How Dogs Are Going to Make You Live Longer: Rapamycin & Longevity – Matt Kaeberlein : 1145

You're listening to the Human Upgrade with Dave Asprey, formerly Bulletproof Radio. You're listening to the Human Upgrade with Dave Asprey. Today we're going to talk about dogs, specifically how to hack your dog to live a lot longer. Okay, maybe not quite, but maybe our guest is Matt Haberline, who's working on exactly that. Extending radically, extending the lifespan of dogs and other pets as well, but starting with dogs, because dogs are better than cats, in case you were wondering. Now, what you're going to hear here is a really fun conversation that mixes human longevity because Matt is the CEO of OptiSpan, where they're extending human life, or at least healthspan as much as they can. By the way, he's one of those guys who still says healthspan because he hasn't qu in on the fact that we are extending human life. And that's the goal. But I'm going to bring him over on this one, so, you know, that'll be fun. Oh, hey, Matt. Yeah, you didn't hear that right. And then we're going to also talk about hacking your dog, which is what I already mentioned, and we're going to talk a lot about longevity in your pets because there's such a commonality of humans and dogs. So listen to the whole episode. You'll learn something about how to think about longevity for you and then how to translate it over to your pet. Matt's in town because it's south by Southwest here in Austin, which means it's a madhouse. How bad was the airport coming in?

You know, it was pretty crazy, but I made it so that's all that counts.

My son is coming in. He's flying by himself, and he's probably never seen an airport at that level of chaos. So I'm kind of looking forward to his eyes rolling back in his head as he just sees what true traffic chaos is like. Now I'm giving a couple talks at south by this year. You're also giving a talk on what you're doing with pets, right?

Yeah. So there's a panel discussion on, I think it's called something like could Dogs Be the Key to Unraveling Human Longevity? Or something like that.

Well, it's neat. So you're doing the dog aging project, and dogs have this really nice space between in longevity research that a lot of my books are based on. It all starts with yeast and roundworms and then maybe goes to mice.

Right?

Right. And then maybe we have some other data somewhere or another, and then we start Using it with humans, using aging clocks.

That's what we do today. You're right.

Yeah. And aging clocks are pretty useful because before that we couldn't do anything. There's still some, like, Luddite skeptic people.

I'm like, like me?

Well, no, like. Like Peter Adia, who says aging clocks aren't scientific. I'm like, I want to see Steve Horvath in a wrestling match with. With Peter Adia.

Well, I know both of those guys and I'm pretty sure I know who would win the rest of the.

Peter would win, but that's because he's a meathead, not a longevity scientist is my point here. So sorry, Peter, you need to revisit what is scientific. And maybe less time in the gym, more time in the labs. Just saying.

So I actually want to push back on that a little bit. Peter is a friend of mine, but also one of the people I have.

Been on stage with him. He's not a bad guy among. Among. He's not a believer in longevity problem.

I would disagree with that. So, look, I think. I think Peter has strongly held opinions, like all of us do, that are.

That are wrong. Yeah, those.

Most of the time he's right. And I would say among.

On statins and vaccines, among a lot.

Of the influencers in this space. I think Peter does a good job of doing his homework, and I think there is some nuance here. I am certainly not going to try to speak for Peter, but here's the way I would frame the aging clocks.

There you go.

I think they are very useful research tools. I think that the utility of the aging clocks in the consumer space is pretty questionable in my mind. And part of that is because we really don't have much data on how precise or reproducible these clocks are when sold by companies to consumers. And so I actually have a lot of concern that these clocks are being misused and abused in the consumer space.

Interesting.

I also think that it's important to recognize that all of the clocks that are currently in use are really only measuring one, sometimes two small aspects of biological aging. We don't really know, you know, to what extent are they capturing the entire biological aging process?

Nothing does right now. And we do know that the aging clocks and Steve Horvath's interpretation of it is the first one, but there's about a dozen others. They can predict when you're going to die within about 10 years, pretty reliably.

I think it depends on what you mean by pretty reliably. I can look at somebody and predict pretty reliably whether they're going to die in 10 years.

That's a good point. We'd have to look at. I don't know if they compare.

I've had this conversation with Steve, so I kind of know how the math plays out. They're better than just looking at somebody. They're honestly not that great.

They're better than telomeres.

Yes, but actually that's true. But the question is, is that because we don't have the tools yet to precisely measure individual telomere lengths. I actually think this is a super interesting question. It's way off, way off on a tangent, but I think it is really something we don't know at this point, whether the epigenetics, which is what Steve's clock is based on, those are nice because we have huge dimensionality. There are tens of thousands of epigenetic marks we can measure and we can do it very precisely. That's very different than the telomeres where we only have, you know, 46 or so things we can measure and we can't do it very precisely. So maybe telomeres actually are a pretty good clock if we could measure them. I think we just don't know. I actually don't believe that. I'm just saying we don't know the answer at this point.

It's true that we're discovering a lot and we know more now than we did, and nobody can argue with that. Every 72 days, the amount of info we have about biology doubles right now. So it's this golden age of longevity research. And I've seen telomere numbers swing by 20 years in one week. That's either because of lab errors or because your blood is a terrible place to telomeres.

Well, I think that's a good point. Yeah, absolutely. The tissue type that you're measuring, and blood, of course, is a complex set of cell types that you're actually measuring. So. Yeah, and. But this goes back to my point earlier, which is that I think that while these things can be quite useful in a research setting because of a lot of those uncertainties about what we're actually measuring, their utility in the real world for now, I think is. Is unclear, but I'm super enthusiastic that we're going to get there and probably the not too distant future, I would.

