Harvard geneticist David Sinclair reveals how 80% of aging is reversible through lifestyle—exercise (cycling cuts heart attack risk by 40%), fasting, and NAD-boosting supplements like NMN—while critiquing modern medicine’s reactive disease model. His lab’s work, including a Nature-published study restoring sight in blind mice via gene therapy, and collaboration with Stanford’s Andrew Huberman, aims to democratize tools like epigenetic age tests. Sinclair predicts partial aging reversal in his lifetime, citing controlled stress (hormesis) as key, contrasting it with harmful cortisol spikes from chronic anxiety. Both discuss personal health transformations—Rogan’s friends losing 60–270 lbs, Sinclair’s own weight loss post-COVID—and urge public support via SinclairLab.com donations to accelerate breakthroughs. [Automatically generated summary]
Well, what I also didn't know about him is he's been too busy to have much of a social life, so you and I and everyone else should try and find him a good woman.
Well, the problem is that we're finding them in our teens and 20s often when we have no idea what the other sex or the partner that you're looking for really is.
And I have a theory that when you're young, you look for the opposite.
You're attracted by what you cannot do.
But as you get older, you really want to go for someone who's more like you.
Jamie thinks that emojis are the beginning of the next hieroglyphs.
And he said it and a light bulb went off in my head and I'm like, I think he's dead right.
I think one day we're going to...
I really believe this.
And maybe you can help me out on this.
I think that...
If someone concocted a universal language, a language that every country could adopt and understand, and they did so in...
You could do it in the form of a game, where it would be like, as you're getting better at it, you score points, and you do better.
Say if you're playing a Call of Duty type game, and in that game, in order to increase levels of the game, you must learn this new language.
And this language is an image-based language that interprets intent through some sort of emoji character system that doesn't require English or kanji or any sort of letters or any sort of way that we interpret sounds and language.
Well, it's similar to the turn of the 19th to the 20th century where all these gadgets showed up and people were hyper-stressed and agitated with anxiety.
And we're seeing the same now with this super change.
And the kids adapt, but a lot of people our age, we're roughly the same age, are just trying to play catch-up.
Well, and for your study, for the study of human life extension and anti-aging, when you look at the stresses that are completely, they're very novel.
To the human experience, like the stresses of social media, the stresses of cell phone use, the stresses of blue light, like staring at screens at night, like all that stuff.
How much of an effect do you think that's having on people and have we even quantified that yet?
There's one thing that people can do and exercise is a good one, right?
Because of the fact that we live these sedentary lifestyles and most of the time people are sitting down and there's a lot of time spent standing at screens.
How important do you think it is to get out and do something and what kind of an effect does that have?
Like what kind of quantifiable effect does that have on life extension?
There are two things you can do that are well known to extend your lifespan.
And when I say extend your lifespan, I don't mean be older for longer.
I mean be healthier in your 80s and 90s.
Like my dad, who's turning 82, who's got the physique and mental aptitude of probably a 30-year-old.
He's stronger than me.
So you want that.
Okay, so what do you have to do?
Well, you have to start early.
You can't just start when you're 80, although it helps, but it's not the best.
Do you want to just get out of the chair?
People say walk, but I think it's better to lose your breath, become hypoxic, you know, hypoxia chambers or hyperbaric chambers that stress the body a little bit.
So run for 10 minutes a few times a week.
That's what I do.
And you don't have to run for hours.
It's just 10 minutes is enough.
Go biking.
So it's a fact that people who regularly ride bikes, and I think it was something like up to 80 miles a week, they would have a 40% less chance of having a heart attack than someone who didn't do that.
So it's a massive change.
It's not just a little thing at the margins.
Massive changes.
The other thing is, which I do, is to skip meals.
So it's not that hard.
I now feel weird if I eat a meal for breakfast or lunch.
And I try not to snack too.
This idea of nutritionists.
Three meals a day plus snacks, never be hungry, is killing us.
It really is.
And we know that if you do these things to animals in controlled settings, they live longer, a lot longer, 20, sometimes 30 percent, because they're healthier for longer.
They don't get cancer and heart disease and dementia.
So when you talk about how eating one meal a day can extend your life, is it because when you're eating all the time, you're taxing your digestive system, which taxes your resources?
Or is there some sort of a mechanism that leads to decay of the human body from overconsumption?
Yeah, so overconsumption or just consumption in general makes your body complacent.
And we know this in great detail at the molecular level.
There are genes that respond to how much you're eating and what you're eating and whether you're exercising.
And these are called longevity genes.
And they give our body resilience and fight aging and slow down what we can now measure, the biological clock.
So I can take your blood, or actually now we've developed a very cheap test, just a swab, to be able to tell you very accurately how old you are, not based on how many times the earth goes around the sun.
That's ridiculous.
Age is just a number.
You can actually take a swab.
I can tell you how old you are really.
But then, using real science, tell you how to slow that down.
And this is really cool.
Just in the last few years, we've figured out you can reverse human aging as well.
It's a group that has a chamber built by Germans, which is ironic, over in Israel.
So I went in this chamber, actually.
I visited them before COVID, some of my good friends over there.
And what they do is they put you—I don't know if yours is the same, but this is a really big room, and you can fit about 20 people in there.
And they give you oxygen, so extra oxygen, and then they raise the pressure up.
And then they drop it and raise it.
Is that what you've been doing?
Yeah, and so what happens, I think, to the body is the body's going, oh shit, I've got too much oxygen.
So it responds.
And then the decreased oxygen makes you feel hypoxic, like running.
So this is a way of getting, in my view, exercise without having to exercise.
And then you turn on these longevity genes.
And I would bet, though I haven't proven it yet, though I am working on it, is that some of these genes that we've discovered, the sirtuins, or discovered to be involved in aging, we didn't discover them, Are activated by this hyperbaric chamber.
And what they showed in this paper that got probably you excited as well as everyone else is they looked at the ends of chromosomes which shorten over time the telomeres and actually got longer after this therapy.
And that is a sign of reversing aging.
It's not as good as the clock that I'm developing, but it is a good sign.
And they decided after examining these people from 90 days doing 60 sessions that it gave you the equivalent of 20 years decrease in biological age because of the length of the telomeres, which is super controversial, right?
I would say that it's not that controversial, but it's certainly not the only determinant of age.
What I think, and as I wrote about in my book, is that this biological clock, which is literally chemical changes to your DNA over time...
Is the real number.
Telomeres are out there.
They're like the wristwatch for health.
That doesn't tell you your real age.
It's an indicator.
And the reason that it's not believed by a lot of people, and I'm kind of skeptical to some extent, is that telomeres get shorter when cells divide.
Not all cells divide.
Your brain doesn't divide, right?
Not typically.
And also, the telomeres can vary quite dramatically if you measure them one week after another, one month after another.
They're jumping around.
The test isn't very accurate, whereas the one, what's called the epigenetic age test, or Horvath clock, named after my good friend Steve Horvath, that's much more accurate.
That doesn't jump around unless you actually do something to either slow down or reverse ageing.
So I would say that you want to do this test.
We should do a mouth swab.
Get you our test.
And you can decide if you want to release that number, but I bet you're younger than you are and we could tell everybody.
I don't need to make a lot of money, but what I need to do, what I want to do, is to make everybody aware of their health and how to benefit.
I mean, you and I, we read a lot about this.
We care.
But most people either don't have the time or the knowledge or access to the people we have.
This is what I want to do.
And it starts with this number, this overall arching top-level number like your credit score.
You can look at things like, did you pay your electricity bill?
