Dr. David Sinclair with Dr. Lee Hood: Why We Age--And Why We Don't Have To

lee hood is a world-renowned scientist and co-founder of seattle's institute for systems biology in 2000 he served as the first president from 2000 to 2017. in 2016 isb affiliated with providence and dr hood became providence's senior vice president and chief science officer he is also chief strategy officer at isb and has served on the faculties of at the california institute of technology and the university of washington he is a member of the national academy of sciences the national academy of engineering and the national academy of medicine please join me in welcoming dr lee hood well it's a pleasure to be with you tonight and i have to say i'm incredibly excited about the conversation that's about to happen i do want to thank town hall for its partnership with isb and bringing good science and i think this is really terrific science and let me say a few words about dr david sinclair he was born in australia and transported himself to mit for a phd and later to harvard where he is now professor of genetics david is probably the face of aging in the us and and and the world today the book you heard about lifespan why you age and why you don't have to i think is really one of those transformational books that when you read it changes how you think about a topic and i suspect you'll get that feeling tonight from our conversation david has many academic honors uh many beautifully published uh papers but it's interesting to note that time magazine in in 2014 declared him one of the most influ hundred influential people in the world and then in 2018 declared him one of the 50 most influential people in health care and i think in many ways you'll see from the conversation tonight that that certainly is true so with that introduction i'd like to begin our conversation and throw out the first question to david and that is you were born in australia david how did you evolve from australia to become one of the pioneers in aging and longevity oh well lee thank you for the introduction i've been introduced by a lot of people but but i think the introduction that you just gave um was probably the the most uh important to me because i've had such respect for you even before you know before you even knew who i was um and so thank you for that and thanks for the opportunity everybody for uh to be able to speak tonight um so yeah the i'm australian so i'm i'm i have to be humble we in australia if we start to boast about ourselves we'll we'll have no friends so i will try my best to talk about myself tonight um as much as you want uh yeah i was born in australia i was a pretty normal kid growing up on the edge of the bush my family had a place with uh oh about a thousand acres of forest in the backyard so i spent a lot of time looking at biology uh but i always had ambition i was the kind of kid that if if i was born in ancient greece i would head to athens um and so i wanted to go where the action was and as nice as sydney is it's not the center of the world where i i like being um i also was raised by my mother and my grandmother um and particularly my grandmother gave me a very special education she was a survivor of world war ii and and realized that that humanity can do terrible things she was from hungary and escape to australia with my dad and so i was raised being told that humanity can do a lot better and that david you should spend your life making humanity as best as it can be and as great as it can be because we know humanity can do much better and uh and so i i remember her telling me that and so i've spent my life really trying to leave the world a better place every day i wake up it's a it's another challenge uh to get to the us really what happened was i realized at the age of 17 18 as i was entering college that we're probably the last generation of humans at least my generation uh to be living a normal human lifespan and the technologies of the future our kids our grandkids would greatly benefit from these the understanding of why we age i was also told by my grandmother that everybody eventually gets sick and dies which to a four-year-old is pretty shocking and we all go through that but i couldn't get it out of my mind so combining all of that lee i i set my sights on the us on boston on mit i met lenny guaranty who became my mentor at mit i coincidentally met him in sydney in 1993. and i said i want to do that i want to study aging in yeast cells and to cut a long story short a famous scientist doug melton interviewed me for a fellowship for a helen hey whitney fellowship they'd never given it to a foreigner before and i just argued that they should give it to me anyway and they did and the rest is i guess history well terrific david one of the most interesting aspects of your book was in early in the book the delineation of the information theory of aging and i say that because i think from that conceptually comes absolutely fascinating hypotheses so can you explain simply in in uh layman's terms just what that means and i'll say it's also interesting because you made the fascinating point that aging is easier to deal with than cancer risks and this all comes out of the information theory of aging that's right yeah so that i've been studying aging since i was at mit this is now 1995. and the first set of genes that we were working on in lenny's lab came out of a random screen for any gene that would make a yeast cell more stress resistant and longer lived and out of that came the discovery that there are certain genes which we now call sirtuins they didn't have that name in the beginning but the interesting thing about the name is that the sir in the name stands for silent information regulator and at the time we really had no idea why a silent information regulator in other words something that controls the expression of other genes turning other genes off why would that be controlling aging at the time the idea was that and still for the most part is that just things break down and there's not much you can do about it you could try to slow it down but we're basically all gonna fade away and and be corrupted and degenerate but that information part of that that um acronym is very important and so i've been focusing on what is it about information that's relevant to aging and um we did a lot of work in yeast and then in mammals in my lab at harvard and so i've always been trying to think about information and the one of the breakthroughs came when um i realized i was reading about information theory uh claude shannon um a big disciple of his and he's a professor from mit in the 1940s and he came up with the mathematics of information preservation and actually his mathematics led to the internet among other things and his idea was that that things to generate over time including signals such as radio signals because of intro of introduced noise and that really clicked with me i could see that we were we could be the biological equivalent of a radio signal that degenerates and has introduced noise and it fit with most of the work that was being done in my lab if not all of it and so i came up with the information theory of aging as i call it and really the idea is that we are born with a relatively pristine set of information our dna is a digital code four bases four letters