The Joe Rogan Experience - #1349 - David Sinclair

Episode Date: September 10, 2019

David Sinclair, Ph.D., A.O. 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. His new book "Lifespan: Why We Age And Why We Don't Have To" is now available.

David Sinclair Lifespan Why we age and why we don't have to I'm so happy there are people like you out there Because I don't want to age I'm aging, clearly But I'm not interested in it I don't like it

Yeah, well I don't know anybody who does Joe Rogan, thanks for having me back on Thanks for coming back The first one was a smash hit, man People loved it All my friends were very excited. But I had a question for you right off the bat regarding metformin. There was actually an article, I'm sure you saw it recently,

like within the last couple of days that was going around through all the mainstream papers. It was talking about how the use of metformin, DHEA, and was there something else as well that was taking two years? Human growth hormone. Taking two years, two biological years off of people's lives in terms of their age, which are natural age, which are actual. I'm 52. It would make me 50. Right. Even 49.5, according to the study.

That's what I'm looking for. Yeah, that was a good study. You know, it's only nine people, so5 according to the study. That's what I'm looking for. Getting back to the fours. That was a good study. It's only nine people, so we have to repeat this. Were they studs? Did you get nine super athletes? Or did you get schmoes that don't exercise? As far as I know, these were just regular schmoes.

Schmoes, yeah, which is good news for schmoes like me. Yes, good news. Yeah, I mean, that's what you want. Some people just respond better. Yes, good news. Yeah, I mean, that's what you want. You don't want, like, some people just respond better. They have super bodies, you know? The great thing about that study is, first of all, I was with the first, the main author on that paper while it came out. I was over in Israel as part of my journey up the great rift of Africa. I ended up in Israel.

Anyway, the guy there, Steve Horvath is his name. He and I and a couple of other guys are trying to figure out not just why we age, why we don't have to, but is aging truly reversible? And that's what this study suggests, is that it's not just about slowing down aging, but one day we could be 80, but biologically 30. Now, when we're talking about the biological age, how is that measured? Is this measured by the length of the telomeres? Is this measured by physical performance? Is it measured by a combination of these factors? It's none of that.

It's something brand new. Most people don't know about it. So it's called the Horvath clock. don't know about it. So it's called the Horvath clock. And what Horvath and others have discovered is that if you read the DNA, and you don't just look at the letters, A, C, T, G, if you look at what's on the letter C, cytosine is called, there are chemical modifications. And those chemicals change as we get older in very linear and predictable ways. And if you use a computer, AI, you can say, if I took your blood sample right now, I could read your DNA, look at those chemical groups on the Cs, and I could say,

you are, okay, you're 52. You might be 46, according to that clock. And also I could predict when you're going to die. Whoa. Scary thought, right? Yeah, like a fortune teller. Yeah. But the good news is, well, now that we know what's not just measuring aging, we actually think that clock is part of the aging process. We're learning how to reverse it too. Hmm. Now, is this just one modality, this combination of growth hormone? Is this one way of going about it?

Are there other ways of going about it? Growth hormone, DHEA, metformin, is there anything else? Well, that's the first that's ever been shown to really reverse. It's just those three things. But I'm sure there's going to be many more discovered. We've only had this Horvath clock over the last few years in humans being used widely. But I think as we use this clock, we're going to figure out that a whole bunch of stuff that we do and things that we can do and combine will not just slow aging, but reverse it. And not just by two and a half years, eventually, and some of the technology that I talk about in my book, we think could

turn the clock back by a decade or more. Whoa. Now, what things are you talking about that could possibly turn it back a decade or more? Well, so the – And who do I have to blow? Sorry. Yeah, you can blow me, but – yeah, you may have to do it a few times. But the amazing thing about where we are now today with aging, and we're right on the cutting edge, so it's great to be able to share this with your listeners, is this clock, it changes on the DNA, right? What I'm saying in my theory of aging is that it's not the DNA that we lose. That's the old theory, you know, the old idea that antioxidants hurt the DNA. Just throw that out for a while, maybe forever. What I think is going on is that the DNA is getting modified and the cell can't read the DNA the way it used to. Okay. That's really important. And so the clock is not just a clock. It's not a clock on the wall. It's also, if you move the hands of the clock,

time changes. That's what I think is going on. Can we pause right here for a moment and explain what you were saying about antioxidants? Well, antioxidants have been the biggest disappointment in the aging field. It doesn't stop 40 million people every day buying drinks with antioxidants in them. But antioxidants have, with very few exceptions, failed to extend the lifespan of any organism. But you are a proponent of resveratrol, at least you used to be. Are you still? I still take it, and we still study it in my lab. But you brought this up. It's really important.

Resveratrol was originally thought to be an antioxidant, and it is a mild antioxidant. But the way it really works, and we know this is a fact from my lab, is that it's stimulating the body's defenses against aging and disease because it's binding to these enzymes that we work on called sirtuins, and these are the defenders of the body. And you were saying, if I remember correctly, you take resveratrol, you take a powdered form, I actually bought exactly what you take, and you mix it with yogurt in the morning. Is that how you do it?

Yep, a teaspoon. What's the dose that you take? Well, it probably comes out to about a gram a gram yeah okay so if someone's taking capsules what depends if probably capsules are 250 milligrams that'd be okay so in the morning yeah you know i'm still alive so that's it's where you look good oh thank you do you um is it important to take it with fats is that why you take it with yogurt yeah yeah either high protein which is uh you know a greek yogurt suffices or fat but water it'll it's like brick dust it won't dissolve and it won't be absorbed but a glass of whole milk maybe would be

okay yeah that's great but it has to have something to bind to is that the deal for sure yeah in in our studies in humans and in mice if we didn't give them high-fat food, it barely got in. It was five-fold less. Now, this study of metformin, DHEA, and human growth hormone does not include NMN. Right. But NMN is also effective. Well, let's delve in a little bit. Please.

If you read the paper, and I have, it turns out one of the effects of this treatment was the reduction in the levels of a protein called CD38. CD38 resides on immune cells, and it goes up as we get older. And what they found, one of the biggest effects of the treatment was the levels of this CD38 protein went down. So what is the CD38? This is the main enzyme in our bodies that degrades NAD.

NAD is required for the sirtuin defenders to work. So one possibility is that, and I'm sure it's complicated, but one way this could be working is by allowing your body to make NAD and store it rather than degrading it as we get older. Interesting. So would supplementing with NMN, which is a form of NAD, correct? A precursor, yeah. Precursor. Would that enhance the effects, do you believe? Like if they tried to do a new study?

It could. Could. It could. Could. It could. Potentially. Each of these patients cost $10,000 for the treatment. So it's not easy to do these studies. $10,000 for the entirety of the treatment and the treatment lasted how long? I don't remember how long they treated the patients for. But I do know that it wasn't cheap. That's why they only did nine. Because at first I said

to my friend, Steve Horvath, nine patients, are you kidding me? Why didn't you do 50? And they went, well, we didn't have the money. That's the problem. Anyway, my point really is that we need to test a lot of different combinations, include Anaman, include, there's one called rapamycin, which is a little bit more risky and toxic, but there are better molecules in development. The question is, what is the best combination? and do you use it with exercise and fasting or is it bad to combine them all together we don't know yet that's a good question too that i wanted to ask you because one of the things that came out of the podcast was input from some other people that i know that are nutrition experts and performance experts that were skeptical about metformin and they they were saying that metformin, although it may have an anti-aging effect,

it actually decreases physical performance in athletes. Well, there is a study that shows that. And resveratrol too, actually, can prevent the great gains from hard exercise. So here's the solution that I think is worth trying, a solution. And that is a theme that I have in my book and in my research. And that is we don't want to be doing everything every day necessarily. We want to pulse it. We want to shock the body and let it recover. We know that you can't just exercise.

I mean, some people have been on this show, run 100 miles every weekend. But generally, you want to hit it hard and let it recover, hit it hard and let it recover. So what I am planning to do and actually started doing is on days that I'm exercising and recovering, I don't take metformin. And then when I'm just sitting around or on a plane, I do. And that way, I think that my body can have the best of both worlds. both worlds. So when you are not exercising and you take it, you feel like it doesn't have a hit when you are exercising and not taking it? So somehow or another, whatever performance hit it has, it's temporary? Yeah, right. So well, this is all just theoretical. It is. We're right on the cutting edge of human knowledge. We don't actually know what the best thing is. But my

best guess is that we want to allow the body to recover. So I don't actually know what the best thing is. But my best guess is that we want to allow the body to recover. So I don't take metformin on those days, rather than taking metformin every day like a diabetic would. Now, what's the hit? What is happening? What's the mechanism behind the performance hit from taking metformin? Oh, we don't know. But I can tell you the best explanation that I can give you. So metformin is a derivative of a plant molecule, the French lilac. So it's not a crazy molecule.

It's pretty natural. But what it does is many things in the body. Scientists will quite annoyingly argue about it. They have for the past 40 years. So there's no correct answer. But what I think is going on is that metformin is interfering with the mitochondria in the cell. Mitochondria, we call them battery packs. They're basically making chemical energy.

Without that chemical energy, we'd be dead in about 20 seconds. So we need that for life. So metformin interrupts that energy production in the mitochondria. But you need the mitochondria to amplify after you've exercised. So they're antagonizing each other. So why does metformin work? By inhibiting the mitochondria, the body gets a signal that it doesn't have enough chemical energy. It's not making enough. So it expands the number of mitochondria. These are ancient remnants of bacteria that entered our cells and we have less if we sit around and like we are now and we have more if we exercise and metformin by telling the body a shit we're

running out of energy the body responds and makes more mitochondria just like exercise does but i think if you're taking metformin and exercising that inhibition is preventing the benefits somehow of what you get with exercise. Preventing it how so? Like what did the study or what studies have been done and what did they reveal? I don't remember the precise details of the study. It was giving metformin every day to people who were in a controlled exercise. I think it was treadmill a few times a week. But then what they measured was the mitochondrial benefit.

And I think they measured a bit of strength. It's so confusing that there's a mitochondrial benefit but a performance hit. Well, no, actually, metformin prevented the mitochondria from amplifying up. Oh. So it must be interfering with the signal that you get from exercise, whatever that is.

We don't know exactly what that is. So you'd really have to be some sort of a guinea pig to try to fuck with this stuff, to go back and forth from taking it and exercising, not taking it and exercising. Yeah, I'm one of those guinea pigs. Yeah. And what do you – no disrespect, but how hard are you working out? Not enough. Yeah.

That's what I'm saying. I spend three hours a week in the gym. That's not bad. It's all in one day. That's maintenance. Oh, one day? Yeah. Really?

One day, three hours? Yeah, that's it. That's ridiculous. It is. Why are you doing it that way? Because I'm a smart. But you're so smart. That drives me crazy when smart people do dumb shit.

Like I had Peter Hotez on the podcast. He's a brilliant man from the University of Texas. He's a researcher in tropical diseases and is obsessed with diseases and the importance of vaccination, all these different things. Then he's talking about how his diet is terrible. He eats junk food. He's constantly eating Jack in the Box and shit. I'm like, what the fuck, man? You're so smart and you're a guy who works on diseases.

What's the number one cause of diseases? Yeah, I don't get that. Some of my colleagues eat the worst food, and they study longevity. Crazy. It's crazy. It's like they can't help their impulses. It's like there's so many people like that that are obsessed with various aspects of health or performance, but they just

they just can't get it together well i would work out more if i had time i'm usually working till midnight and after that i'm not really keen to go to the gym you do have an excuse you have a crazy work schedule you do have an excuse yeah well i'm on planes for a bit so i try to exercise on the planes pretty hard do you really what do you do um you go to the bathroom and do squats so nobody thinks you're crazy yeah he's got to pee a lot or you're doing blowing there or something yeah i haven't done exercise for a while people think you're in there doing meth yeah doing something in there squats yeah um so what do you do when you work out uh i lift weights for an hour um then do a fair bit of stretching, and then I actually do some hot and cold treatment. Oh, okay. Yeah. You remember we did the cryotherapy last time? Yes.

Yeah, that was fantastic. Yeah, you want to do it again? Today, if you have time. Yes, I do. Fantastic. I'm in. I'm in. Yeah. I was planning on doing it today. I did hot yoga earlier, so I like to do hot yoga in the morning and then cryo after a podcast that's how i like to mix it up all right let's do it all right i don't have a cryo uh handy at my place but i do uh the sauna and then the cold tub and you should get a cryo set up they're not that expensive you can get one what about these infrared boxes are they any good oh for saunas i do not know but um some people swear by them laird hamilton who we were talking about earlier. By the way, how good is that coffee?

It's fantastic. I might need a top-up. Superfood coffee. Whoa, we'll get you more. Oh, Jeff is going off to pick up our Pablo Escobar mugshot picture. I'm obsessed with mugshots for some strange reason. Always collecting new mugshot pictures. We've got a giant Pablo Escobar.

It's very nice. The Laird Hamilton stuff, that's got turmeric. It's got coconut milk. It's organic coffee. I'm so addicted to it. I drink that stuff like water. Yeah, I'm going to have to get myself some. Yeah, it's delicious.

You don't need a machine either. You can mix it yourself. He has all the stuff. You just pour it into coffee. Yeah. I mean, he's a hero of mine. He's a stud. What is he?

He's 50-something now. He's 1,000 years old. Guy runs mountains, fucking surfs, tall as the Empire State Building. He's a very interesting character. The last I saw him, I was watching something on Instagram, and I saw him in a sauna with oven mitts on riding a bike like uh one of those uh echo bikes like those rogue you know those uh aerosol bikes riding one of those fucking things in a sauna i was doing his sauna routine i did not like it i was cranking the sauna up to 220 degrees and uh i think i cooked my lungs a little bit. Not bad, but people who listen to the podcast afterwards,

my apologies because I was coughing like that for like four or five episodes and then I had decided, okay, this is fucking stupid. Like, I don't think this is good for me. Right, well, you know hormesis. Yes. What doesn't kill you makes you live longer. That's not exactly true.

