few hundred years into the future and if I see a future where people are able to do multiple careers with you we're talking about career arcs I mean what about a world where if you know not everyone can can have their dream job initially I would love a world where people can live 250 expect to be still playing tennis 120 I think it's doable there's no reason why we can't do that with our ingenuity what that gives you is the time to have multiple careers multiple lives multiple partners if you want although you may find the right one in the beginning but but this is gives you you know let's let's go back in time a little bit in 1840 okay that person who's born in 1840 was not expecting to have first of all a great time at age forty or fifty basically you're worn out by then they don't expect to have multiple careers they didn't have the opportunity anyway so if you extrapolate from there to now and into the future just as much what you have a world is where even if you you're dealt the wrong cards the beginning of life you have multiple chances to correct that there are some risks to take of course and you do need some support you know I'm not running for president I couldn't I was born in the wrong country but what I would love to have is what I call a skilled medical which is well it's another chance it's if you're busting rocks or whatever it's that you hate two years off retrain get another chance and if you have a long life that's 150 years long you can do you know one career could last twenty thirty years become the best you can be at that and then switch mm-hmm and that that's a life that would be well lived with it yeah I think it would it would give people the patience that I think we lack right now like every we're in such a hurry from the moment were born you know it's a it's a Habitrail of achievement and measuring ourselves against others and you know from the moment you enter junior high school and then it's grades in high school and it's getting into cut like you're it's this race right and the brain and the emotional body isn't mature enough to really process that to make the best decisions how are you supposed to know I mean you knew what you wanted to do at a very young age most people don't right but they're kind of you know corralled into a certain path and on a trajectory that for a lot of people they don't it's like a waking dream that they don't kind of come to out of until they're forty and think why am I even in this position but if we could slow things down and say hey you're gonna live to 150 no big rush here like take your time go on a kibbutz you know maybe there's a national you know sort of period of time your your you know of service or you do some kind of Teach for America like programs like that that allow people that mature and develop the self-awareness and a sense of the world so that they can make that decision about how they can best contribute and find meaning and purpose in their lives rather than being in such a rush yeah I couldn't have said it better you take someone like my father who at 70 thought he had a few good years left he'd be getting dementia by this point he wasn't looking forward to the future late 70s is still perfectly fit what am I gonna do with my life he started a new career right and so instead of being you know late part of your life what's my legacy we can turn that into why don't I just begin a new one and you know I'm now 50 you know what it's like normally we should be if anything was right if we look at our parents and their grandparents their parents 50 is the time when you like ah I'm almost done wind down write it but that's not how the world is these days and in the future will be even better we're at 50 like I'm just getting good at this I just understand how the world works although we you never fully get it I I don't feel any different than I did when I was 30 I'm have a bit more wisdom of course but everything else is the same physically mentally and hopefully a greater appreciation for the wisdom of the elderly rather than just warehousing them in nursing homes and and trying to put them out of our line of sight and you know dismiss them which is the tragic situation that we're in now yeah it is that I the older you get actually the more you appreciate these folks what I want is a world where people in their 80s and 90s are not just appreciative but actually utilized if they're healthy they can be advising or running companies or motivating the youth right that's the world that I want because it once you're in a wheelchair or in a nursing home then you're done for and of course young people are not gonna want to spend their time listening to you know who have dementia but in a world where you can have a mentor who's seen 90 years of really interesting stuff how cool is that the flip side of that is and we touched on this last time is the hundred and twenty year old who still on the Supreme Court and lacks the sort of plasticity the kind of adapt to you know modern times who's stuck in an era that is that is bygone and thus is despite their wisdom and experience of the ages isn't in lockstep with what's actually happening right I mean that seems to be a potential downside but it's no perfect thing it's not perfect right they'll still be people who who are in positions when they're too old to deal with right but now it's like finally but you know these people are we're getting rid of all these people so we can get fresh blood in here a new perspective I don't agree with that at all I think that we should treasure those folks that have the wisdom and experience mmm because what history is really the way to predict the future and and they've seen it all right