instead of digital zeros and ones but nevertheless it's digital uh but there's another type of information that's just as important for our survival and that's called the epigenome that controls how the dna is expressed in other words which genes are on and off and you need that because the brain has a different set of genes required for a liver cell and a skin cell and that's what the epigenome does and the analogy is excuse that the old the old fashionedness but a dvd or a compact disc has digital information but the reader which is the the head that moves and uses the laser is analog and the cells have two types they have the dna and then they have the the reader and it seemed to me that everything we were learning was that the readers the readers of the dna and the control systems uh were going awry during aging and that led to the the realization if that was true then here's the really interesting corollary is that there might be a backup copy of of the original information the genetic information and even the epigenetic information and we published a paper in december that uh we were pretty excited to even receive the cover of that issue that said that we could actually tap into a backup copy of the original epigenetic information in a cell or in a tissue in this case we rejuvenated the eye of mice and made them able to see again after suffering from glaucoma or just being old and so what i think is this could be a turning point you know dare i say it at risk of being wrong but if i'm right then there really is the ability of truly not just slowing aging but resetting the body to an earlier age and aging out multiple times and resetting multiple times yeah well i think the really important conclusion from that uh experience was there there are actually two aspects to aging it seems to me one is can we slow it down and the second is can we reverse it and it's never been shown to be reversible before i think your the paper that you described was one of the very first and i think a fascinating question is how far can we reverse it and and another interrelated question i'll leave you with these two is when should we start thinking about aging and actually doing things which will slow or even begin to reverse the process right well like all science i mean seriously i'm standing on the shoulder shoulder of giants there are giants that figured out that you can reset the age of of somatic adult cells to be zero so john gordon and shinny yamanaka did those experiments in tadpoles and in skin cells respectively and won the nobel prize deservedly in was it 2012 i think uh so that that was part of the initiative of reversing aging but we needed to do that we needed to reset the age of cells not to zero but by 50 or 75 without causing cells to become tumors and that was the challenge we spent oh about three years trying different genetic combinations trying genes that come on in embryos trying genes that that are helpful to cancers but not causing cancer and finally hit upon a three gene combination that resets the age of the cell by about 75 percent and you might say well how do you know how old a cell is well we actually now have a very accurate way of measuring the age of a cell or the body some people call it the horvath clock it's also known as the dna methylation clock we can read the chemicals that change over time that are on the dna called methyls and that gives us a really accurate measure of age and so we can now take those mice that had restored vision and truly ask are those cells just acting young are they literally young and the answer was they are literally young again and that was the first just i think the first discovery that in a living organism you could safely reprogram and reset the age of the body um how soon is this available to humans well we're working towards doing our first clinical trial in the next couple of years we've already got two years of work under our belt there well yeah but what about other parts of the body i i think that it's going to be possible to reset most parts of the body the question is you know the safety issue of course but my lab has now had some early results resetting other parts of the body muscle is looking promising we've got other labs doing the brain actually got some early results with alzheimer's disease and old age dementia and there's another lab at stanford i should shout out sebastiano's lab and at salk institute i should credit um one color spell monty for showing that uh you can reverse the age of cells that you take out of a mouse and put them back in and and that also also beneficial so you don't just have to reprogram cells that are in existence ultimately where is this going well it'd be like asking the wright brothers how soon do we get to mars it's it's doable i just don't know when but i can see now if the information theory of aging is correctly that we will be able to one day perhaps have an injection of a virus that carries these reprogramming genes and turn them on with an antibiotic in the mice we use doxycycline it's pretty inert drug and turn on these genes for for four to six weeks reverse the age of the body and then then your doctor will say come back in another decade we'll do another treatment yeah yeah so you in your book discuss longevity genes do you want to describe what this does and their role in this information theory of aging yeah these are fascinating genes they came mostly out of the 1990s and early 2000s discoveries in yeast and worms and flies uh labs like cynthia kenny and gary rufkin lenny guaranty of course where i was and these are genes that you might not suspect are actually controlling aging but were discovered through just looking across the genomes of these organisms and what we've discovered is that they do is that they're they're built for survival they're not built for bit for longevity but what they do is they respond to when organisms are perceiving adversity or future adversity for instance in yeast we showed in a nature paper 2003 that if you restrict the amount of calories that a yeast cell gets or raise the temperature or give it a little bit too much salt or lack amino acids it'll live longer through a set of longevity genes these sortuans i alluded to and that is a defense response trying to survive and so you can think of longevity genes in that way these are like the pentagon that you can call up and say there's an emergency send out the troops even if there isn't an emergency and that's what our bodies are actually doing when we exercise and we go hungry we're making a call to our bodies pentagon to send out the repair troops and if you do that routinely you're going to have longer life this is what has been shown time and time again the question is when should you start well we're starting to age from actually even before we're born this clock is ticking so even even if you look in the mirror and you don't have wrinkles yet trust me you are getting older um and you're heading towards you know decrepitude so i i'm not saying to to you know have intermittent fasting if you're a teenager or a young adult you've got a lot of activity for your longevity genes but for me by the time i hit my 30s you know i was already feeling like uh you know i needed something to assist me and uh so that's when i started but um so there are two answers it's it's good to