Did you pay off your car?
Those are similar to the watch and the rings that you can wear and the heart monitors.
But the credit score is what matters.
And this number that we can tell you is really what tells your inner core age.
And it's irrelevant, really.
Lives are irrelevant how many birthday candles you have.
And what's really cool about it is that we didn't know until recently that if you do certain things like hyperbaric oxygen chamber or there's some things you can inject into yourself in one study, you can reverse human aging.
But I'm not speaking here to professional athletes necessarily.
But there's a third misconception.
It's crazy how this stuff becomes memes.
It turns out that the reason that the exercise doesn't build as much muscle is that you just get a little bit tired when you do the reps.
But if you have the willpower to do the same number of reps, you're good.
So just overcome that feeling.
And the reason for that, I think, is metformin interferes with your energy production in these little packages in the cell called mitochondria, the battery packs.
Well, you know, I'm always – I'm a Harvard professor, and I'm cognizant that they will watch this.
So I'm not prescribing anything, but I take this molecule NMN, which raises NAD, which we've shown in my lab and others, that it boosts mitochondrial activity, gives more energy, ATP, in animals.
And we're doing human trials right now, and it looks promising.
So I try to counteract my metformin with that molecule.
That's a supplement.
Metformin's a drug, which you either need a doctor or you can get it elsewhere.
Other countries, actually, it's over-the-counter.
It's so safe for them.
But long story short, I occasionally, you know, I'll skip a metformin if I'm going to work out, just, you know, in an abundance of caution.
But this controversy is way overblown, as you can tell.
Oh, so you could literally work out and then take your metformin, so then you don't have to worry about the negative effects because they're temporary.
So when the drug goes away, you've now got more energy.
And that also helps the body take up blood sugar, become more what's called insulin sensitive.
And that's why it works for type 2 diabetics.
But by accident, this drug has been shown in tens of thousands of veterans, mainly, but tens of thousands of people, To also delay other diseases of aging, heart disease, cancer, frailty, Alzheimer's.
It's amazing.
When you look at now its association, so for the aficionados, we don't know for sure if it does that.
But this is the closest thing we have right now to a drug that slows down aging.
Yeah, well, part of it's the boosting of the mitochondria number and raising the energy.
But it's got other benefits.
It's anti-inflammatory as well.
And to be honest, as I should be as a scientist, we don't know.
There's other stuff it does.
But we just know that people who take it, a diabetic who is sick and often overweight, who takes metformin, on average lives longer than someone who doesn't have type 2 diabetes and doesn't take the drug.
So it's needed for life, and it seems the more you have of that, the better.
Now one thing that one of my companies that I'm helping, and I've invested in to be honest, to be transparent, is developing is a way to punch holes in that membrane so that the hydroelectric dam is less efficient.
So we've got a leak in the dam.
And so not all the energy is going through.
So what we see happen in animal studies is that they can eat more food and not gain weight.
Well, I think it's also we're dealing with, like, think about what we're talking about here, about your field of study, about life extension and how to maximize health.
The amount of people that don't know what you're talking about and don't know the science and aren't even aware that this is possible is the majority.
So for someone to step out and say, you know what I'm going to do?
I'm going to do sauna and ice baths every day because it increases hormesis and it maximizes my heat shock and cold shock proteins.
And then I'm going to make sure I use blue light blocking glasses and I shut off my cell phone by 6 p.m.
and I don't drink coffee after 5 and all these different things.
Most people don't know that there's an actual...
The most quantifiable benefit to doing all those things.
And if you looked at like, this is an Anthony Robbins quote.
I'm stealing this from him, but it's a very good one.
That incremental change is if two boats are on the same path.
And then one veers off two degrees.
Over time, that two degrees equals a huge difference in the distance of your destination.
So if you have one meal, and say this meal comprises 2,000 calories or whatever, and you have this meal at 6 p.m.
and you fast for 24 hours until you eat again at 6 p.m.
If you have this one meal a day, why is it better to do that than to have, say, you know, smaller meals of like 500 calories multiple times per day, little snacks?
Well, because going back six million years back, you know, we're in the trees and then in the savannah, our bodies were designed, well, or evolved to respond to adversity.
And we've removed that from our lives because it feels good.
But we need adversity to be resilient and to fight disease.
So what I'm saying is that period of hunger.
And it's not even hunger these days.
I don't even feel it.
I feel great if I don't eat.
And it takes a few weeks.
So anyone who wants to start, give it some time.
Give it a couple of weeks.
But what's happening in the body is you're turning on these adversity hormesis response genes.
We call them longevity genes.
And they make the body fight aging and diseases.
And so by eating through the day, the traditional, oh, you've got to have breakfast, best meal of the day, blah, blah, blah.
First of all, it's not true that you need to be full or fed to think clearly.
It's very clear that people who are fasting have as good, if not better, mental acuity.
Okay, that's one.
So I think that that needs to be thrown out the window.
Kids are different.
We're not talking about kids.
We're talking about adults.
And we're not talking about malnutrition or starvation too, let's be clear.
But we are talking about lengthening that window of not eating.
So if you always are satiated, fed, your body says, hey, I've just killed a mammoth.
No problem.
Don't need to worry about survival.
I'm just going to go forth and multiply and screw my long-term survival.
So this is all about long-term survival by making the body freak out that there's tough times.
And that's running away, like running away from a cat, like the savannah, and being hungry.
You know, there's molecular reasons that all this works, but, you know, trust me, the data's very clear that this is the way to go if you want to be healthy in your 80s and 90s.
Well, it actually does make sense when you put it in that way, that your body, when you're fed, relaxes.
And so if you're just doing that all day long...
And I know for a fact that when I am not fed and I go and do things, whether it's perform...
One of the things that I've been doing is I don't eat...
Before shows like I take many many hours before a comedy show and I used to just like eat whenever I just see and then I would do shows and I would have a meal like an hour before the show and I'm really trying to wake up.
I'm really trying to come on come on Come on.
But I've now recognized...
Actually, I saw a video where Cat Williams was talking about this.
I don't like that feeling of a brutal workout and then being starving for four or five hours.
Because then it becomes a distraction.
So I listen to my body.
But if I don't work out...
I don't eat until dinner.
Like say a day like today.
I didn't work out today.
So I woke up, hung out with the dog, had some coffee, sat out, you know, like just went over some emails, did some shit, just a relaxed morning, and then rolled into here, no food.
Yeah, so you're doing the right things, certainly better than most people.
But what I'm trying to build or make are molecules that mimic fasting as well.
So if you cannot fast like I do, then you can just take a pill.
And what we've shown in mice, at least, is that if you give them this molecule that I'm taking, NMN, nicotinamide mononucleotide, which, as I mentioned, speeds up metabolisms and all that stuff, those mice could run 50% further.
These old mice, we gave it to them for three weeks, put them back on a treadmill, and those that had the NMN in their water ran 50% further.
They had better blood flow, better oxygenation, better energy.
But yeah, we're going through the procedure that has been around since, as I mentioned, early 20th century.
But we've done hundreds of people now, certainly dozens, over the last few years.
And we know at least that this molecule is apparently safe and raises the levels of the molecule we want to build up.
The molecule is called NAD. Do you want me to talk a little bit about NAD? Yes, please.
So NAD is what those mitochondria, little, Mike and Ike, little energy producing things, use to make energy.
So there are two molecules in the body that are really great.
You need both for life.
Without them, as I said, you're dead.
ATP is the energy and NAD makes that.
And as we get older, the levels of NAD go down.