that someone like a Warren Buffett I mean I would love to keep them around for a lot longer because someone like that it does a lot of great things but you know yeah Bill Gates same there are people you want to keep around maybe there are a few that we don't but these are the prices to pay for a world where the majority of us can expect to be playing tennis on our 80th birthday right as a result of doing this book tour I would imagine you've probably met some pretty interesting people I would imagine there's some pretty cool people reaching out to you yeah yeah you're gonna be cagey about this right well yeah yeah I mean it's it's you know look we all you know we all we all want to extend our lifespan and this book has been very successful and you've been out talking about it so I would imagine that that's created some interesting encounters for you yeah well I that's part of the the joy that I have every day is I've learned that people are really interesting yeah as a teenager I didn't go to medicine because I thought humans were the evil on the planet I've kind of switched it around and realized that you can learn a lot just by listening I'm talking today but usually I'm quite quite quiet I don't name-drop but but I've I've met a lot of my idols in business in Hollywood a lot of billionaires I probably met a quarter of the right billionaires at this point us but there I learning a little pasta Leone right yeah well you know I am a spokesperson for this field but I should say that there are hundreds of scientists like me working away every day to help solve this problem mm-hmm of course the one thing that everyone wants to know and wants to talk to you about is okay you're the guy who's steeped in this but like what do you actually do and what's interesting you know in hearing other interviews with you and the last time we spoke etc and in the book is that you're very quick to say and very certain to say look I'm not I'm not a medical doctor and I'm not going to you know give you a prescription for your life and I'm not going to give you advice about you know certain protocols and it's not until you get to the conclusion of the book where you actually say actually here but I will tell you a few things about what I do and it's literally like a page in the entire book right so I'm interested in why you because I would imagine in most interviews that this question gets asked right this is what people we're like what do you do like you're the one who knows more about this than almost anybody so tell me what your habits are right well I didn't do it intentionally but as it's worked out worked out is that those who make it to the end of the book get the reward right ok there it is that's not why it's actually more that I'm you know an unusual position right I'm a Harvard professor I'm supposed to be world leading scientists and scientists are like monks monks don't go around telling people that well actually they do but scientists shouldn't go around telling people how to live their lives I'm I'm part of this monastic group of people that are should only say something if it's factual right and I try my best to do that the supplements that that I admit that I take and that's rare for a scientist to admit that stuff even though probably about half my colleagues are doing something I'm out on a limb now anyone who wants to jump to the page that rich talked about right page 3 page 4 eo4 yeah oh do you yeah it's so funny but but I've realized that there's a lot of demand for knowledge about this and so what I've done is I've got a newsletter and so I'm updating people people can subscribe if they'd like it's a life span book don't go on and so I'm adding to those pages now it's not just one page to be fair that the whole of part two is about what you can do in terms of fasting and exercise and why it works where you just kind of break it down and hear other things well this is that's a cheat sheet yeah towards the end but yeah I can't run around saying take this supplement or that brand is good I will first of all I lose my credibility I've got to be objective also I don't spend my time testing products that's not what I do I'm a molecular biologist geneticist but I am willing to go out on a limb and say what I do and what works and how I think you should not sure but can adapt your life the other thing that I hope everybody realizes is that what I do is a guide it's not proven to work but I've got the reason the book is full of references is if somebody wants to do a deep dive into a subject whether it's fasting or the cold or sauna bathing or supplements there's a lot of other scientific work that they can delve into as well yeah the notes I mean the notes go on for however many pay 360 yes like 50 pages of notes at the end right so you know I'm trained as a scientist and everything in that book was fact checked to the nth degree and with references and that's why when you read my book versus maybe some others that are that are not written by scientists you can bet that what you're reading is factual as far as we know well let's talk about what it is that you do like let's in your estimation like what are the most important things that and and again you can preface this whatever with whatever caveat you want but like what do you think are the most important things that people should be doing or looking after on a daily basis to kind of you know take out an insurance policy against aging given the current state of knowledge and understanding that's well put okay now I feel free to speak because I don't endorse and I don't recommend I think the most important thing for anybody to live healthier for longer it goes just one thing I could say it