Nobody has any reason to say that we have this clock that cannot be changed and fact, what we've learned is that about 80% of our health in old age is due to our lifestyle and how we live and only 20% is genetic. And actually that your genes are not your destiny. That's the good news. So 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 eat the cake sit on your fat ass and watch.
The movies that'll get you there pretty quickly. The problem with today's world is marketing branding 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 whole bunch of problems. And if we're not always telling our body things could be problematic our bodies don't care. They don't fight against disease. They don't fight against aging so the bottom line is you've got to get out of your comfort zone. Get your body out of its comfort zone.
That's David Sinclair PhD this week on the ritual podcast.
The
Rich Roll podcast
greetings all you bipedal humanoids. My name is Rich Roll. This is my podcast. Welcome or welcome back. Here's the thing we take as fact that aging is inevitable. But right now all across the globe. There are many scientists who are calling this idea into question hard at work on treatments on therapies designed to extend healthy.
Lifespans well beyond what we know today and intent on revolutionising everything. We thought we knew about human health at the bleeding edge of such breakthroughs. You will find David Sinclair PhD one of the world's leading scientific authorities on longevity aging and how to slow its effects returning for his second appearance on the podcast. David is a professor in the department of genetics and co-director of the Paul F Glenn center for the biology of Aging at Harvard.
Medical school he obtained his PhD in molecular genetics at the University of New South Wales Sydney in 1995 and worked as a postdoctoral researcher at MIT where among many other things hiko discovered the cause of Aging for yeast. He's the co-founder of several biotech companies. He's also the co-founder and co-chief editor of the journal aging and his work has been featured in a variety of books documentaries and media including 60 Minutes night.
And Nova he's also an inventor on 35 patents and has been lauded as one of the top 100 Australian innovators and made Time magazine's list of the 100 most influential people in the world. In addition. David is the author of The Fabulous new book lifespan the Revolutionary science of why we age and why we don't have to it's a New York Times bestseller that proposes essentially a radical new Theory of Aging as he writes in the book aging is a disease.
And that disease is treatable much like our last discussion. This conversation is fascinating. It's all coming up in a couple few but first today's episode is brought to you by on running the world's fastest-growing and most Innovative running shoe and apparel company on the planet what makes their products so different and so interesting is it their attention to clean and minimalistic design their lightness. They're extremely cushioned outsole. Maybe it's their breathability the elasticity
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Our.com / RI CH roll20 recruiter the smartest way to hire. Okay, David Sinclair. So last year I convened my first conversation with David that was episode 436 and I gotta say that was a absolutely scintillating and science heavy primer on all things human lifespan aging and Longevity. It was a runaway hit with the listeners and it really left me.
Wanting to know more. So today we're going to pick things up where we last left off diving deeper into the physiological mechanisms that contribute to biological degeneration and we go further into the current state of research to better understand what contributes to aging and what can be done to counteract it many people call them a dreamer, but David actually believes that living to 200 plus years is a plausible reality. So here's a question for you if you could double your lifespan
How would that impact how you choose to live? What would it mean for the future of humanity and for the ecological stability of the planet? The implications are simply profound equal parts, philosophic and scientific this conversation will forever change the way you think about why you age and what you can do about it and it will leave you armed with simple lifestyle practices that you can deploy things like intermittent fasting cold exposure exercising with the right intensity.
And of course eating less meat all of which will help you live longer and live younger for longer. He's brilliant. He's lovely it is an honor to once again share this man's Wisdom with all of you guys today. So break out the pen and paper because you are going to want to take notes on this one. So without further Ado, this is my conversation with dr. David
Sinclair.
Good to see you. Thank you for coming
out. Thanks for thanks for having 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 had to go back and like wrap my head around what we talked about last time. I was like, well we covered a lot in that right like we went we kind of went through the whole thing and
I 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 are overdoing layers workout this morning, right? I was it was brutal. So walk me through it. Well, first of all, how did that come together?
It was through mutual friends with such a bunch of us that have known about this for a while
the myth.
Declared Hamilton morning pool
workout, right? So I remember hearing what it was like and thinking I really hope I never have to do that and
I life and
actually I was right it was it was brutal. But but I do feel really good now actually they say 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 listeners don't know is you you start out.
Really hot sauna, and I'm not just saying I hot sauce on it. It's like the 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
Mast Hai. I knew he had a 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 shower jump in the pool and you grab of well, first of all, you swim underwater until you
basically out of breath and you want to pass out then they give you weights and then you can go into the deep end you're underwater below the top of your head by by maybe half foot and then you 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 going to take in a mouthful of water, which is what I did, of course the first thing and then but then the other problem is you go into this panic mode. I don't know if anyone's ever.
Experience was like a drowned but now I know what it's like to drown. It is not pleasant. You
think just let go of the weight and surface
it there is that but there's only one that
there's Laird standing there. That's right Judgment of Laird. Yeah, I would rather drown them be embarrassed and give up so, you know, I
look like a stupid fish while 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
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 so on has and hypoxia, but I've never done it so extreme and I know where offers is the guy to beat but I usually go to my gym, which is just four degrees Celsius. I don't know what that isn't in Fahrenheit, but it's not that cold as far as your fridge temperature.
And I found that brutal but actually going into that ice water. I was always fine. I mean the initial shock, right? You can't breathe. I'm going to yeah, and then but maybe 15 seconds later with Gabby Reese telling me breathe slowly very 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 actual is going to do two minutes because she thought I was a bit of a wimp.
Got to 3 minutes and thought I could just keep going. This isn't so bad. No pouring ice on my head at that
point or you're up to your neck. Oh, yeah, I actually went on to further couple of times. Yeah, 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, how many how many people were there this morning?
There are about 10 of us. Yeah, I've
got a I have friends that go to that workout and I've had kind of a, you know, sort of an open invite to drop by me and I kind of do my own 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 don't even like but what I've what I've heard was during a lien there this morning, he's sort of a layered look alike. Like, you know Darren bent on the podcast very good friend of mine.