You can push it a little too far sometimes. Yeah, how about booze? Booze doesn't kill you, but it definitely doesn't make you live longer. That's not exactly true. You can push it a little too far sometimes. Yeah, how about booze? Booze doesn't kill you, but it definitely doesn't make you live longer. That is true. If you drink hard every night, you look like shit. If you look at two people, one that drinks hard and their brother who just drinks water and runs all the time, boy, that water drinking guy looks fucking fantastic, doesn't he? In comparison. Well, yeah, that's probably another one of my advices

i've got to lay off the booze yeah well how much do you drink uh i'd probably have one or two a day when i'm on vacation like you i'd overdo it i just got back from vacation it's my body's way out of shape yeah i get fat on vacation man last time i was on vacation i was doing this i was grabbing my size i was in italy i hard. I was drinking wine every night. I was drinking about a half a bottle of wine every night. I was eating pasta all day long. But when I'm on vacation, I just go, fuck it. And also, it kind of gives me a little project when I come back.

You know, like, all right, now it's time to get serious. Right, right. Well, I was in Africa recently. Right. Well, I was in Africa recently, and I've got to tell you, when you see a wildebeest get attacked and chewed on for 45 minutes by a crocodile, nothing better than going back to the camp and having a beer to calm down. So I did a lot of that. So when you were on safari, how did you – are you in one of those open jeep deals? Yeah, a lot of that.

We did also some hiking. We had Maasai leaders that would go out with a federal officer with a gun to protect us. Oh, Christ. Oh, it was fun. It's so different than being in a Jeep to walk among the cats. Oh, yeah, man. For sure. You're almost dead.

Yeah. It's like you're right there. You feel like you're alive. You know how you get the feeling of what it was like to be an early human. I've never encountered anything other than bears in the woods that are terrifying. I've never seen a mountain lion while hunting. I've only seen two mountain lions ever. One was from my back porch in Colorado, and one was in the street in Santa Barbara. I was driving, and I saw one run across the street.

I didn't realize it was a mountain lion until I saw the tail. I was like, oh shit. I thought it was a coyote or something. Then I saw that long tail. But while hunting, the only thing I've ever seen is a grizzly bear. I saw a grizzly bear once. I've seen black bears. Black bears are

unnerving. Grizzly bears are terrifying. They look at you like this. You could shoot them and they'll still come. They just look right through you. They look like, am I eating you? What's going on with you? Am I going to eat you? Black bears are like, oh, should I get out of here? Should I run? Am I the boss or are you the boss? They're not sure. Grizzly bears are fucking sure they're the boss. They're just trying to figure out whether or not they should eat you. Right. And actually, one of the things you realize when you're amongst these animals it's a huge privilege for us to go for a walk

without getting eaten yes yeah we don't think about it that way because we're so used to being in parks and oh i'm out in nature the fuck you are you're not really in nature you're in some weird sort of nature preserve that we've sort of set up inside cities right and people ask me about my work oh isn't what you're doing unnatural? Fuck natural What about our world is natural anyway? Brushing your teeth isn't natural either, stupid Right

What, you were born with a toothbrush in your hand? Shut up Right, right So dumb I flew over here, what, at 30,000 feet Drinking a cocktail Surfing the internet Not so natural

None of that's natural You're getting bombarded by solar radiation yeah you're boozing it up you're also somehow or another online it's no way that anybody's ever going to be able to explain to me that my puny brain's going to understand right yeah exactly well yeah don't give me the argument that aging is natural therefore it's acceptable but i don't buy any of those natural things because everything on earth is natural even chemicals we're not getting them from the stars we're not pulling them

out of other dimensions like what are you talking about it's all from earth everything right even poisons most of them are derived from plants

sure in Africa I was hanging out with the Batwa tribe these are the pygmies they used to be in the forest and I had the chief take me through the forest and he was showing me

all the drugs they used to take there's this clostridium I think I'm saying it right. It was a leaf they used to chew on. They'd smoke a bit of weed. They'd go a little dizzy. They'd crouch down. After about 15 minutes, they'd stand up, and they felt invincible.

They'd go kill one of those elephants in the jungle. Jesus. Pygmies killed elephants? Yeah, mini elephants. Oh, the smaller elephants. Yeah, but now they can't. Because they're smaller people. Right, it's all mini out there.

They can't anymore? Except for the worms. The worms were about this long. My buddy, Justin Wren, we're a big supporter of Fight for the Forgotten charity. It's a charity that my friend Justin Wren set up, and they build wells for the pygmies in the Congo. And through this application called the Cash App, and I've personally donated to to and we also um we're doing benefits for them we're doing a big benefit in la coming up soon that'll be announcing soon but um he goes over there all the time and he's had malaria three times and just recently has acquired some unknown

parasite that is uh just devastating his health he's trying to figure out what it is. So he's got to go through a battery of tests and they've got to, you know, examine him. But next time he goes over there, apparently he's going to bring his own food. But I mean, the fucking poor guy's got malaria three times. Yeah. Well, he should be taking his medicine more often, I think. Well, no, it recurs. Does it really?

Yeah. Because you can't get rid of it. Well, it becomes systemic Right It's horrific, man I mean, the way he describes it And he's a gorilla I mean, a fucking gorilla

He's a huge man He fights for Bellator He's one of their heavyweight contenders So he's this, you know, 250-pound stud of a guy Who goes over there and catches these horrific diseases And just, like, barely survives And gets the medication and comes back stud of a guy who goes over there and catches these horrific diseases and just like barely survives right company gets the medication and comes back but then when he gets sick sometimes it'll kick back in again it's kicked back in twice another reason we don't want to go back

to natural way of life but you're a good man joe for uh supporting the the pygmies i was just in such a fucking angel when you you talk to him and you see his documentaries that he's put out and his films that they've done with Waterfor and now just with his organization Fight for the Forgotten, like you can't help but help.

Oh gosh, I was on the Ugandan side of the volcano rift and the way they live was just, it was shocking and we're going to help rebuild a school for them

but they need help and they're right on the edge of civilization. The Batua tribe, the pygmies, are in the worst situation than anybody. And they're the lowest of the low. They're picked on racially. They were kicked off their land to save the gorillas and these elephants. And they don't know what to do.

They've got everything they knew how to live is gone. Isn't that crazy? They're kicked off their land to save animals. Right. Right. Yeah. Well, yeah, but there's no way out. You've got to do that. Well, isn't there a way to not kill the animals and have them all coexist?

I guess. You could have kept them in there. It's a national park, so you can't easily have humans living in the national park. I suppose you could, but they are trying to modernize them. So they put them on this small few acres of land which they're trying to learn how to farm and the way they subsist is through uh tourism so i i would recommend anyone who's interested go see them support them buy a lot of stuff we i think we bought up a quarter of the village they love that but we're going to go back and do something meaningful. That's awesome. That's awesome.

Natural. So we were talking. We got way off the sidetrack. So you were in Africa, which is the most realistic environment. I mean, if you want to really know what nature is all about, you were in the most realistic environment. It's all tooth, fang, and claw. It's like whatever survives, survives. And whatever doesn't becomes food and

there's just this constant cycle going on and you're walking around yeah now when you walk were you walking when you saw the crocodile eat the wildebeest no you're in the jeep i was in the jeep for that how does a jeep thing work why don't they just jump in the jeep i don't understand that uh good question and i asked myself that as they were walking by same with the gorillas they've been habituated to humans they they literally don't even see the jeep well the gorillas don't they're you know they're not aggressive unless they think you're a threat they don't eat meat they're just eating plants all day yeah they're still pretty dangerous one swipe from a gorilla oh my god gray God. Grayback. Silverback.

Yeah, it's interesting. The jeeps have been around for so long, they just go under the jeep. They go under? Yeah, yeah. It's as though the jeeps aren't there. You might have six jeeps looking. We saw some lions rip apart an impala right in front of us. And they're just going about their daily lives.

Did you see it catch it? Just missed that. We saw them running away. Oh, God. If I saw them running in real life, I'd shit my pants. Well, they were running towards our camp, so we were running the other way. I heard a horrible story about these people that were on safari camp and this person went to use the bathroom in the middle of the night. Apparently, there's cabins and you have to leave the cabin to go to the bathroom and the cats went in the bathroom and got them

and dragged them out you're kidding no that's the worst way to go yeah it's the hyenas you gotta watch out for because they'll actually eat you alive oh fuck yeah the locals don't like the hyenas they don't have respect any animal that eats another animal while it's still screaming oh yeah they don't give a fuck they don't try to kill you they They don't have respect. Any animal that eats another animal while it's still screaming. Oh, yeah. They don't give a fuck. They don't try to kill you. They just eat. Yeah, that wildebeest had a broken leg.

It got away from the croc. But it's bushmeat at that point. Yeah. But there were people in the Jeep, some other Americans, cheering. It was like a sport for them. Oh, no. I didn't appreciate that. Fucking Americans.

It was a solemn moment. This animal's going to die. And they're like, woo-hoo. Ew. And they were chasing it. Guys must be men, right? It was mixed. If it was girls, I'd be super concerned.

I think it was a few, but... If girls were cheering. Yeah, fuck him. Might have been. Oof. I think it was the guys cheering, but they were chasing this poor animal. Its hoof had been broken off, and it was running on a broken leg, and they were chasing it. The people were?

The Jeep and the people in the back of the Jeep. Yeah, my kids were with me. They were screaming and crying. It was emotional. I don't want to see that. Yeah. Yeah, I've never seen anything take anything out in the real world. It's shocking.

You know, you can see it on BBC or whatever as much as you want, but when you see it live. My friend Johnny Hamilton, he works at a ranch in Colorado. Shout out to Johnny. He was following the trail of this gigantic elk. They'd seen all these footsteps, and then they'd seen mountain lion footsteps, and then there was no more mountain lion footsteps. And then they followed it about 100 yards or so,

and they found the cat on top of the elk. It had jumped on the elk's back and killed the elk. It was a 150-pound cat, a 900-pound elk, a big bull, and it just leaped up on its back and just got a hold of its neck and dragged it to the ground. But it rode it for like 100 yards. Yeah, the croc did this too to the wildebeest. So elephants are interesting.

We saw a lot of those. And what we learned was that the old elephants, because they've run out of their teeth, their teeth wear down. And at some point, they just can't chew anymore. So they have to find really soft stuff. Eventually, they die. And that gives rise to this legend that there's this graveyard for elephants. It's not a graveyard, it's just where the soft food is. But I was thinking if elephants had technology they could easily solve aging. They just get dentures. Yeah, why can't we just trank them

and give them some implants? They do it with people, right? I think in the zoo they might do something like that. Do they? They do it with dogs. My teeth rebuilt. They were wearing out. Yeah. I've seen that before with people. It's cool. It made sense.

They fixed my daughter's teeth. But I said to the dentist, I know we're changing topic here, but it's funny. I said to the dentist, can you fix my teeth? You just did my daughter. They went, oh, no, you're almost 50. We don't fix teeth at 50. Excuse me? Do it.

Because they feel like you're on your way out exactly yeah someone said that to me in terms of uh meniscus i had a meniscus tear and they said well when you're younger you have more blood flow to your meniscus and we would just surgically repair it and hope it would fix or perhaps uh today use stem cells but most likely because of your age, it's not going to heal correctly. And I'm like, okay, I'm confused. Because you're talking about blood flow? Like blood flow. Like what is happening that's different? I think this is like some old medicine nonsense.

Like is blood not flowing? I mean – Well, it's flowing and someone with your fitness is flowing probably as much as a 30-year-old anyway. I'm in better shape than I was when I was 30. I do more shit. I do more running. I'm like, I've got a lot of blood flowing around, man. I think they compare you to sedentary people.

For sure they do. That's the problem with most medicine is that it's tailored to the average person. Yeah. We've got to fix that. It's got to be personalized, tailored, measured. Yeah. We got to fix that. It's got to be personalized, tailored, measured.

I think if I wanted to go on safari like that, like you did, I would have to make sure that I wasn't around any cheering assholes like that. I would have to take some sort of a solo trip, and I'd have to be heavily armed. Right. And then wearing armor, some sort of armor. Well, so that was in Tanzania. And a flamethrower. Yeah.

I bring the Elon Musk flamethrower with me right right fuck those things man did you ever see survivor man do you know survivor man sure yeah less is a great guy but uh he's committed to finding bigfoot now that's all he's doing these days all right yeah but um anyway less uh did an episode where he did survivor man in africa and he the scenario he would create these fake scenarios, you know, just man-made scenarios. Like, what if you were in a hot air balloon, and the hot air balloon got a hole in it

and crash-landed in these lion-infested territories? So he literally did that. That's insane. In the basket. So he had a few items in the basket and the the flamethrower for the for the hot air balloon with him to ward off the fucking lions so here he is it's nighttime in africa and by the way he self-films everything you know the reason why they came out with that other show with that. Who's that other dude? The other dude that got busted sleeping in the Holiday Inn.

He got. Grills? Yeah, Bear Grills. He was going to the Four Seasons at night. He's like, this is how you could do it. But I'm not going to do it. He would show you how to do it. You could sleep in an igloo.

But meanwhile, he was getting room service and eating steaks and shit. Yeah, that's what I did. But Les Stroud really does it. I mean, he brings a series of cameras. So this is him. And Les went and he pretends the thing crash landed. So this is his scenario that he's created for himself. But the reality is he really is surrounded by lions.

And so he has a limited amount of propane. And he would fire up. Look, look, look, look. He would fire up that thing Which is what you use To get in the hot air balloon And scare the shit out of lions So through the night

He would hear He would hear that Look at the fucking zebras and shit So he'd hear it in the middle of the night And he'd have to Fire that thing up To scare everybody the fuck away And then after an hour or so

He'd be like oh fuck time to fire it up again and so he was out there sleeping in this basket trying yeah so crazy he's so crazy and he would also do these things where he would have virtually no food for seven eight days you know and just really just get super super skinny and almost starve to death that's the opposite of being in a jeep he's got like a bottle water i got a pocket knife i got some rope like this is how you do it i got a stick what is that some sort of a machete type thing fucking crazy yeah we we went up in a balloon uh which was beautiful by the way it's fun isn't it i did that in italy. Really wild. Yeah. Anyone who's afraid of heights, don't worry.

It's beautiful. But we had a truck underneath us with people with guns, just in case that happened. Oh, that's good. Yeah. So they're following you. You've got to take along people. There's a whole industry in keeping people alive

that want to do stupid shit. Yeah. Right. You can imagine, oh, sorry, the Serengeti burnt down. Yeah, it was some guy in a balloon. How many days did you go there for? We traveled for 16 days. I took my whole family, my brother, his kids. How old are the kids?

