David Sinclair, Harvard longevity researcher, reveals lab-proven aging reversal via NMN (1g daily) and resveratrol (0.5g), boosting NAD levels to combat diseases like Alzheimer’s while dismissing superficial anti-aging trends like Botox. His father lived nearly 80 years through early metformin, statins, and exercise—approaches Sinclair now applies, including CRISPR-based biodefense against anthrax and Lyme disease eradication. Despite facing skepticism (e.g., Pfizer disputes, MIT peers calling him "nuts") and career threats, Sinclair’s persistence paid off: his first company sold for $720M, and he reinvests profits into ethical, transparent longevity research, aiming to treat aging as a disease and stabilize global health through science. [Automatically generated summary]
Well, I suffer from late night snacking, but I try to skip breakfast and even skip lunch if I'm busy.
So I'm a night eater.
But that seemed to be good, because a study came out about a couple of weeks ago, at least in mice, that it's not what you eat, it's when you eat that's most important for longevity.
It doesn't actually matter if you eat a lot in the morning or a lot at night.
I like nighttime eating.
But you need a period during the day, at least if you're a mouse, probably if you're a human, where you're hungry.
And that puts your body in a defensive mode.
These are the things that we've been studying in my lab for the last 20 years.
What are the processes that diet and exercise do for us that keep us healthy and why does calorie restriction and intermittent fasting make animals live so much longer?
And we think we've figured out a large part of how that works and now we're mimicking that with molecules.
One of the first molecules, infamous molecules, that we are known for is resveratrol from red wine.
That molecule discovered it in my thirties, or at least linked it to aging.
What we showed was that if you give it to a fat mouse, they're as healthy as a thin mouse.
They live just as long.
They didn't get heart disease and all of the other bad stuff.
Then what we did was interesting.
We gave it to the mice either every day in their food or let them skip a meal every day so that they were fed every other day.
And that combination of resveratrol plus every other day feeding, we had the longest lifespan we'd ever seen.
And so it was additive.
Same with exercise.
If we give our latest molecule, called anamn, to a mouse and we exercise it, it'll run even further than it could with either of those alone.
So it's not an excuse to sit around and just eat chips and watch TV. It augments a healthy lifestyle, gets you further than what you could get naturally.
In fact, if you don't have NAD in your body, you'd be dead in about 30 seconds.
It's a really important molecule.
But as we get older, we lose NAD. So by the time you're 50, like I almost am, you have about half the levels of what you had when you were 20. So that's not good.
And these sirtuins, they don't protect the body without high levels of NAD. So what NMN does, and this other molecule called NR, which both you can get on the internet, they boost the body's levels of NAD back up to youthful levels again.
And if we give them to mice, these molecules to mice or even to worms or yeast, they live longer and they're super healthy.
M-E-T? F-O-R-M-I-N. And so out of studies of 10,000 people and more, it's been shown that people who take metformin, even if they have diabetes, are protected against other diseases of aging, even frailty.
And so most scientists, if you ask them in my field, will say, yeah, metformin is likely to extend your lifespan.
It's just that the FDA doesn't let you have it for aging, because aging isn't a disease yet.
So this is the great thing, is that over the last 20 years, we have figured out, we scientists have figured out, that there are universal regulators of aging, from yeast to worms to mice and in humans.
And there are three main pathways that we've figured out respond to what we eat and how we exercise.
And one of them is called AMPK. And this is a target of metformin.
And so when I take metformin, I'm activating my AMPK, which will send out the troops.
The sirtuins I've mentioned, that's the second of the pathways.
And so I take NMN and resveratrol for that.
And then the third one is called mTOR, which is a pathway in the body that responds to how many amino acids, how much meat you're eating.
And it will also protect the body if you tweak it just the right way.
And besides eating low amounts of protein, the only way to affect that pathway is with a drug called rapamycin, which is a little dangerous to try and is used for immunosuppressants.
So it's not something that I would recommend, and I don't take it.
There's a great one, because there's different kinds, and some of them are from the neck down, where they're using liquid nitrogen.
The other ones, they actually freeze the air, so when they're using the nitrogen to freeze the air, and they're pumping in air that's 240 degrees below zero, and you're going to do about two minutes.
I do three, because I do it all the time, but it's awesome.
I do three, and then I take ten minutes off, and then I go back in for another three.
And we know this because if you create a yeast cell or a worm or a mouse and then you knock out the gene for the sirtuin, now the resveratrol doesn't help the animal anymore.
Yeah, this is one of those urban myths that never goes away and still fuels a billion-dollar industry.
But what we're finding is that the molecules in plants, like resveratrol, first of all, we think they're produced by plants because the plants are benefiting from the stress.
We call it hormesis.
A little bit of stress is good for you.
What doesn't kill you makes you stronger kind of thing.
And hormesis was discovered about 60, 70 years ago when people were spraying herbicides on plants, and a little bit of herbicide actually made them stronger.
And we think that these molecules in plants are similar.
They make the plant stronger during times of stress.
So if you stress a grape that's for winemaking, you'll get great wine, but you'll also get a lot of resveratrol.
And so when we ingest that resveratrol from the plants, we get the same health benefits because the plants are activating their sirtuin pathways and we have the sirtuins and they activate us as well.