Darren has said that the people who farewell 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 going to do this better than layered or whatever and they're the ones who get
Crushed and humiliated. Yeah, there's a bit of that
today. Yeah, it's a down and I talked about he's interesting guy, right? He's super
will say yeah, you guys they
talk forever. We will we will meet up again. And the other Justin rain was there. Oh cool. You know, how friend Justin rent that was his first time doing it to ya and he was my
buddy and I'm a fighter
exactly. So Justin was a fight for the of God and that's his charity. He wonderful wonderful guy check him out.
Was my buddy. And first thing I asked him when I was teamed up with him was do you know CPR and fortunately didn't need to rescue me.
Yeah, that's cool. Well you did you do I have this right? Like you have some scientific background and their imagine. He says don't you did you do you know, where a crown ice
did you work with him on some of the studies that he did on that? All right. We just papers together. 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 going to do what you do and I'm gonna be a disciple now we thought okay, you know Ray will you know, I'll see you later. Uh-huh. He did it.
And so now what is that, you know over ten years later. He has trained his life. He is he's a guru for for health and particularly cold therapy and we published a couple of papers one is on the metabolic winter hypothesis the idea that these days we always look for comfort and one of the problems is we never experienced temperature variation in our lives 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 defect as we get
older right raised now kind of pivoted more into the nutrition Landscapes got this new book out with Giuliana.
However, yep healthspan. I think it's called right
hell's man 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 that make a good combination because Giuliana is the cook and yeah brain, he's ER
exactly it is it is a good mix. They live like right up the street.
Here everything. Yeah, they've been on the podcast cool. Well, I think it's interesting that you you did the layered and Gabby 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 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 whole bunch of problems. And if we're not always telling our body things are could be problematic our bodies don't care. They don't fight against disease. They don't fight against aging so these treatments and these crazy things that I did today are all
About turning on the genes that we work on we can 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 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 reservatrol story is what I first was known for in Science World and we discovered a whole bunch of different plant molecules. One of them is Resveratrol.
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 course certain 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 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 of a dry, you know, he'll or you're eating fruit. That's just had a massive drought.
You're going to have molecules in that food that will tell your body. Hey, these plants may not be around for the next month. Hmm, and that was our explanation and it really does make a lot of sense and is fitting with a whole bunch 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 an actually what it means is couple of things one is donate foods that
Are grown under 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 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.
Dia okay. And in fact 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 it was a day or so before they pick the fruit and then gives it these
extra flour. Wow. That's that's interesting. Yeah,
so we got to harm the plants just a little bit but it doesn't need to be all the time. It can be just before you pick them and think about grapes what we do when
Want to have great wine is we pick them just as this stress that we they you try to pick them when there hasn't been rainfall for a little bit. Mmm, and then they fill up with these great tasting molecules, but also the Zeno hormetic molecules as
well. So how does that I mean 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 to this?
Well, you know, there's organic in those real organic.
I'm talking about the plants that you know may have had a grub-eating or are exposed to too much sunlight that kind of thing being out in rougher conditions. Yeah,
hyper organic.
Right? Right, right. Not not not suit
us the name of the new company. All right, 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 55 now? Yeah, thank doesn't look a day older.
Honey, did you know 10 15 years ago and he 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 talked 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 talked about
often. Yeah, right. He's the orange tree with the Nay on
it every day, right
but I totally
We believe it and you but 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 use doing 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 made you healthier that eating less food was healthy because it loaded in
Nation 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 fun guy that we grow that we use for bread and beer what we showed in this is going back to 2003 now is that there's one gene that controls longevity. It's got a name called PNC 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 him a bit of stress.
so if we turn up the incubator to 37 degrees Celsius and stuff 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'll reading that'll make them live longer but it all worked with 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
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 control information in the cell? Not not the genetic information, but how the genetic information is controlled and these genes are called sirtuins so sort of to and so you can think of as The Pianist that plays the generic piano and when they're not active the penis becomes complacent makes a lot of mistakes and ends up becoming demented demented.
And that is what I believe is a large driver of the aging process. But if you're always activating your sirtuins The Pianist keeps playing the concerto 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 one of I think the second chapter on the book write it be demented pianist where you explain all of this the the metaphor that we used was was you know highway traffic right and getting dispatched.
T' 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 cop and going haywire and these these, you know, the NAD isn't going where it's supposed to go be going in 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 formative what we discovered in yeast cells. It's incredible, right? You can learn from a little fungus these big Concepts these sirtuins 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 and I imagine you know you
. Try to know whistle or getting getting 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 the 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, this is the old Theory. So what I think is going on is that these breaks in the chromosome is DNA damage is distracting these sort of tunes 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 the sirtuin
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 four tickets, then they're not distracted by these sort of frivolous situations and they're focused on the the most important job that they're kind of created to deal with
and yes, and the other way to think of it is without enough fuel and NAD is their fuel this little molecule called in ad if you don't have enough NAD, they are very slow at doing their job. They can of they get detached from what they should be doing. And then they drift off through the liquid in the cell and they don't have enough energy to fully fix the DNA quickly. They don't have enough energy. We think to come back to where they came from. But if you do have all the energy in their in their Prime,
The youthful sirtuins they can fly off and come back mmm, but it's without the fuel Enad or you know, Resveratrol is also an activator. That's one of the things we figured out in the 2000s. So the combination of the fuel and the activator Resveratrol in the NAD is a fantastic combination. We think for maintaining that but 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 and thus aging or anti-aging that's a really good question. 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 story that I told you about those one gene that was turned on by temperature and by low amino acids that Gene is makes NAD. Okay in our bodies, we have the same equivalent Gene it it's it's called an MP t-- and ampt and we discovered is now.
Seven that when you stress human cells in the dish and in the body as well that you turn it on. So Ned Beatty comes on and it makes more NAD for the body and thus or two ins can do a better job. So now Pete he's 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 named Petey is the master regulator of NAD production. It's the what we call rate.
Limiting step in making a nadie 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 we call heat shock them and on came this and MPT and they made made more needy. Hmm. So what I think could be going on is that the stress on the body when I'm you know, 200 whatever Fahrenheit and then jump plunging into basically zero degrees Celsius. That is making my body.