Two nephews, and my kids are 16, 14, 12. Perfect age for this. And they don't recommend you being under a certain age if you're going to take malaria medication, right? They all did. Oops. Really? I think 12 might be okay. But I think it's like under 10 or something like that. The stuff is heavy duty.

Did it fuck with you? Did you have crazy nightmares? I took the one that doesn't give you nightmares. But my other siblings had that. My father came. So he's 80. And that was actually the reason we went, his 80th birthday present.

Oh, wow. That's cool. What a cool present. 16 days. It was awesome. We went Kenya, Tanzania, Uganda. What did you like best? Tanzania is supposed to be gorgeous.

Yeah, Serengeti was incredible. It was all good. I really liked hanging out with human beings too. They're interesting species. Oh, for sure. Yeah, I enjoy humans. Yeah. So it was the origins journey, I called it. And so we went to, we started in Olduvai Gorge, which is where humans, the original fossils were found going back a few million years.

Wow. And started there and then just went through looking at the various animals we saw, the gorillas. And we ended up a few days ago, I was in Jerusalem looking at where we come. Oh, wow. A real origins tour. Yeah. Up the crack of Africa. That's exciting.

Wow. That is so cool. So what was the most unusual thing? Besides Jerusalem? Was that the most unusual thing? That's the most unusual thing that's the most insane thing where all the religions are on top of each other touching rocks and blessing the spring and humans are crazy they'll worship anything well i'm sure you've seen i was in germany once and uh there for ufc and i was flipping through the channels of the television and there was uh this live feed from mecca and uh this was pre-instagram i was not on instagram i definitely would have

because i watched it for hours i just sat there in my room drinking a cocktail with my feet up watching this these people circle around this what is that uh square shaped thing in the center of Mecca yeah if you have a religious object that I believe I think says something to do with an asteroid like there's a piece of some find out that makes sense this is important to people but the the watching people circle they're all wearing the religious garb this Islamic garb that they have to wear, they're all wearing the religious garb, this Islamic garb that they have to wear, and they're all circling around this thing for hours and hours and hours. It's oddly appealing. Part of you wants to go, I recognize that there's got to be a very strong sense of unity and community in everybody agreeing that we are all going to treat this,

this is a sacred object, this is a sacred place, we're going to wear sacred clothes, we're all going to follow this path and we're all going to be together in this. Like this super reinforced sense of community that's actually ordained by God himself. Well, we all need that feeling. reinforced sense of community that's actually ordained by God himself. Well, we all need that feeling. For me, it's science and the fossils that I and my colleagues believe were the origins. Everyone needs an origin story. Here it is.

How would you say that? Kabah? Kabah? It's built around a sacred black stone, a meteorite that the Muslims believe was placed by Abraham and Ishmael in the corner of the Kaaba, a symbol of God's covenant with Abraham and Ishmael, and by extension with the Muslim community itself. Okay. Yeah.

So it is actually a meteorite, which how incredible, right? Like a little bit of science and a little bit of religion all wrapped up together. There's a discovery. So this is what it looks like. So you're watching this. right like a little bit of science and a little bit of religion all wrapped up together there's a discovery so this this is what it looks like so you're watching this um the channel that i was watching in germany again this is probably like more than 10 years ago 12 years ago perhaps and watching this circle around this like religious spot very very captiv very, very captivating. Yeah. The one that I remember most from, I think it was Jerusalem. Yeah. Was people touching the stone where the crucifix was thought to be. And they would wind up for hours to just touch it for a few seconds. Meanwhile, the origin of humans, the fossils, there's maybe two or three people

hanging out. No one really cares. Admittedly, it is out of the way. It's not in the middle of the Middle East. But still, it struck me that humans are more focused on these icons of religion rather than where I believe we really came from. Africa. I mean, if you look at it and you see it, you touch it, you feel it, it's the only sensible explanation. I mean, you can still have religion. That's fine. But don't tell me those fossils were put there by somebody. explanation. I mean, you can still have religion. That's fine. But don't tell me those fossils were put there by somebody. No. I mean, obviously not.

But it is that the idea that a human being came from some lower hominid, which came originally from a shrew, is so, so hard to follow. Like if you go all the way back to 65 million years ago to the asteroid hitting the Yucatan and you're like, wait, what happened? Like, yeah, yeah, yeah. Big rock smashed, killed everything except like these little rodent things and they just eventually evolved. Yeah, but that's what I love about science. It's amazing. It's not only amazing. It's actually true.

Yeah. We can prove it. Yeah. I mean, you could really follow the fossil record. That's one of the funny things when people go, oh, what about the missing link? There's holes in the fossil record. Well, there's holes in your education. It's not holes.

I mean, they go out to Australopithecus, explain Australopithecus, explain the various other human beings, explain Homo floriensis, explain the Neanderthal, explain all these different. There's a whole slew of different fucking things that were human. Like, what was that? God's experiments? Was God fucking around? Yeah. I was like, let's try to make them super short and wide and thick and heavy. Like a 5'7", 200-pound person that's way stronger than a person said ah those

are no good listen let's get a taller skinnier one but with bigger brains aha right and let's have them breathe that's what we did let's bang them yeah everybody bang i don't know if it was marriage or rape but something happened i think most rape mostly most breeding was rape until about like 500 years ago i agree with you do you know that to this day, there's a country, is it Kurdistan? What is the, there's a country that 20% of all marriages begin in kidnapping. No way. So there's a shame to the female being kidnapped. She ultimately has to marry her captor.

Find out if that's, is it Kyrgyzstan? Kyrgyzstan? I'm not saying it. Yeah, how do you say that? Kyrgyzstan. Kyrgyzstan. I think it's Kyrgyzstan. Okay.

Silency. Yeah. One in five girls and women kidnapped for marriage in Kyrgyzstan. How fucking crazy. This is 2019. Religion. Right. Shame.

But the fact that you could kidnap someone rape them and then they get shamed into marrying you well i i was shocked in jerusalem i'm going to probably have a lot of hate mail for saying this but it's a fact that uh when you go to the wailing wall as i did and put little note in the wall um which was a great experience by the way there there is a space for men and women. They're separated. But the space for men is four or five times bigger than the one for women. Good. No, sorry.

I couldn't help myself. Yeah, it's all this disparity. Anyway, so. So are there a similar amount of women that are going to this wall and they're just jammed into a smaller area? Yeah. Still. 2019.

Is this ordained? Is this some sort of a religious yeah the orthodox apparently behind that i checked it out so there's there's an actual scripture that says men are supposed to have this oh gosh i doubt that yeah so it's just ancient sexism well yeah and even the wall is just tradition yeah right uh but anyway the history of humankind is interesting and I did that because... Oh, that's the wall right there. What's all the black spots?

That's like grass. That's like plant material, I think. Is it? Yeah. Yeah, yeah. They're plants growing out of the wall. Oh, it is. Okay, they're not black.

We're just looking at low resolution. That's the women's side. That's the men's side. Do you remember the scene in... What is the world war z when all the zombies climb up the wall they pile on top of each other like uh did you see world war z no fucking great movie i gotta say it is there's a crazy scene it's a brad pitt zombie movie where all the all the zombies pile up on top of each other and make it to the top of the

wall you got it yeah james gonna pull it up so make it to the top of the wall. You got it? Yeah, Jamie's going to pull it up. So they get to the wall. And look at these fucking zombie people are climbing up. Yeah. Oh, it's pretty gnarly, man. You've never seen this movie? I've wanted to. The novels are supposed to be excellent. Weren't the novels written by some famous guy's son?

Maybe. Who wrote the novel? But this is a great scene. See, they're all piling on top of each other, and they're just reckless. They have no concern for their health or well-being because they're dead. So they're just making this human thing, and then the soldiers are shooting into the pile, trying to knock them down but they get over the top of the wall and they start infecting people it's a pretty wild ass

movie yeah who wrote that movie it's a wild movie man this is it's one of those um zombie movies where the zombies move fast the slow zombie movies movies, which, come on, man. Like, that's why Walking Dead, like, I feel like you could fuck those things up. I mean, they can only last so long. They don't move fast. Like, how are they surviving? They're just kind of, like,

shuffling towards you. I feel like if you just have a big sword, you can just start hacking away. Yeah. So there are zombie cells in the body. And I make that segue

because people are going to say, why the hell aren't we talking about aging? Oh we will Okay We're here forever Max Brooks the son of Mel Brooks Aha There you go

Shout out to Max Brooks And Mel Brooks Sorry Aging Well we don't have to Zombie cells Yeah So what are they?

Are we done talking about Africa? And your trip? It's your show Because it's pretty exciting Yeah but it's your show too Thank you Africa and your trip? It's your show. Because it's pretty exciting. Yeah, but it's your show too. Thank you. When you're on it, it's your episode. Anything else?

I recommend everybody go to Africa, not just to come back a different person, a better human being, but also to support them. They really need our help over there. When you were in the area where the oldest human-like fossils were found. What's the feeling like when you're in this area? You really are where the origins of humankind are from. I mean, that has got to be a pretty profound feeling. Yeah, it was spiritual. Unfortunately, the people who drove us there were saying,

hurry, hurry, we have to go see some zebras. This is more important than the zebras. These are the people that are the guides? Yeah. They don't know what was important to us, fair enough. But I would have loved to have spent a whole day there. Apparently, there are still fossils sticking out of the walls of the gorge. Really?

Yeah. So the reason that it's a big – Are you allowed to do anything with them? I don't know. What happens if you find a fossil? Do you have to contact the university or do you just like shut the fuck up? Well, actually, I probably shouldn't confess this on live media. Don't do it, bro.

Tell me later. It's not so bad. Okay. You can actually find a whole bunch of stuff in Africa that's interesting if you look down rather than out. And my oldest daughter, our oldest daughter, Alex, she looked down. She's a scientist. And so she, 16-year-old scientist,

she found a whole bunch of stone tools. Whoa. Not there. Not in Alderweireld Gorge that sacred. But, you know, just out on the Serengeti or wherever. Did you get them analyzed? Not yet. They recently found stone tools in the united states that they've brought back to

16 000 years ago the oldest known stone tools of any human being and it's sort of they're they're slowly but surely pushing back the dates of human civilization in america and one of the more recent discoveries was stone tools that are from 16 000 years ago so people had made their way over here or here it is i remember i asked you about this you said you never saw it i don't know if you saw it yet they said it there's i don't know if they have video of it but they said they saw this monkey sharpening that stone before it was actually breaking the glass with it monkey shattered glass with sharpened stone impressive prison break attempt man fuck keeping monkeys in a cage that drives me so crazy i i hate it i went i took a pot edible once like a real strong one and i went to the zoo and it was so depressing staring at the

chimps i just sat across and watched the chimp cage. I'm like, oh, my God, these things are in hell. They're just in prison. Even keeping little birds in little cages like this. But the monkeys are wailing. That's worse. They're wailing. They had some type of monkey that was in a smaller cage than the chimps.

It was just wailing. It was just in hell. Yeah, it is. It's brutal. Actually, the stone tools are interesting because, again, getting to what's natural. What's natural for primates is to change their environment, to take tools. Yes. So what we're doing, genetic…

Engineering. Well, I don't want to say engineering, but we're using genetics to understand why we age and why we don't have to. It is natural. Of course. That's what we don't have to it is natural of course that's what we do all of even all of science is natural you could even argue that an iphone in your pocket is natural sure humans have created it they exist all over the world right i've argued that cities are natural it's a completely normal thing for humans to do to create cities to say that cities are unnatural well why Well, why are they everywhere? And why are human beings making them? Are you saying beehives are unnatural too? Right.

Are clothes unnatural? Well, animal habitat. I mean, animals, like beavers create beaver dens, and they're very uniform. They're real similar everywhere they go. Exactly. Yeah, the other day someone said, humans tamed fire 500,000 years ago,

and I said, that can't be true. 500,000 years ago? That's know too long ago i checked it out it's true and these weren't even humans these were pre-human i think it was probably one of the two species back we've been doing this we've been changing the environment using tools using fire for that long the fire one is crazy right because it's not just manipulating a physical thing it's changing the state right you're you're doing something whether it's with flint and and you know some something to spark and some tinder you're really creating changing the state of matter well we are and we'll continue to do that we'll continue to evolve and one of the the reasons that i wanted to see human origins is uh in my book I talk about we've evolved to our natural lifespan. We're now at a maximum.

122 is the longest lived human that ostensibly is on record. So without intervention, we've reached our maximum. But why not now give us what evolution failed to give us? Why can't we be like other species that are at the top of their game? Are there any factors when you look at the oldest people that are alive? Are there any common factors? Actually, not really. They do seem to have a collection of gene variants that predispose them to get to that long.

There's one called FOXO3 that if you've done your genome, we can have a look. 23andMe. Have you done it? I have. We should look at it. I will check. We can tell. You need an A or a T at a certain position. I've got one of them out of two. My kids got two of my kids out of

three have both. So if they look after themselves, might have a better chance of living longer. But anyway, these long-lived people, they tend to live a long time no matter what they do. They tend to live a long time no matter what they do. Often they smoke until 90 years old. Really? Yeah. They quit at 90? There's a few cases of that.

And they live another 12 years? Right. Or more, 22 years, right? You said 122 years old? That lady. That's one lady in France. But one of my friends, his name is Nero Barzlai. He was with me in Israel. He's got a story of when he asked the centenarian lady, the lady that lived over 100, that he knew, why didn't you quit smoking?

And she said, all four doctors I went to told me to quit smoking, and they've all died. So I'll keep going. That's hilarious. What did she do for a living? Jean Calment. I forget. The French lady, I don't remember what she did. I would imagine that would play a part, like how stressful your occupation is.

Yeah. She had a great sense of humor. That was probably part of it. She used to make jokes with the reporters all the time. One was, how many wrinkles do you have? She says, I've only got one and I'm sitting on it. The other one I think is even better is a reporter who was young said, you know, you're 116. I hope I see you next year for your birthday. She says, I don't see why not.

You seem pretty healthy to me. Wow. And she made it to 122. Now, have there been any anecdotal reports of people that lived longer? Well, Methuselah and biblical figures. Yeah, but not biblical, like not unsubstantiated reports. Because I had heard of, you know, there's some people that claim to have lived like ridiculously long, but they've never really figured out whether or not it's accurate. Sure, there's a few of those. They've never really figured out whether or not it's accurate. Sure. There's a few of those. But even John Coleman at 122, there's a big argument now between us researchers whether that's even true.