start early the animal studies suggest and or actually show but it's also i wouldn't say it's never too late but it's you can start late we can intervene in a mouse that's equivalent of a 70 year old and have a lifespan extension of 15 or more percent so it's in that in that window but i wouldn't go too old i don't think once you're 100 years old you're going to go back to 20 unless our science improves so the how do the longevity genes then relate to these these now classic nine hallmarks of aging again that seems that whole process is a part of this simplicity we spoke about that marks aging as a contrast with something more complicated like cancer right so yeah cancer has been described as a hundred different diseases aging is is really just a in my view a relatively simple process there are three levels we've got the environment and what we eat and how we live so this is external and internal inputs and i've already mentioned that putting yourself in a state of adversity walking not eating this kind of stuff does that second layer are the longevity genes that sense that adversity uh and uh control the systems below it so what's below that at the very fundamental level well of course there's the epigenome which i've explained is my best theory so far to explain the fundamental causes but tied up with that perhaps influenced if not controlled by the epigenetic changes are what you mentioned which are the hallmarks of aging you many viewers will remember telomere loss the ends of chromosomes get shorter we have we lose stem cells we have senescent cells the zombie cells that accumulate in the body to make us old these about 10 years ago we we in the field agreed on nine hallmarks that contribute to aging primarily and uh what they do is that they control the troops they are the various divisions in the pentagon that go out there's the army the navy the air force space force that's what these whole these these longevity genes will control now what i don't know yet but what's exciting is that maybe if we can reset the age of the cell through the epigenome these other hallmarks of aging will vanish and we have some evidence that some of them do actually go away meaning that the information theory is you know perhaps valid but that doesn't mean that we're just going to be able to i think just tackle the epigenome these other things need to be addressed and so there are many researchers and companies working towards finding ways to address each of the individual hallmarks as well yeah so you spoke about the environment being the higher level starts the whole chain of uh the aging process what are the environmental manipulations that we can use to influence the hallmarks of aging that ordinary people like you and me can actually incorporate into the way we live yeah well it's not that hard to live another 14 years uh on average if you just do the right things which is don't become obese do some exercise eat good food um what are the other ones i think it's get sleep and uh and don't stress that the basic stuff that that in itself will give you 14 years um it's been calculated uh you know bad luck notwithstanding but you can go beyond that that's just that's just the minimal if i could recommend one thing for people to try uh it would be to eat less often you know i've totally changed my life about around this so is my father who's 81 without any any medical issues at all we we now eat uh one meal a day i might have a bit of lunch but not much and the rest is just warm drinks which i love anyway there are some really good experiments that show in many different species and we've known this for 80 years that reducing the amount of calorie intake particularly if you restrict it during certain times of the day it's beneficial one of the best experiments i could point to or it's a set of experiments is by raphael de cabo at the nia which is the national institute on aging in bethesda and he did a very interesting set of experiments in mice admittedly but it was really telling he was trying to figure out what are the differences between diets and you can give mice more calories in form of fat or protein or carbohydrate and he did all those combinations 10 000 mice but he did something also interesting which was fed the mice either all during the night when they typically eat called ad libidum feeding or only at for a little window during the day or during the night i should say and the mice ate almost the same amount of food because you can imagine if you're a hungry mouse you're going to gobble it down really quickly within that hour of feeding the only ones that lived longer were the ones that had the restricted time restricted feeding it didn't matter what they were eating so what that tells me most likely and there's epidemiological evidence this is true in humans that it's not as important about what you eat you know of course you can't eat a terribly horrible diet and expect to live longer but within reason it's more important when and how often you eat and so that's what i do i i've really cut back of in a lot during covert i've lost no what is it nine kilos what's that it's a lot of pounds i'm down to the weight that i was when i was 20 now and i feel great um there are plenty of other things you should be doing lifting weights especially if you're a male an older male keeping up the muscle strength but even for women keep your muscles tone because falling over is the quickest way to dying actually is somebody in the u.s falls over every 19 seconds and breaks their leg or their hip and that's that's you know eventually fatal for most lovely people so a really interesting question i mean uh intermittent dieting intermittent fasting is presumably stressing the body and it activates longevity genes and sets in place this whole anti-aging process so my question to you it seems to me the most challenging aspect of that is how do you persuade people to change their behavior and adopt activities that are really good for them in the long term i mean that is i'm very interested in wellness and the issue is exactly the same there so i'd be curious about your thoughts on how can we get people to change yeah yeah right you and i we've talked about this and it's really difficult what what i find is helpful is information um and even thinking about my own life if i didn't get any feedback positive or negative i gave up right you step on the scales but that's about it once you start measuring things and and getting feedback i find it makes the world of difference um you know not everyone does this but i wear an aura ring for sleep and motion i um i monitor um my blood work as well just to know what's happening so that that's the future so that people won't just go for an annual checkup they'll actually be constantly seeing when they they did this or they took that supplement if things are working now that's that's still futuristic we still have you know close to 50 of the us overweight so how do you reach those people um it's really hard and it's one of the reasons i wrote my book is to hopefully reach more people and make those people that hear or read my book realize that 80 percent of our longevity in our health in old age is based on how we live and only 20 is genetic so you really can control how long and how healthy you are in old age um so there's the education part