More NAD essentially mimicking the effects of exercise and hunger 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 of the last 2,000 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 no most all the time. What's the best combo of diet right exercise? We're
figure that out and then you know 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
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 because you acclimate to that right and it's no longer. It's no longer creating the stress
response exactly. So I
exercise every day. Not that I could but I don't it's a convenient excuse. Yeah, really true. You got a pulse it 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 got to 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 going to 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 to hormesis, right you're trying to create a stress response that activates certain, you know Pathways in your in your system that relate to aging or anti-aging but I would imagine that you could you could develop a set point without as well kind of acclimate to that get used to it and then your
No longer experiencing that benefit the way it is. That is that is does it work that same way with the eat?
Well, it's complicated because the there are two experiments have been done one is to consistently just give my low-grade food basically mix their food with cardboard. So you lows and that works. So if mice and nibbling all day on low calorie food that's still work so you don't have to do intermittent fasting for this to
work. You never get used to not
eating yay.
Everybody will still respond. But at least we understand what's going on. And again, it's this named Petey 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 volt has been up an old friend. We used to by the way, you used to study yeast cells together as yeah. Well we both came from the intermittent fasting for me is is better because it means you can eat instead of
80% normal calories you can eat 95% or hundred percent calories 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 ship but basically they all extend lifespan, but the mice that are 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 somebody
that I need to get hormesis hormesis. I'm going to starve myself.
Well, yeah, I'm skipping one to two meals a day and it's changed my life. I feel great and a lot of people say I it makes me feel queasy or my stomach's burning. I found a guy 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. Mmm.
Yeah, I've been playing around with it and experimenting weather 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
Fly when you get when you get on a long plane and I use those generally as opportunities to play around with this thing because I'm not going to 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 four to six hours unless you're going to Australia, which we're going to 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, are you sure you don't want anything and they'll 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 that this thing but you've paid for this it's free. You have to eat it. Do you want some ice cream and cookies? No, go away
the more you say. No the more they come back the three mics and I think yeah, but 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 not 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. But 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 yeah. Sorry 50 51
52. I'm still I'm still 50 but yeah, no gray hair. I'll let you know.
No, yeah, definitely not a gray hair on your head yet and what?
But maybe this is a good place to talk a little bit about the difference between the biological clock and what you call horvath's clock right the horror 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 inside engaging is we didn't have a real measure of what aging was you could look at a mousetrap.
So human and say, okay they look younger. They look old big deal, but we needed a mathematical in a non subjective measure and we finally have 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 is Steve. Hope that's one of my very good friends. Great guy. He's a mathematician by training and somebody got their clock measured by him a look tell you in a minute about how the clock works, but someone said, oh, I got a really bad result on my clock on biologically 10 years. Older. Are you sure the clock is ripe and he said as in true German for me is a 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 rock
is and it's not so hot at the bedside manner though. No know that he'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 a hold 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. That's the most important thing the basically The Pianist not the piano the clock is
measuring the pianist's a state of mind, right and when so what Steve's doing with his clock is 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 the the notes are for a symphony the the Rays score.
But 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 Sea letter, you know on DNA it is actg, right? So the Seas get this methylation. It's called just a chemical sticks there and doesn't come off unless the body takes it off. It's a permanent Mark and that's what says that g 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 the changes over time is what drives aging now what Steve found independently from me is that if you can read the pattern of those metals
Lll change over time and if you use machine learning and say, okay, this is the pattern of a 50 year old twenty-year-old even a five-year-old. You can draw a straight line. Mmm. 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 please 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 2015. Oh wow.
Imagine that gets more and more accurate every day right is 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 does you know that that sounds fanciful, but what?
It's telling me and 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 going to do a jellyfish clock because jellyfish can be Immortals. 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 as figured out a way to 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 going to die? What do you mean? You don't
know? No, no been too busy. But now I've done just the the old-fashioned blood tests and uh-huh, but I'm going to do it. I'm not avoiding it. I tell you what we are doing.
In that I haven't told anybody it's 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 at least 300 sometimes thousand bucks to do so, it's not cheap and he can't do it every week can't do it every month. But we're working in my lab. We just had a breakthrough. We think we can bring it down to five or ten dollars and then you could do it at home. Right? If you're if you're brave enough
as another business for you.
Yeah. Well that
We'll 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 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.
On recently last year the at least suggested was 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 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 extrapolate from that 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
Here you are that the anti-aging longevity guy. You're gonna die in two years. Yeah, that would now not be good for bad day for business.
Yeah. Well, you know, I don't live perfectly that's for sure. I don't everyday 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 than I look who knows. I will I will tell everybody when I get that data, but his the really important.
Stretch, which is that.
Data is important. I'm data-driven as a scientist, but everybody with their body should be cognizant of how they're doing just ignoring aging is not going to 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 it 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 going to die 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.
Yeah, lots of everyday I before I get out of bed. I'm actually reading scientific papers and you believe it pretty much every day. I'm excited by something new there was something couple of weeks ago that came up that I'd been hoping to see for at least 12 years. And that was to find out why does Resveratrol activate the sort to an enzyme? Why is that so one idea is that we're sensing the stress in and versus adversity about food, but we also
so have hypothesized since we first discovered Resveratrol and its role in aging anti-aging is that it's probably mimicking something that our bodies make 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're when you're hungry producers monounsaturated fatty acids.
On 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 ingesting it but also it means that we kind of been Vindicated because we got a lot of crap for Resveratrol.
Yeah in the early years you if you Google your name and Resveratrol there's a there's a lot of
Shit talking coming in your direction. Yes 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 enzyme by actually literally sticking to and binding to it physically and making it more active like a pacman 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 brutal when that happens and everyone almost everybody except close friends said we're going to believe the companies and David's wrong and that that's a tough time in anyone's career and my lab shrank down to about a 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 a professor in Canada. He didn't give up everyone else in my life 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 going to test this and he worked really hard and figured out that the experiment that we originally did to 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 the scientific huh? Bob went down. Basically, we were largely accepted that we were correct but out in the media, you know know what 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 resolve the controversy about whether it's true or not 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 mmm. 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 trying to trigger this lipolysis, you know situation 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 lipolysis we're going to be doing with intermittent fasting anyway our hearts 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 Sir one. So, what does that mean? That means that when you eat olive oil, you're actually activating your sirtuins quite potent lie because it's also just like Resveratrol
mimicking this lipolysis effect and maybe the and I and the authors of that paper have written that this could explain why the Mediterranean diet is so healthy. Hmm
or alternatively 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 Rose.