That seems, I mean, for a dummy like me, it seems counterintuitive because what's making you perform better currently, you would think, especially something like amino acids, a natural part of the human body, you would think that that would be beneficial.
You're adding to your body something that it needs.
So the idea is you're limiting your calories, you're limiting your carbohydrates, you're limiting your protein, you're limiting your amino acids, but you're ramping up on all these beneficial molecules.
Yeah, well, it's hard to ask the mice how they feel, but we do test them, and we do frailty studies, and we can see that they've got better memory, and they can run further on a treadmill.
They're stronger.
Those kind of things, they see better, and we think that that probably means they're happier as well.
So, this is really fascinating to me because the idea that you're trying to balance out the concept of a mouse growing very quickly but dying quickly as well versus something that can extend and live longer and be more vital or have more vitality for a longer period of time.
Well, so here's the great thing is that now that we believe we've figured out why, not just why, but how this all works, what are the genes and pathways in the body that control this?
We can have our cake and eat it too.
We can, at least in a mouse and probably in a human in a few years' time, and maybe even with these supplements, we'll see.
We can trick the body into being hungry and being in adversity even if you're eating a lot or you're not exercising.
And so we're slowly but eventually turning a mouse into more like a human so that even though you can grow and reproduce quickly, you still turn on these protective pathways and live a long time.
The best example is the nematode worm C. elegans.
It's been studied a lot for longevity.
And the mutations that make those worms live sometimes two and up to ten times longer are activating genes that are normally only turned on when they hunker down and turn into a little dour stage, which means that they're not really reproducing, they're just hibernating.
So you can have a hibernation of benefits, but still live a normal, healthy life.
The other thing would be that some muscles are secreting molecules called myokines into the bloodstream.
And we don't know what they all are, but when you exercise, you do release some of these, and they may also be contributing.
Because muscles are signaling to the whole body.
When you go for a run, it's not that your muscles get an exercise.
Everything in your body gets an exercise by these communication molecules.
And that's why if you fuse an old mouse to a young mouse, you can have these benefits that the young mouse imparts on the old and actually negatively vice versa.
Right, but what we actually do, because that's too hard, you can do it in humans, but in mice what you do is you sew the skin together so that the blood flows between them.
Yeah, it's not so pleasant, but they don't seem to be too badly affected once they learn how to walk in sync.
What are your thoughts on, if you have any, about the startups that are actually taking the blood of young people and injecting it into the bodies of older folks?
But what they're going to do, what they're doing actually is treating people with neurological disorders.
A lot of these startups, I'm involved in probably 15 startups right now, What we're trying to do is to treat diseases of aging, and even rare childhood diseases, because you can't treat it aging as a business model.
There is no disease called aging yet.
But anyway, getting back to the science, I think that it's based on sold science.
But the future is, I think, a better way to go about this is to find what the actual molecules are in the blood and just make those.
I saw an old gentleman yesterday and it was painful just to watch this poor guy walk, you know, hunched over and just struggling to move at an incredibly slow pace.
And imagine if we were on a planet now, or an island where everybody lives 300 years, and we'd show up, and you and I in our midlife, we're starting to look old already, and they're going to look at us and say, what is wrong with you guys?
We need to treat you urgently.
We need to call this...
A new type of syndrome.
And it's only because we all tend to go through this that we think it's acceptable.
But I would argue it's the biggest threat to the healthcare system.
It's the biggest threat to the world's economy, actually, is the inability of us to treat people in their old age and keep them healthy.
Because I was having this conversation with someone the other day that as people become more affluent and society becomes more urban, people will have less and less children and the population will stabilize.
Well, so my understanding is that the first thing you do if you educate young women is that they can make choices for themselves and they're not just subjugated.
You know, most men would like to have more children.
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Right.
So you're thinking of like Third World and… Right, the real developing world.
But that's where the population is a real problem.
In Europe, they actually are struggling to keep up with their population.
They've got an aging tsunami, so to speak.
Same with Japan.
The average farmer in Japan is 65 years old.
They've got a real problem.
China's about to head that way, too.
And that's going to drag the economy of the planet down, and it's going to be a real problem.
We're going to waste so much money on keeping older people alive for the last 10, 20 years of their life with dementia, frailty.
That could be trillions of dollars, just $50 trillion just in this country alone that could be spent on figuring out how to solve global warming, better education, the environment, saving the one-third of species that are becoming threatened.
That's why I think tackling aging isn't a selfish act.
It's probably the most generous act that I could give the planet.
And they were selling something about their mineral-rich diet.
Remember they were selling, it was like a big thing for a while, coral calcium, and they were using that as an example of why the Okinawans were living so long.
Once I'm in it, I just want to keep shoving it in my face.
But I've done a good job over the last few years of tapering that off, and the intermittent fasting, I think, is probably one of the best things I've ever done.
In terms of, you know, just maintaining energy levels, maintaining body weight, that kind of stuff.
I was going through a scanner and I said, I don't want to go through the scanner and they got quite upset because it's a bother.
But they said, you know, it's just as much damage to your body as the flight.
And so I said, why do I want to double it?