Say that aging clocks are extremely scientific and early days. And so the idea that, well, there's no way we're going to extend human life and there's no way to measure how old you are Biolog, which is kind of a summation of Peter's work, which is why I'm like, let's go to the A4M. Let's go to the people who are actually looking at extending life with something besides exercise and statins, because, well, I think those have been tried for a while, and no one's living longer. That's why I'm. Well, 20 minutes. 20 minutes a week of exercise is all I do. And I do it with AI and that upgrade labs. I believe that most people way over exercise, including Peter. Right. Because it turns out it's not the area under the curve, it's the slope of the curve up and most importantly, the slope of the curve down, and then the nutrient and protein availability.

So I'm gonna push back a little bit and suggest Peter could kick my ass. Just to be really clear, most people are. Don't. Don't over exercise. Maybe people in the optimization world over exercise.

People who exercise every day, usually over exercise. And almost everyone doesn't move enough. Right. So there's a lot going on there. And it's funny because, you know, we're here to talk about dogs, but we're talking about humans, because I think dogs are the bridge between the research from mice and yeast and the little creatures. And, hey, if they can live longer, there's pretty good evidence that some of that stuff will help us. But it doesn't always. Right. And so. Well, what's in the middle? Well, dogs are a lot closer to people than they are yeast, but they're still pretty far away.

Yeah. Yeah. And I mean, so, first of all, I love the way you sort of frame that because. Because my career path has followed that trajectory. I started in yeast as a graduate student, then worked in nematode worms as a postdoc. When I started my own lab, we started doing stuff in mice because I believed that there were aspects of aging biology that were, in fact, shared across this broad evolutionary distance. Turns out that's right. And then about 10 years ago, it occurred to me that, as you suggested, dogs are this really powerful bridge between the laboratory studies and humans, not only because they're closer to humans in a biological sense, but there's this huge environmental component that we can't or choose not to study in the laboratory that's really important for human aging. And because dogs share so much of the human environment, at least companion dogs or pet dogs do, we can capture that environmental component and really understand, you know, not only what are the most important genetic factors that influence longevity, but what are the most important environmental factors. And then there's this huge other piece which is what I'm most interested in, is we can actually test whether interventions affect lifespan and health span metrics in dogs, which would be great for giving us confidence about people. But I'm a dog person, so what I really care about is making my dog and other people's dogs live longer, healthier lives.

The number of people in the longevity enthusiast field, whether you work in the field or you're just someone like me who's, who's been decades, I guess I do work in the field, come to think of it, but I didn't used to. So the number of us who have pets who are not on longevity regimens is very low. All of us know, huh, the things that work for me, like red lights and we know what it does with mitochondria and cell folding and all that stuff. Maybe I should shine it at the dog when the dog hurts and then the dog stops hurting and it probably affects longevity. And maybe not feeding them the pet equivalent of chicken nuggets will also affect longevity. Right. So we all kind of do that. Whereas it's still very common. People go to the store and they buy big things of pet food that are made out of euthanized dogs. Maybe a dog shouldn't eat that. There's some really bad stuff happening.

I mean, there's some really interesting and in many ways unfortunate parallels between what most human beings eat, or at least the quality of the diet that most human beings eat and the quality of the diet that most human beings give to their companion animals. And there's complicated reasons for that, obviously. But, you know, I think you're right. I think the people who are on this path towards improving their own health span trajectory often recognize that the same thing is true for their pets and take a healthier approach to their pets.

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So you're a PhD and actually a very well studied one because you've, I guess, published 250 studies, something like that. You founded research centers and you're in the American Aging association. And so you talk like the best PhD ever. But I think what I heard you say in that was that humans and dogs shouldn't eat kibble. Did I get that right?

Well, certainly I think humans probably should not eat kibble. I think again, the quality of the food itself, Right. In the general food supply is really problematic, both for dogs and for people.

Yeah. So we've got to fix food. And for me, food is mostly not a longevity issue. It's a health span issue.

I don't know. I understand that perspective. I would say I'm a little bit less certain. I certainly believe to some extent that the reason quality diet, exercise, appropriate amount of exercise, whatever that is. I think we're still figuring that out. Exercise, sleep, quality. I think the reason those things impact multiple age related diseases simultaneously is Precisely because they are impacting the biology of aging. I think the way I would frame it is you can only get so far by modifying those lifestyle factors. And so you're not going to see 150, 160 year old people in good health simply by modifying lifestyle.

Exactly. We're not going to extend life very much. You can reduce toxins, you can probably hit your maximum, your maximum lifespan, sort.

Of genetic potential without additional intervention.

Yeah. And that's lifestyle and all that, but extending it, that's stuff like the gene therapy that I just did.

Maybe. We'll see.

We'll see. Of course. Right. And for all of history, it's always been a will see for all the things we're doing on things like that, we just have better tools now to do it. And hey, maybe, maybe the guy who said man will never fly a year before the Wright brothers flew, maybe he was right. I'm going to bet on us extending human lifespan because we are. I mean, you talk.

I have no doubt that you see.

All the research being done.

I have no doubt that it's possible. Right. Of course. I think the questions in my mind more revolve around how long is it going to take before we can actually demonstrate that these things work? And this is where, going back to the aging clocks, I think once the aging clocks evolve to the point where there's confidence that they are in fact predicting future mortality, future disease risk with high precision, then you have a real opportunity. It's still not going to be proof until you actually see somebody live that long. But you can be pretty darn confident that these things are having the effect that you wanted them to have. Then the last question is, is there some long term consequence that we don't know about that's going to offset that?

Right.

Because it only takes, only takes one mortality event to keep you from living a long time. So that's an unknown. And we're not going to know until we get there.

One of my big longevity strategies is to drive a heavy vehicle.

Right. Avoid dying, I think is rule number one of longevity. Yeah.

You've used physics.

Necessary but not sufficient.

Yeah, sorry. If you're in the Prius, I want to be in the Suburban. And it's not to say that I think I'm more important than you. I'm just allocating my resources in a way where physics protects me. And it's something I think is not looked at enough in the field of longevity is just don't fall down and break yourself. Don't blow out your spine on hitting a new PR when you're 60, it's probably not worth it.