Troll has no calories. So I basically been drinking res olive oil the last decade without the calories,
right? That's good thing. What is we talked 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 in your body's ability to kind of metabolize
it. Yeah. So Resveratrol is unfortunately a
Pretty in soluble molecule. Now in the plan 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 like to purified 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
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 Resveratrol extends the worms is you have to dissolve Resveratrol in some sort of solvent. So for worms, we use a thing called DMSO 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 resurrection.
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 shown the benefits other ones where they've just given a dry capsule to the patients or the subject and those that work are those typically that are given it with a meal or something that the Resveratrol would dissolve
in right? So there is some sense that that that definitely increases the bioavailability and
absorption. No question. We did these clinical trials a long time ago as we were working our way to making a
But we actually we ended up making synthetic molecules that were a thousand times more effective than Resveratrol. We didn't know the time we were making the equivalent of olive oil like acid, but I guess now we do know that those molecules actually went into clinical studies with humans. That's also not very well known and there's a the skin condition psoriasis. It worked really well. They 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. And that's actually one of the brutal take-home messages actually is I don't want to complain because I've been very lucky in my life. It saddens me that that in science. You can be derailed by decade for a decade by a you know by your naysayers and I'm hoping to get things back on the rail seems like so far so
good. Well the last time we spoke, you know, this book had 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
who's that are going to revolutionize how humans live their lives and think about their lives and on the other hand, you know some pushback from the conventional scientific community and some grumbling amongst the you know, the old guard saying not so fast, you know, Leslie, you know what I mean like Fast. Yeah your you've got your foot on the accelerator and they seem to be saying, you know slow down. 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 only think that I know what's published but we've got all this other stuff. So when we were challenged by these companies, even though it was sad,
Said I had a whole body of data from my lab that said 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 rapped because I'm out there right 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.
I really do think that it would be a real shame if our generation was the last to live a normal life span.
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 and what is the purpose of a lab? If not to test the limits 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 do you say here are the facts are the facts and the headlines out for me. Typically is Harvard scientist says we're all going to live 250 right which I'd never have said but then the university says David what the heck are you saying as I got so, you know, it's easier for me to not now talk to sensationalist media and I've now a much more comfortable doing this kind of
Thing where I can talk directly to the public, right and I appreciate it are
getting this quoted. Yeah, and and and how's the lab doing like how and how are the colleagues like in the wake of the book Success New York Times bestseller, like, you know books everywhere everywhere. You look I see it. You know, how were they kind of, you know acting towards you now
good. Yeah. I've had no backlash of about the book which surprised me because of it's a bold thing to say. Yeah, we figured this out.
Sets 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 at school. The book is
I mean congratulations. I think it's a it's I really think that it is a paradigm breaking Masterwork. And what's what's really interesting and unique about it and and I suspect Unser, you know, sort of unexpected for somebody's going to pick this up is that is that it's not just this hard.
For scientific Tome. It's sort of you even a little 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 title. So it's a different experience than I was expecting looking into it. Like it's it's kind of General genre-bending in that
regard. Well, thanks. I appreciate it. You know anyone who knows?
Is me, I'm not really a scientist. I'm doing science because I have a goal in life in high school. I was an artist and the the some of the illustrations the back of the book. I drew myself move the head shot. 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 metal plan who took a whole bunch of crazy ideas that I had.
Synthesized demand 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 that a lot of things are said about the work that we're doing. Oh, we're all going to run out of jobs. We're going to have not enough food. What do you do with all these people overpopulation? If you look back at history, we've always been worried about that. Right and there are solutions. I mean, it's not all perfect. We can't have one.
Limited number of people on the planet, but that's why I wove history in there because you forget that people have gone through these kinds of things before and come out the other side much better and I don't think you'd want to go back to the 1840s with cholera rampur 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? You're Australian last time you were on the show. You told these Amazing Stories
Your grandmother Vieira 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 as 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 Sydney and amidst these fires and it's
No, 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 Coastal. I mean, it's just 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 as actually circumnavigated the entire.
Is now back to Australia after going all the way around the
planet Yeah. Well, yeah it did. 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° you walk out. There you go. This is this is craziness. Yeah, 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 except in the bit of Steel on the ground everything else.
Just toasted it really brings home. The fact that we are living 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 fucking up and we are cook 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 their full of oils eucalyptus oil mainly and it's not hard to start a fire you bit of a 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 burnt down. The problem that I see now is that this is this is not a one-off fires in Australian normally starting around February. And you know, where are we were in December January and this could be the new normal in, California.
Now 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 say
fire singular, but it's a lot of different fires, but it's that are meeting up with each other Etc.
Yeah. Yeah. It's a scary world and we have to do something and so what so most people look at me and like our 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 can summon them 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 want to do that. What about Healthcare right now? We waste billions of dollars taking care of the
The Lee 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 yeah, that's a world where you globe that would save trillions of dollars. Okay. So now it's easy to say save trillion dollars, but that's money that can be poured into solving these problems like to think about Old London a lot because old London in 1840 the cholera thing I didn't mention
And 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 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
There was interesting when I was there as 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 p.m. 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 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 really, you know, the government's and the politicians who are tied up in Old systems that are holding us back and basically exacerbating the problems were 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 are were under pressure because people didn't want to admit that the fecal-oral route of infection was true. They thought it was in the air. So they actually the politicians put the pump handle back on and for another couple of years there were still cholera plague.
In London, so, you know talk about politicians screwing things up. I absolutely agree that if we can mobilize human Ingenuity, we can solve anything but we do a very bad job of that. I think where we are here in California is a hotspot for Innovation, but most of the world doesn't really innovate.
Yeah, when we look at the state of health care in the United States, I mean, it's just 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
The way it goes I'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 work on Aging is one of these things. Whoo, 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 of 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 endpoints and show things are actually working. They are well prepared to consider calling aging the 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, nobody has any reason to say 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 our lifestyle and how we live and only 20% is genetic and actually that that's done by studying twins who you know some smoke some don't say live different all this stuff.
Your genes 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 the ways to extend.
Lifespan and and not be frail in old age. Like my father. I talked about him a lot. I'm very proud of him as a Beacon of Hope at 80 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 write really and our trainer who's currently training the two of us together. He says, you know what? I think my dad was dead lifting or was it a something like a hundred and eighty pounds something a lot and he said the
Stadia role that I trained was learning how to get out of a chair, right?