Anyway, so I go through scanners, but I try not to.
But let me tell you why I think it's so bad.
Because scanners are going to change what we call the epigenome.
Now, a lot of people haven't heard of the epigenome.
The genome everybody knows.
It's your DNA. The code of life.
The epigenome is what regulates and reads those genes at the right time.
And so we knew about DNA. We know how to read the genome pretty easily.
We can do that now on a Mars bar sized device in a day.
The epigenome is quite different.
The epigenome is the structure of how the DNA is looped around.
If you look at the chromosome, you're not seeing the genome.
You're basically seeing the epigenome.
And what I think is causing aging is not that you're losing the DNA structure.
You're not having mutations.
You're actually changing the epigenome, which is the reader of the genes.
To put it another way, Compact disc.
For the young audience, compact discs are little things we used to put music on.
But anyway, these are digital information, of course.
And the reason we switch to digital in the first place is that it's very copyable and it doesn't wear out.
Whereas a cassette tape, people our age know that if you try to copy that a thousand times, there's not much left at the end.
So the compact disk information is the genome.
The epigenome is the reader of the CD, that little laser that goes around.
And what I think is causing aging is not the loss of the digital information, but it's the reader, the analog part.
And that's like a cassette tape that eventually runs out.
And what's going on really is that your cells are losing the ability to read the right genes the way they did when you were 20. And that's basically noise, informational noise that gathers over time.
And so what we end up with when we're 80 is a compact disc or DVD that's scratched.
So the reader cannot read the right genes at the right time.
And the cells become dysfunctional.
Now what we're working on is how do you polish that CD or that DVD to get that information back again?
And if you could do that, I think that's really the best way to reset your age.
And we haven't polished it yet, but we're working on ways to actually reset that genome and actually get back the information that we once had when we were 20. So what is happening to the epigenome when you're going through those scanners?
Well, so what we found is the biggest disruptor of the epigenome is a broken chromosome, a DNA break.
And I don't know about scanners, that's just an abundance of caution, but an x-ray will damage your DNA, no question.
Even going out in the sun will do a bit of that.
And we think that the cell's reaction to that break, having to unwrap the DNA from its chromatin, we call it, and then rewrap it, is what eventually disrupts the ability to read the right gene at the right place.
So DNA damage is essentially a little scratch on the DVD, and that accumulates over time.
Your body produces more vitamin D... Yeah, well, so there's also a theory called antagonistic pleiotropy, which is what's good for you when you're young comes back to bite you when you're old.
So you might look good and feel good and get vitamin D when you're young, but the accumulation of these scratches on the epigenome ends up, you know, I'm formerly an Australian, originally an Australian, I'm now American and Australian.
I grew up in the Australian sun, and I can tell you that, you know, most Australians look older than they should.
But what we're working on is how do you get back that original information into the cell and make a cell not just believe that it's 20 again, but actually be 20. So what do you do?
We reprogram them.
There are a set of genes that we and others have found, three main ones, that when you put them into a cell or even into a mouse, they become younger again.
We've put these reprogramming genes into a virus, which is already used to treat genetic diseases in the eye, and we inject it straight into the mouse's eyeball.
Well, if you're going blind, one injection from your doctor, and then you take an antibiotic to turn the genes on for as long as you need, and you get your eyesight back, that's not horrific at all.
Well, 2020 will be the first safety study, we hope.
Wow!
Yeah, but the crazy stuff, the future is, if this all goes well, you have an injection in your vein, let's say when you're 30, and then those viruses infect your body, and they sit there dormant until you need them.
So when might you need them?
You might have a car accident.
Turn them on.
You can turn them on with just an antibiotic in a drip or in a pill, or you start to lose your eyesight, take an antibiotic, So you put them in your body almost as an insurance policy and then you have the option to turn them on in the future.
So with the molecules that we've been testing for years now, like NMN, we haven't seen any downside, just longer endurance and protection.
So there isn't always a downside to these things.
In fact, if you just think NMN is replacing a molecule that we lose over time as we get older, it's just becoming, you know, it's a fairly natural process.
Get your body damaged enough that it can repair itself but give you the benefits without having a lot of x-rays or radiation overdoing it and scratching that CD. Yeah, that's always my thought on people that do extreme endurance activities like ultramarathons and things along those lines.
I mean, I marvel at their willpower and their ability to push themselves through that and the physical condition they have to be in to perform such feats.
But I always think, man, you're probably doing X times the amount of damage to your body that a normal person does at your age.
So we live in an age that is still fairly primitive.
This is why I like the future.
These days we go to the doctor.
Most of us go to the doctor for annual physical, which is ludicrous.
The idea that your doctor will take hopefully a blood test or prostate exam once a year, that's kind of crazy.
What happens if you've got a tumor that develops the day you leave the doctor's office?
So the future, and actually partially for those who are on the cutting edge can be done right now, it's monitoring your body in various ways, genetically, epigenetically, we can measure those scratches right now, and also with blood tests.
You can also have companies tell you if you're out of range, if you're not optimized, and how to get it back in order.
So I start at the gym at 2pm on a Sunday, and I'll have a salad wrap or something like that, so I'm not feeling hungry during it, and I won't pass out.