Oh, really? Yeah. It's a massive debate. I've got an inbox full of long, angry emails from scientists. What's the evidence point to the contrary? So the hypothesis is that her identity was subsumed by her daughter to avoid paying taxes. Oh. And there's photos of them and there's a blotch on one photo that matches the daughter.

So there's a lot of forensics going on and people want to subsume the grave. And the French government's not – or French researchers aren't giving up the blood samples. They don't want to know. They don't want to know. They don't want to know. Exactly. So it's probably horseshit. She's probably like 100 years old. It could be horseshit.

I would say it doesn't actually matter. Goddamn French. It doesn't matter. People have lived to 117, and that's still pretty good. That's what we – if we can all live that long, who's going to complain? Wouldn't you like to get one of them old, old, old, old, old people and start doing work on them? Yeah. Just pump them up with NAD, get them on a drip.

Well, my dad's experimenting on himself. So he's not 100 yet, but he's 80. How's he look? Well, I wouldn't say he looks young, but his fitness is like a 30-year-old. Really? He's stronger than me. We tested it out in the gym the other day. No way.

That's embarrassing. He can lift more. He's fitter. We were going across the Serengeti, and he was leading the charge. If you saw him, if you didn't see his face because he's got gray hair and whatever, physically, he put a bag on his head. You'd say he's 30 the way he moves. People are very wary to put a bag on your dad's head. Yeah.

I shouldn't do that. Sorry, Dad. You would think he's 30, really. Well, he's reinvigorated in life. So in my family, we've got some Ashkenazi bad genes. We tend to die young. And my grandmother died. My grandmother is actually only 15 years older than my dad, and she died a few years ago.

Last 10 years of her life, horrible. So we know what's going to happen in my family, probably, to all of us. So your grandmother had your father when she was 15 years old? Right. Whoa. Yeah. Back in the early days of World War II, she apparently was playing around with her boyfriend. She claims to be a virgin at that point.

Whoops. But something got somewhere that shouldn't have. She got pregnant. During high school. Right. So I was raised by my grandmother. She was in her forties when I was a kid. And she was the one that taught me to always stay young, keep your, you know, adults ruin everything. That's probably why I work on

aging. Adults ruin everything. What was her advice? Like in terms of like, why, how do you avoid what adults are doing wrong? you know she'd she'd uh grown up uh during the depression and then world war ii and then the communists came into hungary and raped a lot of people uh she had no uh um she had had no respect for humanity so by the time i came along first of all she put all of her energy into me, and I was a spot bright as a kid. So that wasn't helpful to me, I think, now as an adult. But more importantly, she wanted me to do the best I could with my life. She said, David, do what you can to make this world a better place.

Make sure that you leave this place better than you found it. And that's what I'm trying to do. Wow. What a profound piece of advice for a grandchild. She was a rebel. She taught me, forget the rules, right? Kind of like you do. I'm going my own way and we'll see how this goes. So she went to Australia. She said, fuck Europe. I'm out of here. She went to Australia, the furthest place she could find from Europe, never went back. She went on Bondi Beach in Sydney in a bikini, which was rebellious. She got taken off the beach by the police. What did you have to wear back then? The full little British thing. Down to your knees?

Down to your knees? I think so. What did they look like? Maybe it was a one piece. You wanted to show your belly. That's what I think so. What did they look like? Maybe it was a one-piece, but it certainly wasn't a bikini. You wanted to show your belly. That's what I think. But she was a rebel. She went to New Guinea by herself in the 60s. What year was this where she was wearing a bikini? Oh, that would be 56. You couldn't wear a bikini in the 50s?

Wow. Okay, like those pin-up girls, right? When you see them, they always had one-piece suits on. Yeah. those pinup girls right when you see them they always had one-piece suits on like yeah so imagine new guinea in the 60s as a woman on her own up in the highlands she claims to have eaten human flesh and i'm sure she spent most of the time drunk as well did you see that article that was yesterday where they were interviewing an australian uh a guy who's a doctor or a scientist who was talking about climate change. And he was saying that we have to start eating human bodies

and that human bodies are very nutritious and that we just put them in the ground. And I was reading it and I was like, okay, is this guy trolling? Like what is he doing here? Is he a completely insane person? But his advice was our dependence on meat is ruining – like in some places where they're stripping the rainforest to make room for cattle grazing. He was saying that we are getting rid of perfectly good meat every time we put someone in the ground. Well, we are. But to suggest that, it sounds insane to me. Yeah.

Because we throw away half our food anyway, at least in this country. It was a mainstream publication that this guy was talking about. It's like, the last thing you want to encourage is people getting used to eating people. I think he's been watching World War Z. Maybe. Maybe. Yeah. I mean, it's just one of those things.

It is meat, but come on. I was going, is this guy just trying to get attention like this seems like such a or is it did he was he joking and it's hard to tell in text you know yeah well yeah did you see that not every australian is sensible i found the article but i don't see anything about him saying wasting human bodies or meat it's been a more than several articles written on it. Maybe somebody extrapolated. But the idea was he was saying that people should eat meat,

and if they want to eat meat, they should eat human meat because it's going to waste. Well, maybe he's an animal rights activist. Might be just an idiot. Eat your relatives, yeah. Yeah, but just the last thing you want is people getting the taste of people, you know? Right. No, I do not need to go that far. Not yet.

Speaking of the food supply, one of the things people worry about if we all live longer is we're going to run out of food and run out of space. Yeah. And one of the things I address in the book is what really will happen if you do the calculations. If you look at human history, that is not going to happen. I'm of the strong belief that we can engineer our way out of just about any problem. Probably the only thing we can't engineer our way out of is if we get hit by a five-mile-wide meteorite. But everything else, I think, we're going to be –

You think climate change, we're going to be able to engineer our way out of that? Well, I don't think we can stop climate change at this point. It's definitely happening. You can see it all around. But will it wipe us out? No. Will it cost us trillions of dollars? Yeah. And so I don't think it's going to be the end of us, but it's going to be a challenge to continue to survive and proliferate as a species in the face of all of those costly things. And that's the biggest problem of climate change, besides species losses, the expense.

And there's only a certain amount of human capital that we have to spend, and we call that money. And that's one of the reasons that I'm excited about extending people's health and lifespan, is that that'll save tens of trillions in the globe each year. And that's money that can be put to combating global warming, saving species, besides wonderful people who donate their earnings as well. But really, to solve the big problems on the planet,

one of them is to solve what are we going to do with all the frail elderly people that are coming every year more and more. Make them productive, like my father. He could be in a nursing home like his mother was, whereas now he's hiking in the jungles looking at watching gorillas with his five grandkids. How cool is that? That's pretty cool. Now, what kind of protocol is he on? Pretty much the same as me, although he does more exercise. So it's a combination of NMN, metformin, and resveratrolrol And what kind of exercise?

I'm not sure of his protocol We're going to post that on social media Once we get that written But I know it involves a fair amount of aerobic exercise He does rowing and walking upstairs So he managed to climb I think it was 40 flights of stairs in 15 minutes, which for an 80-year-old was quite a record. 40 flights of stairs in 15 minutes. Holy shit.

Yeah, the guy's a phenomenon. What has happened, though, is that his outlook on life has changed. He was depressed, not just because he was fearful of getting old and my mother was sick at the time, but now he's looking forward to another 10 years of vigorous life, traveling. And when you're healthy, you're happy. So when he was depressed, was he sedentary? No. No, he was depressed because he was worried about his health. He figured he's going to be like all his other friends, getting frail, can't walk, losing your mind. And it hasn't happened to him.

So just a few years ago, he went back and started a new career. Whoa. Oh, we talked about this last time, I believe. What's his new career again? He's on a committee that evaluates clinical trials for ethics. Wow. Which is what you want older people to do, use their wisdom and knowledge to-

Be excited about something as well. Right. Something that stimulates you and keeps you going and gives you something to be interested in. And talk about wasting human flesh. What a waste it is for someone with that knowledge to die prematurely. Right. That's the more interesting thing to me about longevity is, look, I'm so much wiser at 52 than i was at 42 i just am i make less

mistakes i'm more aware just across the board and i'm wiser at 42 than i was at 32 and at 22 i was basically a chimp so it's like as time goes on you understand how you're interfacing with the world you you communicate with people better you know how to get by you know what you have to do and what the consequences are of not doing what you have to do in terms of being disciplined and being healthy and just meditation and making sure you you understand the consequences also of not doing the work that you're supposed to do in terms of the way you feel about yourself, your self-respect, and the way you just feel about your sense of self-satisfaction.

To me, it takes a big hit when I'm lazy. It takes a big hit when I don't get things done. And I don't expect everybody to do the same things that I do or have the same sort of work ethic or none, I don't even say work ethics that implies like some sort of superiority. It's more of just the idea of what you want to accomplish, like your tasks. Everyone has their own idea of what, but if you enjoy doing something and you're working towards something, I feel like there's more purpose to life. You have more satisfaction in accomplishing tasks. And that's one of the things that's been highlighted when you read books on happiness and studies on happiness.

One of the things that seems to be most important is goal setting. Goal setting, working towards those goals, and achieving progress. These are critical components to happiness for human beings. And without them, there's this aimless sort of drifting of life. People, for the most part, obviously everyone's different, but for the most part, people don't find satisfaction in just an aimless sort of drifting existence. Yeah, 100%. I just turned 50 while I was over in Africa, or just before that. Imagine being 80 and healthy, like my dad, or 90 or 100. It just keeps getting better. Of course, of course. I'm so less stressed than I was in my 20s and 30s.

And anyone who's listening who's in their 20s and thinks that they're way better than a 50-year-old, I can tell you from experience, like you, Joe, when I was in my 20s, I thought I knew everything, or at least I looked at myself as a 50-year-old, and I thought, what an old fart. Yes. Yeah. It's not like that at all, especially with today's health. 50-year-olds are just like they were, like a 30-year-old was 20 years ago. There was no 52-year-olds like me when I was 20. They didn't exist. Maybe Jack LaLanne.

Right. Well, it's been talked about, I think it was in The New Yorker, that this movie Cocoon, I don't know if everyone's seen it, but it's a pretty interesting movie where these 50, 60-year-olds were given the fountain of youth. And they still look old, but it was really supposed to be quite funny to see these older people with gray hair jumping in the pool and acting 30 years old. But a 50-year-old isn't old anymore. A 50-year-old is just getting going.

Yeah, that's what's crazy about it. I mean, if you see old movie stars from the 1960s, when they were like 50, they looked like they were dead men you know like we were we were we were looking at i forget what the movie was but it was a movie where i was like how old was he when they made that movie it turned out he was 44 i'm like that guy looks 100 years old looks like he's never worked out he probably smoked cigarettes all day long never exercises never drinks constantly this looks like a dead man it's crazy

right so so in the future 90 will 90 will feel like 50 and well we were talking about laird earlier and laird i think is 55 years old and just as fucking fit as a human being can be and he's doing crazy shit where he's he's got this whole exercise routine that he does inside the pool where he brings like 70-pound dumbbells and he carries it with one arm and swims across the pool and the other. He does two-handed dumbbell things at the bottom of the pool and leaps to the surface, catches a breath of air, drops back down to the bottom again, leaps to the surface while he's carrying these dumbbells. I mean just ruthless, rigorous exercise at 55 years old. Well, there'll be a time when you can't really tell how old somebody is, especially when we figure out how to reprogram the body to be young again. Yeah.

And it's going to be such a great world when people with 80 years of experience can continue to run companies and be teachers and educate the young people. Now, there's a bias, though, against the elderly. We've always had this in society. And we have to overcome that. My dentist was biased against me as a 50-year-old. Didn't want to fix your teeth. You're dead, bro. I'm not fixing your teeth. Not worth the money. Screw it. I'll pay for it. Just do it. So it was a 20- minute argument. Do it. Do it. 20 minutes. It was a lot. In fact, the time ran out and she said, fine, I'll do one tooth just to check. Because she had all these reasons why she shouldn't do it. It'll break off.

I have to polish back your original teeth. And I said, look, I'm not going to get angry if it doesn't work. Just try it. And she did it. And first of all, she said, I have to eat crow after it. And then my wife came a week later, and she said, man, your husband's a pain in the ass. But he's on to something. And actually, she's offering this as a service now to people our age.

Yeah, she's trying to make money. I guess. She's giving a fuck. But it hasn't cracked off, and I'm pretty happy with teeth that are – But if it does, fix it again. Right, why not? We fix everything, and we should do that. While you're alive, yeah.

But here's the problem with some aspects of medicine. When we're young, we don't get the medicines that will prevent us getting sick when we're old. Yeah. So drugs like metformin, you're not going to give to a 20, 30-year-old. But when you get old, you don't get the medicines that they give the young. But everyone should be treated equally, in my view, as long as we know it's safe. For sure. You know, there's the cost, but some of these treatments like metformin, that's probably less than a dollar a day, a cup of coffee,

and might extend your lifespan. Where are you getting a cup of coffee for a buck i get free coffee from here from laird hamilton superfood machine but coffee is even more expensive than that yeah it's um the the limited idea of what you should or shouldn't do to fix people as they get older my friend uh got his acl torn and he's 60 and he said his doctor recommended he just rehab it and don't get it fixed. I go, what the fuck are you talking about? Get it fixed, man. You want to have a bum knee that just buckles on you all the time? Go get it fixed.

Six months later, it'll be done. You'll go through the rehab. Otherwise, six months later, you still have a shitty knee. It's like, your call, man, but I'd just get it fixed. Bite the bullet. Go fix it. Right. But his doctor was like, come on, man, but I'd just get it fixed. Bite the bullet. Go fix it. But his doctor was like, come on, Bruce. Come on, Bruce.

Let's be honest. We're at the end of the movie. You're not 20 anymore. Yeah. That limited thinking is so frustrating to me. Yeah. I first encountered this when I was 29, actually. They were telling you at 29, it's a wrap?

Well, they were. No, actually, this is the problem with the other end of the spectrum, which is I was too young to get a medicine that could help me when I get older. Oh, wow. do you want to get on this drug? I know you've got high cholesterol, but you're only 29. Come on. And I said, look, why wait till I get the disease to treat it? Now people use statins more, but in those days- Aren't statins very controversial though? They are. They apparently have a huge health hit. Well, I haven't noticed and I have high cholesterol and I think it's worth it. But yeah, if there's nothing else wrong with you, you wouldn't take them.