would be eat less often don't eat three meals a day I literally think that that people who recommend three meals plus snacks trying to keep your glucose levels always at a pretty high level are doing the world a disservice and I'm gonna go out on a limb to say that a lot of nutritionists would disagree with me but I've been doing this for thirty years I've seen what happens to people and animals when you restrict their food and it it's all good I mean you don't want malnutrition or starvation of course but putting the body in a state of want every day um for as long as you can do it I do it you know like I said hopefully until late afternoon dinner that's the easiest and best thing you can do mm-hmm other things are at the high-intensity interval training or jumping up and down with weights in a swimming pool almost drowning that's pretty good right you're going back tomorrow right yeah well I will do it again actually I'm now I'm actually think I know not to go too far into the deep end but but honestly we now know we all have the the power with the scientific basis to actually live at least 15 years longer mm-hmm okay so there are actually and I talked about this I think on Twitter recently that there are there are five things that are pretty obvious and easy to do that'll give you 15 years and that's just off the top of my head things like you know exercise the fasting don't eat too much eat the right foods try to be plant-based get sleep have social network that gives you 15 years that's amazing that's not even going it delving deep into my book which takes it to another level of what the best exercise and supplements probably are so that's the good news I do list a lot of things we could we could talk for hours about what I do page three and four you'll see more I'm conscious that we have a microbiome that is that needs to be healthy so I make my own special yogurt mmm which I mix my resveratrol in I think I'll release the recipe of that pretty soon to the in the newsletter if anyone would like to make it so that these are the things on the sorry to interject but on the you sure sort of said you know eating eating plant-based predominantly plant-based I mean a lot of that is is informed by the relationship between excessive protein intake and that that impact on Aging correct well it's but from yours from your perspective in the work that you're doing so the so the plant-based food I think a little bit of meats find especially if you work out you're trying to bilk up bulk up some muscle but I think that what we've learned is by studying the Sardinians and Okinawans is that those diets are the best for humans and they are mostly plant-based with a little bit of meat like fish so why does that work okay why do we think that works the two reasons one is that you don't want to overload on some types of propel amino acids which you'll find in me leucine isoleucine valine these are turn off our body's defenses through a pathway called mTOR will probably be a Nobel Prize awarded for that stuff by the way it's big deal mTOR but if you're always eating a lot of protein in terms of meat then you'll you'll never really optimize your body's defenses so I try to eat plant-based foods but there's another thing that that most people miss which is the Xena or hermetic molecules from plants you get those you don't get those from meat as much so what do you make of a carnivore diet yeah I'm on this on the other side yeah I it is an interesting phenomenon good long just like sort of culturally to go how did this suddenly happen and there's a cohort of people who are all about just that's all they eat right this hasn't been going on for very long this story very much has yet to be fully told but you know if somebody's listening to this and perhaps was flirting with the idea of that I mean you know what would be your response to that person alright well so I'm a scientist so let's talk some science briefly the what what you do when you activate this mTOR pathway is you're telling your cells in your body that times are good you've just caught a mammoth okay basically and now is the time to build your body and actually fix things heal things and grow and it turns out that there are two things your body can do there's grow and then there's on the other hand the other side of the balance is to protect growth protect growth protect and if you're always in this growth mode by telling your body now is the time you got umino assets grow that's great when you're young and middle-aged you'll bulk up right you'll feel good you'll actually burn energy more you'll lose bit of fat but long-term you're gonna sacrifice your longevity in my view because you're not turning on your body's defenses which typically are turned on when your body senses that there's adversities a need yeah so being hungry and eating plants aren't gonna be telling your body times and not as good we've run out of mammoth meat let's hunker down but you could soar on around we're on our own so we're gonna have to you know do the heavy lifting here it's it's basically catalyzing these systems these biological systems to protect the body right yeah and and in turn promote longevity versus oh this we've got an endless supply of food coming in here we can just shut everything down because we don't have to worry about it right think of it this way when we're young our defenses are on hyper alert our bodies don't get diseases you don't find babies with Alzheimer's disease their cells know how to repair and and defend against issues by eating a lot of meat I think what you're likely to be doing is accelerating that process towards older age so because your body will ya be in a growth state but you