They're actually more difficult than running on a flat surface.
It's where regular treadmills is actually easier than running because the treadmill's moving and you're just kind of lifting your legs up and keeping moving.
With this, actually, you're powering it.
So by you pushing on it, it's actually more...
It's like running...
I forget what the degree incline is, but it's like an X amount percentage harder than a regular run.
Well, I actually had an inflated idea of how bad it was, apparently.
In talking to another research scientist, he was telling me that the actual amount that they gave to rats when they're diagnosing them with cancer is almost impossible for a person to consume.
You would have to have ungodly amounts of aspartame in order to get these effects that everyone's terrified of.
He said the other thing to take into consideration is look around at how many people are drinking Diet Coke.
He goes, if it was really that bad, they'd be dropping like flies.
The consideration though is upsetting your gut biome.
The other thing, as a scientist, what you need is you need to see a thousand different sets of data and put them into one thing and see the connections.
So I'm exposed to so much information.
It's drinking from a fire hose every day.
I'm reading papers.
I'm talking to dozens of people.
I've got dozens of companies.
I've got two labs in the world.
It's just coming in and for my brain to take it in Yeah, I would imagine.
I haven't, but I've talked to many people that have.
I've been scheduling it or wanting to schedule it, putting it off for weeks, but I'm going to do that soon because I just know too many people that have extreme benefits from it.
I mean, we're still at the cutting edge of figuring out what's true and what isn't, but NAD is thought to not be well absorbed in the body as compared to these other smaller molecules that the body then turns into NAD once it gets in.
Yeah, so I said to her, I thought you were one of the world's best dentists, and she said, okay, fine, I'll do it, but don't blame me if it doesn't work.
Doesn't work?
Well, she was worried that it might snap off or not.
Well, you see that with athletes, like athletes that were fit when they were young and never lost it, really maintained and stayed in the gym and stayed active.
You see them in their 50s and even their 60s looking great.
Whereas, you know, it's just once your body deteriorates, it's very difficult to bring it back.
But if you maintain it, it seems like there's people today that are doing that and it's much more common.
If you go to a gym, for instance, go to a nice gym, you'll see a lot of folks that are in their 60s and 70s that are really active and they're there all the time and they're regulars at the gym and they look great.
Like, for you, you get your dad hopped up on all these awesome new drugs, then you get him working on the ethics panel for clinical studies, and then you get him to give you some death row patients so you can try it on, right?
So he's on a statin as well because he has the same predisposed condition.
Right.
That's an awful condition, man.
One of the things that I was talking to my doctor about, he's saying that there are people that just have high blood pressure or higher, you know, higher blood pressure or higher instances of heart disease in their family and it's just a really unfortunate genetic issue.
But fortunately, we're able to tackle heart disease pretty well these days with blood pressure drugs and cholesterol drugs.
There are some side effects, no question.
But what we're talking about with these longevity drugs that are in development is that, sure, you can be prescribed this medicine for your Alzheimer's or for your liver disease.
But as a side effect, it'll keep the rest of your body healthy as well, protect you against cancer and all these other things.
Yeah, so CRISPR is a term actually was invented in my department partly, so I know it pretty well.
Bacteria have an immune system that cuts invaders, cuts their DNA. And what we've done now, as scientists, we've now utilized that system, take it out of the bacteria, and we use it to create designer mutations, designer gene changes, In animals and also in humans.
So it's a bacterial immune system that corrects genes.
And we use it all the time now.
It's actually what's interesting about it is we've been able to mutate genes for many years.
But this is dial-up a gene mutation.
You can choose exactly where you want to make it.
And so I think many of your listeners will know that recently, late last year, a Chinese researcher in our field came out and said he's engineered a couple of twin girls with CRISPR to be resistant to HIV, the AIDS virus.
So the chance of getting HIV in China is one in a thousand.
So that doctor was seemingly, he thought he was ethical, protecting the babies from something that's, I would say, really rare.
Whereas if you really wanted to do something helpful to those kids, and we agreed it was something you should do, why not make them resistant to heart disease or to cancer?
I think because it was a very well understood mutation that would, if you just destroyed the gene, it would work.
Whereas with these other diseases, you have to be much more precise.
But the reason that we scientists got really upset was that he did it in secrecy and then just launched it on the world.
And that kind of thing, because it's a fine line in ethics, you want to be doing that I think he was hoping to win a Nobel Prize or be a star, and it backfired on him because he just did it in secrecy.
In the real world, in the media, I was shocked how little discussion there was.
If this news came out in the 2000s during the Bush era, there would have been panels, investigations, it would have been in the news for months, but it wasn't.
Yeah, so I advise governments around the world about what's going on under the radar, as best I know.
And there are countries, I'm not going to name them, that are doing research under the radar and are preventing people like myself from entering those buildings to have a look at what's going on.
So I'm sure that what's going on in there is actually a little bit broader than what we hear about.
But in countries where there are different standards, what's stopping a mother who wants to prevent their child from having heart disease, which could kill their child, you know, 40% chance versus one in a thousand.
And eventually, you could make a child that could live 200 years.
Once we know how to do it, that could be the future.