there's the feedback positive feedback hopefully but other than that lee i'd be interested in hearing what your thoughts are on how to have people more interested in this well i would agree with you i think i think there are two really important aspects one is you have to give people a metric that show they're succeeding or failing and the metric can show they can change their behavior and i think being able to measure something like biological age the age your body says you are as opposed to your birthday i think is one of the most valuable tools we're going to have in convincing people that this is a unique opportunity did you want to talk a little bit about that i'd love to uh yeah so we've been working behind the scenes in my lab on trying to democratize that test now that test if you haven't heard of it i mentioned it earlier it's the horvath clock typically it's called what we can measure are the chemical changes on the dna itself in in blood or in a cheek swab and that will quite accurately tell you your your real age not your birthday candles i like to joke that i mean who cares how many times the earth has gone around the sun that's not what's determining your health it's really more about your true biological age and so in my lab we've we've been able to develop new technologies to be able to read that test and you know i'll say publicly for the first time that we're planning on making this commercially available to the public because i think it's so important that everyone who wants this test should have a cheap way to do that and i totally agree it changes your mindset when you can really measure how well you're doing and also see if you can improve it i'll tell you the second thing david i think is really important is education at the k-12 level so for example isb is putting together a program on health where we have 20 units that are based on this vision of a health that's predictive and and personalized and participatory and one of those units is going to be on aging and wouldn't it be wonderful if all high school seniors came out of school with an understanding uh of the kinds of things we're talking about now and for young people it's easy to change for a lot of things in older people the easiest way to get them to change is to have them die off and let their kids change so anyway but i think education and i think metrics are but you know there there is a third really interesting opportunity i'd love you to talk about and that is you know americans really like the idea no i mean your big new idea is that age aging is really a disease and we know how we can deal with the disease and the way americans like to deal with disease is with pills so do you want to talk about pills and aging and where that's going in the future yeah it's a it's a really hot area right now um going back when i started my first company 19 2004 it was crazy to think that you could develop a medicine that would tackle the root causes of aging or slow it down and people didn't even understand how to think about it let alone build companies out of it i think we we showed that it was possible um and we're now in a world actually where longevity research and longevity development of drugs uh development of longevity drugs uh is one of the hottest areas in in biotechnology um you know i sit in in the center of a tornado of activity and i see that it's really gone almost vertical uh in in a graph of interest of investors um i'm part of a group actually that that uh recently said we were going to invest in a company related to longevity we haven't picked out which company yet um and there was a billion dollars of interest so this is we're in a it's a zeitgeist in other words that i think the science has reached a point where uh wall street um and ho main street increasingly has realized that the science has come of age and that we can truly develop medicines that will use this knowledge uh not only to treat aging but to treat the effects of aging and actually 85 percent of of all suffering on the planet including most major diseases are due to aging we we're in denial that aging is is not important but actually it's far more important for lung cancer than smoking is for example by at least an order of magnitude so this is a major issue but i'm i'm optimistic now that we've seemingly turned a corner uh similar to yeah i use the wright brothers as a good example and you know we're talking we're now in the 1920s where people have seen that the right flyer works and there's a lot of interest in building you know eventually a boeing 747 you know i think one of the most exciting ideas i extracted from your book was this idea that aging is the dominant cause of virtually all chronic diseases let's say you can control aging then we can begin to think about controlling all these diseases so the argument is why don't we spend the six or seven billion dollars on cancer in the 11 billion on whatever else why don't we spend it on figuring out how to control aging wouldn't that be more efficient than taking diseases one at a time it's a it's as i would say a systems integrative global approach and very powerful year advocating right well what i wrote in my book i still believe which is i'm not going to try to rob peter to pay paul i think that all medical research is important and there isn't enough of the funding um the amount of money we spend on aging research though if you just look at the biology of aging and if you don't include alzheimer's and other things which is sometimes included unfairly i think it's really just a few fighter jets in the us has spent on this and so i would say that as a country the u.s can afford to put more money into understanding the biology of aging even without robbing uh or not robbing but taking from other places but i i definitely agree with you that the impact of of this could be far greater than tackling one disease at a time one of the problems with the approach that we have right now is that we've been effective at treating some areas of aging such as heart disease we've got the statins for for cholesterol we've got very good blood pressure lowering medicines and so we're we're generally living longer because of that but the brain still ages and now there's an increase in dementias and that's the wrong way to approach medicine i would rather try to keep all parts of the body younger and healthier for longer and have an extension of our health span rather than just our lifespan yeah well look this discussion really brings us to a fascinating point you and i have discussed before and that is our determination to push forward in the vision we have your vision for aging and so forth so my question is to you where do we go beyond government funding to get the resources to be able to do the science that really is going to transform aging well i've seen a lot more interest from philanthropists and non-profit organizations so i think that that's that's an area where people can make a big difference yeah uh george church and i talk a lot about this um just for a couple of million dollars you can have a big impact in a lab you can develop basically a drug that's almost ready to go into humans if you're very efficient with capital um and often people who have the wealth to to fund these kind of things are shocked that such a relatively small amount can have such a big