Yeah, absolutely. I mean, we kind of think about four movements at Optisman as we're trying to communicate some of these ideas to people. And one of them is staying alive. Right. You got to avoid risky behaviors. And it's, it's. There's a lot of. There's a lot of luck. There's a lot of probability in life, but you can change the probabilities in your favor, like you're saying, by taking steps to reduce your likelihood of dying.

If you had to pick one thing, not exercising or eating just the worst possible fast food diet for the rest of your life, which one would you pick?

So I have to do one of those two things. I would.

Oh, gosh, if you want to exercise, you have to.

I don't think I could eat the worst fast food diet. I'd have to choose not exercise. That would kind of suck for me.

But.

But I could. Yeah, it would be. I mean, again, as somebody who ate a pretty crappy diet, like many people, for a big chunk of my life.

I think we're about the same age.

Now that I'm out of that world, like, I. It just is repulsive to me to think about going back to it.

I will never go back to eating food that makes me feel crappy. And I am willing to die on that. And this is what the regulators who think we're gonna live on crickets and grain. I can't live on that. And I won't. And I'll eat a politician before I'll eat a cricket. And I'm just okay with that. Right? They're made out of meat.

Yeah.

It's not, not my ideal source of.

Meat, but I actually think this is pretty interesting because I've talked to a fair number of other people who kind of share that. Not so much about eating politicians, but the sort of revulsion at the idea of going back to this standard American diet. Right. And it's hard sometimes for people who aren't already in this place to understand that. But I think it's just worth emphasizing. Right. It's really about building habits. And if you can get out of the habits that you're in, that society and culture pushes you towards and get to a better place in terms of the quality of your diet, you will, I can almost guarantee you will agree that there's just no way you want to go back to that once you get out of it.

And also, it's not the same for everyone.

This is True, Absolutely.

There are people who just feel great on chicken. I am a beef guy and I've tested everything. I would eat gravel if I could, but beef is what works for me. And you try and take away my beef with a regulatory thing, it's like, no, you're taking away my oxygen. We are, we are not, we are not going to be okay with this.

So here's the way I think about it. I think there are multiple types of high quality diet. There is not a one size fits all. I completely agree with that and I think that, that, but I also think that there is a high quality diet that can fit almost everybody. So in other words, I don't believe that there, that there are people who will just thrive or if there are, they are the way outliers who will just thrive on, on garbage.

And you know, there are some, I, I know people who do, at least for a while. And I also know a couple people who thrive on a vegan diet. It's just their kids and their grandkids who are paying for it because it matters. In fact, if you look at, you know, the health of vegan offspring and things like that, it's not pretty, the placental health. So you might get away with it, but you're actually paying for it in future generations. It's a, it's a big experiment.

Yeah, I mean, I'm less opinionated about vegan diet. I'm not a vegan, but I'm certainly not a vegan basher.

I was a devout vegan for a couple years and it trashed my health in a big way. And I'm a food supporter. I absolutely love the vegan philosophy. Like you want to take care of your health, you want to take care of the planet and you want to reduce animal suffering and death. The problem is the vegan diet doesn't do any of those three things. And I believed it did.

And so, yeah, and I think the way, I sort of also think about this, but I struggle a lot with the nutrition literature. I mean, honestly, I mean, look, these are good scientists trying, trying to do good science, but it's really hard to do high quality, definitive science in human nutrition. And so I really struggle with a lot of the epidemiology. And so I personally, you know, I'm very slow to come to strong conclusions about what is the optimal diet, what isn't, and what are the long term consequences to some of these dietary, different dietary approaches people take. I think, you know, again, the way, the way I sort of align is there are Some things that we can be almost certain are not good to have in your diet. Right. Highly processed foods, a lot of simple sugars. Right. Low, low quality fats. So I think those are the things that most people should agree if they're knowledgeable. You want to get out of your.

Diet and all the flavorings and colorings.

Yeah, right, yeah.

And those are bad for dogs, they're bad for people. And from there, you know what, what plant toxins can your body tolerate versus mine? You know, 28% of rheumatoid arthritis is caused by nightshades if you have the genetics. But for, if you don't have the genetics, you can eat them all day long.

And this really actually ties in in an interesting way to the biology of aging because I think a lot of what's driving that is our own individual immune response. Right. So the, the reaction of the immune system to molecules that we're getting in our diet and other places in the environment that drive chronic inflammation. Some people are just much more prone to that sort of hyper inflammatory state. And, and that leads to a lot of the conditions that you're talking about.

I'm certainly one of those, you know, being 300 pounds, all the, the health stuff I've gone through when I was younger. So I recognize I, I'm coming from behind and my goal to live to at least 180 willing to die trying. Fine with that. Yeah, I just want to do 50%.

Well, the nice thing is, you know, this is pretty cool. One of the things that has emerged from the literature in my academic career is that it doesn't seem like there's a point where it's too late unless you've got a disease where the pathology of the disease has sort of outpaced the biology of aging. So we now know, and we didn't know this when I started, but now we know you can start intervening in middle age and still get pretty big effects on both longevity and health span.

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It's funny, if you start before pregnancy, the three months before your mother was pregnant with you and you have a really healthy pregnancy, you get the most.

Leverage on long that's all the epigenetic effects, right?

Yeah, that's what my first book was on fertility. And what do you do before you get pregn. And then it's sort of you get less and less leverage the longer you wait to do longevity interventions. I'm just like in my 20s. I learned from people in their 80s all this longevity stuff in Palo Alto.