Yeah. You are you post 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 Crush.
Seeing it. It's very
inspiring. Well, I think most of us can achieve that in life. Now that will be unlucky people that of course disease is still hit us, but most of us are wasting our lives because we're basically not you but most people don't think about their longevity they'd if they think oh when I'm old I'll deal with that when it comes but now in early and mid life is the time to invest because it'll pay off dividends later in life.
Hmm. We've done such a good job.
With medicine and Pharma and increasing. I mean you would probably disagree but 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 process 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 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 aging process is already pretty
Advanced at that point an aging is let's not 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 only the these diseases are real but they're the end point 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 what 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 Paradigm of come in with the disease will treat it. Hopefully fix it. Kick you out the door wait till you get sick again come back and repeat until failure. Mmm.
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 a symbol of
You know climate change in action and I kind of degraded planet Earth and a certain trajectory that were 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 exacerbation to the climate change problem that we're trying to solve. So let's kind of dig in to this.
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 a hundred and fifty a hundred and seventy-five. 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 to date. Haven't been so good at dealing with
so everything you said was right, except one thing.
Mmm, 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 you are the fewer of them. But let's look at the planet. We do have an issue on the planet. Of course, we've been going on exponential growth for the last couple of hundred years for our species, but it's not the
Say that we thought it was in the 1970s Malthus and the ehrlich's used to panic make all of us panic because they said
it's global population growth.
Well about your running out of resources. If you extrapolate this curve vertically, of course, we're all going to starve to death in the next 30 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 what happened? I think most of us didn't predict is that as populations across the globe become.
Healthier, they become wealthier when they are wealthier, they become healthier.
And then you lead you have women who become educated and women don't want to have 15 kids. They don't want always be pregnant when you give them the choice. They have you noticed a few and we're also 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 I family are my grandparents 15 kid or 13 kids. I exaggerated. I have five brothers and sisters.
What about you? Oh, we only want to have to because we want to give them an education that's happening across the planet. So we're 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 eleven 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 going to hit a sister.
Sustainable level and actually start to decline in population based on projection. Why
wouldn't we just continue to populate until we blow through that
feeling because it lets look at even in the u.s. Actually population is going down and is barely a replacement level in Western Europe. It's declining couples on average are having less than two kids and there's plenty of people who choose not to have
kids. Yeah. I mean, this is one of Paul Hawkins big things when he and his book dry down one of the most powerful tools.
In the war against climate change or the you know, the the battle to solve this problem is educating girls the more we can educate girls in the developing World. There are less likely to you know have as many kids,
right exactly. Exactly. So we're going to help build some schools over in Kenya that if anyone who can see this wristband 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.
Right being a woman in the these countries is the worst there. If they don't have a well they have to walk. No, thanks for to Justin. Rani'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, which 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
Years 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 hey let's do this again. Yeah,
right you I'm sure they'll be people and we know people like that I won't name names, but I know an idea.
Eight-year-old who has a kid who's in their 70s and also in their 20s. Anyway, I'm proud of him. He won't know how mentioning his name - Norman Lear. He's fantastic. Okay Norms are one of those guys, but but most people don't do that. Yeah, but but if
but if you sir but what I'm saying is when you're not just extending the number of years of your own 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
Andy 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 270 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 decade in a nursing home before they die. This is really personal but it also weave
got to throw away. Our preconceptions of what being old is why we talk about Laird Hamilton in his 50s is basically got the body and the looks of someone much much younger being 50 is not old anymore certainly 60 even 80 like my father that's not old anymore. If you take care of yourself you extrapolate that into the future. They'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 will be sick at 60 that will always happen but on average people will continue to live longer.
We've been on this trajectory of living healthier 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 US can expect not just hope but expect to live to a hundred and four. Okay, that means that they'll still be healthy 80 and 90, 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
55 year-old Laird Hamilton doing what he was doing. It would just be it would be 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 craziest thing you'd ever heard of sack leader. 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 a crazy world we live in but it's wonderful and also young people
Have access to information you go back to when we were kids. How do we get information? Well, there was the local library which was books that were basically old and musty or you could go to World Book Encyclopedia or 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.
Give and my kind of playing it 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'm interested in and how that impacts like risk assessment right? Like if you're if you're like
Hey man, I'm 18 and I'm going to live to 300, you know, borrowing me getting hit by a bus like, you know, I have a lot of life to live. So am I really going to go skydiving because then the risk of that seems so much more severe than it would if you're looking at well, I'm going to only live to you know, life's short and I'm going to die at 80. Anyway, like I'm going to 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
be on that path. I don't think people in the 1840s and 50s. We're worried about bicycle helmets if they had bicycles, you know what I mean? The longer we live the healthy. We are the more protective. We are of our bodies and our children and that will
continue right now that we're seeing a rubber banding with that with like Jonathan haidt and what he's doing in terms of like, you know, we need to re wild our kids because we're so worried about we want will want them go outside without a helmet on I've walked down the street it's extreme. I just
got back from Shanghai where there are cameras that shame you on billboards.
Across the street when the lights are really the red. Yeah, and it's and it's got data
shame you it like a photo of
your face. Yeah, right on the street. You can see the lady the cross the street this morning that disobeyed the rules and she apparently oh my gosh demerit points on her social system her social score.
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 at any time soon.
But yeah, the the risks will you don't want to take massive risk, but you know what? I think that we're exaggerating maybe if we live for a million years. We're going to be a little bit more cautious crossing the street, but I think that if we lived 250 say there were those of us who like taking risks. Anyway, I don't think somebody says I'm going to wait till I'm 90 to jump out of an airplane door when you're 20, right? So it's there are Risk Takers and most of us will still take risks in life. People. Actually funny funny side is
I 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 taking or originally on the road. I'm not well not anymore. I'm now hard it sedated but I got I shouldn't say sedated but I'm more calm about my driving but I do drive a fast car. I drive a Tesla okay floor 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 because I took a lot of risk.
When I was young to get here point being, you know, maybe I'll live to a hundred. Maybe I'll do 250. I don't know. Maybe I'll die tomorrow. 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 were going to live but I think the trend in the world is that the longer we live the more scared we become of danger right fireworks. Are we going to what worry about?