There's always a concern that someone is doing something that is beneficial in one way, but negative in another way, and if everyone doesn't get to examine the research, it's very difficult.
Like, if we in the United States wanted to do something similar to what they're doing over there, we would want to have access to what they've learned, right?
And what's not really stated, but it's my belief, is that one of the reasons there was such a backlash against this CRISPR designer baby experiment, and it really was an experiment, it's not just that it was potentially dangerous and you could end up with kids that have deformities.
But also that unless we do this in a measured manner under supervision, there could be a backlash, like there was against stem cell research in the 2000s.
We don't want that again.
We want to be able to do this the right way this time.
It's Brian Fogel's documentary on the Russian doping program, state-sponsored doping program in Sochi, the Sochi Olympics, and how they, this incredibly complicated system of stealing the urine and putting it through a hole in the wall and putting fake urine back through.
It was really amazing.
Amazing, amazing documentary, but details this incredibly Complicated state-sponsored doping system.
I would imagine that with something like CRISPR or some various new forms of genetic editing, that that's one of the things that they're going to be looking into.
That they're going to be looking into things that are going to enhance athletic performance.
I also write reports for governments, and one of the things that I predicted within the next 15 years was CRISPR being used to engineer the human genome and make a baby.
I didn't realize it was gonna happen within one year.
A lot of these technologies that I'm trying to predict happen way faster than even I think are gonna happen.
Yeah, what do you do if you turn a dog into some new kind of thing that lives 30 or 40 years?
Do you tell people?
Like if your dog, like right now you're talking about on the podcast and a bunch of people are probably going to remember, but a lot of people forget.
But if like 15, 20 years from now your dog's still chasing balls and people are going to come over your house, hey Dave, what the fuck's going on with your dog, man?
Well, I mean, especially if you drink them in the juice form.
I know a lot of friends who really enjoy fruit juices and vegetable juices, and I always say, well, I mean, vegetable juice, yeah, it's probably great, but fruit juice, man.
Drinking a big glass of orange juice, you might as well be having a Coca-Cola.
The one thing that worries me about children that are overweight skipping a meal, though, is that they're not as disciplined and they're not so good psychologically with struggling and having hunger pangs and that you're going to fuck their head up.
But I worry that it's in some way, shape, or form abusive.
Like to say, hey, you're overweight.
You need to lose weight.
I don't think they're really designed to go without the way...
The way a grown adult does.
These are my own perceptions.
I think that it's probably far better to adjust their diet.
And if you've got a kid, just slowly get their body weight down with exercise, particularly with resistance training and doing things that really burn off a lot of calories and then just get them off the sugar.
And then I think the weight will slowly slip off, probably not even so slowly if you can really get them off a significant sugar binge.
I just have to make sure it's nothing that's confidential.
But there's a lot of interesting stuff going on on the planet.
There's areas of biodefence that are pretty scary.
So some nations are apparently working on using CRISPR and other gene editing systems and modifying bugs that could wipe out a few hundred million people pretty quickly.
What do you do?
How do you detect that?
Even the flu.
That's a massive bio-threat and it may just be natural.
And that could wipe out another 100 million people like it did exactly a century ago.
So I work on that stuff, detecting viruses, wiping them out, cleaning a room of DNA, making sure that everything's clean.
So I'll give you an example.
So the Navy SEALs came up to my lab, and they'd like to ask our group to solve some hard problems.
And so the problem they set us on was, how do you kill anthrax safely?
Now right now it's very difficult to kill, of course.
When the anthrax letter was opened in the Senate, what was it, a number of years ago, It cost $25 million.
They had to seal it off and put hydrogen peroxide all over everything, destroy the computers.
So they're wondering, how do you kill anthrax safely so that you don't have to be in a hazmat suit to do it?
And so what we came up with after thinking about it for about a week was we need a biological solution, not a chemical solution.
And so we found an organism, its whereabouts I cannot disclose, but it's a very interesting organism that grows at high temperature, and it destroys all bacterial and viral life.
And it wipes it out, and it doesn't hurt humans at all.
Or at least in animal studies, you can breathe it in, you can put it anywhere, and it's fine.
So this is a cocktail of enzymes that destroys the microbes, including anthrax.
What we're hoping to do is to do a clinical trial soon on removing biofilms.
So in the wounds of patients, the problem, the reason they don't heal very well, especially these diabetic chronic wounds, that, by the way, every 10 minutes someone's losing a limb thanks to that, These biofilms, you have to digest them off.
And do you know how they do it right now?
They scrub them off.
It's horrific.
Then they cut the skin and they keep cutting and they're cutting and eventually you lose a limb.
This looks really promising in animal studies that we should be able to not just kill the bacteria in the wound, which is a problem, but get rid of that biofilm.
So we want to detect if there's another virus coming across the planet.
So how do you do that quickly?
And how do you do it if you don't know what you're looking for?
So we can take a drop of blood or a swab off a table, and we can see all the organisms that are there.
We can do your microbiome, but that's easy.
So a drop of blood will tell you all the bacteria and viruses in there, And it'll tell you how to kill it.
Which is great for healthcare because right now, microbiology labs, I've worked in one.
I used to swab urine and poop on plates.