But do you have arterial plaque? No, not yet. i'm perfectly clean right but shouldn't isn't but isn't there some there's there's doctors that are arguing that the idea of high cholesterol that high where it's ldl hdl whether it's good cholesterol bad cholesterol there's like this sort of uniform approach people with high cholesterol need to take something that lowers their cholesterol. And doctors that I've talked to are saying, well, not necessarily. You could be incredibly healthy, especially if you're not sedentary, with relatively high cholesterol if everything balances itself out, if you have the appropriate ratio of HDL to LDL.

Do you have the appropriate ratio or is it out of whack? Now I do. But when I was 29, I was off the charts. I had blood that looked more like cream. And that's where one of the things apparently where dietary cholesterol does make a hit. It does have an effect on people with genetic predisposition to high cholesterol in certain ways, right? Is that correct? Right.

Yeah. Right. But changing my diet had a big impact as well. What did you do that was different? I went more – well, I ate less. I lost weight. That helped. Do you do intermittent fasting?

Yeah, as much as I can. One of the other guys that was on this tour of Israel with me is Volta Longo, and he's arguably the world's expert on this. What a great name. Isn't it? He's an Italian guy. Volta Longo. Longo.

Yeah, like the coffee. Sounds like a guy you call in when you've got a real problem. Yeah. Well, he's written a book, and he is probably the world's expert in human periodic fasting. For everyone who wants to know about what the best periodic fasting protocol is, there isn't one. We don't know yet. We're right on the cusp. There haven't been enough studies, but there are a few types.

I go through them in my book because we won't have time to go through all of it. But there's the, what is it, the 18. 18 hours. Yeah. If you can skip breakfast, have a late lunch, that's a good start. That's what I try to do every day. It's not always possible, like when you're in Africa and they're feeding you massive meals three times a day. But that's what you want to do.

Be hungry for part of the day. Or you can go a little more extreme and skip two days a week. And what's the benefit of being hungry? Great question. And this is what my lab and others figured out in the first few years of the 21st century. We figured out that these genes that extend lifespan, these sirtuin genes, are activated by being hungry. these sirtuin genes are activated by being hungry in part by raising nad levels which you we nmn will mimic the effect of so being hungry actually raises your lifespan in some sort of way right so caloric restriction is what we used to talk about a lot uh if you restrict the calories

of a rat was actually discovered back in the early 20th century will make them live up to 30% longer, not in an old state, but it prevents them getting old. So the rats don't get cancer, heart disease, and all of these other good things. And that was the only thing that we knew up until about 20 years ago, even 10 probably. And so we used to think you had to be hungry all the time. And there still is a society called the Calorie Restriction Society. And they were hungry all the time. They ate very small meals, which is pretty tough. I tried that and gave up after a week. But this new paradigm is that you don't have to always be hungry, similar to you don't

always have to be on a treadmill. You can do it for a short time, make it intense, and then you can let your body recover and go back to a normal life for a little bit. And that's great news. That means that we can have our cake and eat it too, so to speak, as long as the cake doesn't have a lot of sugar in it. Now, when you are on this protocol of restricted eating plus metformin, when do you take what and when do you exercise and how do you balance it out? Like when do you know what to do what? I use my body as a guide.

You know, now that I'm 50, I have a pretty good, like, you know, how your body feels and reacts. I'm also measuring it, a ring that measures my pulse and my sleep. Is that the aura? Yeah. Yeah. How do you spell that? O-U-R-A. O-U-R-A.

O-U-R-A. Yep. Is that, isn't Kevin Rose a part of that company? Is that, is he? Is that it? Yeah.

Jamie says yeah. Okay. From Dig, you know, dig.com. You don't know Dig? No, I'm high school.

How dare you? Sorry. It's a good place to go find cool shit. Okay, I'll go. Dig.com. Shout out to Dig. Yeah,

I go there every day because real interesting stories on the internet. You're always finding cool, weird videos and just fascinating science stories, human nature, human interest stories. Sounds good. I have a watch. What kind of watch are you using? The Apple Watch. Okay. How does that measure?

By the way, they just released Apple Watch 5 today. Apparently it's better. You might want to get it. What does it do? What does the Apple Watch do? Yeah. How's it? Well, it changes songs in my headphones. It tells the time occasionally. But yeah, what's useful with it is pulse and activity And if I haven't moved enough during the day I've got a standing desk And that's been helpful to make me move around a little bit more But mainly it's And I also do occasional blood tests To make sure that my body's optimized as best I can

Personalized And using all those measures You read the data off your watch? Like how do you read it? What application are you using? Nothing special. Just on my phone, have a look. Okay.

So you just have a look, like, what your resting heart rate is, how much activity, how far you're walking, how many calories you're burning, that kind of deal? Yeah. Yeah, pretty simple. And I'm happy to say my resting heart rate's really low, which means things are going okay so far for me, even though I don't do enough exercise, as you rightly point out. I think my resting heart rate's 46. That's very good. It's pretty amazing for a guy that barely does exercise. Yeah, you must have good genetics. Well, obviously, you do. Your dad's in phenomenal shape at 80. No, we have terrible genetics. Well, how's he in such great shape at 80?

Well, we don't know. But it could be that he's been exercising and he's also been on this paradigm. So one of the effects in mice at least of NMN, which is what we're taking, is improved blood flow. You get the benefits of exercise without having to exercise if you're a mouse. And those mice, they were running on a treadmill for 50% further because the blood flow and the lactate was reduced. Really? So maybe that's happening. That's incredible.

Now, what is the difference between the effects of NMN and IV NAD, which is very popular? There's people that take IV NAD, and I've never done it, but we've talked about doing it many times and having it brought in here and sometimes people do it and they do it very quickly when you do it it only takes 10 minutes but it hurts like hell apparently it gives you like stomach knots and you feel terrible right alright have you done it I haven't admitted

publicly that I've done it do it but I but I try everything once pull up that microphone I try everything once yeah and so that microphone. I try everything once. Yeah. And so last time I was out here in L.A., I gave it a shot, so to speak. Yeah? How was it?

It was fine. It was fine. Now, let's get to the science in a minute. But what I found was it was a shot in the butt with some NAD. So why didn't they do it intravenously? I thought that was the move. They did it intramuscularly? Right. Right.

This doctor is experimenting. Oh, Jesus. Yeah. It was a friend of a friend, so I had a... He's like, I got an idea. Come here. Yeah. Come here, David.

But here's the thing. It felt... I had tingles in my legs. I felt a little different for a few minutes, maybe 10 minutes, and then it went away. But the science, we don't know yet. We're still trying to figure out if that actually works or not. So instead, I'm taking the molecule that we've studied in my lab, which is taken as a pill.

Now, there are a lot of people that swear by the IV version of NAD. And when they do it intravenously, apparently you feel phenomenal. And there's quite a few people I know. My friend Kyle Kingsbury's done it several times. And he's very big on the latest and the greatest of health crazes. Well, I know it's being used widely,

especially down in Florida, to treat addiction. NAD. Interesting. IV. And I get emails all the time, which is best. But, you know, I'm a scientist. I'm at Harvard Medical School, so I have to always be based on facts. And the fact is we don't know if it works yet.

Right. Anecdotes are anecdotes. My father's story is not a clinical trial, right? We need to do more. But what's interesting about this field is that because people have access to information through podcasts like yours and through the internet now that papers – you can go to what's called PubMed Central and find papers. People are educating themselves just like scientists used to, and they can go to the doctor or go to the internet and try experiments on themselves. Now, I don't condone that.

I can't. I'm a researcher, not a doctor. But I find it really interesting that we're in a new phase of society where people can learn more in many cases than their doctors actually know. Sure. In particular, when it comes to nutrition, because that's one of the things that I've found it's shocking when you talk to some doctors and you talk to them about nutrition, particularly supplementation, and they'll say things like, like well you can get everything from a good diet like can you really can you really like how much time did you spend in school motherfucker

like how much time did you study nutrition this is nonsense talk you can get everything from a good diet what's a good diet tell me what a good diet is what are you getting from that good diet how are you getting that vitamin b12 in high doses what do you get where are you getting your c where are you getting your d3 what are you getting huh What are you getting from that good diet? How are you getting that vitamin B12 in high doses? Where are you getting your C? Where are you getting your D3? What are you getting? Where are you getting your essential fatty acids? What's the optimal level of essential fatty acids? And they don't have a fucking clue what they're talking about.

There's so many doctors that go through their entire medical, orthopedic surgeons or what have you. They go through their entire medical school with like maybe four or five hours of nutrition research. Right. I have to be careful what I say. I work at the medical school, but I do. I love doctors. Don't get me wrong. Right. We need them. We're not going to do surgery on ourselves. Right. That said, some doctors will listen to their patients and do research. Those are the great doctors that actually stay on top of things, But it's really hard, right? They're already working 12, 14 hours a day. So let's be fair to doctors.

Plus they have to work within the insurance system. I understand that. The only problem that I have is when they say things like, you get everything you need with a good diet. You remember our three square meals a day. That's bullshit too. Make sure you follow the food pyramid

and eat a lot of grain. Right, right. Remember that? Well, and don't eat eggs. Don't drink milk. Hilarious. eat margarine yeah hilarious well milk is a sketchy thing yeah quite honestly because you're drinking this dead liquid it's been homogenized and pasteurized and i i find my body reacts very differently to raw milk than it does to milk that has been processed well i wonder if anyone studied the microbiome, that might be helpful too.

It just makes sense that it's got all the enzymes in it. That's how the human being or a body, any animal, is supposed to naturally process that milk. Yeah, I guess it's mostly sterile. Yeah. But yeah, I use whole milk in my day. It's surprising, right, because I'm trying to avoid calories. But yeah, I use whole milk in my day. It's surprising, right? Because I'm trying to avoid calories.

But the benefits in the taste and how I feel, that yogurt, I make myself out of whole milk. You make yogurt? Yeah. What are you, a wild man? Why don't you buy it? You're so short on time. What are you doing? Are you making your own butter too?

You got one of them churners? Yeah. Well, you know, we all have our hobbies. One of my hobbies. That's your hobby? Not really. That's your hobby? That's a cool hobby. No, here's the problem.

I got so hooked on this type of yogurt, which I first made for my son, trying to help him. He has a weight and eating issue. I was thinking that would help him, but I got addicted to the yogurt, and so is everyone in my family now. So if I don't make the yogurt, they're like, Dad, where's the yogurt? Oh, no kidding. So how do you do it? Oh, they're like, Dad, where's the yogurt? Oh, no kidding. So how do you do it? Oh, it's really easy. You get packets.

There's three different packets. You rip them open, put them in whole milk, shake it, and stick it in the oven on defrost for 24 hours. Really? In the oven? So what is defrost? Like what temperature is that around? It's 35 Celsius, whatever that is.

95. Is that 90? 95? So you're using like a Dutch oven or something like that? That's a regular oven. But I mean in terms of the pan that you put in the oven. Oh, you mean what's the bottle? Yes. It's just a large, I think, mason jar.

Okay. And just heating it up with the probiotics inside of it, the bacteria inside it, it just starts to coalesce. Yeah, and I've perfected it. The first few ones were not great, but now it works every time. And actually the protocol on the internet said you have to boil it, measure the temperature, get it all right, sterilize it, and I just pour it straight in, shake it, stick it in, it's fine. Really?

Yeah, so far. Huh. Did you ever get it analyzed no no but you're a scientist you don't want to send it a little cup of it to somebody go hey man take a look at this what are you worried about i don't know i'm not worried i'm not worried at all i'm just curious as to whether like how potent it is you know there's various levels of uh you know acidophilus that you're getting from yogurt. Yeah, I researched it before I started,

and this is a company that makes a yogurt that matches a healthy microbiome. It's the only one I'm aware of. That's great. And you use whole milk. You don't use raw milk. Right. I don't have good access to raw milk. Where do you get it?

Like a health food store, like Sprouts or something like that. I should try that. Yeah, I think they have it at Erewhon. Maybe Whole Foods has it. It's really tricky because it's not even legal in some places to have whole milk. In fact, people have been arrested and just locked up for having whole milk. Yes. Google that because it's pretty preposterous. When you think about how easy it is to buy whiskey, right,

and then think about people buying whole milk, that whole milk is apparently for some people. I mean, it might have just something to do with skirting FDA regulations and things along those lines. It gets very complicated for sure. And then the reason for homogenization and pasteurization is obviously health. We're trying to protect people. And also it's shelf life.

It stays on the shelf longer. But I've definitely bought it. Yeah, there's a small, what does it call it, a small food group, raw food club. They were raided in 2011 for sharing raw milk or something the latest raw milk raid an attack on food freedom federal agents organize a sting operation against a tiny raw milk buying club and ignore more serious food safety concerns yeah like twink I mean, how hard is it? Look, you can, I'm sure, get food poisoning from spoiled milk, right?

But isn't spoiled milk yogurt, ultimately? Right? Well, here's what I do with food. If it stinks, I don't eat it. Good move, bro. Yeah, and I think milk, you smell pretty quickly if it's going bad. This involved unwashed room temperature eggs. The other count, unwashed room temperature eggs, a storage method Rossum members prefer.

By the way, when we had chickens, we were these nasty coyotes that killed all my chickens, we would store our eggs at room temperature. We'd put them in a bowl. We would wash the outside of the egg and put them in a bowl we would wash the outside of the egg and put them in a bowl and they would sit on the counter and i was eating them all day long nothing happened healthy as fuck agents dumped gallons of raw milk and filled a large flatbed with the seized food including coconuts we seized your fucking coconuts watermelons and frozen buffalo meat what the fuck like what is this

agents who who are these assholes that are getting paid government money from our taxes to steal frozen frozen meat jesus christ christopher darden who helped prosecute oj simpson appeared at stewart's arraignment just in time to lower his bail. All right, so Christopher Darden's out there helping people. Whatever. Gross. It's just a gross, I mean, I don't think you should, you know, we should somehow or another find out

whether there's a way to test if this raw milk is fresh enough for people to eat. But if it is, people who live on farms have been drinking raw milk since the beginning of time. It's normal and healthy. It tastes better. It's way easier for you to digest. Like, I get a little weird when I drink, like, straight. Like, if I have milk and cookies, which I love.