won't be turning on your body's defenses and actually as you get older your defenses go down and down and down and that's one of the main reasons that we end up getting old okay so you've got to get your defences up like you're a baby speaking of which I've been on on much healthier diet the last few years including intermittent fasting including the supplements that I've got written page 304 one of the people say oh I'm not noticing anything after you know maybe two weeks on the unsummon of course you're not gonna see that I've been doing it for some of them for ten years but what I've noticed most recently with my current lifestyle all of these things combined the biggest things that that has changed for me is that I don't get sick anymore that's amazing I used to be the kind of guy that would go from one cold to another I even had a sniffle in years I can't remember the last time I had a cold and I'm on planes people are sneezing on me I'm shaking hands at people pretty much all the time so my immune system must be on hyper alert and why is that good if you ask a centenarian what about your younger years in your 50s 60s they'll say I never got sick never got a cold my father's like that he doesn't get colds even yeah what about sleep have you looked at the impact of sleep on all of this some people have well we we've done a little bit in mice what we've discovered is that the sort to ins that we work on these protectors that respond to the NAD levels in our body they cycle through the day and they're actually controlling our sleep/wake cycle that's really fascinating because what it means is that longevity protectors these adversity sensing genes are also controlling our body's clock uh-huh and if you're screwing up your longevity defenses you're also probably screwing up your body's clock yeah so another a side effect that I get with this new lifestyle is I get much better sleep and I know that you know we've got rings that can tell us that now and I feel great I don't wake up tired anymore the so this nem MPT gene we talked about earlier the one that makes nad that's actually going up and down in levels throughout the day goes up in the morning gown it's changing the nad levels and and if you get that out of whack we get this thing we call jetlag mm-hmm and another side effect actually I find it anecdotally it's not proven is that if I raise my nanny levels either by fasting exercising or taking a supplement I don't get the effects of jetlag that's interesting that's a super interesting all right so fasting trying to create some or missus in your life basically living up Blue Zones lifestyle in terms of supplementation you know I know you're not gonna give like you know specific recommendations but basically walking through what you do you take a daily resveratrol you take an nmn supplement which is basically a supplement oriented around promoting NID correct correct a different version of that would be NR right which is like one step removed from that same process yeah so the body uses NR which is short for nicotinamide right aside it'll convert n R into n MN and then n MN into nad and that last step know that first step is this an amputee gene aha okay so yeah you can people are taking in are or they're taking in a man in our is a little cheaper than any man I've studied any men people ask me why not in our well any man first of all is more stable on the shelf so that's good but also I find that it produces some better effects in mice when say for endurance but the truth is even though there's a lot of chatter on the internet and some of my colleagues have their stakes in some companies I by the way I don't benefit from any supplements ever so I have no stake in this but some of my colleagues and on the internet they're saying all one is better than the other the truth is we really don't know yet which is better or if it if they're the same I will take any man because AI have a ready supply because we're doing clinical trials but also because I've studied it the most mm-hmm and that's it right there's no other or is there anything else that you're taking yeah yeah there's a there's a bit of a list I'm also taking a drug ooh a drug a drug called metformin which is the rise yeah so metformin has been around since the 1970s and been in tens of millions people it's relatively safe it's not perfect it's not totally risk-free but most people what they experience is an upset stomach and lack of appetite which can be mitigated by a slow-release tablet you do need a doctor's prescription in the u.s. to get it or in Canada or an Australia or the UK other parts of the world you can just go buy it at a pharmacy because it's on the list of the World Health Organization's list of essential medicines for Humanity so what prompted you to get on metformin oh yeah really simple my best friend told me to to take it no but in all seriousness so his name's NIR Barzilai he's considered the world's expert in this but you know I don't just do what my friends say I have to research this so I looked at the literature and there are a couple of studies that I cite in the book they're worth reading don't just take my word for it if you look at over a hundred thousand people some cases they're veterans but mostly older people of all walks of life who have taken metformin because of their type 2 diabetes high blood sugar if you look at other diseases over the next I think it's five years time those that have a high risk of Alzheimer's who don't take met Foreman have a much higher risk of Alzheimer's than those that took metformin and the same is true for some cancers and frailty and heart disease so what is that interplay like why would that be the case