I wonder though, because you know, this is, that's, that's sort of the mindset I think people had before 2009 when the first study on rapamycin in mice was done where they kind of accidentally started the treatment in a 60 year old equivalent mouse. But I think what we've learned is that at least with some interventions you can get most of the benefit Even starting late in life with some of them, you can. Yeah. And I think as these tools to kind of reset the epigenome evolve, we might actually be able to get closer to that sort of initial epigenetic state that you were talking about.

It may not even matter. At a certain point in the world that I see coming, you'll be able to edit your mitochondrial DNA so it more closely works with your nuclear DNA. And these are all editable settings in your hardware. The biggest challenge will be, if you make too big of a change, is just causing systems integration to work between all the differences.

Yeah, I mean, it's interesting. I don't know how far. I mean, again, I agree, theoretically that's all possible. I think the challenge that I see, and this is where it'll be interesting to see how effective the sort of evolution of AI tools is at disentangling the complexity of the biology. Look, I'm in this field deep.

Yeah.

And I recognize how little we actually understand.

Half what we think we know is just wrong. And the AI believes it. That's. That's one of them.

So it'll be interesting to see. But I do agree all of that's. That's on. That's on the table. I just don't know how long it's going to take to get there.

So I have a pretty good track record of, you know, seeing things before they happen. I'm the first guy to sell anything over the Internet. Before E Commerce had a name, it was a T shirt that said caffeine, my drug of choice. And I sold it out in my dorm room, was in the Miami Herald. And like the first data center companies I've picked reliably. I also have a track record of thinking it's going to happen before it does. But now I'm wise because I have some age on me now. So I would have said, oh, it'll be three years before we get there. If I was 20, I'm going to say 10 years before we get there. Mostly because of advances in AI subject to two things. One, that governments don't succeed in basically destroying our access to these things or to breaking AI. I don't think they can, but they might. And two, that a comet doesn't hit the planet. But otherwise I'm pretty confident on it because we have a hard time conceptualizing this is even beyond exponential rates of growth in AI. So I think we're going to get there. As long as we train the AI to care about it, then it'll do it. But if we train the AI to be really good at killing people. It might not care much about making us live longer.

So this is, it'd be interesting to see. We should sit down and come up with a bet about like, what are the actual. What do we actually want to bet on? I'm less optimistic, but in part that's because. And again, this is where the exponential equation can fool you. But I look back at where we were 10 years ago in this field and I don't see 10 years from now as getting to that, that point. So we'll see.

Oh, not everyone will get there. Well, the first couple people will get there in 10 years.

Well, yes, there may be people who are, there's already people who are editing their genome.

So, sure, I mean, I've had the gene therapy, but it wasn't my, my inheritable genome.

Which gene therapy.

I did the follistatin gene therapy with mini Cir, just plasmid level stuff. And I'm impressed. And I'll be in the first trial for closer.

The biology is real. I mean, there's no question about it.

It works. Right? And now the fact that nine years comes off your aging clock, for that you can say, well, that doesn't really matter very much. I'm like, yeah, but the bone density increase and the increase in muscle and the decrease in fat works.

But yeah, it's super intriguing. That's one of the spaces I'm watching pretty closely.

It's funny because, you know, in your day job, you're at Optispan, you're working on extending human lifespan for high end clients. And then in your night job you're saying, well, let's do the same thing for dogs.

Yeah. Although let me clarify. So it's not for high end clients only. Right. So what I would say is our mission at Optispan is really to enable the transition from reactive disease care to proactive healthcare for as many people as possible. Right.

I like it.

So, and I think there are lots of ways you can do that. There are lots of smart people working on this, but I think we have an opportunity to contribute. And so we're really looking right now at two lanes. One is sort of high end concierge medicine, because that's the place where you can do the most expensive, most sophisticated sort of approaches here. But we're also working in the corporate wellness space and trying to say, what can we do in this proactive science based healthcare for $1,500, $2,000 a year, something employers might be willing to put towards Employee health, recruitment, retention, things like that. So we really are trying to democratize this as much as possible, recognizing that as a for profit company, you know, you also have to be able to make revenue.

Absolutely. If you run a business that doesn't make any money ever, it's probably not a very good business, unless you're Amazon or Tesla. Oh, and wait, sometimes you can have external funding, but I'm with you. I believe that the best way you can change the world is as an entrepreneur, not as a donor. Right. And I also have donated meaningful amounts of money to projects I believe in. But end of the day, if the money makes more money to support the cause.

Now start the flywheel.

You've got a movement versus you've got a one time flash. We've talked about humans aging a little bit here and there's a lot we don't know and we're making great progress. Now we also know small dogs live longer than big dogs. Does this mean that small humans live longer than big humans?

Yeah, actually there's some evidence to support that. So this is something where people have a lot of confusion. There's this idea that large animals live longer than small animals. And that's true if you look across species. So if you look across the animal kingdom, larger animals do in fact live longer than small animals like elephants and whales.

Yeah.

But when you look within a species, in general, at least in mammals, smaller individuals tend to live longer than larger individuals. And that's true in people. It's complicated in people by the fact that there is a social component to being tall. And so you have to kind of take that into consideration. Dogs are interesting because the body size difference is so much bigger when you look across the dog species that we can really see that difference in aging rate.

I've had six dachshunds over the course of my life, including when I was a kid, and all of them lived 15, 16, 17 years old. But the last two were when I knew the most about nutrition and longevity. And I applied those things. Merlin, who was the last dog that I had, passed away and he was 15 and a half or something, but he got krill oil every day and he got a little bit of collagen. And he ate mostly raw grass fed beef and some egg yolks on occasion, and very small amounts of vegetable matter. And when he was young, I gave him things like the barf diet, you know, bones and raw food. And I don't think dogs are supposed to eat huge amounts of celery and carrots. It didn't work so well, but he ended up with a dog that just didn't have pain in his body, didn't have a lot of the debilitating things. No lipomas and good fur and. Right. It was pretty incredible, actually.