I don't know what made it. It's the cookies or the milk. Hmm. I might be full of shit here. Now that I'm thinking about it, the cookies might be what's messing with my stomach. I don't think so, though. Because you get this feeling from the milk, like the... It's probably both.

Now that I think about it, it's both. Well, in France, you get the unpasteurized cheese. Yes. My friend Jean-Marc used to bring it back in his luggage. He would smuggle back for a raclette. You know what that is? Yeah. It's like a dish that he would make with meat and cheese.

Yeah, that's good. But I don't hear the French dying in droves either. They seem to be healthy as fuck, and they're not as fat. Right. Yeah. Their bread is better. They have bread that is not from their their they don't have modern wheat so the wheat that they have is not engineered to

have more complex glutens and higher yield like we do so we don't buy bread in my family my wife makes it oh nice yeah and uh so we sourdough yeah A lot of sourdough. The yeast is even wild. She got that from Belgium. A friend of ours hung some yeast, what is it, some stuff in a tree, collected the yeast, brought it back to the U.S. Really? And shared it with us. Caught it? Like caught some yeast?

Well, he put some wet dough up in a tree and left it there for a few days and caught this wild yeast up in the Belgian forest where apparently it only occurs, he claims. But we have the best bread at home. It's crunchy. You crack on it. You break it open. I mean, I'm trying to avoid carbs. And this is the hardest thing when you get home and the bread's just come out of the oven. Why are you avoiding carbs? Well, I'm trying to keep my blood glucose levels steady, not spike too much. That's pretty clear that that's not healthy. And just eating a bunch of bread will be a good way to spike that.

One of the things that I've heard about the French and Italians in general is that they eat their bread with either butter or olive oil. And that these healthy fats that you're getting along with the bread is one of the reasons why it doesn't have the same sort of health hit. And then the complex glutens, the engineered wheat that we have. When you eat pasta in Italy, it has a different effect on your body. It just feels different. Yeah, exactly. a different effect on your body. It just feels different. Yeah, exactly. So there are a number of people that I know, maybe people you know too, who are putting glucose monitors on their arm here to see what foods they react to. Rhonda Patrick's been doing this for a while.

And actually, I asked her, what's the worst food you've seen in your body to spike glucose? She said grapes. Avoid grapes. Really? Avoid grapes? grapes yeah I wish I hadn't asked her that so now it's so counterintuitive right you think you're eating healthy when you're having some fruit as I said what was the biggest surprise she said potatoes aren't so bad well there's a thing that you can do with potatoes right where you boil them and then cool them off and then reheat them and apparently has a profound effect on the way it impacts your blood sugar levels that it's far healthier when you there's some sort of a process see if you can find out what that process was who explained that to us do you remember was it ronda probably

was 99 of my nutrition knowledge i get from ronda patrick um but i believe it's something to do with the way the potato reacts to being boiled and then chilled and then reheated again. There's something about it. So the starches are less available somehow. Somehow. And it has a much more healthy effect on your blood glucose levels and doesn't spike you in the way that just a straight up baked potato would. This would be coming from Chris Kresser. Aha!

That's the other 1% of my nutrition knowledge. It's probably like 60-40. Potatoes for gut health and weight loss. The potato hack. It says potato intervention is a short-term tool to check the reactivity of the gut to resistant starch reset the hedonic system create metabolic flexibility resolve inflammatory conditions and provide the patient with an empowerment tool to increase the fat loss of their dietary plan it's not meant as a standalone, but rather a dietary tool to decrease hunger.

Blah, blah, blah, blah, blah, blah, blah. Scroll up there so we can find out what the fuck the potato hack is. Explanation. Poor potato has been maligned. Do, do, do, do, do, do, do, do, do, do. Here's an explanation of functional medicine. Chris Kresher on the Joe Rogan Show. Ha!

Right here. Look at that. Scroll up. Magic of this plan, at least its clinical effect efficacy is the amount of resistant starch resistant starch is a type of starch that is indigestible to us but feeds our microbiome when a potato is heated and then cooled a significant amount of its starch is retrograded into resistant starch this means that the effect on blood sugar is greatly dampened. The potato can be even be reheated and it will still retain its resistant starch content. The nourishment to

our gut biome and the subsequent metabolic benefits cannot be overstated. I've seen this be crucial in some patients who have stalled on a low-carb or keto eating plan but still have significant body fat left to lose historically resistant starch would have been present in most roots tubers unripe bananas plantains etc but is often devoid in our current diets chris crasher in the house yeah well there you go so when when i was in africa you reminded me Chris Crasher in the house. Yeah. So there you go. So when I was in Africa, you reminded me, they eat a lot of blueberries. And so these colored foods are also good to eat.

So resveratrol comes on when – Yams, dark things, right? Beets. Well, yeah. Leafy vegetables, but also fruits that are very colored. Colorful. So why is that? Why is that?

Well, I'm glad you asked. So we have this idea called xenohormesis. And it's a terrible name for something that's quite simple. And that is that these molecules from plants are produced to make the plants healthier. These are stress response chemicals. And if you stress plants, they turn colored. Turn on a UV lamp or put a plant in the sun, it'll turn reddish, you know. Those are stress chemicals to survive. And I believe that we've evolved to sense those chemicals in our food supply. Oh, so we're attracted to juicy red tomatoes as opposed to pale tomatoes. We're not just attracted to it.

I think we're attracted to it because they're colorful. But what our bodies get out of it is that these chemicals go into our bloodstream and they turn on our defenses against disease to survive. Why is that good? Why did that evolve or potentially evolve? It's, I think, because when our food supply was stressed, we need to get ready for adversity because we probably run out of food. adversity because we probably run out of food. And if you're a bird or some other dumb animal, dumber animal, or even a yeast cell, how are you going to know if your food supply is going to run out? You've got to know it chemically. So these chemicals are a heads up that adversity is coming. So if you eat a lot of these chemicals through, say, red wine, which is stressed grapes and other things like that, blueberries, these chemicals, they're probably not working mainly through antioxidant activity.

They're giving us this stress heads up. That's a controversial thing, the red wine thing, correct? Like whether or not red wine, the actual compound of resveratrol is where we're getting our benefit from because it's apparently a very small amount of resveratrol in red wine. Yeah, sure. It's not really controversial except when people exaggerate and say that it's all resveratrol. Resveratrol is a component of dozens of healthy molecules in red wine.

Quercetin, which is good for a number of things. There's a whole bunch of polyphenols, they're called. So resveratrol is part of that cocktail. Is this due to the fermentation process? Because we're talking about grapes themselves with a high sugar content actually being something we should avoid, right? So don't eat the grapes. But wine, if you don't have too much of it, will have a concentrated amount of these xenohormetic molecules like resveratrol and quercetin. Is this apparent in red wine? It's really only in red wine, white wine. xenohormetic molecules like resveratrol and quercetin.

Is this apparent in red wine? It's really only in red wine. So white wine is just for chicks, right? Not as healthy. That's a joke for my friend Bud. Yeah, you'll get in trouble for that one. No, it's just for my friend Bud. He loves white wine.

I'm like, that's for chicks, bro. I'm joking, folks. Just jokes. Don't get touchy. Yeah, that's for chicks, bro. I'm joking, folks. Just jokes. Don't get touchy. Yeah. So you don't need to – so when we treated mice with resveratrol, they were immune to the effects of high-fat diet, Western diet. And we've traced this down to a single genetic pathway that we work on, these sirtuins I talked about, these NAD-responsive pathways. Really? So they were immune to eating shitty food,

like the negative aspects of eating shitty food? Yeah. This was 2003. That's why it hit all the newspapers, because it was the first molecule that was safe and could mimic the effects of fasting or caloric restriction without actually having to be hungry. Wow.

And what kind of dose were you giving these mice? It was the equivalent of about 250 milligrams a day in a human. Okay. So it was one quarter of what you recommend people take. Right. I don't recommend people take anything. Okay. What you take.

Right. Let's just say that. No recommendation. Sorry, folks. Yeah. I'm taking a higher dose because I've looked at human clinical data and I think that a higher dose may be required to have an even better effect on longevity. But the results are very clear. When we opened up these mice, maybe I shouldn't have said that, when we examined those

mice, carefully put them to sleep for scientific purposes. It was clear that they were healthier. Now, they were still fat. That was interesting. They were still fat, so we figured the experiment didn't work. But their arteries were clean. Their livers were like a healthy, lean, young mouse. And when we looked at their metabolism, it was like a younger mouse. So let me ask you this then, because you take statins.

If you are fairly convinced because the research of the positive benefits of resveratrol in healthy aging and healthy metabolism in their arteries why you taking statins because you know that there are some negative effects of statins right well if i had five lifetimes i'd probably try that experiment okay i don't want to you just don't want to risk it. Yeah. Is there enough? I mean, have you looked through the papers, the research papers on statins?

A little bit. There is some correlations with dementia, and the brain does need cholesterol. So that might be one of the problems. Is your dad on statins? Yes. Really? We have a whole bunch of genes that predispose 23 and me said basically give up now wow it's pretty horrible uh so yeah if i make it to 80 i'm doing pretty well damn

interesting because um bourdain when he was alive um he had made a decision to take statins versus change his diet. This is before he got into jiu-jitsu. When he was traveling the world and eating the finest foods and drinking wine to excess every night and enjoying the shit out of it, we had a conversation about it. He's like, I would rather eat well. He said, I'd rather eat well and take these drugs. He goes, I know the side effects.

I know they're dangerous. So then we have a conversation maybe two years later. He gets really into jiu-jitsu. His wife at the time was into jiu-jitsu, and she had convinced him to try it. And he went and tried it and immediately got hooked. And he has or he had an addictive background. First it was heroin and some other unfortunate substances, and then cigarettes for a while.

He quit that, and then jujitsu became his new addiction. And he got ripped. I mean, he really, I think he started training at 58 or 59. He started. And then by the time he was 62, he had a full six-pack it was crazy to see like i'm like look at you man this is nuts like this is an image of him walking down the street and i mean he has no shirt on and he's fucking shredded got off all the statins got off everything has uh changed his whole his issue with cholesterol Yeah good on him Just through daily exercise Yeah I should try

Yeah you should Yeah a little bit ashamed That I haven't been able To get off the statins But They just scare me man I've just read too many things Well you know

I could have gone off them When I was on a really lean diet I tried this Okinawa diet From Okinawa Okinawa yeah So just fish mostly And tofu Yeah How'd that go? That was great I tried this Okinawa diet from Okinawa. Okinawa, yeah. So just fish mostly and –

And tofu. Yeah. How did that go? That was great, but then I had kids. Oh. You can't feed tofu to kids every day. Right. But you can't have separate food just for yourself?

I'm not going to. No. I understand. Yeah. Well, that's the thing is like you're so limited by time. You have such an involved research schedule and life schedule and travel schedule. I'm a pretty average guy. I'm not militant about what I eat. I try my best every day to do what I can. But this statin thing, I just haven't had the chance to do it. But resveratrol,

I don't think is sufficient to keep these cholesterol levels down. So combination so far. When you first got on, how long you've been on statins since 29 oh wow so you really have been on them for 21 years not only that super high dose uh so it's uh 80 milligrams what's a normal dose 10 that's crazy yeah my doctor one of the best at harvard looked at my genetics and said you're're fucked. Wow. Yeah, I've got all the wrong genes. These tiny little lipoprotein particles, the ones that oxidize. So the fact that my arteries apparently clean is good news for me. Well, that's good news.

Like I said, you look good. Oh, thanks. I mean, obviously, there's a lot of biodiversity when it comes to human beings and some things that are bad for others. Yeah. Good for some. Well, I'm not losing my mind yet. I'm still pretty functional.

When it starts slipping away, what are you going to do? Are you going to ask your wife or your friends or what are you going to do? Yeah, what am I going to do? What if your dad's the one to tell you? Yeah, that could happen. You're like, fuck. Right. He's 85.

Yeah. My dad's changing my diapers. David, you asked me the same question three times in a row. The way it's going, that could definitely happen. Well, do you get a lot of sleep? I do now, now that I'm monitoring it, yeah. What's a lot of sleep for you? Between six and seven hours.

Oh, that's good. Dr. Matthew Walker was a guy that I had on my podcast who studies sleep, and he was fascinating, and he changed my entire opinion about what's necessary. There's a direct correlation between limited amounts of sleep and Alzheimer's. Direct correlation. He's like, it's one of the most established links that you can see between a disease and a cause. I'm misquoting him. It's an association. I always wonder,

you know, I'm a scientist, always have to be skeptical as to whether if you're predisposed to Alzheimer's you have trouble sleeping. Oh, interesting. And you start taking Ambien,

now people say, well, Ambien and Alzheimer's are correlated. Well, yeah, maybe it's the other way around. Yeah, Ambien scares the shit out of me you don't take that do tiny bits oh that stuff's nuts because people take it and they say things they don't know what they're saying right well the recommended dose at least it used to be for men is 10 milligrams

which is massive i nibble on it i take maybe a milligram just to nod off if i'm desperate with jet lag but yeah doctors many i know say that 10 milligrams is probably too high. But check with your doctor. Yeah, well, Matthew Walker says stay the fuck away from that stuff, period. He said you're not getting real sleep anyway. You're not going in through full sleep cycles. You're just drugging your brain into a state of unconsciousness. Probably with 10 milligrams, that makes sense.

For me, because I'm monitoring it, I know that I'm getting good deep sleep. Have you tried other, like mel melatonin things along those lines? Sure. Not effective? Not as much. Sometimes melatonin with a milligram of Ambien is necessary. But a big change for me has been just don't stay up watching TV. Get the screens off.

Wear the glasses. They really help. Yeah, the screens. Watching those goddamn screens before you go to bed. I love doing it, though. I love watching a TV show before I go to sleep. It's probably the worst time to do it, though, right? Yeah, it is.

Really. I mean, you can watch the shows. Just put the yellow glasses on. Oh. Like blue light emitting. Yeah. Blocking glasses. One of my sponsors, Movement Watches, they have blue light emitting glasses.

Need to get those, huh? Blocking or emitting? Blocking. Blue light blocking. Yeah. Yeah, not emitting. How can a glass emit? You know, blocking blue light emitting sickness.