Looks 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 house band, you know, we also have to solve these other kind of, you know cultural dilemmas that we find ourselves in that are
attributing to mental Decline and emotional decline the disconnection the you know addiction to technology the lack of purpose that underscores most people's lives and we talked about this last time too. Like how does the how does like the work of Gann buettner on 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.
Then to be happy and have you no purpose for living that long
Yeah a hundred percent. So there's the there's the world of molecules and genes 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's also what I what drives me and so I think you're right. But if you're someone who's prone to depression giving up giving
An up. Hope you 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 not sure I can do that and winding around I'm a cunt slapping around find a goal go for it. This is your opportunity and don't come to me with an experiment that will advance science by one step come to me.
With an experiment or a question that will advance US 20 years into the future and that's not easy, right? That's the hardest part of science. 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 it's 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
Fused with this, you know this drive this passion to you know, solve this problem or you know, it wasn't lightning Advanced Humanity in this
way. Well, you know makes a good story and of course looking back on it. It looks pretty easy. But there were there 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 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?
Well, of course that's never going to 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, we you were talking about career arcs. We what about a world where if you know, not everyone can have their dream job initially. I would love a world where people
Can live 250 expect to be still playing tennis a hundred and twenty. I think it's doable is no reason why we can't do that with our Ingenuity to what that gives you is the time to have multiple careers multiple lives a multiple partners if you want, although you may find the right one in the beginning 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 40 or 50 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're dealt the wrong cards beginning of Life, you have multiple chances to correct that there are some risks to take of course and you do need some support and I'm not running for president. I couldn't I was born in the wrong country. But what I
I would love to have is what I call a skill by article, 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 a hundred fifty years long. You can do, you know one career could last 20 30 years become the best you can be at that and then switch. Hmm. And that's a life. That would be well lived
with it. Yeah. I think it would it would give
If people the patients that I think we lack right now like every were in such a hurry from the moment were born, you know, it's a Habitrail of achievement and measuring ourselves against others and you know from the moment you enter junior high school and that it's grades in high school and it's getting into cut it like your it's this race right and the brain and the emotional body isn't mature enough to really process that to make the best.
Visions how are you supposed to know? I mean, you knew what you wanted to do at a very young age. Most people don't write but they're kind of, you know Corral din to 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 40 and think why am I even in this position? But if we could slow things down and say hey you're going to live to a hundred and fifty no big rush here like take your time go on a kibbutz, you know, maybe there's
The national, you know sort of period of time where you're you're you know of service or you do some kind of Teach for America that like programs like that that would allow people to 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 be getting Dementia by this point. He wasn't looking forward to the future late 70s is still perfectly Fair. What am I going to 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 what I know just begin a new one and you know 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 our
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 never fully get it. I don't feel any different than I did when I was 30. I might have a bit of 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 trying to put them out of our
Of sight and you know dismiss them which is the tragic situation that we're in
now. Yeah it is that the older you get actually the more you appreciate the these folks. What I want is a world where people in their 80s and 90s are not just appreciated, but they're 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 going to want to spend their time listening to you all 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's still on the Supreme Court and lacks the sort of plasticity kind of adapt to you know, modern times who stuck in an era that is that is bygone and thus is despite their wisdom and experience of the
Is isn't in lockstep with what's actually happening, right? I mean that seems to be a potential downside of it's not 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
recurrent but now it's like finally that you know, these people are we're getting rid of all these people so we can get fresh blood in here and New Perspective. I don't agree
with that at all. I think that we should treasure those folks that have the wisdom and experience them because history is really the way to predict the future and
And they've seen it. All right that someone like Warren Buffett mean I would love to keep him 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 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 birthdays
right as a result of doing this book to her. 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, you're going to be cagey about this right? Well, yeah, I mean 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 that's part of 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 realize 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 I've met a lot of my Idols in business in Hollywood a lot of billionaires. I probably met a quarter of the way billionaires at this point is let's look at it. But they're I'm learning a lot of
pasta Leone, right?
Yeah. Well, you know
No, 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. Mmm.
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 etcetera 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 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 most interviews that this question gets asked right. This is what people are 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? Okay. There it is. That's not
why I did it. 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? Hmm 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?
To jump to the page that Rich talked about page 308 Wario 4.
Yeah, I get asked that a lot. Oh, do you yeah so funny,
but it 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 lifespan book.com. And so I'm adding to those pages now, it's not just one page to be fair that the whole of part 2 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 here are
the thing. Well that this is that's a cheat sheet. Yeah towards the end. But yeah, like I can't run around saying take this supplement or that brand is good. I will first of all, I'll 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
Not short, 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 trying to decide test and everything in that book was fact-check to the nth degree and with references and that's why when you read my book versus maybe some others 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 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 ageing 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 if there's 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 going to go out on a limb to say that a lot of nutritionists would disagree with me, but I've been doing this for 30 years. I've seen what happens to people and
Moles when you restrict their food and 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 for as long as you can do it, I do it, you know, like I said hopefully till late afternoon dinner, that's the easiest and best thing you can do are the 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?
Well, I will do it again. Actually now I
I'm I actually think I know at not to go too far into the deep end. But but honestly, we now know we all have the power with the scientific basis to actually live at least 15 years longer. Mmm. Okay, so there are actually and I talked about this I think on Twitter recently, but 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
Ed things like 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 304 you'll see more
or I'm conscious that we have a micro biome that is that needs to be healthy. So I make my own special yogurt, 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 the that impact on Aging correct? Well, it's but from Europe from your perspective in the work that you're doing
right right fair enough. So the there are at least a couple of things to talk about one is so Dan buettner is right and I've got a lot of good friends that study populations that live a long time. I think that's a very good guide as to what we should do. Its eat plants that are full of polyphenols that are stressed out.
Out and this is what the okinawans and the Saudi Indians do makes a lot of sense. They're activating longevity genes. So the plant-based food, I think a little bit of meets fine, especially if you work out you're trying to do Bill couple cups of muscle, but I think that what we've learned is by studying the sardinians and aachen Owens is that those diets are the best for humans and they are mostly plant-based with a little bit of me 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 amino acids, which you'll find in me leucine isoleucine valine these turn off our body's defenses through a process pathway called mtor for 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 never really optimize your body's defenses. So I try to be plant-based foods, but there's
another thing that that most people mess which is the zener Hermetic molecules from Plants you get those you don't get those from me as much so what do you make of
the carnivore diet?