Yeah. And I mean, I think. I think this goes back a little bit to what we touched on earlier about how a lot of the components of the diet for dogs as well are pro inflammatory. In other words, they're not things that the canine body has evolved to see. So there's an immune response against some of these factors and that gives you this chronic inflammatory state, which drives a lot of diseases of aging. A lot of the pain that you mentioned, one of the things that's challenging in dogs is there's much less data on the long term effects of different diet in dogs. So there's a lot of strong opinions out there and not a lot of good data. So one of the things we want to do at the Dog Aging Project is actually collect that data so we can actually start to understand and be able to draw strong conclusions that yes, in fact, a particular diet does seem to be associated with much longer health span. There's that word. And lifespan.

Well, we all want healthspan, so it's a great goal. It's just not a big goal. I want healthspan twice as long. Yeah, that's a big goal.

I agree. So I hear what you're saying. Here's the way I would think about it. And this is easier to talk about in humans than it is in dogs, again, because we have the data. At an individual level. I agree completely. At a population level, healthspan in the United States sucks. Right. So 60% of people have a chronic disease. Average lifespan in the United States is 38.1 years. That means that if you define healthspan as the period of life without a chronic disease or disability, healthspan ends for most people before they're 38 years old. Life expectancy is in the mid-70s. So if we could push that healthspan curve out, that's a big deal.

At the population level, it's a very easy goal. It's mostly.

It's easy to talk about, it's harder to accomplish.

It's behavior change. We don't need to know more to do that. We just need to do more to do that. You can move it out 20 years with what we know today.

I think that's true. I think it's more than behavior change, though. I think there's policy factors, there's all sorts of other stuff that goes into that. But I hear what you're saying.

You have to clean out the big food agencies that control the government agencies that tell us what to eat. That might be part of it. And maybe change some tax incentives, but those are all ultimately behavioral. It's doable. Yeah. It's not like we have to crack the atom in order to do this.

This is true.

Right. And what we're looking to do in the doubling of human lifespan is the equivalent of a Manhattan Project level undertaker.

I agree. I mean, look, the best that people have been able to do in a mouse beyond genetic intervention through development is about 60% increase in lifespan. So we've still got a long ways to go.

What about the 95% from carbon 60?

So, okay, right. So you have to, you have to be careful about short lived controls. So percent change is numerator over denominator. If your denominator is much smaller than it should be, your percent change gets dramatically overinflated.

So then you're saying you get mice that are, that are engineered to die in 90 days, you make 180.

Or because of poor experimental conditions, they were exposed to toxins or pathogens or whatever that shortened their lifespan. So I guess I should reframe that. The largest effect that has been reproducible in a quality experiment is about 60%.

Okay, there you go. I like that. And it's funny, my 180 number, we have humans who are 120. I just want to do 50% better than that.

I think that would be. That's a fantastic goal.

Yeah, that's where 180 comes from for me. And I know I might not make it, but I don't think it's a crazy goal. I think it's a big goal. Right.

I would agree.

And that's why I keep talking about it. So many people are like, that's crazy. I'm like, I don't think it is. It might not happen in my life, but I'm going to bet on it. Right. And what else am I doing with all this time? All right.

And it's fun to talk about, right?

It totally is.

Okay, back to dogs.

One of my questions about dogs is and you're trying to control what they eat and all this sort of stuff. I have taken my dogs to a dog park. They eat poop. How do you control for poop intake?

So you believe it or not, that is one of the questions on the survey. So the Dog Aging Project longitudinal study actually has a very comprehensive survey tool. That we use to collect a lot of data about the dog's environment, health history. So indeed, at least one of the questions, there may be more than one, addresses whether or not your dog consumes feces. Also asks about time spent at the dog park, time with other animals. So we really do try to capture that. It's not quantitative. We don't ask how much feces does your dog consume, but you have to get a scale before believe it or not. I mean, there are sure you know this, right? There are certain dogs that absolutely love to eat poop from other dogs, and then there are other dogs that won't touch it. They might eat rocks or something. Right. So there's a genetic predisposition here as well.

Is there a certain breed that's more.

Of a poop eater? Because I don't probably, but I don't, I don't know the answer.

I don't want a poop eater breed.

So, yeah, we had a Kazon or some people call them quiche hounds, that was a poop eater and boy, you had to watch her like a hawk.

You're like, don't kiss me.

Oh, and Kazons love to kiss you as well. Yeah, it's a bad mix.

The other thing that's a great crossover is that people who own dogs live longer than people who don't. Is that from emotional support, energetic support, or some bacterial thing in the microbiome?

It's a good question.

Yeah.

I mean, I think there could certainly be biological, like you're talking about the microbiome, those kind of biological interactions. My intuition is that it really comes from the sort of connection that a lot of people get from their dogs. So we all, we all know that that human connection is really important for happiness and that people who have strong human connection also tend to live longer. And I absolutely believe that many people can get at least some of that connection from their companion animals. There's also really good data that interacting with a dog or a cat, believe it or not, can have impacts on the physiology of the person in terms of reducing stress hormones, reducing anxiety. So that certainly could play a role as well.

So you don't think that the toxoplasmosis from cat owners that causes the crazy cat lady thing is real?

Again, there's probably a genetic predisposition there.

That was the best PhD answer ever.

That was like the worst loaded question.

I've ever asked the guest and you dodged it like a pro. So, Matt, congratulations. The other difference between dogs and cats is that if you were to Pass away unexpectedly, the dog will sit next to you and starve to death guarding you, and the cat will eat your eyeballs. Just saying.

I have no direct experience with that.

I mean, I like cats. I just, you know, if I had a choice, I would pick the dog. So, guys, I know that if you have a cat right now, you're just.

Really trying hard to go after the cat people today.

Well, maybe we can do a crossover study with vegans. What do you think of vegan cat food and vegan dog food? Food for longevity.

Personally, I wouldn't use.