It was very glamorous.
That's how it's still done.
That's 19th century, early 20th century technology.
Grow it on a plate, wait a few days, see what grows.
But that's useless for diseases like viruses and Lyme disease.
Lyme disease, you know, the one from ticks in your spine.
My daughter got Lyme disease and she was really sick.
She was losing her eyesight.
It was serious.
It got into her brain and the hospital wouldn't give her the antibiotic because the tests weren't quick enough and they wouldn't give her the antibiotic until the tests were positive for insurance reasons.
And I said, just give me the DNA of my daughter, the spinal fluid.
I'll test it.
They wouldn't do that.
So I was furious.
So I spun out a company out of my lab with some very smart bioinformaticians, mathematicians, software engineers.
We built supercomputers to be able to do this.
Teamed up with a guy in Stanford.
My friend, I mentioned him, Carlos Pustamante.
He's the guy that did...
Oh, maybe I shouldn't.
But he did a famous person's genome recently.
He's been trained on mummies, and he did Kennewick Man.
So this technology can be teamed up with what I've done to be able to get rid of all the human DNA out of a blood sample, leave the viruses, leave the bacteria, and then run that through a supercomputer, all the DNA, and tell you within probably seconds, eventually, what it is.
So my daughter would have a diagnosis within, eventually it'll be just 10 minutes, instead of waiting a week.
There are so many people that are infected with it, and I know personally maybe 10 people that have it, and a couple that have had significant issues with it that have lasted for years.
I know a guy who was hospitalized for a full year on it.
Oh, so again, one of my friends, got a few friends here, she was working at MIT and she's developed a way using the CRISPR system to kill these, as you say, damn little fuckers.
And so there is possibly going to be the first test of releasing a modified organism, the Lyme organism, to kill them off.
I didn't say it was Russian, but it was a biological weapon.
It's just an awful thing.
And now there's the, I'm sure you're aware of the Lone Star tick that gives people that alpha-gal disease, the one that makes you allergic to red meat.
Well, they're morphing, and there are a lot of bugs we don't know.
Somebody just published a few days ago that they took surveys of the microbiome on the skin, mouth, gut, across the planet, different races, different foods, geography, and they have 100,000 different organisms living on humanity.
But these wounds, they're actually, if you want to kill the bacteria in a wound, they're different in the wounds of people in India than they are over here in the US. Oh wow, that's interesting.
But I would think that with a guy like you who's so – you concentrate so much, you're so focused on anti-aging that having a gigantic workload would seem to me to be – that would be an issue in terms of like overtaxing your system, stressing yourself out.
We've figured out that the lining of the blood vessels needs NAD as you get older.
Well, they need it all the time, but as you get older, you don't have enough NAD. So the NMN replenishes that and allows the blood vessel lining to respond to exercise and even grow blood vessels if you don't exercise.
So it's an activator of one of these sirtuins that we found in yeast originally, these sirtuin protective enzymes in the body, and they're anti-inflammatory, and so it worked well against that disease.
So this mTOR I mentioned earlier where the drug rapamycin, which is too dangerous to try on normal people, that drug has been tried on elderly people and it boosted their immune system in the same way that you see with calorie-restricted mice.
And so that was an early signal that you might be able to reverse aspects of aging in the elderly with that drug.
We're about to announce, maybe there's a sneak preview for everybody, an academy for aging research of the top, I think, 20 scientists in the world are banding together to produce white papers and opinions.
But yeah, we call it longevity research.
And so anti-aging is more the Botox and that kind of stuff that we don't want anything to do with.
But I think one of the most important questions they'd ask to tell if we were an advanced nation or advanced species is, have you figured out aging yet?
No, not everyone works with molecules, but what I can tell you is we get together in conferences and we talk about discovering a new gene that extends lifespan and a new molecule that's working in mice or sometimes in humans.
But it's a big field now.
It's grown.
And when I started it was the backwater of biology, antioxidants, etc.
I was very lucky to start when it was really small and stick it out.
There was a fair amount of criticism in those days.
So I came to the US from Sydney in 1995, went to MIT, and the scientists in the lab that I joined, Lenny Garanti's lab, two students had just started working to figure out why yeast get old.
And I joined as the third senior person to join.
And all the other people in the lab, there were about 18, 19 people, they said, You are nuts.
Lenny's lost his mind.
He's working on aging.
That's not a thing.
You should be working on what we do, which is understanding how genes are regulated.
So I called up my mom and I said, I think I've made a big mistake here.
I thought this was the thing and the guy and everyone here says he's nuts.
And also, and this may be true in Hollywood, in science, if you come up with a new idea and you're young, you're a young Turk, and you're upsetting the status quo.
Thomas Kuhn's book on the structure of scientific revolutions just had it right.
He wrote it in the 60s.
About chemistry and physics, but it applies to biology.
If you come up with a new theory that's that disruptive, the current leaders will attack you, and it's a period of chaos, and you just have to get through it.
And fortunately, I'd read Kuhn's book, and I knew that this was normal.
But a lot of people around me were saying, oh no, people are saying we're wrong, and it's controversial.
We don't want to be controversial.
I'm like, controversy is great.
Let's do more of that.