Yeah. Well, you can have blue light emitting glasses too. That'd be good. Really? Well, for the middle of winter. Oh, if you're getting depressed. Yeah. Well, you can have blue light emitting glasses too. That'd be good. Really? Well, for the middle of winter. Oh, if you're getting depressed. Yeah. Well, where you live.

Right. There's no real middle of winter here, buddy. Well, you used to live too. Yeah. Not too far from where I live. Yeah. It's pretty tragic. Middle of winter, I want to kill myself.

Do you get that seasonal affective disorder? Oh, for sure. Do you? Yeah. Yeah, because I'm working indoors. I don't see sun for months well that gray sky when it's every day is gray over and over again you see no real sky for so long it's so weird it yeah i miss australia for that reason i get reinvigorated if i come out

to la and it's blue sky you really feel different for sure. There's a reason why there's a fucking billion people out here. But what is your strategy for mitigating the impact of seasonal affective disorder? What do I do? I try to go outdoors and get some sun in my eyes when I can. Do you take vitamin D? Oh, for sure. Does that have a difference? It seems to have helped.

Make a difference. Yeah, yeah. So, yeah, vitamin D, it's questionable whether it's as healthy as people thought it was. That said, I think it, at worst, doesn't hurt you. Some people do sunlamps for that reason. They'll go into a tanning booth for that reason, right? They will. I actually found this season, I went to the sauna in the cold shock bath, and that really helped a lot. I don't know if it's related, but I needed to shock my body. In the middle of winter, if you're just sitting by a fire and barely moving around, I just felt like I was a sack of shit.

Yeah, a lot of people get fat in the winter too. That's another thing. They get indoors because it sucks outside, and they never wind up doing anything. And then you're dealing with the depression of being a little bit heavier too. Oh, for sure. And then you're drinking by the fire, all that kind of stuff. But it's all about shock your body, get your body out of complacency. And our lifestyle, everything we do, everything we buy, everything on TV that's being advertised to make your life better

is shortening your lifespan by making it easier for our bodies to exist. You don't want that. You've got to stress it. Yeah. What other things do you think that people should be doing on a daily basis that most folks aren't? Well, we covered a lot. So there's the be hungry, get the exercise. There's all sorts of exercise, which are good, but the main ones are stretching and running and lifting. Okay. Cold and hot, we've talked about. And then there's the supplements that mimic the benefits of those, plus probably more things. That's my regimen. There's some other little tidbits that I put in my book, which it's a laundry list of things that I found work for me. But those are the main things we've covered.

This sounds probably pretty boring, but I'll say it again. Wear sunscreen for two reasons. I mean, you'll look better anyway. Not that probably young people care, but it'll make a difference by the time you're our age. It'll look better anyway. Not that probably young people care, but it'll make a difference by the time you're our age. But also because DNA damage does age you, we think that it's breaking the chromosomes and that's the major driver of aging. That sun will do that.

X-rays will do that. Maybe even airport scanners. Certainly, I'm not a devotee of getting scanned. I thought there were radio waves. They're millimeter, and they don't penetrate very deeply, so they're probably not too bad. But I've looked into it. It's about the same radiation as you get on the flight. And given that I'm doing probably a million miles a year, I don't want to double the amount of exposure.

So when you go through that radio scanner, then the more modern TSA scanners, they give you the same amount of radiation as a flight? Because a flight gives you the same amount of radiation as multiple x-rays, right? I don't think it's that bad. I believe it is. Well, let's look up. Let's find out. How much radiation do you get on a five-hour flight, and is it comparable to multiple x-rays? Because I believe that's what I read. Well, the x-rays, I can say definitively, based on our research, would age you, age your tissues.

What's it doing to you? Well, it's breaking your chromosome and causing that clock that I was talking about earlier, that biological clock, to accelerate. Is there something you can do to mitigate that? If you know you have to get an x-ray, should you do something right afterwards? Potentially. Potentially. You could take NMN, which we've shown in mice, protect them against the effects of radiation. And that's one of the things we've talked to NASA about for getting to Mars and back safely.

So when I'm on a flight, I take some NMN in the expectation that it's going to boost my body's ability to prevent those changes to the clock. Now, is there a commercially available NMN that you would suggest if someone wants to purchase it somewhere? Well, so I don't divulge company names. And there's two reasons for that. One is I haven't tested them. So I actually literally don't know. But the other is that I want to stay above the fray and i understand not get involved but but there are if people want to go google and go look online they can find commercially available nmn right um so yeah again i've got a number of pages in in the book on that so it's it's all laid out but in summary this book right here ladies and gentlemen look at that

lifespan why we age and why we don't have to thanks joe that's my npr voice yeah you can donate if you enjoy programming like this you're putting me to sleep that's what they do man something happened with people they thought to be intelligent you have to talk like you're ready to put people to sleep. It's time to get sleepy. Anyway, so the NMN. Yes. So there are people who are selling it on the internet.

Just to get the facts straight, I don't sell anything. I understand. My name is all over the internet. If you see my name with a company, it's BS. Aha. Beautiful. That's good. Anyway, so the NMN, there are companies that sell it. It's more expensive than another molecule that's related called NR or nicotinamide

riboside, which is also what the body can use to boost NAD levels. And that's a little bit cheaper. And they've both been shown in animals to boost the sirtuins and help those animals be healthier in old age and reverse some aspects of aging like endurance, loss of endurance, that kind of thing. Protect the eye, protect the hearing as well. So we don't know if it works in humans. Let's be honest. We don't know if these things work. But let's also be honest. We know what's going to happen if we don't do anything.

And that's also be honest. We know what's going to happen if we don't do anything, and that's not pretty either. Do you have any high hopes for things like CRISPR, things where there's going to be genetic alterations? And they are starting to do some experience. You have a big smile on your face right now, so I'll let you talk. Go ahead. Tell me what's up. Well, so I'm a geneticist, and I'm just down the hall from George Church, who's in my department at Harvard. So I'm a geneticist, and I'm just down the hall from George Church, who's in my department at Harvard. And I'm a big believer in CRISPR in the sense that it will revolutionize medicine.

Now, right now— Can you explain it to people who don't know what it means? So CRISPR is an acronym for basically a system that is from bacteria that they use to kill and destroy the DNA of invading organisms like a virus. But we can now use that system to cut and change our own genomes. It's basically a DNA cutting enzyme that doesn't cut randomly. You can give it a barcode in the form of what's called RNA molecule that tells where that enzyme will cut in the genome. Let's say you, Joe Rogan, have a terrible gene that's causing heart disease. We take this CRISPR system. We say, here's where you need to go to cut. We can tell the enzyme to go and cut it, put it into your cells. It'll go cut it and destroy that enzyme and delete it. And you

can also use it to cut the genome and insert new pieces. So you can both subtract and add DNA at will now, not just randomly, but what's important is you can tell it where to go. And that's the big breakthrough. And they're doing some experiments on human beings. I know there was something that they were doing i believe somewhere in asia if i remember correctly i believe it was china where they had done some manipulation to people to help prevent aids and in the process of doing so they may have boosted intelligence or the potential for intelligence which was so convoluted that my puny little brain cannot understand the study i was i was i had to go over the same paragraph

like four or five times just try to figure out what the fuck they were saying am i making any sense uh yeah you are you are and that was a study that that uh i don't believe it's been published but it's been reported right that uh is his name, his last name is he – he took embryos and engineered them to delete CCR5 gene, which is required for HIV to infect cells. Now, that was – most of us scientists think that that was reckless for the fact that, first of all, HIV isn't a huge risk in China. It's a one in a thousand chance of getting HIV. There are plenty of other things that you could do that could be more helpful.

Let's say, why not mutate what's called PSK9 to prevent heart disease, which would probably have 50% to kill a boy. So anyway, it wasn't the most risk-benefit ratio modification. That's one thing. But the other is we don't know what happens when you cut genes in embryos. Does it have changes to the DNA clock? Did it accelerate their aging?

Did it mess with other genes? Did it cut in other places and screw up those genes? We don't know that yet. And so that's why the scientific community had a negative reaction to it. But what's interesting is that the scientific community and the press has pretty much gone quiet on this. Imagine if this happened during the Bush era. We'd have protesters all over the place.

It'd be outlawed. And that hasn't happened. And I think it's because we live in a world with a 24-hour news cycle. But isn't that also because it's being, if it was during the Bush world, I mean, where the protests would really take place if it was done here. The thing about things that are done in China or overseas, it's like it's so far away, like, well, let's keep an eye on them. Yeah, that's true.

There is the fear that some country is going to engineer an army of clones. Superhumans. I mean, we have the technology to do that right now. Yeah. We believe we understand how to slow aging. There are genes that predispose you to long life. We could make offspring, a family that would potentially live a lot longer. But is this something that can only be manipulated in embryos or in fetuses? No. Now we can do it in adults. Actually, there are drugs that are in development to actually correct genetic diseases, such as vision loss.

Really? Dude, my eyes are gone. I can barely read print on a laptop. I need glasses to read my laptop. online on a site called BioArchive. Anyone can go there and see it. Just Google my name in BioArchive, B-I-O-R-X-I-V. Reason that's interesting is that what we're showing is in mice at least, we can reverse the age of the retina and restore the vision of old mice. What do I have to do? Well, I think you have to blow me a few more times Hey, come on, man

You're going to lose your job You've got to let me crack those kind of jokes Sorry Harvard, I was joking I started it, folks It's not his fault So what would someone I mean, is this going to be available to the general public

Any time in our lifetime? I'm trying my best We're hoping to do clinical trials starting in two years from now. Really? And what would you do in those clinical trials? So we'd reprogram the eye to be young again. So we now know that there's a set of genes called reprogramming factors, also known as Yamanaka factors that are named after this Japanese fellow who won the Nobel Prize in 2012. These factors are used all over the world, even probably in high schools, to reprogram skin cells, other cells, to be what we call pluripotent stem cells.

These are cells that can be used to make new organs or new blood cells. But what people hadn't tried until recently was, can you do this in a living animal, or are you just going to mess it up? And what we found out is that if you do it the wrong way, you mess up the animal and it'll die. But what we've shown for the first time in this paper is you can do it in a safe way. And not only that, reverse the clock, make the cells young and restore how they work and get back vision. And what's the methodology? Right. Good question. So the current method is using a virus that's on the market. These are called AAVs, adeno-associated viruses.

You put them in the eye. There are already patients getting this on the market. Really? Yeah. Spark Therapeutics is an example of a company that is curing genetic diseases in the eye with viruses. We're in a new world. Most people don't know about it. Wow.

So what is the company again, Jamie? Look up this. Spark Genetic Engineering? Spark Therapy. Jamie's already got it. Look at that. Bam, motherfucker. Jamie Vernon in the house. So these folks are already doing this to people. So is this for people that are sort of desperate

and they'll try something experimental? Right. Well, they're desperate in the sense that there's no other choice, no other cure. I mean, we're now curing genetic diseases. Someone was just treated and cured of sickle cell anemia. That's phenomenal. And I learned that that comes from malaria, right?

That was the idea that people were, the resistance to malaria, it was that trait from people that evolved in the area where they would get malaria was also what led to people getting sickle cell, correct? Correct. So I learned that from Tiffany Haddish, by the way. Amazing. Tiffany. Shout out to Tiffany.

That Lux Turner stuff, is this something that someone like me could take right now? No, not easily. Your doctor would need to prescribe it. And so if he did prescribe it, I could literally get vision back? Well, this is not the same technology that I'm talking about from my life. This is inherited retinal diseases, our commitment to IRDs. This is gene replacement, not reprogramming the body to be young. But it's the same virus that we'd use to correct aging

so they're using this for certain retinal diseases where they're correcting it now how is this bacteria fixing your vision well the viruses are just a way to get the genes into the cells that's all

and these are benign viruses they don't hurt you but they're a carrier and maybe eventually we'll have other ways to do this, but right now the virus is the best way. And in the mice, to restore the vision, we have this three gene combination of these Yamanaka reprogramming genes. We put them into the eye and then we turn them on with a drug. In fact, the same drug that I took when I was in Africa called doxycycline is the same drug we can feed to the mice, turns on the reprogramming genes for a few weeks, restores their vision back to a young mouse. And then we just take away the doxycycline, an antibiotic, and the mice have their vision back. And how long does it take before it starts deteriorating again?

We don't know yet. But we think that it's permanent. Because the age of the cells has gone back. Those are young eyes again. So you might have a whole full cycle from like 20 or 10 to 40 years old again. That's the future. That you'll get a delivery of this virus. You'll take the antibiotic for a few weeks, be fully rejuvenated.

And the doctor says, come back in a couple of decades. We'll fix you again. We'll give you some antibiotic in a couple of decades. But then it gets really weird if you engineer your children to have this system. If that ever happens, let's imagine it could. We could do this right now with technology. And you have people engineered to be able to be reversed in their age. Or let's say they have an accident and their optic nerve gets damaged or they lose their hearing from a bomb or something, a spinal injury. Give them a dose, an IV of antibiotics, and they become just like an embryo. They can rejuvenate. They can regrow their optic nerve, regrow their spine, fixed, back like new.

The vision thing, do you think that we're going to see that in our lifetimes? I mean, is this something that you're going to see that's going to be available to the general public? Well, so I'm an entrepreneur, as we discussed before. And so one of the companies that I've started is exactly that, raised money to be able to make this virus. We're making it now. It takes a few million bucks. And we'll hopefully, with the FDA's approval, inject it into people's eyes. Now, first, it won't just be guys like you.

First of all, we have to go into an area where it's FDA-approvable, which is a disease like glaucoma, which is pressure in the eye, or macular degeneration. That's our first goal. But then if it's safe, why not do old eyes? Wow. That's incredible. Now, what about people with injuries? Yeah. Well, yeah, you could theoretically put it into the spinal cord or give an IV.