difference but it really can at the early stages discoveries can be made just by a graduate student who's staying up at night dreaming and this is what changes the planet not the billion dollars of investment at the late stage of technology well i think another approach that you and i share is this idea we can take useful knowledge and spin it off to companies which can generate enormous resources for the maturation of the ideas and that amplifies enormously the kinds of things that you can get done and you've certainly been very successful in in taking that approach as well oh thanks um you know i have a few uh idols uh in you're one of them lee i'm not kidding it was very difficult as a as a young scientist in my thirties at harvard uh spinning out companies in the 1990s especially in 1990s and even in the 2000s it was just not something that assistant professors did right you how how could you do that let alone go in the media and talk directly to the public that was totally frowned upon um i looked to people like you as inspiration um and to give me the courage to do that and i'm so glad i did unfortunately now we live in a world where um it's quite acceptable it's pretty common for us to do that but it wasn't always the case and you were doing it before me and you had the courage to do that and i assume it's because you didn't want to just publish papers you wanted to change the world and that's where we both are i think so one of the things that's utterly necessary for changing the world is convincing the ceos at every level healthcare industry the high-level people in government of the validity of the vision and you have ideas about how to do because that is one of the most challenging if you can get to leaders you can change organizations but getting to leaders and changing their thinking is enormously challenging yet there are approaches one can use obviously yeah so there are leaders in industry there are leaders in government uh leaders in regulatory authorities such as the fda and i think we have to talk to all of them and you and i have been doing that um actually in my estimation i haven't been that good at it it's been quite difficult to change the world from the top down i i'm actually having better success from the bottom up but i do think we have to take both approaches to be both approaches yeah that's cool yeah and the fda surprisingly a few years ago said that they were open to calling aging a treatable disorder if we could just prove that it was and that those experiments are actually ongoing with a drug called metformin which many of you will have heard of it's a frontline diabetes type 2 diabetes drug for the elderly and people have high blood sugar and that drug seems at least based on tens of thousands of patients who've taken that drug had protection not just against their blood sugar but also cancer and heart disease and even alzheimer's frailty for sure and so this could already be a drug for longevity that's that's available it's very cheap it's probably a few cents per pill it's available over the counter in many countries not here in the us unfortunately but if the fda allowed doctors to prescribe metformin before you had type had type 2 diabetes that would be revolutionary this would be the equivalent of having um the statins for heart disease or blood pressure medicine um yeah this is a massive change but right now doctors are most doctors are either ignorant or reticent to prescribe such a medicine that would prevent multiple diseases how would you categorize rapamycin in that regard another drug that is uh it manipulates a major one of these central systems to set up the defense that leads to uh reducing aging yeah well what you said really resonated earlier which is that you and i believe well i certainly believe i think you believe that that aging is simpler and easier to treat than cancer which is a bunch of different diseases when it comes down to it aging is not that complicated yes the effects downstream and all of the various things you see in old people older people are complicated but at the the core of what's controlling all of that are really just three main uh systems that we've discovered there may be a few more but we know of three one is the sirtuins that i work on another is called ampk or amp kinase which metformin works on and now leave brought up the third leg of the stool which is a protein complex that senses amino acid intake called m tor and so mtor which is little m capital t o r uh if you eat a a steak that's full of leucine isoleucine valine it this protein complex will sense that and say oh times are good we just killed a mammoth let's build you know more more skin let's make more reproduce yeah exactly let's reproduce but there's a trade-off the trade-off is that this the body shuts down its defenses such as recycling proteins called autophagy a very important hallmark of aging that declines with time and so by taking this drug rapamycin which is definitively shown to um or selectively shown shown to selectively target mtor which is used actually to modulate the immune system it's in low doses it looks really promising as a longevity molecule in rodents it's it's probably the most successful molecule for extending lifespan even late in life the problem with rapamycin the way it turns out is that if you take doses that are high i think higher than 10 milligrams for a long time it can damage kidneys and among other things so it's not a perfectly safe drug which you'd want uh for something that you'd use for longevity that said uh rapamycin taken once a week uh or in low doses three milligrams are things that people are talking about um and i'm aware of people who are trying it um you might say well why would you try something if it's not proven to work well if we wait till it's all proven to work you know a lot of people listening to this and watching will be dead so there's a risk-reward ratio um calculation that goes on in people's minds and that it's all done under doctor supervision because it's prescribed medicine but we're actually at that turning point i think in human history where we are able to say that there's a pretty good likelihood that some medicines that are already approved uh could affect the aging process in a positive way right well you know one thing we promise to have a conversation with one another about it in the future is my idea if we can measure in patients enormous amounts of data that assay all the major systems and everything in clinical trials like we're talking about with aging we can one reduce the number of patients that give you compelling results and two we can see results much more quickly because we're looking at many more features to see if there are subtle changes and so forth and it seems to me this is going to be a really key part for accelerating the acceptance of some of the kinds of things that we've talked about here so my last question because we've got to turn to the audience now is if you had to prioritize for the audience things that they could do now what would be your priority list for them to uh live in a healthy aging manner right well i've mentioned uh eat less often i think the three meals a day plus snacks is misguided and i'm happy to debate nutritionists on that uh other things you can do is make sure that you keep your muscle mass we lose