And if it's not controversial, I don't want to do it.
Do you think that's because the people who are the old guard are upset they didn't find it themselves, or are they upset that your new findings will make their work look irrelevant?
Yeah, there's an amazing documentary on the Sphinx where these geologists are talking about some of the water erosion outside the area of the Sphinx, and they're saying this points to the fact that construction was thousands of years older than they thought.
And you see this one Egyptologist freaking out.
He's like, what evidence?
What evidence of this culture are you talking about?
Because apparently it would have predated the known dates of 2500 BC, would have made it like 7000 years older than that.
Because it would have to be back when there was rainfall in the Nile Valley.
And you could see this guy's ego kicking in because he was a professor.
He had been teaching Egyptology and he was freaking out.
Instead of examining this evidence like, whoa, like talking to this geologist who studies rocks and erosion, who is really steadfast, he's a Boston University geologist, Dr. Robert Schock.
And he's saying, this is evidence of water erosion.
And he's showing it.
And he even showed it to a bunch of other geologists, and they all agreed.
And this guy, this Egyptologist in this documentary, was freaking out.
I was like, wow, that's what happens when you think your whole life's work is horseshit.
See, the problem with how biology and actually most facts are taught or theories are taught is that there's a textbook and that's the Bible equivalent.
What I try to teach my students is, can you please just forget everything you've just learned?
And what's important to know is that most things we think we know are not correct.
They're going to change over time.
All theories change.
Newton was wrong, but he helped us get here.
Expect that we only know 0.01% of what we need to figure out, and a lot of what we think we know is wrong anyway.
So even if you have the greatest theory, expect that it will be overturned, but you can at least cherish the fact that you've helped us get to that point, because without Newton we wouldn't have quantum physics.
It's disheartening as a scientist, I can tell you.
There was a time of great change in the aging field where we discovered genes control aging and molecules like resveratrol could extend health and lifespan.
It was brutal.
I'd get up and I'd give a speech and someone would say, you're wrong, this is crap.
That must have been a tough time, though, for you as a young man, and, you know, you're hearing this from these established scientists, and part of you must have been, like, thinking, like, geez, are they right?
You have to entertain the possibility that you're wrong.
That's what we do.
But you go back to the lab and you retest it.
So I went through a really brutal period in my career where we had data, we interpreted it, we published it in the top journals, and it was about how resveratrol works on that sirtuin enzyme that I mentioned.
And Pfizer came out with a paper that said, it's all wrong.
And I had people call me up saying, it was nice knowing you, I'm really sad for you.
Yeah, bad luck.
And so I went back to the lab.
We had some data already from years before, which I knew were interesting.
And it took another, I think, four years to get to the bottom of it.
But it turns out in the end I was right.
But there were days when I said, screw humanity, I can't even be bothered getting out of bed if this is how I'm going to be treated for trying to devote my life to the betterment of people's lives.
It's tough.
I think anybody who's in a position in their career like that has to have gone through really hard times.
It's just discouraging from a non-scientist who relies on people like you.
For someone like me, who relies on the folks like you out there doing the hard work, that you would face that sort of, I mean, I guess the best way to describe it would be ignorance.
The early data was that we could mutate or change the enzyme so that it wasn't going to be activated by resveratrol, and we found that mutation.
Now that just technically, or non-technically, technically means that we could change the enzyme in a way that wouldn't work.
So we then put that non-working enzyme into a cell, and now we have a mouse that doesn't work, and we give it resveratrol.
And if it works, it means I'm wrong.
If it doesn't work and it's blocked by that change in the enzyme, we're probably right.
And that's what we did.
But the real change was that there was a company that I started that was making drugs, the one that cured, or at least seemed to cure psoriasis.
And they had made these very synthetic molecules that were not related to the plant molecule resveratrol.
And so I said to myself and to the student who was working on it, the very brave student, If the change in that enzyme also blocks the drug, then we're on to something.
Because that means two separate groups working on separate types of molecules, different people, different systems, all get blocked by this one little change in the enzyme, then we're right.
And so he walked over to the company, got the molecule, threw it on the enzyme, and it didn't work on the mutant.
And that was me rejoicing because I could say there is a universal activation mechanism on this one enzyme.
Resveratrol works.
The molecules at the company work.
And now there's an interesting thing that just came out from Spain that metformin, the diabetes drug, may actually work the same way as these other molecules by activating our favorite enzyme, the sirtuin.
It gets so bad because you've got this tight-knit group of scientists and you have lab meetings and you present your results and usually you're very supportive, trying to help.
I had one guy saying to my student, David doesn't know what he's talking about.
You shouldn't work on this.
It's been proven wrong.
He was dead against me in my own lab.
I'm paying his salary.
And it's okay to be constructive but vicious within my own group.
Well, suffice to say, he wasn't in my group for that long.
But still, it's got to be beautiful to come out on the other end and be proven correct and actually be at the forefront of these emerging technologies.
I don't mean to rest on any laurels, but the What I do is I pause and I remember how hard it was to get here and how fortunate I am to have made it this far.
And I'm working with hundreds of collaborators around the world to make this come true, this idea that we can really treat aging and prevent deterioration.