Our body makes less and actually also degrades it more.
So if you take my skin, or in the study that they took people's skin, when you're 50, you've got half the levels of this NAD than you did when you were 20. Which is scary because this molecule is required for life.
Without it, we're dead in 30 seconds.
So what we're doing with our clinical trials is giving a precursor, a smaller version of this, that the body will turn into NAD and bring those levels back up from where they are when you're old to where you are when you're young.
And we see at least in animals and hopefully in people that it revs up their metabolism and makes them fight aging and disease like we do when we're young.
I mean, there's a reason we don't get a lot of heart disease when we're young or Alzheimer's because our bodies fight against disease as we get older and especially if we sit around or smoke and don't exercise, our bodies just give up.
My assumption is that they're working the same way, same effects, but nobody's put them head to head.
I'm yet to see a clinical trial that shows that literally any of them actually work the way they're advertised, but the theory is that you'll have the same effect.
I don't know if NAD IV is better.
I mean, it's certainly more direct than eating it, and your gut's not eating it.
And to my Harvard colleagues, it's just an anecdote.
This isn't a clinical trial.
So I wrote my book.
It took a couple of years.
I sat down for most of that time.
And my piriformis muscle, which is one of the main ones in your – holds your hip up – Cramped up.
And for probably 12 months, I had a permanent cramp in my ass.
That was really painful.
I could barely walk.
Made me really grumpy.
And I couldn't get rid of it.
Exercise, building muscle, physiotherapy wouldn't go away.
And this happens fairly frequently to people who don't stand up.
So I now have a standing desk.
That's another good tip.
But I went out to California and met with some of the power broker people in Hollywood who shall remain nameless, but there's plenty of people you and I know out there who are doing this.
They recommended this one person who's well known and very kind.
She said, go to see my doctor.
Get an NAD shot.
And I thought, come on.
NAD shot?
Who believes that science?
So I went anyway.
Honestly, out of courtesy.
I thought it might work, but I'm always up for something.
And the doctor injected it into my ass.
And I felt a tingle, as was supposed to happen.
And I walked away thinking, yeah, that was fun.
Been there, done that.
And I flew home that night, and I was at the airport, LA airport, and I found that something was different.
I was kind of skipping in my walk, and I thought, it's gone.
After a year, this damn thing is gone.
Now, Gabby Reese, the volleyball player who was at her place jumping up in the pool the other day, that's hypoxia.
I almost drowned again.
But anyway, Gabby says, it's probably just the needle.
And she might be right.
This is not a clinical trial, but it's certainly interesting.
Yeah, they basically take acupuncture needles and they stick them in stiff muscles.
And a lot of times they do it in conjunction with electrical muscular stimulation.
So they'll put these little clamps onto the acupuncture needles and it just goes doot, doot, doot.
It gives you this weird pulsating thing in your muscles, but it's really beneficial for releasing and relaxing really tight and tense muscles.
I have an imbalance in my back because of power kicking on my right side.
My left side is what stabilizes it, so the left side of my back is thicker than the right side of my back.
Because if you think about it, if you're standing here like this and you're doing this all the time, you're leaning into the left side and throwing a kick with the right leg.
And then also when I draw a bow back, I always draw it with my right side.
And so my right shoulder is stronger than my left shoulder.
But my left shoulder is stronger pushing because the left shoulder pushes and the right shoulder pushes.
I've got all these fucking weird imbalances in my body.
If you smoke some marijuana before you get an NAD drip, I did it in 10 minutes.
Yeah, I just sat high as fuck, sat there, but so high, I got paranoid.
But if you, there's something that happens with, you know, marijuana reduces nausea in patients with cancer, going through chemotherapy, a lot of people that have wasting issues, different ailments where they have a difficult time eating.
Marijuana reduces nausea.
And whatever that mechanism is, marijuana has a profound effect on the way your body processes the NAD drip.
Because the difference for me between NAD drips with no marijuana is rough.
The fastest I did it with no marijuana was like 30 minutes, maybe?
So a good friend of mine at Wash U, Shin Amai and colleagues, showed that the NAD levels in the body of an animal, probably in a human, they cycle through the day.
They go up in the morning, get you ready, and then they go down at night.
So you don't want to be taking these supplements or having this stuff injected into you late at night because it'll make your body believe that it's the morning.
And I also believe, and it really is backed up by the mouse studies, that jet lag is caused by a disruption of this cycle of NAD going up and down in your body.
And so I've been using NMN, this supplement, to reset my body when I travel.
And what actually happens, unfortunately, is even if you get your light in your eyes, which resets your brain, your liver has a clock, other tissues.
Do you know that?
There's separate clocks within the body, and if they're out of sync, maybe your liver is looking for a meal, but your brain says it's the middle of the night, and you don't know what to do, and that's why you feel like crap.
The winding down thing is really hard for people that are like high-performance people that are working all the time and you're go, go, go, go, go throughout the day.
And then sometimes when you lie down, it's the only time where you're not engaged with an activity.
So then your mind starts racing and starts doing an assessment of all the various things that are going on in your life and throughout your day.
That's my issue.
When I go down, I have to make sure that I do not allow my mind to start going on a rampage and thinking about various projects I'm involved in or different things that I'm working on.
Then I'll get stuck.
Because it's one of the rare times where I'm alone by myself, not thinking.
Like, I'm not by myself, but you know, I'm just, I'm not engaged in anything.
I'm just laying there.
And sometimes when you're just laying there, your mind's like, oh, we got nothing to do.
Terrific, because there's a lot of shit I've been wanting to talk to you about.
It's like, you know, it's like if you don't have a conversation with your spouse and then, you know, you don't talk all day but a lot of things are going on, then finally at the end of the day, like, okay, here's the things we need to talk about.
Like, that's what it's like with my brain at night.
It's like, hey, fuckface, there's a lot of shit you need to work on.
Like, let's do this and then that and what about that and how about this?
Like I feel myself starting to think about maybe like a bit that I'm working on that I need to correct or, you know, this is not the right way to do it.
I gotta go, hey, hey, hey, stop and just think about your breathing.
So my number one trick is just concentrating on in and out and in and out.
It's not even.
Along the way, I will go right back into the things that are bothering me and write down, oh, I screwed up this, or I shouldn't have said that, and in and out, and in and get myself right back on track, and eventually I fall asleep.
But you're pretty confident that with further research, it's most likely going to determine that all these things are extremely beneficial to basically the overall population.
So there's a photo of the two of them in the Top Gun movie where she's young and beautiful and he's young and handsome and then there's a photo of the two of them now and she's kind of let herself go a little bit.
He has not and he looks fucking fantastic.
It's kind of crazy when you see the contrast of the difference between someone who's taking care of themselves and someone who's not.
Yeah, I wrote about this in my book and in fact I used Tom as the example of what you can do and If you look at somebody his age that was in a previous generation, those actors look really old, and he looks great, right?
And he has taken care of himself.
I'm sure there's probably some other work that he's had done, but it can make a huge difference how you live your life.
That's the goal of me now, is to say, don't wait, because you don't want to waste away or have an accelerated age clock, the one that we measure.
And often it's going to be too late if you just wait.
In my life, I've been doing this since I was 33, doing various things, adding things along the way.
So even if you're older, look, it'll definitely have some effect, but the correct way to approach this is if you're a young person, don't wait until you get old.
Because you've got your high levels of NAD. You've got your longevity genes activated.
But there are things you should definitely do in your 20s that I did.
I didn't eat a lot of food.
I skipped breakfast my whole life.