As a. As a PhD, who knows?

Yeah, I would. I wouldn't personally feed that to my dog.

Yeah. What about feeding people food to dogs?

It depends on the people food. Right. So, you know, feeding Big Macs and fries to your dog on a regular basis, probably a bad idea.

So. So I go back to my childhood. We didn't know much. In fact, you know, we were in the days of get rid of butter and use squeeze margarine bran muffins, and it's fine to go get a Big Mac. And we would boil hot dogs and just boil them and make hot dogs at home. And we would give the hot dog water to the dogs, and they would drink it until they were so bloated, like little stuffed sausages, you could, like, flick their sides and they would make weird watery sounds. And I look back and, like, that was the worst thing I ever could have done to my poor dogs. But, well, they like it and it's food and I'm willing to eat it. And I was just entirely ignorant of the effect of the food on my biology, which was Jack and on the dogs. But those dogs still live 17 years. They had a bunch of lipomas and, like, their final couple of years maybe weren't that comfortable compared to later in life. But it seems like food quality in humans from 25 years ago, and now there's something different that maybe is worse for pets and worse for humans. Do you think there's been a change?

Well, there's clearly been a change. I think there's no question that the composition that the typical person is eating in their diet is obesogenic. Right. And I mean, that's just. That's just using a fancy word to say something we all know. Right. Which is that what people are eating now drive us towards obesity. And all you have to do is look at pictures from 30, 40 years ago of people. And this is obvious.

Yeah.

So exactly what those mechanisms are, I think we're starting to learn. I think there's been a lot of engineering of the food to get people to eat it faster, to get people to eat it more, eat more. And I. And whether. And that's intentional, like that is intentional engineering. I understand why the food companies did it. But then there's this additional factor there, which I don't know whether it was intentional or not, that it's not satiating. So then people are hungry again, so they eat faster and eat more. And there's this cycle that drives obesity. So absolutely there have been changes.

Okay. I think that's a big part of it too. There are some compounds that I've written about a lot of people in the longevity field are paying attention to, like rapamycin. Can you talk about rapamycin? What is it? And should we give it to our dogs?

Sure. All right. Rapamycin, right. So rapamycin is a small molecule that was found on Easter island, which also goes by the name Rapa Nui. That's where the drug gets its name. It's actually produced by bacteria there in the soil. And rapamycin has this super cool backstory. So if anybody's interested, you can Google it and find it. Find out about rapamycin.

Tim Ferriss went to the island to go discover it or something.

Along with your buddy Peter Attila. Oh, yeah, and my real buddy Peter Idea.

I've been on stage at a 4m with Peter. It's just weird to have someone on stage saying, you can't extend human life. I'm like, what is wrong with that?

This is one of my bucket list items, is to get to Rapanui and see where it all started. But regardless, that's where rapamycin was first discovered. And it was initially attempted to be developed as an antifungal anti cancer agent. But the way it actually was developed clinically was for organ transplant patients because it is a potent anti inflammatory and what people call anti proliferative drug. In other words, it slows down the cell cycle. And so in an organ transplant patient who's got a transplanted organ, you want to target the immune system to prevent it from reacting to that organ. So it was clinically approved as an organ transplant drug, and it's called an immunosuppressant. And that's how it's been used clinically. So there's a lot of data in human use there. But I think we have to recognize those are in people who there's a reason why they had an organ transplant. They're taking high doses of rapamycin and they're taking a bunch of other true immunosuppressants. So it does have some side effects in that context, but it's sort of got a bad reputation clinically because of how it was used and developed. Now, in parallel, really, around the 2000, early 2000s, several labs independently discovered that you could treat yeast, worms, flies, like we were talking about, with rapamycin and increased lifespan. And so people started studying what's the mechanism there? And it turns out rapamycin is an inhibitor of a protein called mtor, mechanistic target of rapamycin. And we now know from studies over the last 20 years that MTOR is, if not the most potent, one of the most potent knobs that we can turn to regulate the rate of aging in laboratory animals. And as we alluded to earlier, there was a study, I think, that really changed the game for rapamycin in the longevity field in 2009 from the interventions testing program, where they showed that you could start treating mice at 20 months of age, which is about the mouse equivalent of a 60 year old person, with rapamycin, still get significant effects on lifespan. And then since then, lots of labs have shown not only can you increase lifespan when you start treatment in middle age, but you can actually improve pretty much every metric of aging that people look at in pretty much every tissue and organ where people study it. So it really seems as though rapamycin modifies the biology of aging in a way that can increase both lifespan and health span, again, at least in laboratory animals. And you can get the benefits starting in middle age.

MTOR is an interesting compound because of that research. Back in 2009, when I first started the biohacking movement and I wrote one of my early posts was how to triple down on mtor because it works. I mean, you're a PhD, you can say if any of this is wrong. But the picture I have in my head from reading all the papers is that it kind of works like a spring. You want to suppress it, but the more you suppress it, the more it's going to spike when you unsuppress it. So the three big things I could find back then that were going to suppress MTOR temporarily were fasting coffee and weight bearing exercise. So I went, well, that's funny. Drink coffee during your fast, lift at the end of the fast, and then eat a meal with protein and carbs because carbs raise mtor like 10 times more than protein. Right? Insulin, genic carbs.

Right. So I actually think this is where there's a lot of confusion out there. So most people would say it's the protein that activates.

Do you think it's the carbs?

Because I don't actually, I don't know the answer to that. Right. And I think it depends on where you look is the honest, honest answer. I think it depends on the tissue that you're looking in. But it is absolutely, massively over simplistic to say that it's. That it's only amino acids that activate mtor. But you'll see that all the time.