right well there's a lot of debate about how metformin works the main explanation is that there's an enzyme called AMPK or a MP kinase that talk to the sirtuin so they're actually interplay and actually mTOR so if there are three main anti-aging pathways I've talked about sirtuins that we worked on in yeast and now in mammals the middle one is the NPK which metformin works on and in this mTOR which responds to low amounts of protein and they all talk to each other so we used to fight as scientists my pathway is more important than your pathway blah blah blah and it was vicious people were trying to kill each other now we realize that there's a network and if you tweak one you can tweak the you'll tweak the other but I think what the best is to tweak them both just at moderate levels and get the best anyway NPK what it does to the body is it for one thing main thing is it ramps up energy production mitochondria like it's called mitochondria most people may have heard our the battery packs of the cell and the more you exercise and if you fast calorie restrict you'll have more mitochondria that's a good thing mmm that as far as I know it is you can't have too many mitochondria that's the key to being a good endurance athlete mitochondrial density it is it really is and actually as we get older we lose about half of them attic Andreea but one way to boost that is to take med foreman or two to do these other things like exercise but it's not all good news there are some studies that show that metformin can interfere with endurance and muscle hypertrophy and there's been a lot of talk about it actually on the internet peter attea has done some some work podcasts on this NIR Barzilai my good friend at Albert Einstein College of Medicine was on that study so I I called him up and I said what's the skinny on this tell me and he said it's overblown and so when you look at the data and I'm gonna be using my hands for graphs but basically the the two bar graphs are overlapping there's some minor differences but there are plenty of people in that study that took metformin that gained more muscle than those that didn't but overall on average there was a slight grow slight increase in muscle mass in those that weren't taking metformin and doing weights but there were benefits to the metformin there was lower inflammation lower oxidative stress in the people that took the drug so what do I think is the take-home message number one it don't panic if you're an average person if you don't make a living from bodybuilding it's not gonna matter that much but in an abundance of caution what I do is I don't take mid for men on days I work out pretty simple solution but I still think on days where I'm not working out mid Foreman's gonna protect me against these major diseases so your impetus to get on metformin didn't have to do with elevated blood glucose or insulin resistance it was pure it was more from this sort of longevity self experiment perspective well it's both you know there's never a one answer to these things my father and his father and myself were susceptible to obesity diabetes I'd be I'd be twice my weight if I ate what I felt like eating and my son struggles with this a lot he's 12 and it already struggling so we've got obesity genes and my father went on metformin years ago and I think is one of the reasons he's probably still healthy so that's that's also a fact or no question that I took that into account I didn't take med Forman before I got diabetes until recently because I just wasn't sure it was worth the risk versus the reward but when I dug into the science of this it was a no brainer the risk for me is very low the worst that I get is an upset stomach and actually I feel less hungry so that's a side effect that I like and then on the up side is some of the chances of getting I forget which type of cancer but it's in the book can be lowered by 40% now that's a massive massive effect so you always got to balance that so I don't prescribe anything to people and then what I would recommend to do is to think what at risk am I willing to take what are the potential downsides and with a drug that's been in millions of people there's a risk but the risk is pretty low how old am I you know if I'm 110 I've probably only got two more years so what's they lose so that's obviously a calculation and then how expensive is it right some some of these things are still just very new to the market and all of that has led to me adapting my life over the years admittedly some of these discoveries are fairly new so I haven't been doing them longer than I would have preferred to have done them earlier but that's the calculation and so I think that we all know what's gonna happen in the end if we don't do anything if we just sit around and do what you know we think feels comfortable the end is not pretty I've seen what happens the other thing that that I want to talk about I'll just mention at least is is smoking so my mother died of lung cancer it was brutal to see her pass away she had a lung removed her and she did and then a final lung gave out 20 years later so she lived for 20 years on one lung she did it she managed to live a pretty good life she visited about 18 countries after that but the way that she passed away I don't know if have you ever seen someone die mm-hmm no not in that way yeah I've never seen someone die except my mother but she basically was was drowning in her own fluid and it happened pretty quickly so all I had a chance to do was to whisper in her ear while she was choking to death that I wanted to thank her for being the best mother I could ever hope for now a lot of people die like that do not smoke if you smoke please