And then exercise.
I used to go to the gym a lot and do a lot of aerobics.
And I definitely don't regret that now.
I've still got that core.
So I think in your 20s, do the basic stuff.
But then the supplements, I think, save till your 30s because your body has the longevity and resilience in those years.
But I'm speculating based on animal studies.
We don't know.
Nobody's done this kind of experiment.
And this is the problem.
They're going to know in 20, 30 years what I'm saying is true or not.
But we can't wait that long.
So I do my best to extrapolate from animals and look at societies that live a long time and make the best I can scientific judgment as to what will work.
Well, you know, our brain is designed or evolved to crave energy.
Makes sense, right?
Because we used to go through periods of famine.
We don't do that anymore.
So one of my points in the book that I'm writing about how we got here and how we get out of it, this treadmill that we're on, is that we're slaves.
Our limbic system that you and Elon talked about, the core of the brain that we don't seem to control very well with our frontal cortex, it's telling us Eat all the time, eat high calories, sugar, fat, have sex.
That's the evil part of our brain.
But we need to overrule that in general with our frontal cortex, which we have in abundance, the lollipop species.
Probably not because of all the shit you're putting on it, but would not fresh French fries then be kind of good because they're frozen and then you're reheating them?
It's surprising she made it as far as she did to 92. So when she quit smoking, it wasn't the addiction, but she had this thing she needed to put in her mouth.
So she had one of those cigarette holders, and she was chewing and sucking on that for a couple of decades, which as a kid was really off-putting.
To me, it's very odd that people have such incredibly ingrained patterns that physical activity of just putting something to your mouth can help alleviate some of the cravings.
I don't even think it's marketed towards smoking, even though it obviously is, but it's calling itself aromatherapy as opposed to smoking or something like that.
They're planning on doing studies with former UFC fighters and dealing with people that have CTE. Yeah, because neurogenesis, because psilocybin in particular.
PTSD, I had Rick Doblin in here the other day from MAPS. And he's the one who is at the forefront of all this work and pushing this forward and getting approval to use all of these Schedule I substances and trying to make them available for therapeutic use for people with all sorts of issues, PTSD and all sorts of trauma.
It's an exciting time for brain research actually and for the patients because there hasn't been much you could do for people who had mental issues and even Alzheimer's.
Now we have these tools that are only going to get better.
Super exciting.
One of the things we're doing in my lab that's exciting is we can age the brain forwards and backwards now.
So since we last spoke, we published a paper in the journal Nature in December that showed we could not just accelerate aging, but now we can reprogram cells to make them, you know, a little bit.
So we were able to reprogram the eye of a mouse.
A blind mouse became able to see again by making the eye younger again.
It's a gene therapy, but ultimately you want to make it just a pill that reverses aging.
So we package it in a virus, and it's drug-inducible, so we could just take an antibiotic and turn it on.
But literally, it's just a quick injection in the eye, which we do to mice.
It's easy.
In humans, people get that all the time if they have macular degeneration or need gene therapy to correct their genetic defect in their eye.
And it doesn't hurt.
It's very quick, in and out.
And what we did with those mice was we then turned on these three genes that are normally only turned on in embryos, And we reversed the age of those eyes, and the mice could see again.
And now we're just ticking off the various tissues and organs that we can rejuvenate and turn the clock back.
And this is the same clock that I'm talking about with the cheek swab.
We now have the ability to turn that clock back, and it looks like it's permanent.
And so you set the clock back 50% in the body.
Now we do the eye, but hopefully the whole body.
And then you age out another couple of decades, take another course of antibiotics, go back again, and just rinse and repeat.
We know that the proteins in the cell that alter the clock are necessary for the vision to come back.
So the clock isn't just a clock on the wall.
It's actually representing time itself, which is amazing.
And we can read that with the same test we use for the cheek swab for people we use on the mice.
But we do a blood test on them.
Or we measure their eyes.
We can extract their eyes, forgive me.
And then we measure the age of their eyes using the same clock test.
But literally what it is, is we take their DNA out of each cell.
Each cell has about six feet of DNA. And of course it's bundled up very tightly and how it's bundled up determines the age of the cell.
So a young cell will have beautiful loops of DNA and bundles that tells it to be a nerve cell at the back of the eye.
But over time what we see is in part due to DNA damage and cell stress and injury, those loops and bundles get disrupted.
So now instead of this beautiful loop bundle pattern like a symphony on a piano, they come unraveled.
So the bundles get unraveled.
And instead of it being a symphony, the cell is playing a cacophony and no one wants to listen.
And it messes up the cell's ability to work.
They're still in the eye.
They haven't died.
But they're just not working like a nerve cell.
In fact, they think they're more like a skin cell.
They lose their identity.
So when we put in our three gene combination and turn them on, somehow, we don't know how, Those loops and bundles of DNA go back to their original structure, like playing a concerto again.
Or, I mean, I use the analogy of a compact disc.
For the young people, that's a little disc we used to put music on.
But the aging process is analogous to scratches on a CD, so that you skip songs when you get older, and literally we're skipping genes reading when we get older.
And our treatment is polishing the CD so that the cell can now read the beautiful music of youth.
And so down the line, this may be a thing that people do where every X amount of months or years, you go in and you get a shot and it backs your age up a few years.
I mean, your gut is so important, and the gut-blood barrier is increasingly known to be important for aging.
As that breaks down, bacteria in your gut leak across, leaky gut syndrome, and we're finding, we scientists are finding bacteria showing up in cancers and even in the brain of Alzheimer's patients, and we think that they might be a cause of these diseases.
Well, you know, how much goodness and happiness has he brought to the world?
That's what scientists should be all about.
It's not just about publishing.
That's what is the immediate goal.
But there are a lot of us, like Andrew Huberman you mentioned, a really good guy, a good friend of ours.
He also wants to change the world, and he's from Stanford, one of the lesser universities.
But I love guys like that, people like that, because a lot of scientists are just about what's my next publication, but there are a few of us that look at what is the goal?
What are we really trying to do here?
We're trying to make the world a better place.
How do we do that?
Well, we'll innovate, we'll have IP, we'll start companies, we'll make drugs, and hopefully we'll be saving lives.
One of the things I really like about Huberman is he does things publicly.
So he's really big on using social media.
He puts videos up on Instagram explaining these things, puts videos up on YouTube, and they're really easy to follow.
And he'll show you and demonstrate to you, like he had one today, on the benefits of focus and posture, that there's some actual real benefits in terms of alertness just by posture and where you're looking at with your eyes.
Science.
And he's talking about this stuff.
It's not anecdotal evidence.
He's talking about the real neuroscience behind all this stuff.
He looks like a guy that you would say that if you saw a Marvel Comics movie and that guy was a scientist, you'd be like, that guy's not a fucking scientist.
Well, you certainly have a lot to offer, and you certainly have a perspective that I think a lot of people could benefit from, and you understand things that are super important for life that most people are unaware of when it comes to longevity and the strategies and the actual significant impact of all these things that we've discussed so far today.
I mean, it's amazing when I talk to people that are seemingly health conscious that are not aware of all this stuff.
And I kind of get it, because one of the beautiful things about this podcast is it's my job to talk to people like you.
So I've gotten this sort of accidental education over the past 12 years.
Guys like me, people like me and scientists, we never had this platform to come and speak to you.
Before that, we were speaking through reporters, newspaper reporters, typically.
And it was mangled and hyped and it was embarrassing and every story there was a lie or something wrong in there and a headline that was, we're all going to live forever.