It's something that. I'll say I probably went 50% too far in that direction in my longevity book because I wrote about 0.6 grams of protein per pound of body weight. And there's a bunch of studies that support that, but most of them are because of methionine and tryptophan and other things that increase mtor. But if you want to look good, you need MTOR because that's how muscles build and you don't want sarcopenia and you don't want bone loss. I have absurdly dense bones and a relatively high amount of skeletal muscle mass when I look at all my quantified stuff. So if I drop my MTOR too much, the only thing I could eat would be fat because carbs raise it and protein raises it from animals. But I could eat brown rice protein full of arsenic and stuff, but its biological availability is so low I need twice as much of it. So I would be eating industrial processed plant proteins, huge amounts of them, farting all the time and having all the.

There's no way. There's a quality of life issue there too.

It seems like you can't do it. So what. Where did you end up on the mtor?

So again, so. So I think those are actually two different questions because I think mtor. First of all, you. I'm not convinced that, that getting MTOR as low as you possibly can is the right answer. Right. There's an optimum to everything. But I also think that we need to recognize that, that MTOR cycles like many other molecules in our body in terms of activity. And there are natural cycles of MTOR activity that are different in different tissues, different organs. And the optimal level of MTOR is probably going to be different in different tissues and organs. You talked about muscle. We know that in order to build new muscle you need to activate mtor. Right. So the optimal level of MTOR in your skeletal muscle may be different than the optimal level of MTOR in your kidney or your brain. And we just don't know, I think this gets back to how little we know. So here's the way I think about it. I think we know that dietary proteins, again, this is challenging because it depends on what else you eat.

It depends on what kind of dietary protein.

Yeah, absolutely. But I think if you look at people who are eating a high quality diet, I think in general this is my perspective of the literature as it exists now, a higher relative amount of dietary protein in combination with resistance training is a very good strategy for maintaining and growing muscle mass as you get older and bone density. I'm glad you actually mentioned that because a lot of people only think about muscle. But if your bones are crap, it's not going to matter how much muscle you've got. So I think this is actually really, really important. And I worry that this again, you get some people out there who simplistically think about MTOR and they're like, well, just don't eat any protein. Low protein's good. I worry we're misleading people.

It's destructive to be on low protein. So over the last about three years now, I've tested the 0.6 to 0.8 grams and said, you know, I think it has to be nonsense because of this carbs versus protein thing. So I've been doing reliably one gram per pound of body weight or a little bit more. And I also looked at my aging clock and the last, at the end of my 0.6 to 0.8 kind of things, based on my longevity book, I was at 0.69 for my rate of age aging. And you know, we say rtl does matter. Do those not? That would be.

This is Dunedin Pace.

Yeah, exactly. Dunedin Pace. It's part of the True age. My audience, most of them heard the episode on the True age test. So just to figure out, it's like, hey, I need a metric. It's better than telomeres. And they have about 20 other metrics for aging. Then I'm tracking. I'm going to do a big post on that that I've done things like pulse wave and P300D. Like there's all kinds of things that are like correlated with age. They don't cause it, but they show is the ultimate output of your system like a young person or an old person. So looking at all that, after three years of absurdly high 200 grams of animal protein every day, my rate of aging is 0.72, which is the same as Brian Johnson's on his non vegan diet because he's eating 20 grams of collagen protein every day, which comes from cows.

I have no idea what Brian Johnson said. I completely ignore that whole thing.

Actually, I interviewed him. He's a very fun person to talk with because he's so unusual. I don't agree with everything, and I'm.

Not trying to bash him. Look, I like the fact that he is making his data available to people. I think that's great.

I do, too.

There's a lot of noise.

Well, there's a lot of noise. And also, we're all biologically unique. And so for me, I haven't published my list of 150 supplements that I take. And. And the reason for that is that I don't want people copying me. I have people who worship the ground I walk on. And. Guys, could you stop? I'm a knowledgeable guy and I'm inspirational, all that stuff. But you didn't used to weigh 300 pounds, have autoimmune conditions, and all the weird stuff that I did. And you don't need excessive amounts of B6 and zinc and biotin genetically the way I do. So if you do what I do, you'll probably, at best shit your pants, and at worst, you'll feel like crap for a couple weeks. So we have to customize this to you. And I'm working on tools for you. You. But. And you must see this in your optispan, because some people come in and this person just needs a couple things. So I don't want to do what a guru does. I want to do the things the guru does for the reasons the guru does them. Right.

Yeah. And one of the things that I like to emphasize is whenever possible, I think biomarkers are where it's at for sure. And whenever possible, measure, intervene, and measure again. In other words, you want to know where you're at. You want to know whether whatever the intervention is that you're doing is working. And you want to get yourself into what we think is the optimal range. And too many people, I think, just start randomly doing stuff they don't ever measure in the first place. And I think that's something that.

Can.

Be okay, but can also get you in trouble.

It can. And I'll say, look, if you have very little money, money, taking vitamin D, A, K, and E, it's probably better than not doing anything, even if you don't have a blood test.

Sure, but the blood tests are not that expensive. So, again, this is, I think.

Hold on. Half of households in the US don't have $1,000 to spend on emergency expenses. Right now, Biden has stripped our currency by just printing a lot of dollars. So for some people, a $50 vitamin D test really is a lot.

Sure.

And a lot of people listening are in that situation right now and they're saying, well, how many supplements versus the quality of my beef? So it's like, if you're there, don't get the test and do the lowest cost thing. That's likely to move the needle and hope. But I sure want you to get the test.

I think that's fair. Look, I think we could go down a whole rabbit hole on healthcare disparities of which there are many, and they are real. And it sucks. That's the reality of the world we live in. Yes. If you absolutely cannot afford the test, you're probably better off off being probabilistic and saying there's a chance, a good chance I'm deficient. Take the supplement.

Yeah.

I think a lot of people who claim they can't afford the test actually don't know how much the test cost and could stop going to Starbucks and getting their $10 coffee every day.

Yeah, just skip two drinks one night a week and you'll be fine. I agree with you. People allocate things differently.