So I'm blessed.
I have an app on my phone that I've helped engineer.
Well, it's a little company that we bought in New York, and nurses and dentists use it to pass medical information around.
But we use it to share information between scientists around the world and coordinate activities between companies that I've started.
Oh, that's amazing.
I think I mentioned to you that I've started a few companies.
What I'm trying to build are companies that are the 21st century version of a pharma company that actually has a decent reputation in the world.
I think it's pharmaceutical companies, whether it's deserved or not, have a pretty bad rap.
I'm trying not to fall into that trap, but I'm also trying to use 21st century technology to not become too bureaucratic as well within the organization.
You were also talking, I don't know if you could talk about this, before the podcast about How you have to make sure you have zero conflicts of interest.
But if you look on the internet, if you Google David Sinclair and NAD or aging, you'll see that people put my name and my face all the time on their websites and I get questions every day.
Every morning I wake up, which product are you endorsing?
That's what would be, yeah, that would be the thing that, I mean, especially because most people aren't going to do real research and develop the nuanced understanding of your work and what you're doing and what it means and how long you've been studying it.
They go, oh, he's doing it because he's making money.
Well, you know, I've made a fair amount of money in my life.
My first company, even though I wasn't the major shareholder, was sold north of $720 million.
So that money I'm not immune to, but I do reinvest almost all of it.
Actually, all of it, my wife will tell you, into new ventures to change the world.
So the Lyme disease company and the MIB 626 company, Metro, these are funded initially by me.
Now the conflict arises because I'm studying these molecules in the lab and I'm on the board of directors and advising these companies as chairman, vice-chairman.
The only way around that as a scientist that we have as our defence is we disclose everything.
So initially I would disclose it to the government and to Harvard.
All scientists have to do that.
But I've gone a step further just to try and be ultra-transparent with the public.
And so I have a website.
If you go to my lab's website, you'll see everything that I do.
And hopefully that's protection from being accused of being biased.
But what I definitely do in my lab is I say to the students, if you get a whiff that I'm doing anything biased, I wouldn't do anything consciously, but maybe there's some unconscious bias.
Let me know.
Let the university know.
And we'll be fine.
But I've been doing this for 25 years.
I think I'm pretty good at putting a wall between the two.
And the other thing that I want everybody to know is, in the lab we do very basic research.
We try to understand the fundamental reasons why we age and how to reverse it.
The companies are more worried about how we're going to do a clinical trial, which is a very different world, so they don't overlap much.
So it's a few years of often making a better molecule, but let's say you've done that work.
Now you spend a year testing it on at least two different species, usually a rodent, a mouse, and a dog.
But you try to do everything you can before that to make sure it's not going to be unsafe, testing it on cells and other things that are not living, or at least don't feel anything.
But the FDA, Food and Drug Administration of the U.S., requires if you're going to make a drug, you have to test it on at least two different species.
So that's what you do.
And then you go into what's called phase one, which is safety testing.
It takes one to two years.
Phase two is what we call efficacy, which is does it really work potentially?
So you test that on 50 to 100 people.
Maybe it works, maybe it doesn't.
Most things fail.
If it looks good, then you go into phase three, which is $50 to $200 million worth of experiments.
I'm testing it on hundreds of patients.
And if that goes well, then you apply to the FDA to be licensed to sell a drug.
It's staggering to raise that much money, and that's one of the reasons that these big numbers come up.
Often we have to tap the public markets to be able to afford it.
A typical drug will cost hundreds of millions of dollars.
Some drugs have failed after $700 million investment.
But look at the upside.
If we're successful at having a drug that treats aging, we'll treat a disease like diabetes first, but then it could become the best-selling drug of all time if it's proven safe.
Who wouldn't want To have a drug that could protect them from all these major diseases.
That's how it usually works, but for the first time, I'm in control of many of these companies, and I have a large say in them.
At least.
And I, as an individual, am pledging that we won't do that.
We're not going to put our prices up to what the market can bear.
This is a gift to the world.
And so that's a very different approach and that's one of the reasons that I've, in large part, used my own money to do these things so I can have that say and do what's right for the planet.
Because pharmaceutical drug companies are always thought as being a devil.
Meanwhile, they're responsible for so many things to keep people alive as well.
But because of the fact they're connected to things like OxyContin and Fentanyl and things that kill people, and it's been proven that there are certain unscrupulous drug companies that have pushed things out there that they know have negative effects because they knew they could profit from it.
Yeah, and so we just recruited to one of the boards of the company someone from a consumer company, which is a strange choice, right?
But this is a person who's done right at that company for the world, a company that used to make just some consumer products that weren't healthy, and he turned that around.
And that's the kind of person I want to work with who cares about the planet more than they care about the ultimate profit.
I learned some really interesting things too about my origins and I'm carrying cystic fibrosis gene and whatever.
But what's cool is now we're merging.
You can merge that data with the inside tracker data and have this ultimate personal angel for health that will hopefully one day be on all of us that we've got a personal tracking device.
It'll tell us if there's something going wrong.
If you got a cancer cell detected, go get that eliminated.
It's crazy these days we have to wait till there's actually a tumor that's making you sick before you actually go to the doctor.