And I rarely talk to the old media anymore because it's just too risky.
I want to talk directly to the public and it's been great.
That's why I don't do interviews because they'll take my words out of context, they'll edit it, they'll take something that I've said and put meaning to it that's not true.
And they do it because of clickbait, because their business is to sell things.
And I think it's very unfortunate.
I think it's changed pretty radically since the internet.
It's one of the few things that I think true journalism has suffered in some ways because of the internet.
I think independent journalism, like the Matt Taibbi's and the Glenn Greenwald's and the people that still practice independent journalism, they've thrived because of this vacuum that's been created.
I think there's many publications today, particularly the ones that are online, that survive by clickbait.
They need clicks.
And if they don't get clicks, they don't get advertisements.
So if they can twist things a little bit in the title or give you a deceptive title but then sort of correct itself in the body of the work, they'll do that.
But a lot of people just read the title.
And they're like, did you hear David Sinclair says he's living forever?
And then next thing you know, you have to talk to your colleagues.
And even your doctor, they find it hard to keep up with all of this.
They don't know what's true.
I recently saw my doctor after a year indoors after COVID, and it was a virtual meeting with my doctor.
And he's a Harvard-trained, Harvard specialist.
So you think top of the world.
And so this is how the meeting goes.
Hi, doctor.
Hi, doctor.
Whatever.
So how are you feeling?
Feeling good.
Okay.
So how's your sleep?
Blah, blah, blah.
So it was just questions.
Okay, we're done.
Hang on.
That's not enough.
You know, don't you want to know about this or this or this?
And I said, for example, give me a prostate-specific antigen test, PSA, which is important for people our age because prostate cancer can show up.
So his question to me was, well, do you have a family history?
And he said, your father's not alive.
I went, half the world knows my father's still alive.
You don't even know that my father's still alive?
That's firstly a problem.
Second of all, I said, no, he doesn't have prostate cancer, never had it.
He goes, okay, well, do you have any symptoms?
No, but why the hell am I going to wait until I get prostate cancer before I come and see you?
Get the test.
And he goes, okay, get the test.
But that's the problem with medicine right now.
You either have to be sick or have a family history before they treat you.
So one of the things I've been saying for years, in my book especially, is aging is a disease and it's treatable.
And, you know, I think we all have a family history of aging.
So let's treat it.
Let's try to prevent it.
And, you know, I think that we'd really have a much better society if we came in early and tried to stop things before they actually occurred and we went in and we were sick.
So here's the good news, that there is a massive megatrend, zeitgeist revolution in aging research.
I used to be in the backwater of biology 20, 30 years ago, 25 years ago.
Now billions of dollars are being poured into research and development.
It's super exciting.
There's new breakthroughs all the time in leading scientific journals and companies being developed for new ways to treat skin, to rejuvenate that, livers, kidneys, and eventually whole bodies.
So is it going to happen in my lifetime that we can reverse aging in part of the body?
Yeah, absolutely.
I'm going to die trying.
And I think if we're really lucky, in two years we'll have a success.
I don't know, but I know that just in the same way as the Wright brothers built the Wright Flyer with powered flight, it was an inevitability that there was going to be a Concorde and a jumbo jet, 747, and go to the moon.
It's going to happen.
It's just a question of how much we as a world want to invest and accelerate it.
In the future, let's not even put a timeline on it, but let's think about how this technology progresses and just assuming we don't blow ourselves up or get hit by an asteroid or the aliens land and stop all the nonsense.
When you look at the future, you anticipate human beings, science, to have complete control over this process.
and the ability to literally bring the body back to peak form in their prime absolutely We are toolmakers.
I'm like Elon, but the way I think about biology is we can do anything.
We can understand it.
There are many species that live longer than us.
We've got an elephant clock, cheek swabs from elephants.
They've figured out how to not get cancer for 100 years.
They have multiple copies of a gene called P53, which protects them.
We only have two copies.
And that's just an example.
We can engineer ourselves either through medicine or through even genetically changing our species so that we don't ever get cancer, at least not for centuries.
Well, what COVID taught us is that your age matters, not just for how you look and diseases like heart disease, but dying from infection.
So if you can stay young, let's say you've been exercising, eating the right things, eating less, you will be literally younger based on that clock and you will have a much better chance of surviving COVID if you're obese and you don't exercise.
We saw those were the most susceptible to infections.
So one is stay young.
The second is there will be medicines to rejuvenate the body.
We're testing our NAD boosting drug right now in COVID in 30 hospitals around the US. So fingers crossed for that.
Maybe not for COVID, but eventually the next virus that will definitely come.
By the way, I don't know if you remember in my book, which came out a few months before COVID, I said we're going to be hit by a virus, a pandemic.
And most people went, yeah, here he goes again.
But it happened.
Unfortunately, I'm not proud of predicting it, but I knew this would happen.
And so I was getting ready for it.
Anyway, so that's what technology is.
There's a third technology, which is we could engineer our genes.
Just the way vaccines work, you stimulate the production of antibodies that recognize certain proteins, like the spike protein on the outside of COVID-19 or SARS-CoV-2.
And so we could definitely make children that would never have a problem with SARS. The problem, though, is that viruses are smarter than us in many ways because they evolve super fast, and we always are one step behind them.
So I don't think it makes sense actually to genetically modify for specific viruses.
But there might be ways that are universal.
An antibody that recognizes all flu proteins.
We could put that into children and they never get flu.
Now, when you look at human bodies, one of the things that's always been interesting to me is how much variety there is in terms of how we react to certain things.
How allergies and things along those lines and how people react differently to different foods.
Is there a way that you can anticipate where one day we'll be able to give someone a test and say, oh, your ancestors thrived on these particular types of foods and these are more beneficial to your body?
It seems like this one-size-fits-all approach that some people preach, it's just not effective for everybody.
It might work with that one person.
It's sort of like, do you remember that book, The Secret?
So if someone says, like, you know, the key to health is to only eat meat.
Some people, that fucking works.
It really works.
There's some people that eat carnivore diets and their eczema clears up and their brain fog goes away and they're healthier.
These sort of diets where your elimination, elimination diets.
But I know other people that go vegan and they go vegetarian and they just, they basically get all their protein from plants and they feel much better.
So there's obviously some sort of a biological variability that exists in people.
We know it is, right?
I'm not allergic to peanuts, but you can't even eat peanuts on planes anymore because some people are so allergic that the dust from you chewing peanuts can get them deathly ill.
Well, thank you for saying that because for far too long we've treated the average human and none of us are average.
And we're changing the way we treat people in medicine and with wellness because we have to personalize it.
And the only way to personalize something and to know if it's working for you is to measure it.
Hence, you know, the company that I'm building to measure things.
But that's really important because it now means we can tailor your food to you, your supplements, your exercise.
Because they're really, like you say, everybody responds differently.
I have a different microbiome in my gut than anyone else on the planet.
And how do I know?
Well, I measure it.
I can measure these things.
And so in the future, and not too distant future, we can even have an app on our phone that will say, all right, your latest reading from your heart, from your swab, says that you're deficient in these things and your epigenome, the scratches on the CD are looking like this.
That would be the most bizarre thing if you go to a restaurant and a restaurant would serve you a meal that's been genetically engineered to correct all the issues that you have.
And the problem today is that we can measure our genome and there are a number of companies that can do that.
But we're missing the other half of the information, which I would say is even more important for health, which is the epigenome, the control systems, this clock that I'm talking about, which we can measure.
And that together tells you whether you're going to be an asthmatic or susceptible to diabetes.