a percent or so every year as older males females too as well females have to particularly watch about watch their bone loss as well so doing exercise whether it's so is the exercise primarily to keep up muscle mass or does it do other things too oh it does lots of good things some of which i'm not even going to mention but um testosterone will go way up uh if you build up the big muscles in your body so i exercise my quads so my leg muscles my back muscles are the main ones you know the rest is just probably uh mostly just for vanity but the big muscles are really important uh in males and females if if you have strong hips um and there's a piriformis muscle which holds your hips basically your legs together the problem with current lifestyle is that sitting all the time causes those muscles to degenerate and it's very easy to um to just be weak there and most people don't realize they're weak one of the things you know i'll get back to the question lee in a second but there's an easy way to tell how old you are roughly it's called the sitting standing test and it'll test these muscles you sit cross-legged and if you can get up without touching the floor with your hands and stand up you're young a middle-aged person like me might need to use a hand to get up and an elderly person will have to get on one knee to get up and that's really just testing your muscle strength i think doing 20 push-ups is considered really good at my age too but those are not very accurate compared to the the other things we talked about um but you're you're right that making your muscles stronger has multiple benefits it's increased uh testosterone for males and uh to less extent females the muscles give out give out hormones that are beneficial there are what you know leo called myokines which uh we think circulate throughout the body and provide uh improved health as well we don't know all of them but we know some of them the other thing that muscle strength and aerobic exercise in particular will do is it'll make sure that blood glucose levels don't get high in your body and when you eat a meal the levels of sugar in your blood don't spike um and and having high blood glucose levels is one of the rapid ways to to suffering and death anyone who's had type 2 diabetes in a bad way will tell you that um including lack of circulation heart disease etc and dementia yeah so that there's all those benefits um besides just feeling great and being able to still walk in old age and make sure that if you fall over you'll bounce back up yep yep okay well uh with that i'll start reading some questions from the chat box that the audience has asked so uh the first is when do you plan to have the horvath clock test available for consumers oh that's hilarious um uh only because that that that's one of the questions that somebody was just asking me before i got on um all right so this is public information so let me think what i can say we are right in the process of making that happen uh the test uh will be coming down a lot in price and i mean i i hope to be able to have something available uh conservatively speaking before the end of this year um yeah that's probably all i should say at this point but it is coming and it'll be it'll be backed by my signs will be backed by my reputation it'll also provide feedback and suggestions on how to improve your score well you know i will make uh one comment on a i guess competitor now called longevity that has a test for biological age that uses blood analytes yeah and again it is now available so you can look up longevity and read about that but i think both possibilities are absolutely fascinating second question what is the ideal window for eating with intermittent fasting you eat just a single meal does that mean the window is just one to two hours of eating per day not even that i'm i'm i'm like everybody i'm a regular person i like eating cheesecake you know but but what i've realized is that i feel so much better i'm more alert i'm excited i have a better outlook i'm optimistic if i don't constantly eat i've never been big on breakfast so that's just my physiology some people need breakfast i don't uh but i then i started skipping lunch and having a hot tea instead i might you know eat a piece of fruit but that's about it and then at dinner time um you know i'll look at a dinner if i go out to dinner socially i'll just eat normally that's fine i'm not gonna reduce my joy in life but most dinners are small they are more like what a rabbit would eat than a lion i eat fish i try not to eat big steaks but generally i've reduced the portion sizes really way down um and you know i've never felt better i you know i've boasted probably a little too much that i've got my 20 year old body back but i really do and it's it's invigorating to be like this and it wasn't that hard i really started in earnest in february and you know we're now in april it wasn't that hard um i hope that everybody can consider it if they are not already doing it um i would encourage you to do it for at least two weeks before you give up because it takes two weeks to get used to it you know we've all got habits we go to the fridge we eat snacks and once you get over that psychological thing just have warm drinks hot water tea whatever you feel like then it's easy i definitely don't feel hungry in fact i feel way better uh not having all these meals one question i get though is should i should i fast longer than 18 hours which is what i tend to go for and you you can do that i'm not that good at it actually i'm i don't have a lot of willpower to be honest a lot of people are better than me so some people go for three days um maybe every few weeks if you go for three days you get real deep cleansing by this process called autophagy the body will start to recycle more proteins than it normally would using a system called uh chaperone mediated autophagy or cma i would love to try three days i just haven't been able to do that yet and then there's the extreme version which is a colleague of ours peter dr peter artia who's become pretty well known for this he does a week of fasting uh just with water and he does that i think every every few months and uh and apparently that that's extremely um good for you according to his um estimations but it's hard to do i would say at least try not to eat three meals a day that's a good start and then if you can get to one that's even better so yeah you you really do start to appreciate food that's for sure but it doesn't dominate your life i lived a childhood where my mother used every meal to discuss what was for the next meal yeah and i'm pretty happy that i don't live like that anymore great so in your book you write about uh reserve verital nmn and other supplements what does the latest research say about these would you give advice to people that are what advice would you give to people interested in adopting them all right so the technology in my lab has been improving uh steadily resveratrol was a very early discovery back into the early 2000s what we were trying to understand was can you activate these longevity pathways mechanisms with a safe molecule and at the time we didn't know that now it seems obvious of course because everyone's talking about it but we didn't know and so what we discovered co-discovered with my co-authors was that plant