Yeah. I'm on the on the other side.
It is an interesting phenomenon good long-term like crusher 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 the 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 to you know, what would be your response to that
person. All right. Well, so I'm a scientist. So let's talk some science briefly the what you do when you activate this mtor pathway is you're telling your cells in your body. The times are good. You've just caught a mammoth. Okay, basically and now is the time to build your body.
And actually fix things he'll 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 your amino acids 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 better.
That but long term you're going to 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 and need. Yeah. So being hungry and eating plants are going to be telling your body times are not as good. We've run out of Mammoth meat, let's hunker down,
but you could desire on our own. We're on our own. So we're going to have to you know, do the heavy lifting here. It's basically
Ali catalyzing these systems these biological systems to protect the body, right? Yeah and and in turn promote longevity versus oh this we 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 were young. Our defenses are on hyper-alert 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'd 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 got to get your defenses up like you're a baby speaking of which I've been on much healthier diet last few.
Including intermittent fasting including the supplements that I've got written on page 204 one of the people say, oh, I'm not noticing anything after you know, maybe two weeks on the on supplement. Of course, you're not going to see that. I've been doing it for some of them for 10 years. But what I've noticed most recently with my current lifestyle all of these things combined the biggest things 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 called to another Ivan 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 of 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 cold. Even. Yeah,
what about sleep? Have you looked at the impact of sleep on all of this?
Some people have well it we've done a little bit in mice. What we've discovered is that the sirtuins 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 bodies clock. Uh-huh. And if you're screwing up your longevity defenses, you're also probably screwing up your body's clock. So another 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 nem PT Gene we talked about earlier the one that makes in ad that's actually going up and down in levels throughout the day. It goes up in the morning down. It's changing the NAD levels. And and if you get that out of whack we get this thing, we called jet lag. Mmm and another side effect. Actually. I find it anecdotally it's not proven is that if I raised mine are D levels either by fasting
exercising or taking a supplement. I don't get the effects of jet lag.
That's interesting. Wow.
That's super interesting. All right, so fasting trying to create some or mises in your life basically living a blue zones lifestyle in terms of supplementation your I know you're not going to give like
You know specific recommendations, but basically walking through what you do, you take a daily Resveratrol you take and nmn supplement which is basically a supplement oriented around promoting NAD. 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 beside it'll convert in R into n MN and then animate into
NAD and that last step? No that first step. Is this name Petit Jean. Uh-huh. Okay. So yeah, you can people are taking an hour or they're taking out a million in our is a little cheaper than an omen. I've studied nmn people ask me why not in our polenta 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.
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've no stake in this but some of my colleagues and on the internet they're saying I'll one is better than the other the truth is we really don't know yet, which is better or if if they're the same I would I take a demand because AI have a ready supply because we're doing clinical trials but also because I've studied at the most
mmm and that's it, right? There's no other are you is there anything else?
Taking
yeah. Yeah. There's a there's a bit of a list. I'm also taking a drug a drug right a drug called metformin which is the rise Drive. Yeah. So metformin has been around since the 1970s and being 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 a lack of appetite which people 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 in 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 is Neil. Barzillai. 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.
There are a couple of studies that I side 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 Metformin 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 into play and actually mtor. So if there are three main anti-aging Pathways I've talked about sirtuins that
Worked on in yeast and now in mammals the middle one is the am PK which metformin works on and then this mtor which response to low amounts of protein and they all talk to each other. So we used to fight a scientist. My pathway is more important in your pathway 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 to moderate levels and get the best anyway and PK what it does.
Does to the body is it for one thing main thing is it ramps up energy production mitochondrial activity? It's called mitochondria. Most people may have heard our battery packs of the cell and the more you exercise and if you fast calorie-restricted more mitochondria, that's a good thing. Mmm that as far as I know. There's 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 our mitochondria. But one way to boost that is to take Metformin or two to do these other things like exercise, but it's not all good news. There are some studies that show that meant form and can interfere with endurance and muscle hypertrophy and there's been a lot of talk about it actually on the internet Peter a tier has done some some work podcast on this nir. Barzilai my good friend at Albert Einstein College of Medicine was on that study. So
So 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 going to be using my hands for graphs, but basically the 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 gain more muscle than those that didn't but overall on average. There was a slight very slight increase in muscle mass in those that weren't taking metformin and doing weights, but there were benefits.
It's to the metformin there was lower inflammation or oxidative stress in the people that took the drug. So what do I think is the take home message? Number one don't panic if you're an average person. If you don't make a living from bodybuilding, it's not going to matter that much but in an abundance of caution, what I do is I don't take Metformin on days. I work out pretty simple solution, but I still think on days where I'm not working out metformin is going to protect me against these major diseases.
He's
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 second one answer to these things my father and his father were and myself we're susceptible to obesity and 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 already struggling.
Like so we've got obesity jeans 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 Metformin 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 that on the upside is some of the chances of getting I forget which type of cancer but it's in the book can be lowered by 40% That's a massive massive effect. So you always got to balance it. So I don't prescribe anything to people but what I would recommend to do is to think what 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 a hundred and ten of probably only got two more years. So what's that lose so that's obviously a calculation and then how expensive is it right? 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 going to 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 I want to talk about 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, right she did and then a final long gave out 20 years later.
So she lived for 20 years on one
lung. She did she manage 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 you ever seen someone die. Mmm.
No not in that
way. Yeah. I've never seen someone die except for 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 is to whisper in her ear while she was choking to death that I wanted to thank her for being the best mother. She could have hoped 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.
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, 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 the target targeting aging with metformin something anyway, so that's getting underway.
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 the susceptibility to diseases and if we're right we'll be able to show with those numbers of people that ADA clock is slow down but be that they remain healthier because of in this case metformin but you know if I had a billion dollars I take the top 15 drugs or
molecules are supplements 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 what are you working on it's
pretty darn exciting I got to say I'm very privileged to run a lab there are 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
Using the cost of this clock. Maybe we'll bring it down to the five bucks. That's a great breakthrough 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 is 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 to meant it and reset the clock and get get it cooked to go backwards. So we 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 be ior XIV. Okay, if you type in reprogramming and my name Sinclair, you'll probably find it too
will link it up in the show now great. So we're very proud of
that that paper which is still under review. So it hasn't hit the media.