Because the DNA itself is just...
We don't know how that code is being used throughout our life and it changes.
Every time we have a meal, every time you see something, it's changing in your body.
So you've got to measure both of those to get the real answer to whether what you're doing is working and how to fix it.
This has got to be a very rewarding career path for you because you're not just engaged in something that's intellectually stimulating, but you're engaged in something that could potentially benefit the human race in a spectacular way.
What is that like knowing that you're working on this stuff?
Well, even in the US now, population is declining.
The fertility rates have gone down.
And when you do the math, the rate of people who die from aging is barely the replacement of...
Well, birth is barely replacing the people who die, especially in most of the world.
I mean, there's still certain parts of the world that are reproducing at high rates, but even those are coming down.
I was in Africa a while ago and there were these people I talked to on the ground, literally on the ground, were saying, "Yeah, we used to have 10 kids and now we have two and we want them both to go to college." So we are in a world now where if we don't do anything, population is going to decrease, which isn't that great either to be honest.
But we also have technology to solve the way we treat the planet.
There's no way we can continue exploiting the planet the way we do right now, even with the current 79 billion that we'll have on the planet steady state, which is predicted.
Bill Gates talks about this wonderfully on YouTube.
Please check it out if you haven't seen it.
And so the future of humanity is it's going to be steady state.
Maybe it'll top out at 10 billion.
But even with aging, not being cured, but slowed down and extended health-wise, we're not going to run out of room.
But resources, yes.
But that's going to happen anyway.
So what we need to do is to solve the healthcare problem.
We spend 17% of GDP in the US on sick care.
It's not even healthcare anymore.
And if you can save, let's say, even a few percent of that, Within that decade, that's trillions of dollars that you save that can be put towards research and development for climate change and other things that we need to solve as well.
There was a woman that I had on recently, Dr. Shanna, the woman who talked about phthalates and all the various—she's an environmental epidemiologist, Shanna Swan, and she was amazing.
And she wrote a book—what is the book called?
She wrote a book on declining fertility rates, declining testosterone rates, increase in miscarriages, and declining birth rates in people that's directly related to the amount of phthalates that we find in their body, which come from environmental toxins, primarily from plastics.
There it is.
That's the book.
It's called Countdown, How Our Modern World is Threatening Sperm Counts, Altering Male and Female Reproductive Development and Imperiling the Future of the Human Race.
It's an amazing, amazing book.
And the podcast was incredible.
She's so interesting.
And she's really funny.
She has a thing on her Instagram called The Jizz Quiz.
Because literally, if you track the phthalates in the water supply and in food supply and in human beings, there's a direct correlation between the introduction of petrochemical products and the decline in sperm production and the decrease in the size of the taint.
Which is really crazy because taints apparently in mammals are one of the very best ways of telling the difference between males and females because the taints in males are generally fifty to a hundred percent larger than the taints in females.
But the introduction of phthalates is shrinking these taints and it's making male penises smaller, it's making the testicles smaller, and lowering the sperm count.
And people are on testosterone replacement earlier in life, they have lower fertility, lower sperm count earlier in life, and generally they have less energy, they have less vitality, and it's these fucking chemicals that are in our plastics that are leaching into our bodies.
But it's measurable, and it's only really been studied to the extent where she's describing it in these peer-reviewed studies that have come out over the last decade.
This is a new science and a new understanding of this impact, and it's really terrifying.
And it's on the theme that I mentioned, which is we've gotten to this point with technology, but technology screws us.
So we have to engineer our way out of the problems that we've created for ourselves.
And this is a treadmill that we may never get off.
But we need to embrace science to understand what's making us sick and then solve that with ingenuity and the FU gene.
I don't microwave plastics anymore for that very reason.
It's scary.
There's PCBs and all sorts of stuff.
I truly believe that that is an issue for us.
There's a real problem with testosterone, too, with men, that it goes down with aging, but it's just going way down.
One of the best ways besides taking either a cream or an injection of testosterone is what you do, and what I do a little less than you, is to build up your core body muscles.
The big muscles actually tell your testes to make more testosterone.
And for me, that's been helpful.
I do hip hinge exercises a fair bit, try to build up those muscles.
Well, any time you're adding weight, like any weight-pushing exercises, you're building bone density.
And one of the problems with sedentary people is when you're not weight-bearing, you're not carrying things around, not lifting, and you don't have any resistance exercises, your bones get fragile as you get older.
Especially with our mineral-poor diets, you know, there's just...
Mineral poor diets, no weight resistance, not good.
But if there was like one exercise that you can do that is like if someone said, all right, I just want to do one thing, I might say kettlebell swings.
And so I've lost a fair amount of weight since COVID. Stopped eating large meals.
And I've never felt better.
I'm not calling it prescription, but what I've done to my body over the last 10 years, if you measure my blood biochemistry, and even this mouth swab test, I'm younger than my chronological age.
In fact, I've been getting younger over the last decade.
Do you think it's an NMN? Well, I think it's the combination because I'm a scientist and I add things one by one and then measure them.
Again, you've got to measure something if you're going to fix it.
And so I add things.
Sometimes they do nothing to my age or to my health or how I feel or my mental ability.
And then I don't do that anymore.
And then I add something.
Oh, great.
That worked.
I keep that.
And then I'm just adding that on.
I would say I'm not the smartest guy in the room by any means.
At school I was, you know, reasonably intelligent.
But I wasn't the smart one.
But I think that through what I'm doing and through mind exercises and just running a marathon in my mind, figuratively speaking, every day, I am smarter than I used to be.
And it's interesting, right?
I'm engineering my body to be better and better and younger and younger as I go.
I think definitely mentally this is as smart as I've ever been.
Physically there's certain things just because of injuries, particularly like back injuries, that my body has a hard time doing at full clip, like martial arts.
But it's just because of the unusually extreme demands that the things that I'm interested in require.
Like jujitsu and kickboxing are two very explosive things.
So the pressure on the tendons and the joints is pretty extreme.
I think you're making a ton of sense and I think also as you get older, there's something that happens to people as you live your life, hopefully, where you keep making mistakes but you make less of the same mistakes because you go, oh, I remember the last time I fucked this up.
I'm not going to do this like that anymore.
And then you anticipate, well, if I do that, that's going to cause problems, so I'm going to do this.
And then as you get to be 50 years old, you have a lifetime of these things that you can draw upon.
Hopefully, you have a lifetime of corrections of mistakes that led to success.
Unfortunately for some people, it's just disaster after disaster, and they never develop either a strategy or a pattern of behavior that leads to improvement in the way they think and behave.
And this is us as the time traveler species that makes us different than all of the others, is that we have a very good ability of, in general, learning from our mistakes.
And people like us, every night, are like, oh man, I screwed that up.
I've got to fix that.
And that's a way of improving yourself throughout your whole life.
And that's what we call wisdom.
And, you know, I know when you're 20, probably you and I, as well as most 20-year-olds, think that we're the smartest people on the planet.
We can solve everything and the old people don't know anything.
But if you're 20 and listening to this, I can tell you, guaranteed, that when you're our age at 50, you've got so much wisdom to refer to because you will make mistakes and you will learn from them.
And that's why I like being an educator, is that I don't want my students or anyone on the planet to make the same mistakes I've made, and I've made plenty along the way.
Well, overall, the problem with the thought of do you care about older people is it's so abstract.
Like, yeah, you care about them, but they'll be fine.
They're over there.
They're just doing their thing.
