That's all I needed

...

the, uh, so let's start with resveratrol.

I try not to bore everybody.

Um, SIRT1 is an enzyme.

I'll use my hands.

It's an enzyme that carries out reactions that stabilizes the epigenome so it doesn't decay.

And what happened with NAD, NMN?

Okay

... we found.

Uh, there was a person, uh, whose name, uh, is well-known in science circles called Shinya Yamanaka from Japan obviously, and he discovered that there was a set of four genes that could reliably make adult cells like skin cells, uh, into stem cells, and he deservedly won the Nobel Prize for that in 2006.

But that wouldn't be useful here.

We c- if I turned you into a bunch of stem cells, you'd probably die within a few minutes, so we don't wanna do that, and cancer is also a potential.

So it took us about, well, s- from 2019, it took us a while to figure out that if we leave out one of the Yamanaka genes and just use three, OSK, leave out the other one called M, we'd get safe age reversal about 75, 80% back to youth but no further.

We don't go back to zero, which is what Yamanaka did.

Wow.

Yeah.

That's what we strive for.

You know, I was, I was coming here, uh, flying out, and I'm looking at all the roller bags and thinking, and h- I'm carrying my two bags here, and I'm thinking, "Should I put it down? No, I'm gonna walk with my bags," 'cause that's what people used to do.

Mm.

Um, and the simple answer is, uh, do as much as you can, and the more the better, uh, in general, without losing your energy.

But the other fact is that nobody knows the true answer.

Anyone who says, "This is the way to do it-

But maybe you can explain.

Yeah, there was a study before us that actually beat us... partly to the punch.

Juan Colas Belmonte's lab showed that if you turn on all four of the Yamanaka genes, you get a dead mouse in a few days.

But they persisted and they found that if you turn on the four genes for two days and let the mouse recover, and do it again the week after, if you keep doing that, a short-lived mouse, not a normal mouse, but a short-lived mouse could live longer, what we call a progeroid or a short-lived accelerated aging mouse.

Now that raised a lot of eyebrows.

People were saying, well, all you're doing is just stressing the heck out of a mouse and that's why it lived longer.

And there was no real... proof that it had anything to do with aging.

And so I just want to know what your current thoughts are on the pros and cons of all this stuff.

And even if this is true just for mice, it really is amazing.

We find that with our reprogramming, we can make the nerves be just like a, a newborn baby.

They grow back.

Uh, and then we also tested on glaucoma, pressure in the eye.

We increased pressure in the mouse's eye, and they lose their, largely their eyesight, and we can recover that.

And then we also test old mice that don't see very well, and we also seem to improve their eyesight almost back to normal.

So what I...

With every action, we assume there's some negative consequence or potentially negative consequence, right?

Can you talk to us about that and what your studies on cancer have revealed? And it work- you've done some wonderful work with it.

Yeah, well, my views are, are fairly novel still in the scientific community.

So the, the current model, which is true, it's just, is it the whole story? The model is that when you get damage to your DNA, the genome, you get mutations that cause cells to divide uncontrollably, and that is a very simple way of describing cancer.

But there's another very important problem that happens to cells that in large part is necessary for cancer to happen, but it's largely, largely been ignored.

And that gets to the second part of the cell called the epigenome.

Okay? So I've, I've stressed the genome, which is the DNA, but the control systems that read the DNA are equally important, and that's what we call the epigenome.

And the epigenome is much more likely to get disrupted and corrupted because it's the software of the cell, and we know software gets corrupted much more than, uh, than the actual physical computer over time.

In a decade, do you believe that we'll be living longer than we are now?

Just talk about how you piece those things together, the season in context, how Canyons, Transvulcania, and Western States fit together.

Yeah, well, just, it just kinda came, came together.

I wouldn't say there was a, you know, a big master plan be- behind it.

I, I went to Canyons as just a little tune-up race to check, check fitness early season after, you know, a winter of just doing base training and hadn't done a lot of hard intensity or, you know, wanted to check and that was to get my qualifier out of the way so I can come back to CCC.

I needed to earn one stone, and that went surprisingly well off of, you know, kind of an up and down winter.

Like, I honestly wasn't sure how training was going, and that gave me, you know, just, just enough confidence to go to, be like, "Okay, you can be ready in two weeks for, uh, Transvulcania." So yeah, I got over there, and the plan was to come back just after they invited me back after the DNF last year, and I really wanted to come back and, you know, just put together a good race there and, like, mostly just get to the finish line feeling, you know, proud of the efforts.

I way exceeded those expectations.

So maybe just talk us through the early part of the race, what your strategy was, whether I'm interpreting that correctly.

[laughs]

We- we're doing, we're doing a lot with, with AI, not with Lila yet.

I haven't worked with Jeff, but backstage, we, we, we hope to.

We, we are working, uh, with companies and academics that do a lot of AI now.

We, we can't survive without it in, in my lab, and it's accelerating our work exponentially.

Uh, we're doing now what would've taken hundreds of years before.

It's amazing.

How can we explain that, and why aren't we using genetics as part of the tool set that we use to drive longevity?

Tell us about that.

Uh, well, if, if you've been under a rock, uh, let me tell you that, uh, we've worked out...

Uh, maybe we could talk a bit about the science behind it.

But we have a, we have a drug candidate that came out of my lab.

Uh, it was published first in twenty-twenty on the cover of Nature magazine, and the title on the cover was "Turning Back Time." And rep- we reported, um, and I wanna give big credit to my student, Wan Cheng Lu, who, uh, worked for many years to try and find certain genes c- and combinations that could safely reverse aging but not go so far that you could cause cancer or lose identity of the cell, and he found it.

It took a long time, and in retrospect, it looks easy 'cause we now know the answer, but it was tough at the time, and he was ready to quit.

He was in my office almost crying, uh, and I said, "You gotta try.

Mm.

What about aspirin? I read that somewhere.

Yeah, that, that, that could be a whole podcast actually.

But the briefly, I take a baby aspirin every day, even though some doctors, um, and some institutions of doctors say don't take it anymore, even though it used to be prescribed and recommended.

Why? A large study looked at the risks versus benefits.

So the known benefits are you inhi-inhibit platelets, you get less clotting, you get less potentially, uh, stroke and heart attack.

But there are also some downsides in some people.

You can have more bleeding in the stomach.

And I understand they're not rigorous and they're not scientific.

So why is it that having elevated blood sugar, glucose and insulin ages us more quickly, and/or why is it that having periods of time each day, or perhaps longer can extend our lifespan?

Well, let, let's start with, with what I think was a big mistake, was the idea that people should never be hungry.

Some people never experience hunger in their whole lives.

It's really, really bad for them.

It was based, I believe, on the 20th century view that you don't want to stress out the pancreas, uh, and you try to keep insulin levels pretty steady, um, and not have this, this fluctuation.

What we actually found, uh, my colleagues and I, uh, across this field of longevity, is that when you look at, first of all, animals, whether it's a dog, or a mouse, or a monkey, the ones that live the longest, by far, 30% longer, and stay healthy, are the ones that don't eat all the time.

Um, it actually was first discovered back in the early 20th century, but people ignored it, and then it was rediscovered in, uh, the 1930s.

Along the lines of supplementation, what about NMN? How does one incorporate that into a, a supplementation protocol, should they choose to do that?