polyphenols these are a variety of molecules that are made by plants when they're also under adversity uh and one of which is resveratrol which is found in grapevines and red wine was pretty effective at activating one of the sort of enzymes that uh my lab and others have shown to be beneficial for health in in mammals and even in humans so resveratrol got a lot of of hype actually it was kind of unavoidable uh there were a couple of things going on the red wine industry loved it sales of red wine went up 30 plus percent and have stayed up um and then there was the commercial entity so i started a company called citrus which you know had a professional team of people talking to the media so all of that you know 60 minutes barbara walters interview all that was pretty fun um but what really came out of it was the realization that a safe small molecule could be used to mimic the benefits of fasting so we fed resveratrol to mice that were on a high-fat western diet and they lived as long and were just as healthy as the mice that were lean so that that in itself was i think a radical um departure from what people were thinking would i take resveratrol well i i do still take resveratrol i take a teaspoon full of it uh every morning um i take it with a tiny bit of yogurt just because it needs to dissolve it's like brick dust otherwise it doesn't dissolve i mean i've been doing that since my 30s and i'm still alive uh so it's we don't know if it's going to make me live longer you're the good test subject yes well i'm an australian so as you know that there's a tradition of australian scientists experimenting on themselves like barry marshall discovered oh yeah yeah uh that the ulcers in the stomach are caused by bacteria he actually drank the bacteria and caused himself and then cured himself so i but he won a nobel prize so sometimes it works yeah well instead of waiting 30 years for the clinical evidence but you know i'm not doing this to try and live forever i don't really worry about that but i am very curious and i do like to learn things quickly my father's been on resveratrol for the same amount of time and as i mentioned he's 81 and is as fit or fitter than i am um but i don't i don't recommend supplements i i i'm not an md and we don't know if these are going to work but there is a lot of evidence i would say in animal studies that resvertrol uh is relatively benign and also can be beneficial to your metabolism um and protecting the organs so i continue to take it until i see evidence that it could be dangerous i haven't seen anything like that in 20 years i do take another molecule that's fairly prominent in the media which is called an nad booster you can buy these they call either nr or nmn i certainly don't sell anything at all i don't promote anything but i find that a lot of people are interested in it so i'm mentioning it tonight nad boosters are came out of research out of my lab as well as lenny guarantees we discovered that the sertuan enzymes are controlled by the level of nad this is a molecule that our bodies make for metabolic reactions but also control this through tunes activity and when you're hungry if you're a yeast cell or a human your levels of nad will rise and but as you get older it declines and so what we we're trying to do is to artificially boost up the levels of nad in the body and that's why i take the molecule called nmn which is a precursor to nad um interestingly and what's very rarely recognized is that uh one of the companies that i founded co-founded called metro biotech has been doing clinical trials in people for over two years now uh with an nad boosting molecule that is related to nmn and found you know really great results so far i'm not at liberty to say what they are yet but you know i'm still taking in a man having seen all the data but i don't want anyone to get the impression that i'm a cowboy who's just experimenting on himself it's not that you know i only take very calculated uh you know barely risks but i also at the same time do clinical trials on these molecules to try and rapidly find out a are they safe and b are they affected okay i love this question is it totally a good thing to get younger wouldn't that over populate the world with a bunch of newly young people uh well so i don't think that the world is a pie that has only certain number of slices um i think we can keep growing the pie now the world has limited resources of course we can't keep burning oil and we can't keep overpopulating we're continuing to populate uh growing in population but as i explained in the last part of my book when you actually do the math um and we're actually going to publish a mathematical model in the journal nature aging soon on this what happens is it doesn't if you stop aging or slow it down certainly if you slow it down it doesn't appreciably contribute to global population despite what you might think there aren't that many people dying from old age actually it's the problem is birth and fortunately fertility rates or at least reproductive numbers in families is steadily declining across the planet and is even in the negative for most developing countries or developed countries the us would go negative if it didn't have immigration so don't worry i don't think you should worry about population world resources yeah we need to solve that but i'm hugely encouraged by for instance the energy transition to renewable resources i drive a tesla for good reason and i think that humans are capable of engineering themselves and innovating themselves out of really any problem it's just a matter of will and the investment and we can solve any problem i think the other point is to be younger means you're vital energetic curious creative i mean it's hard to believe that virtually anybody wouldn't like those those traits another question if someone were interested in a career changing into a field of aging from a business related field where would you recommend starting yeah what the i mean start if you're in high school have a great interest in science um you want mathematics you want a bit of physics you want chemistry you want biology when you get to college i would do some basic biology i would do some philosophy i would do some history if you're interested get a broad education it'll help you greatly in the rest of your life um and when you get to my age it's it's very difficult to to do those kind of broad thinking and learning so do that but then start to focus um maybe in your second third year on genetics which now covers molecular biology as well as even nanotechnology kind of stuff that lee has developed in his career we're now in a in a revolution both in our ability to read and write the genome to read and write the epigenome um and to do experiments by the millions per day uh just as as one person something that took me a whole phd which was to discover three genes and read the read the code uh can now be done well it wouldn't even be done it would the whole genome can be done in an hour by a graduate student of yeast cell so we're at a point where um it's a great time to join uh molecular biology and genetics and and uh and science in general because we've got these tools that people like lee have built for us that we can now do a million experiments a day so i that's a long way of saying also get some experience