But then when you find out that there's a disease that targets old people disproportionately, and then unfortunately what happened in places like New York State where they were taking people that are COVID positive and bringing them back into nursing homes and it ran through them like fire...
That kind of shit we hear about.
It just makes you so sad when you think about the last few years with your grandmother that you could have enjoyed and now she's gone because of this fucking disease.
People say, oh, well, she was 86. What'd you expect?
Well, didn't expect someone to bring a COVID-positive patient back into the nursing home and infect her and everybody else around her.
Like, she could have lived a few extra years and enjoyed her family a few extra years and they could have had those memories.
So I think it made us directly aware of many, many things about our mortality and about what's precious and what's important.
And because so many people were forced to stop working and so many people lost their businesses, I think it made people rely on community more, too.
There's a lot of negatives that happen during this COVID, this pandemic, where a lot of really hysterical people, and I don't mean that in a funny way, I mean people that were prone to anxiety and people that have a difficult time with stress.
In a difficult time with adverse conditions and situations, this accentuated them past their breaking point.
And you see them on Twitter just freaking out, wearing three masks and screaming out the window.
There's a lot of people that lost their fucking mind.
And I'm hoping that we can bring some of those people back to baseline over the next few months and slowly, you know, just...
Everybody calm the fuck down.
Let's learn something from this.
Let's do better.
And what I really hope people learn as they go over the studies and they look at all these things that we've learned is your health is of paramount importance.
It is the most important thing.
The number one comorbidity besides vitamin D levels is obesity.
I've been in situations where I gained weight, and not even that much.
But then when I lost the weight, I was like, ah, I feel so much better.
Like, that's...
A guy gaining 10 pounds and losing 10 pounds.
That's not a lot, but if you're 50, 60, 70 pounds, like my friend Laura Bites, she's a hilarious stand-up comic, and she was on a podcast recently and I hadn't seen her since I was in California, and she lost like, how much did she lose, like 60 pounds?
50 pounds?
A lot.
She lost a lot.
She looks fantastic.
She just...
She found out...
She's really funny.
She found out at the beginning of the pandemic.
She's like, well, what's the thing that fucks you up the most if you're fat?
She goes, well, shit!
I'm fat!
Time to lose weight!
And she just decided to go on a sensible, reasonable diet and exercise.
She used online programs, she followed someone online, and is now on a total health path.
And when you talk to her, she's like, everything feels so much better.
I have so much more energy, my body feels better, I can move better.
So, a friend of mine who I've co-published a couple of papers with, Ray Cronus, he advocates the cold therapy.
And we came up together and we published this thing called the Metabolic Winter Hypothesis, which is when we were out in caves where Cro-Magnon people...
We would go through winter being hungry and cold, and that is what we need to be healthy, or at least mimic that.
And so the fasting and cold therapy is what we've evolved and what our bodies need to be in tip-top shape.
And the problem is we basically stay warm.
Especially here in Austin, it's pretty warm mostly.
And so his prescription, which has worked really well for some celebrities he's worked with, among others, is that you want to be slightly chilly.
Keep your house temperature down, sleep without blankets, and don't eat a lot.
And he says, I think it was something like, if you don't shed half a pound a day, you're not doing it right.
And then the other time one of them leaked and it was my mattress was wet.
I was like, what the fuck is going on?
You know, because what it is is essentially like you put this cover over it and the cover has these tubes in it and the tubes have water and then there's a machine that sits by the bed and the machine cools the whole deal.
I did a show last night at Vulcan Gas Company, and then we went to Golden Tiger, which is maybe the best fucking cheeseburgers in the world, and I had two of those bitches.
Yeah, there was a great podcast that I did recently with Ethan Suplee.
How do you say it?
Suplee or Suplee?
Suplee.
Ethan is an actor, and at one point in time, he was more than 500 pounds.
And now, he looks like a football player.
Now he looks amazing.
I mean, he looks like an athlete.
He's like this big, muscular, healthy guy.
That's him.
Look at that.
Look at the difference between him on the left and him on the right.
I mean, substantial.
I mean, really, really impressive.
But what he's done on top of all this exercise and diet and taking care of himself is express himself and talk about what the struggle was like.
And part of it was like, at one point in time, he had lost so much weight that he had to get his skin cut and removed, and then he gained 100 pounds.
So he goes back and forth and back and forth.
And he did this over like 20 years until he got to where he is now.
And he's a really, really bright guy.
Super smart dude.
So it has nothing to do with intelligence.
Like willpower and intelligence, they're not necessarily directly related.
And willpower doesn't even like cover all of it.
Because there's so much...
Weird psychological shit that's going on with people that do things that they know are bad, but they keep doing it anyway, whether it's cigarettes or gambling.
But he got it dialed in, and it's a massive inspiration to people because you see him now.
Anybody that would say you shouldn't talk badly about obesity, you shouldn't say that obesity is bad because you're going to make people's feelings hurt when they're obese, I'm not trying to do that.
I'm trying to inspire you to try to achieve what that guy's done, what my friend Laura's done, what many people that I know have done.
I'm trying to inspire people because it's possible.
You're alive.
You're breathing.
You're moving around.
Can you do all those things?
You can get to a better place.
And once you do that, you'll have extreme satisfaction.
And I think you'll also have the knowledge That you are capable of great feats.
That you can do this great thing.
To lose 270 pounds like Ethan did?
My God, that's an incredible thing because that's a mountain that you chop down over years.
This is not an easy thing to get to.
For years and years and years, he slowly avoided temptation and then even fucked up and gained all this weight again and then slowly got back down again and now he's at a completely healthy weight where he looks amazing.
And actually your social circle has been shown to work against you in many cases.
So Ray I mentioned, he said that when he works with his clients, I think it's okay to mention that Penn Jillette has lost a lot of weight thanks to Ray.
And he found that you shouldn't tell people that you're trying to lose weight because there'll come a point where they say, you've lost too much weight, you should eat something.
Lonely people, that's got to be like a painful existence.
The feeling of, you know, that's why like the concept of incels, you know, involuntary celibates, like that is one of the most depressing things in our culture.
These angry people online, like...
Like, big grown-up man babies that no one wants to fuck.
Well, yeah, that's the issue that we do need friends and we need partners to take care of us when we're older.
But I think, generally, the reason that my guess, those people live a long time, and it's a fact that they live longer, is that you're countering cortisol levels.
When you're stressed out and worried and you don't have a lot of friends, you have these stress hormones, and cortisol is the worst one, the insidious one that causes you to age more rapidly.
Is released by the body under situations of uncontrollable stress or situations where things are unmanageable or you've gotten past your breaking point?
What is the difference between the stress that one experiences through cortisol or where cortisol is released versus the stress of, say, high-level chess playing?
You know, where this is obviously very beneficial to the mind.
From my understanding of the science is that if you reach a tipping point and you have real anxiety, that's going to secrete cortisol.
But being focused and having a high focus on what you're doing and taking your mind to the next level, even if your heart rate goes up a little bit, That challenge to the body and the mind, my understanding is that doesn't release a lot of cortisol.
But the hormesis effect, it's a U-shaped curve that once you get a little bit of intensity and biological stress and even mental stress, it's a good thing.
But you go over a tipping point and then it becomes bad again.
Actually, hormesis, the way it was discovered was people were spraying herbicides on plants, and they kept diluting them down, and everyone thinks, you know, the less you have, the less it'll work.
But the plants that got the really low dose, this is not homeopathy, this is real science, plants got low-dose herbicide that would kill a plant at high doses, grew better than the untreated plants.