Actually, I got to say I know I'm rambling Hibbett podcasts are a fantastic way of getting news out before the actual newspaper if I figure it out, so you're hearing it the here first, but we hope that by sometime early this year maybe by June will have this published. We were revising it for the journal Nature, which is one of the top in the world. We're excited that we got good reviews from our colleagues who do blind or Anonymous re-review. That's a long way of saying we are pushing the boundary of this reprogramming.
Method just
quickly and the abstract of that study is what yeah.
Yes. Yes. So the summary is that those methyl groups that are counting that we used to count the clock we can tell the cell to remove the right one so that the SEL remembers how to play its genome correctly like it was young. There are three genes that we take from out of the book of embryo. So when you're an embryo you're using three particular genes to grow and
Healthy they get Switched Off by the time we're young adults even while we're babies. If you put them back in just at the right time the right place at the right moment.
We found that it's rough. We don't see any safety issues. So that's the good thing but we see is the clock gets wound backwards. Those methyl groups. Go back long story short, the cells are programmed to be young again completely not just a little bit not 2% not two years, but we can take it for exactly example in this paper. You'll see fuse if anyone takes 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.
The vision comes back as though 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, I've
seen a lot pretty remarkable 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 as I to save my life, but our colleagues that did these experiments with us. They're Blown Away Mike.
Colleague Bruce Cassandra at Mass Eye and Ear 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 disease is like glaucoma macular degeneration. These are not reversible the best you can do is slow them down slowly. 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?
Work and where is the reset switch? What what's the repository of the information put another way was the backup hard drive of the cell,
right? So when that analog 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.
X 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 until 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 a human context
right? Well, we we
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 Pianist amended 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 got it in mice our eyes and our biological systems aren't any different than a mouse's really so I'm optimistic.
The Mystic you know, but until we know in humans that 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 will 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 in an in the optic context like it should it should be applicable across the board or in other you know with yeah we 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 I get sold very quickly if you damage your eyes so I'm going to go back like your skin so we thought let's go for it my student
Chang Liu's is a brave brave student. So if we can do that to the ion much more optimistic that these other organs and systems whether it be a kidney that's failing or a liver skin, who knows what we're going to test that rigorous so we can even try 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 sure everyone else wants to know the answer but his what's holding us back.
Back in in the technology. The ability to deliver genes is not as easy as everyone thinks they are 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 were working on and having some successes 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
Which is typically wear these jeans go when you deliver them IV But ultimately imagine a world. Let's be a little bit of dreamers here. If for my colleagues will allow me. Imagine a world where you have these three genes put into your body. Let's say it 50 and then you're basically like Deadpool. If you get injured you can have an IV turn on these jeans heal better. You lose your eyesight. Turn it on in the I fix your eye.
Who knows what have an IV 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 didn't off your door ten times or infinitely. Hmm,
what more will be revealed
we will come back. I'll come back and tell you how
things go. Yeah, please do we're all counting on you. You have the executive civilization rests on your shoulders. The future of all of us
will end in the meantime deed of your lab. There's a lot we can do to stay.
Yeah healthy for longer and actually that every year you were alive you get an extra three months of life because technology is
changing. That's encouraging that's going to that's going to 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 in.
Keep us up to
date on everything that's going on. I'd love to 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
old and David is easy to find on the internet. It's just at David Sinclair PhD on one Instagram on Instagram
and Twitter is David a
Sinclair. Cool. Awesome at anything else. You want to let people know about before.
And it here let's all celebrate 80 years from
now. That sounds good man. It's a plan. Where's the party going to be your house? I think we'll do it at your house. Right? Good. Thank you man. Talk to you soon. Peace. Brilliant mind lovely human that David Sinclair. I really enjoyed that bit of a mind blower. Do me a favor. Let David know how this one landed for you. You can hit them up on Twitter at David a Sinclair or on Instagram at Davidson Claire PhD.
Don't forget to pick up a copy of his new book life span the Revolutionary science of why we age and why we don't have to I think you guys are going to really enjoy that and as always be sure to check out the show notes on the episode page at Rich world.com to dig deeper into David's World and work. If you'd like to support the show, there are many ways to do that subscribe rate and comment on the program on Apple podcasts or on Spotify for all you Android users. And of course subscribe to our YouTube channel where we are sharing
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As always by an Alum, I appreciate the love you guys see you back here next week with another PhD Cyrus Kim bada along with Robbie borrow to discuss all things diabetes, including some pretty incredible stuff about this devastating illness how it can be prevented and treated and in many cases reversed. I think you guys are going to really enjoy it. I think it's going to really surprise you and here's a clip to take you out until then peace Appliance.
I think part of the problem here is that doctors are not trained in nutrition. First of all, so they go through medical school, you know, they go through four years of medical school plus a residency plus a fellowship. Sometimes I can be almost a decade worth of schooling and you ask your average doctor. Hey how much nutrition do you learn and they're like, I don't know. I learned one class one day maybe six hours, right and their studies that actually show that your average doctor learns nutrition for a maximum of 20 to 25 hours while they're in med school. So they're just not given the training to talk about food.
And it's not their fault because doctors are phenomenal human beings and they go into it with altruistic Tendencies, but they're just not given the right tool set. So they leave medical school. They go into their practice and then when they when somebody with diabetes or high cholesterol or hypertension presents to them their
solution is like, well I have this pill that I you know can prescribe for you because
that's the system that I know how to do and that's part of the confusion around diabetes is one of the few chronic conditions. You can monitor on a meal by meal basis you can look at
At your own place because meter back all day long, right and like you said we're going to get into the Weeds on the you know, the cause and what's going on here. But yes, there is particular confusion in diabetes that is very nuanced. And that is part of the reason I think this approach has not caught on yet because people don't understand the confusion of the headlines in the studies that are being cited just a lot of misinformation the disconnect between the research and what the public believes and understands is mind-boggling its massive.
mind-boggling