But people with eye injuries? Oh, for sure. So one of the things we also did in this paper that we put online is we pinched the optic nerve. And what normally happens is it just degrades. I mean, nerves don't grow back, right, unless you're a baby mouse or a baby human. But we made those cells so young that the optic nerve grew back to the brain. Wow. First time that's been able to happen. I know a guy from fighting. He's got a detached retina, detached so bad that his vision and his

right eye is extremely poor. Shout out to Michael Bisping. Do you think that that's something that inside of his lifetime they could see something, the use of this technology that could regenerate his eye? Well, I get a lot of emails, so I'm not really trying to overpromise anything. What I think is possible is that initially it will be used for disease, a chronic disease. Then it will be used for injuries like that, but fresh injuries. I think it's probably likely to work better if it's fresh. I don't know where this technology is going. I can imagine a lot. We can all imagine that you could get vision back

and people walking again. But that's where this technology is going. So I described the discovery in the book. Actually, what happened while I was writing the book is we were making these discoveries, and they were remarkable. And so I wrote them down in the book as we went along, so people can see how it feels to be a scientist to make these discoveries. But it's only been a year or less that we've known about this. So imagine 50 years from now what we can do, even 10. It's going to be a remarkable future. It's very exciting. Now, what kind of a timeline

are you anticipating for bringing this to people with injuries? Well, injuries, already we have a study plan for spinal injury in mice, and that we'll probably know the results in less than a year. And then we could, as fast as the FDA allows us, go into a clinical trial. Now, is the same scenario applicable for people with spinal injuries as vision? Like people that have a more recent spinal injury will be more likely candidates than people that have had older spinal injuries? I think so. That would just be my guess that it's easier to fix a recently damaged system, anything in the body that's fresh. But I wouldn't rule out anything.

When we first discovered this, the experiment was to have a fresh injury, the pinching of the optic nerve. But then I said to my student, why don't you just try old mice? And he said, come on, old mice, are you kidding me? How's that going to work? Just try it, just try it. So he did it, and in collaboration with another lab at Harvard. So they're the experts. And so Bruce Cassandra is his name. So Bruce called me, a professor at Harvard. It's 10.30 at night. I just got off a plane.

He said, David, you won't believe it. I didn't believe it. I just looked at the data. It freaking worked. Old mice are seeing again. He said, I want to go down to the FDA and tell them about it. Because right now, eye diseases typically, all you can do is slow them down. And here's actually a reversal of lost function. Now, does this apply to injuries as well, do you believe, old injuries or just old macular degeneration?

We haven't tried old injuries. Now, we've done glaucoma, which is an old injury. So theoretically, what we could do is at least with the existing nerves, if they're still attached, we should be able to rejuvenate those and make them work better. Because he has some vision in his eye. So, yeah. So that's possible. That makes more sense. But very little.

Very limited in one eye. Yeah. Well, we'll have to see. Interesting. Because you didn't think it was going to work on the old mice. I did. But no one else did. Wow.

Crazy. Well, we're literally reversing not just the effects of aging but aging itself. So if I gave you those retinas, very little retinas, here you go, Joe, and you were a scientist,

you could look at that retina and analyze it molecularly, measure its clock, and you'd say those are young eyes and you wouldn't know the difference. Now, do you feel like this kind of technology is also going to be applied

to people's skin? Because, you know, one of the things that for women, it's devastating when they develop wrinkles. You know, they fucking hate it. Men get a few wrinkles. They kind of look distinguished, you know. But, man, when women get wrinkles, they freak the fuck out. They don't like it. Yeah, we're going to try it on aging on the skin.

Yeah, we're going to try it on aging on the skin. Though, you know, when I talk about making people walk again, potentially, it's probably a higher priority. Oh, for sure. But I think it's feasible. So there's a lab at the Salk Institute, Juan Carlos Belmonte, who may win the Nobel Prize for his work on this. In 2016 and a couple of years since, he's been showing that it doesn't just rejuvenate old mice. It actually is also rejuvenating the skin. If he puts it on a wound that's in an old mouse, that mouse will heal better.

Now, that doesn't prove wrinkles, but it does prove the skin can be rejuvenated as well. So there could be possibly some sort of a treatment to skin, maybe re-injuring like if you there's this thing that they do i think it's called a vampire facial have you ever heard of that they take platelet-rich plasma and then they micro needle your entire face and then they somehow another apply this platelet-rich plasma to the areas that have been microedled and it has some sort of an effect in increasing collagen and elasticity of the skin and tightening of the skin. Have you heard of this? I've heard it for hair loss.

I didn't realize people get it all over their face. For hair loss as well, they're doing that? It sounds painful. So to me, it makes sense that it might work. The PRP, as it's called, is full of factors that we know some of these are rejuvenating in mice. You know, this system where you can hook up an old mouse and a young mouse circulation. Yes.

And you get rejuvenation. There are factors that many of which we haven't discovered or identified that exist that you can rejuvenate. And I would bet that they're working most likely through this reversal of the clock and so one of the things we're doing in my lab is taking what are called exosomes which exist in these uh preparations and seeing if they reverse the clock i've had exosomes shot into injuries for stem cell procedures yes yes did work that makes sense yeah i had a full length rotator cuff tear that's completely gone. Yeah, so maybe what's going on is you've reprogrammed your body there.

Yes, well, it's a weird thing, the exosomes and stem cells, and there's a new product called Wharton's Jelly that's also very effective and potent because there's not a lot of papers on these things. It's all, you know, the research on it is, some of it's a little shaky. But the efficacy, at least anecdotal efficacy, is pretty substantial. And I'm one of those pieces of anecdotal evidence. I've had a bunch of shots. I just, whenever I get injured, I'm like, shoot it up.

Yeah. Well, your listeners may not know about exosomes. So exosomes are little compartments that are pinched off from cells and put into the body and communicate between cells across. So your liver can communicate with your brain through exosomes. And within these little cargos, there are things that we're just discovering, little proteins, RNA, and they're full of goodies. And drug companies are being built on these exosomes. Yes. drug companies are being built on these exosomes.

Yes. I'm glad you brought up the study of the old mice and the young mice, where they put the blood in the old mice, and then the old mice started behaving like young mice, and the blood of the old mice and the young mice, and the young mice started behaving like they were tired. Because there's a company in Northern California that's supposedly doing this with humans, where they're injecting people with the blood of old people, or young people rather, some sort of transfusion. Not anymore. Not anymore. Are they out of business? Well, my understanding is the FDA sent my letter

and said, stop it. That's it? Just a letter? It's all text? Oh yeah, you don't want to go to the next step. Can't you just move down the street and change your name? Oh, I got another letter. Move down the street, change my name. I think that's risky. Check to see if that company's under. Alcovers?

I do not remember the name of it, but I remember they were erroneously linked to Peter Thiel, and then Peter denied that he's ever used that. The billionaire founder of PayPal, who I've met is a wonderful man they uh erroneously someone just some story linked that said that he's getting it he's like actually shut the fuck up no i'm not don't say that i've never done it not doing it um so it was one of those things where there was a lot of legend to it because of these mice studies these mice studies get people super excited about the idea that all you have to do is get young people's blood,

so you get a bunch of young people that are healthy, disease-free, drug-free, donating their plasma, donating their blood for X amount of dollars a quart. Right, you have a blood boy. Hook yourself up. Yeah, blood boy. Hey, man, when I was young, I needed some cash. I was healthy.

Come on. Regenerate that shit. Take a quart of blood. I get it back in a couple hours. I think it might work. It's just that we don't know the consequences, and the FDA's job is to protect us. Yeah, just like they're protecting us from raw milk, bunch of pussies. Just recently shut down about a month ago.

I missed the boat. Could have been in there, man. But if you did that, that's something you'd have to do on a routine basis right it's not like something you do one one shot probably give you like a little boost for a short amount of time yeah well that's what's different about this reprogramming you do it once you come back years later yeah the eyeball thing is very enticing to me because it's so weird watching my eyes deteriorate like slowly but surely I'm watching it happen. It's really. It sucks. And it's a short sign you're getting older.

Yeah. Age-related macular degeneration just seems pretty standard. Except my friend Cam Haynes, that motherfucker, he's 52 years old. He could see. He's got like 2018 vision at 52. It's crazy. He could see anything. I drop my phone on the ground.

He's like, oh, you got a crack. He saw it from like, I go, where? Where's the crack? I go, I'm trying to look at it in the light. It's like right there. And I put reading glasses on. I'm like, son of a bitch. I'm like, how the fuck did you see that?

He saw it from like where you are, like looking at the phone. I'm like, that is crazy. Well, so let's keep in touch. We will. And if we get this on the market, then, yeah. Yes. It turns out he has started up again pretty recently, but it's not being sold as young blood for plasma.

It's just plasma. Oh, just give it a shot, bro. Just here's some. Just no promises. What do you think? Want to go in there with me right after we do the cryotherapy treatment? Go get some blood Some young blood

Doctors behind failed anti-aging blood clinic tries again We tried to ask him some questions But he was very evasive Good for you, sir Duck and move Do the old Muhammad Ali rope-a-dope Be like Pernell Whitaker, sir Yeah, I hope he stays evasive i mean it's also like maybe it's nonsense maybe it's not

would you like to do studies on people that are doing that and find out i mean well what they should do is measure the clock now that we yes right yes that would be interesting but based on what we know about how it works with mice you think it's likely that there is some effect. It's possible. It's possible. I like how you're very cautious. You're a real professor. I like that.

I try. You're the real deal. I'd like to keep my job. You should. Stop making those blowjob jokes. Funny that that is actually controversial. Two friends can't just joke. Is there anything else that you think is promising that is on the horizon or that's being discussed or is theoretical at this point?

Yeah, there's something that is really interesting, and that's called senolytics. Senolytics. Yeah. So senolytics are drugs that kill off senescent cells. So what are senescent cells? These are often called zombie cells. And what I think is- Back to World War Z. Yes. A lot of zombies, this podcast. So senescent cells we've known for decades exist in the body, but what was not clear was whether they cause aging. Now it's pretty clear, from animal studies at least, is that we get lots of these accumulating and that they do cause aging. And one of the best experiments that was done from Mayo Clinic was to genetically delete the senescent cells that accumulated in an old mouse and it became young again, or at least it delayed its aging by a fair bit.

Now, senescent cells are pretty rare. There's not a lot of them, but they cause havoc because they don't just sit there in the body, but they send out these inflammatory markers, and they cause cancer, we think. So you want to get rid of these. Just I want to mention that in the biological clock clock when I was saying that the clock is part of the aging process what we think is that as we get older that and it's detailed a lot more in my book so if people read it they'll understand a lot more what I'm saying but this this clock

is messing up the cell's ability to be what it used to be. What do I mean by that? Let's take your eye. In your retina, your nerves are getting older, but your nerves, we think, are losing the ability to read the nerve genes. So they're forgetting that they're nerves. So now they're starting to behave actually more like a skin cell. And having a skin cell in your eye is not going to really work very well. So we call that epigenetic noise, epigenetic aging. Reprogramming resets that. So why is that interesting? We think that the ultimate problem for the cell when it loses its total identity or gets a long way towards that is it shuts itself down because it says, fuck, I don't even know what I am anymore. I'm not a nerve cell.

I'm not a skin cell. I'm not a liver cell. Senes. anymore. I'm not a nerve cell. I'm not a skin cell. I'm not a liver cell. Senes. Senes means stop dividing. Just sit there and tell the body, come kill me. So now they're putting out these panic factors. There's a problem. You get inflammation. The problem is that as we get older, the body's not very good at clearing out these cells. They sit there and they wreak havoc. You get inflammation. We think you get aging. So getting back to senolytics, these drugs are designed to be a pill or an injection into your joint to kill off these zombie cells, these senescent cells. And theoretically, rejuvenate the tissue and reverse that aspect of aging.

And that's another treatment like reprogramming that could be a one-shot delivery and take you back a decade. Wow. And how far away are we from seeing those? Much closer, actually. There's a few companies. There's one called Unity. There's one that I'm involved with in full disclosure called Sinalytic Therapeutics in Europe. And at least Unity is in clinical trials right now for osteoarthritis. Really? Now, what about the company in Europe? Pre-clinical, still a mouse.

Wow. So we're looking at like a decade from the general public? Well, for Unity, they hope not. Usually when you're in a phase two study, which they're in, it's a few years away if it works. Oh, wow. Amazing stuff. It's such a cool time to see all this medical innovation and scientific innovation. Well, my head's spinning.

Yeah. There's CRISPR and then the reprogramming, which is new stuff. This is stuff that we dreamed of for thousands of years. And I don't think it's a dead end. And it may not be as, you know, we're not going to go back to being 20 anytime soon. That said, I think we've had a major breakthrough. The equivalent I like to use is we figured out how to fly. We're the Wright brothers, the Wright sisters.

We've got – I've got to include all sexes now. My daughter will tell me. Wright non-binary people. Yeah. So my daughter changed her name, by the way. To what? To Alexander. She was Madeline me. Right, non-binary people. Yeah. So my daughter changed her name, by the way. To what? To Alexander. She was Madeline.

She didn't think that was appropriate. Why? She's a tough chick. She's a they. So I'm not allowed to call her a she, I don't think. She doesn't want to be identified as one or the other. Interesting. Is she 16?

Yeah, she changed it at 11. Whoa. She's a tough girl. You know, in my family, we tend to be rebels, and unfortunately, it passed along. I'm getting everything back. Fortunately or unfortunately? Well, I guess I'll be proud of her, but raising her in the last few years have been pretty annoying at home. Can't say anything without the PR police.

That's hilarious. So PC police or PR? Did I say PR? I meant PC. Yeah. That's hilarious. So PC police or PR? Did I say PR? I meant PC. Yeah. That's interesting. What was I saying about my daughter? Oh, about the name change.

Yes. Why was I talking about a name change? I don't know. You tell me. Jamie, do you remember? Man, we've got a million people screaming at us. Yeah. Well, you were talking about so many exciting things on the horizon.

True. Yeah. And so it's just head spinning. And so much is happening in our lifetime that I thought was just imaginary or for the future. Now, the question is, are we going to reap all the benefits of this or are we going to be the last generation to lead a normal human lifespan? And I don't think we are. I think that we already have things we can do in our daily lives, just in lifestyle and in molecules you can take that give us a very good chance of living beyond what's naturally possible.

This is amazing, man. It's so exciting. And the last time you were here was about a year ago, somewhere around that range? Yeah. Yeah. I mean, and think about how many new things you have to discuss now versus then. It's I mean, and think about how many new things you have to discuss now versus then.

It's really interesting, man. And I'm so happy there's people like you that are out there doing this. It's just so exciting. And it makes me very happy to know you're out there. Thanks, man. So thank you. And your book. People can find out all this stuff in detail, much more detail than you can get in a two-and-a-half-hour conversation.

Lifespan, why we age and why we don't have to. David A. Sinclair, Ph.D. Thank you, brother. Always a good time. We'll do it again next year? Deal. Yes! Bye, everybody.