in bioinformatics because being able to analyze all of that data is invaluable and i cannot find enough good bioinformaticians at this point yep absolutely presumably you currently do your own sequencing for your methylation age calculations is this the kind of thing somebody could do themselves today on a regular basis with their own dna sequencer uh who has their own dna sequencer for goodness sakes um if you had a dna sequence well with o-link you can actually have a little dna sequencer that doesn't cost i mean with uh with the single cell sequencing technology from england yeah i mean you mean or is this something yeah the min that's right yeah right a little candy bar size sequencer you can do that for sure um if i think you can do your own test at home it's you'd need a a bench and you'd need a centrifuge and you'd need a pipette um and a kit you probably don't want to make your own reagents but it would probably cost you a thousand times as much as getting it from somebody who was a pro it would it would so so you know come to lee will come to me uh we'll get it done um routinely um and and be able to help you interpret the results as well but i think it's an interesting point that science has reached genetics has reached a point where you can edit the genome and read the genome even in your garage or your kitchen if you want absolutely yeah you can take a dna sequencer out on field tests and look at organisms in the field so it's amazing what is the most accurate way to measure nad levels after consumption of precursors what is your perspective on nad plus via iv for longevity similar to what we've done for addiction detoxification well for iv nad i haven't seen any solid data yet i'm aware of it being offered um you know i went i went to the one of the hotels in in hollywood and they offered it to me at the reception desk which was funny but and and also it seems to be helpful at least anecdotally with uh helping with addiction and there are clinics um around the country particularly in florida but i i can't say as a scientist that i've seen convincing um you know placebo-controlled kind of experiments that would tell you if that's working or not and i'm i'm open to it i certainly think it's possible and if anyone has data that they'd like to share with me please go ahead and send it to me and i'll i'll judge it as i would any other study go ahead okay i think we have to close down with the last question i'll ask you david i know from our conversation that you're writing another book and i'll offer you a chance to make some comments about it or to decline at this point in time whichever you choose right well it's late in the night over here on the east coast so you know maybe i'm in a talkative mood but yeah i'm excited uh the first book lifespan was a new york times bestseller it was super exciting i've enjoyed the process the feedback that i've received um from you lee and and many others but particularly your your voice was was very meaningful to me has prompted me to want to do it again right you get enjoyment you find fulfillment you do it again so i am uh writing another book with my co-author matt laplante who's a genius at bringing together a whole bunch of disparate crazy stuff in my mind i know lee you work with matt so you know what i'm talking about uh my new book uh we're still not disclosing exactly what it's about um but i can tell you that uh a i'm very excited about it it's gonna be as interesting and revolutionary as the first book we like to take what seems obvious to the world and look at it from behind the mirror and and actually see what's what's going on and it's it's going to be a journey of understanding where we've come over the last few million years as humans why do we exist with with crazy hands like this why do we look like this why are we a lollipop physique that's pathetic you put us in a cage with a chimpanzee and one hit and we're dead we're pathetic as a species why did we evolve genetically to be this pathetic and then what happened to the world that we've made around us obviously we've got technology to try and make our lives easier to cope with all of the faculties that we've lost over time since we've been out in the wild but we built a world that that isn't perfect for our physiology i'm staring here into lights i'm not going to sleep well tonight you know we we suffer from social media we've got a lot of depression and and anxiety in our young kids we've got other problems we sit all day time and time again our technology solves one problem and causes another um and i call this the treadmill that we're on and really ever since humans have picked up a rock and used it to bang an animal on the head or maybe one of their enemies on the head we've been on this treadmill and the question is can we ever get off and what does the future hold and that's what i'm writing about yeah well david i want to thank you for an absolutely stimulating and wonderful conversation i thought you did a terrific job in bringing the world of aging to uh to to everyone and i just say a few lessons that i took home when i read your book was something we haven't talked about is that this aging process david and others have discovered is conserved all the way back to the simplest of single-celled organisms and i think there are two interests with regard to that conservation one is it underscores the idea of simplicity and elegance and something that's shared in all creatures and number two is the idea we can use model organisms like mice and yeast to discover fundamental things that apply in very straight forward fashion to humans and that's really an exciting idea i think number two the idea that aging is a disease and that we really have powerful tools for curing and slowing and even potentially reversing that disease and i think number three if we can do that we can begin to think of a very powerful way for attacking the broad set of chronic diseases whose major predisposing factor is in fact aging itself and i think finally with all of the revolutionary changes that david has discovered in the next 10 years we're going to see remarkable opportunities presented to each of us for fundamentally changing our lives and and presumably moving us into the 80s and 90s and hundreds physically capable mentally alert enthusiastic about life now that poses other really interesting issues about where are we going to get enough money to do all the fun things that we'd like how can we are we going to have multiple jobs all sorts of exciting things anyway i want to thank town hall for allowing us to do these wonderful exciting programs i think to the audience please we'll have other exciting programs in the future that combine together isp and town hall and if you're interested in keeping up with all of these go to our website at isb which is isbscience.org so thank you and especially you david have a great evening we really appreciate your contributions and your expression of them well thank you lee and and thanks to everybody uh the town hall folks and everyone who tuned in tonight i thought it was a wonderful discussion and lee thanks for everything you've done for science and technology as well pleasure you

Channel: Town Hall Seattle

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Length: 71min 23sec (4283 seconds)

Published: Tue Apr 20 2021