please try to give up because it's not pretty and not only are you increasing your chance of lung cancer smoking will age you we know that that clock the horvath clock is accelerated by smoking because it's damaging the DNA and distracting the distracting The Pianist yeah if you could what is what's the study that you would like to see perform like if you could design you know the perfect human trial for example where you could do whatever you want what would that look like and what would you hope to establish well we I don't have to imagine that we're doing design one well so I mentioned near again NIR Barzilai he and a number of scientists have devised a study that the FDA has approved as being reasonable test of whether you can slow aging down it's going to involve hundreds of people and a few hospitals around the country it's called T AME or tame what is a target targeting aging with metformin something anyway so that's getting under way that I think is a very good start the idea is to take people who are elderly who are not yet sick and monitor them over a period of five years and test their frailty and their susceptibility to diseases and if we're right we'll be able to show with those numbers of people that a their clock is slowed down but be that they remain healthier because of in this case metformin mm-hmm but you know if I had a billion dollars I take the top 15 drugs or molecules or and test those as well because otherwise all we're left with is you know what we're doing just trying to figure this out ourselves and what's going on in your lab right now like when you go back on yeah you're working on it's pretty darn exciting I got to say I'm very privileged to run a lab there were good days and bad days but most good days are my students are every few days coming to me saying it's finally worked we've had a breakthrough so for instance we've had this breakthrough in reducing the cost of this clock maybe we'll bring it down to five or five bucks that's a great break through that and that keeps me happy the big thing is is reprogramming we've now gone from slowing down aging with resveratrol and nad boosters reversing some aspects of aging like endurance in mice and hopefully people but the big thing that's just happened over the last couple of years in the lab and and increasingly excitingly in the lab is the ability to replace the pianist that's gone demented and reset the clock and get get it to go backwards so we we've put this paper online and anybody in anywhere in the world can look at it if you'd like you can go to a place called bio archive VI o R XIV okay mm-hmm if you type in reprogramming in my name Sinclair you'll probably find it too will link it up in the show notes great so we're very proud of that that paper which is still under review so it hasn't hit the media actually I gotta say I know I'm rambling hibbett podcasts are a fantastic way of getting news out before the actual news people figured out so you're hearing it here first but we hope that by sometime early this year maybe by June we'll have this published we were revising it for the journal Nature which is the one of the top in the world we're excited that we got good reviews from our colleagues who do blind or anonymous peer review that's a long way of saying we are pushing the boundary of this reprogramming method just a quickly a nice track does that study is what yeah yes yeah so the summary is that those methyl groups that are counting that we use to count the clock we can tell the cell to move the right ones so that they that the cell remembers how to play its genome correctly like it was young there are three genes that we we take from out of the book of embryos so when you're an embryo you're using three particular genes to to grow and be healthy they get switched off by the time we're young adults even while they're babies if you put them back in just at the right time in the right place at the right moment we found that it's it's rope we don't see any safety issues so that's the good thing what we see is the clock gets wound backwards those methyl groups go back long story short the cells are reprogrammed to be young again completely not just a little bit not 2% not two years but we can take it for example in this paper you'll see if anyone looks at it can take mice that have gone blind from old age if we put these three genes into the eye and turn them on for a few weeks their vision comes back as though they were young again what that tells me is that a lot of what we regard as a one-way street in aging is reversible if we can restore eyesight what else can we reverse I mean that's got to be about as exciting as it gets right I mean yeah I've seen a lot of amazing Wow and and our colleagues and I have to credit we have a lot of help I don't know my way around a mouse's eye to save my life but our colleagues that did these experiments with us they blown away my colleague Bruce Cassandra at a Massiah near Hospital in Boston he called me up at 10:30 at night and he said David you wouldn't believe what we've just seen excuse the pun we've got restoration of vision I want to run down tomorrow and tell the FDA this is possible because right now degenerative eye diseases like glaucoma macular degeneration these are not reversible the best you can do is slow them down slightly anyway that that's a whole story but what we're now trying to figure out in my lab is how is it possible to reset the cell how does that work and where is the reset switch what what's the repository of the information put another way where's the backup hard drive of the cell right so when that analogue system gets scratched there's an ability to reboot it with you know a