And so what you want to do, even if you're a plant, is to experience adversity, whether it's a plant like a grapevine making wine.
It's a little bit dried out or fungus.
They make the best wines.
They make these molecules that I call xenohormetic molecules.
Xeno meaning cross-species, hormetic, hormesis.
And we get the benefits of plants that are biologically stressed out or have adversity without actually having to do it ourselves.
So I try to eat plants that have color in them, have been stressed, organic, not grown in a perfect greenhouse condition.
And when your body's releasing cortisol because of the high stress that you're in, this unmanageable stress, that is also one of the benefits of exercise that you can actually reduce that cortisol.
And it's one of those things that if you can just write down a routine and force yourself to do it, in the beginning, you'll still be stressed out.
It'll be hard to concentrate.
You'll be like, ah, fucking everything sucks.
But if you just keep going, if you just keep going, and when you get through the routine, you will literally experience during a one-hour exercise routine the actual alleviation of stress.
I think people it's entirely too easy to get through life for most folks and I think we're not wired for that.
We're wired for overcoming great odds and obstacles.
I think human beings are wired for predator attacks and all kinds of shit and we're worried about things that are real that are and when they don't happen I think we fucking stress ourselves out about little things.
Somebody said something once, I forget who said it, but it's a great expression and I like to repeat it all the time and I wish I could attribute it to that person, but they said, the worst thing that's ever happened to you is the worst thing that's ever happened to you, even if it's not much.
You gotta always remember that.
Human beings respond to the worst thing that's ever happened to them.
If the worst thing that's ever happened to you is your mom took your phone away when you're 16 and you're a brat, you know, like, you're like, fuck it, mom!
What the fuck, mom?
This is bullshit!
That is a person with no character because this is the worst thing that can happen to this spoiled baby is his mom took his phone away from him.
Whereas if you grew up in war-torn Serbia, if you, you know, whatever, you've had a very difficult life on the farm, you've been wrestling since you're 10 years old and you're preparing for tournaments all the time, that kind of person has experienced a level of stress and difficulty that makes normal situations in life far more easy to manage.
My grandmother grew up in World War II Depression, and she never got stressed.
For her, there was nothing that could compare to that.
I became a different person after I saw my mother die in front of me, and I couldn't do anything but whisper into her ear that she was the best mom I could ever have.
After that, nothing was as bad as that.
I would have a bad day at work and I'd come home.
How was your day?
Everyone would ask at home and I'd say, nobody died today.
It was a good day.
And that sets the baseline, right?
Once you've gone through something like that, every day is a good day.
If you could stay on this earth and enjoy your friends and enjoy your loved ones and do something that you actually love and get satisfaction out of for an occupation.
It's just so many people, unfortunately, get so stuck in whatever path they were initially on that it's so difficult for them to course correct.
They get stuck where they develop debt, they got a lease for a car, and they got a mortgage, and they got a this and a that, and then they have a family independence, and then they're moving up the corporate ladder, and the company needs you, Mike.
The company relies on you.
You're a big asset to the company.
And then you're like, shit, I really wish I was a pianist.
Anyway, my grandmother, I said, are you going to always be around?
She said, no, I'm going to die.
What do you mean you're going to die?
She says, everything that you love, your pet, cat, me, your parents, and you are going to die.
And it's not going to be pretty.
And as a four-year-old, that really freaks you out.
And that was a turning point in my life.
I said, that's not fair.
And then over the next few years, I thought, that's cruel to have consciousness, a species that knows that's going to happen, the future seer species, and be burdened with that knowledge that everything that you love is going to die, in many cases, horribly.
So I decided at age four to make that my purpose, and I've been working back from that goal ever since and figuring out how to get there, get a PhD, come to America, MIT, Harvard, make discoveries, go on a podcast.
And it's heavy also that through horrible tragedy and the worst part of human nature...
through genocide and war that she comes out of it the other end determined to only concentrate on important things and good only focus on what's significant and then to look at you and to think that you can really change this place I think you can man I think she's right I mean I think you've you've honored her with your choices trying every day thanks Joe Now
It's also optimizing the quality of the time while they're still alive, which is so important as well.
Just because someone's alive and in a vegetative state, just sitting in the corner drooling for the next 15, 20 years while they're still alive.
I experienced that with my grandmother, unfortunately.
My grandmother had a stroke when I was young.
She had an aneurysm.
And no one was home.
And she fell down and was in the backyard.
And by the time they found her, she had been there for quite a while.
And they gave her 72 hours to live.
They're like, you know, prepare.
She's not going to make it.
And she made it for 12 years.
And it was rough.
And when I moved to New York, when I was...
24 or something like that.
I stayed with my grandfather in New Jersey and my grandmother.
And so she was under, she had bed care and she couldn't move.
She couldn't go anywhere.
You know, she's paralyzed.
She would moan in agony and occasionally she would talk.
I remember my grandmother when I was young.
She was this really eccentric, interesting lady who always home cooked all of her food.
Home cooked her pasta, made her own sauce.
And she was just an interesting lady.
She's just a really unique lady and then to see her in this and she was so fiery and she was always like yelling about things and she's always passionate about things and then to see her completely immobile for the last 12 years of her life and then When I moved to New Jersey, well, I stayed in New Jersey for a while with them trying to save up money for an apartment.
And when I was doing that, I just got to see firsthand, like really clearly, like this life doesn't end well.
And it can end the way it ended for my grandmother.
In a terrible way where she was just in agony and it just it was me at really the beginning of a new stage in my life where I was signed by a manager who's still my manager to this day as a comedian and I was embarking on this like very promising aspect of my life and I was very excited.
It was a new beginning.
And here I am.
And then I move to my grandfather's place and stay with him and my grandmother.
I'm watching her die.
And she's dying slowly.
And it's ugly.
It's ugly.
I would just hear her in the middle of the night.
You could just hear her moan.
It wasn't a big house.
You could hear everything.
unidentified
And it was just a reminder, man, like you gotta get going.
I would love to go back and correct some of the things I've done.
Particularly things if I hurt people's feelings.
But you can't.
So what do you do?
You gotta keep going.
And you gotta learn.
And honor your mistakes and who you were and feel that pain and recognize that regret is very valuable.
Because regret teaches you that there's a real there's a cost to mistakes There's a tangible feeling that coincides with knowing you did the wrong thing or you fucked up or you you made an error Learn from that and use it as fuel and be the best person that you could be and it's possible for everybody to do that everybody can improve and It's not impossible.
And even if it's just incremental improvements in the quality of the relationships that you have, or in the way you interact with people at work, or in the amount of exercise you get in a week, or in how you stick to your diet...
All those little incremental steps, as we were talking about earlier, the little shift of a couple degrees of the path of a boat over the course of the entire journey, it's going in a completely different direction now.
You're a way better person.
This is one of the things that I concentrate on probably more than anything in my life.
It's just trying to just be the best person I can.
Listen man, you are in a weird position right now.
Just imagine if you kept people alive for an extra 10-15 years and those people that you kept alive had an incredible impact on the way our culture is formed because they've drawn from their lifetime of experience and all the things that they've learned and they've expanded on that and had the opportunity because they stayed alive for 20 extra years or 30 extra years.
To spread that to so many other people that also learned and it has this overwhelming effect on everybody.
The comfort that you get after growth is so much more enjoyable.
Because if you've gone through difficult things, especially self-imposed difficulties, the comfort that you get afterwards, like when you can actually earn relaxation.
When I plop down on the couch after a long, hard day, and I watch some TV, it's like, ah!