digital replicant that is perfect yeah and we don't know where that information resides we know we can tap into it by using these three genes called OS and K for short but how that works and where it goes to find the old information to be young it could be a chemical on the DNA it could be a protein that sticks to DNA for our whole lives we're actively searching and so we got a whole bunch of very smart people in my lab look working hard on that and obviously you know human beings are infinitely more complex than mice but what can you extrapolate from that to give you confidence about applicability and in in a human context right well we we don't know but we do work in human cells so we can take human neurons and grow them making mini brain in the dish and we can both accelerate aging make the penis demented in those cells and we can reverse the age of those cells and make them grow again like they were young so we've done it what we say in vitro in the dish we've done it in mice our eyes and our biological systems aren't any different than a mouse's really so I'm optimistic you know but until we know in humans so we can do this I can't declare victory so what I'm doing as I typically do is try to spin out the technology get it into patients as safely and as fast as possible but in hopefully in the next few years we'll have the first patient tested and the results will be pretty quick this isn't like a long term longevity study if we can restore vision to a patient with glaucoma we should know within a few weeks and I would imagine that I mean basically you're dealing with a reversal mechanism so there's no reason to believe that it would only be operational in you know and in the optic context like it should it should be applicable across the board or in other you know respect to other problem you are exactly right we didn't choose the eye because it was easy we chose it because it was hard and because the eye gets old very quickly if you damage your eye so I'm gonna grow back like your skin so we thought let's go for it my student one chain lose is a brave brave student so if we can do that to the I are much more optimistic that these other organs and systems whether it be a kidney that's failing or a liver skin who knows we keep we're gonna test that rigorous here we can even try it to reprogram the entire animal we've started doing that one of the now you're just getting crazy right well you got to do it I'm sorry everyone else to know the answer but but here's what's holding us back in in the technology the ability to deliver genes is not as easy as everyone thinks there it is right now there are some drugs on the market that can actually fix genetic diseases in blood and in the eye but trying to get gene therapy to the rest of the body is still a challenge and so one of the things we're working on and having some success is being able to deliver it to every cell in the body or nearly every cell in the body and not have it all concentrated in the liver which is typically where these genes go when you deliver them IV but ultimately imagine a world let let's be a little bit of dreamers here if my colleagues will allow me imagine a world where you you have these three genes put into your body let's say at 50 and then you're basically like Deadpool if you get injured you can have an IV turn on these genes heal better you lose your eyesight turn it on in the eye fix your eye who knows what have an AVO whole body rejuvenation that would be pretty interesting and we've only reset aging once in the eye we don't know if you can do it twice we don't know if you do it 10 times or infinitely mm-hmm what more will be revealed we will come back I'll come back and tell you how things going yeah please do we're all counting on you you have that civilization rests on your shoulders the future of all of us will end in the meantime seat of your lab there's a lot we can do to stay healthy for longer and actually that every year you are alive you get an extra three months of life because technology's changing that's encouraging that's gonna that's gonna like allow us to end this on an optimistic note I think thank you super interesting I really have so much respect for the work that you're doing you did a beautiful job with this book there's so much to learn and I know that you're at the cutting edge of learning it for all of us so come back and keep us up to date on everything that's going on I'd love to yeah thank you so much pick up the book lifespan support local booksellers if you can't find it at your local bookseller tell them to order it for you or go to Amazon yeah right wherever good books is sold and david is easy to find on the internet it's just at David Sinclair PhD on one Instagram on Instagram yeah it's a series David a Sinclair cool awesome man anybody anything else you want to let people know about before we end it here let's all celebrate 80 years from now that sounds good man it's a plan whose where's the party gonna be your house I think we'll do it your house alright good Thank You Man [Music] you you

Channel: Rich Roll

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Keywords: rich roll, rich roll podcast, education podcasts, David Sinclair PhD, resveratrol, aging podcast, how to stop growing old, resveratrol benefits, nmn supplement david sinclair, lifespan david sinclair, longevity david sinclair, metformin david sinclair, epigenetics aging, david sinclair nad supplement, rapamycin longevity, rapamycin anti aging, the secret power of fasting for longevity and healing, mtor pathway aging, resveratrol anti-aging, epigenetics david sinclair

Id: DGC-Cyz0X_4

Length: 122min 21sec (7341 seconds)

Published: Mon Feb 10 2020