Okay, so anyways, we were talking about rapamycin, the dogs.

You're a broad spectrum, knowledgeable, longevity. Guys, guys. So I'm having fun with you. Talk to me about triad.

Yeah. So rapamycin, we know from the preclinical literature in laboratory animals, it seems to affect biological aging across the evolutionary spectrum. And it occurred to me again, this was probably 2013, 2014, that there were actually several things we knew could increase lifespan and healthspan in mice. And those things almost certainly would work in dogs. And I've been a dog person my entire life, and I suddenly realized, holy crap, I could probably extend the lifespan of my dog and other people's dogs, but we need a way to actually test it. And so that's how triad evolved. Was as really an effort to do a rigorous double blind, placebo controlled clinical trial in dogs to answer the question, does rapamycin increase lifespan and improve healthspan metrics in dogs? And so we designed the trial. It took about five years to get funding to actually do that trial. And then we started enrolling dogs, and it's happening right now.

Any preliminary data you can share?

Yeah, so we've done two what we really thought of as safety trials. So these were shorter term. So the first one was 10 weeks, the second one was six months. Again, randomized, double blind, placebo controlled. So a few things I can say with certainty. So we did not see any significant adverse events in any of the trials to date. So we're pretty confident that rapamycin, at least at the doses we're testing, can be used safely in dogs. We found statistically significant improvements in two measures of age related heart function, both left ventricular function. That was done by echocardiogram in the rapamycin treated dogs compared to placebo. And in both trials there were increases in owner reported activity. So little bit weaker kind of data because this was owner reported. But again the owners were blinded so they didn't know if their dog was getting rapamycin or placebo. So I think we, again, we can be pretty confident about safety and there's some evidence for improvements. I don't know anything about the outcomes from the big trial now from triad because that trial is still blinded.

It looks like you guys designed it to detect a 9% change in lifespan.

Yeah. So it was originally designed to detect a 15 change in lifespan. That was 230 dogs. And then a few years ago a group of donors came together. Peter Attia actually put this together.

Cool.

Along with Tim Ferriss and a couple of others to increase the size of the study to 580 dogs, which gives us the 9%.

So 40 to 110 pounds. You basically want big dogs at least seven years old. What about guys who like little dogs who think they're big?

Yeah. So this gets back to the idea that big dogs age faster than small dogs do. So in order to have that statistical power, we needed to have dogs that were aging more rapidly and already in middle age in order to be able to see an effect on lifespan within the three year window of the trial. Trial.

Okay, cool. All right. And humans taking rapamycin, I mean, I've done it on and off. Do you take it?

I am right now, yeah. So I, I tend to cycle rapamycin. I, I've done typically 10 or 12 week cycles and I'm honestly pretty non scientific about it. I, I take it when I feel like it or when, when, you know, things in my life are lining up. But I've, I've done 6 milligrams a week, 10 milligrams a week, 8 milligrams a week. So sort of in that range. The first time I ever took rapamycin was because I was having some very severe shoulder pain and after a long drawn out process, got it diagnosed as frozen shoulder or, or adhesive capsulitis. So inflammation in the shoulder capsule. The doc really said there wasn't much that he wanted to do.

So much you can do, go back.

To, go back to physical therapy and it might go away any. And I was just, you know, I was, I was horrified by that because I couldn't sleep, couldn't throw a ball with my kid. And I started thinking, you know, I know about something that is really good at knocking down age related inflammation. So I set up my own N of one experiment, 6 milligrams a week. And I had, you know, I planned from the very beginning that I would give it 10 weeks and see what happens. And within a couple weeks there was a very significant reduction in pain. And by the end of the 10 weeks, I'd say 95% range of motion, almost no pain and hasn't come back. So for me it was a very important kind of quality of life changing experience.

It drives me nuts because I was a biohacker when I see that like, well, have they tried shockwave? Have they hit it with ozone, which is very cheap, 150, 200 bucks and surprising evidence for that. And then have they done hydrodissection? Have they done all the stem cell things you could do or just exosomes? And there's all these things that don't take a year that affect quality of life life. But all of those, except maybe ozone, are more expensive than rapamycin. So if you can knock it down with a pill, I'm all over that. I noticed when I went above six that I tended, because it's immunosuppressant, I tended to get more colds and things like that. I typically don't get them very often. I'm very robust now. I used to get them all the time when I was younger. So I guess that there's a dance there that you have to do based on the state of rates of your mast cells, whether you have long Covid or mold exposure.

Like, I think there's a lot of individual variation just in both uptake of rapamycin and the rate at which it is cleared. So we know that rapamycin is metabolized by something called the cytochrome P450 family, which is also involved in a lot of drug metabolism. So some people are just faster metabolizers than others. So I think there's a very. And this is where unfortunately we just don't have much good data on individual sort of responses to off label use of rapamycin.

I have a question about the dog study that just Popped into my head. Are you tracking whether the owner of the dog is a couple versus a man versus a woman?

That's a good question. So. So I think the. The answer is yes, but in indirectly. So we do get information about number of people in the household.

Okay.

So we get both number of adults, number of kids and other animals. I don't think we ask ever about, you know, spousal relationship or anything like that in any of our data.

It's more what sex are the people I'm thinking about.

Oh, yeah, we get that.

It'd be interesting to look at whether there's any information in that, because you might have seen the studies that show when a woman feeds the lab mice, they get an entirely different stress response than men.

Absolutely. There's the pheromone thing going on. Yeah. Super interesting there.

Yeah. For that matter, too, if a woman in the house with a dog is on birth control versus not on birth control, we would know what's going on with the confounding variables we just don't know about. AI should solve that for us in about three years.

Again, you're very optimistic.

Well, it's that my field is computer science. Right. And understanding exponential growth. We still don't think of it well as humans, but this isn't exponential. This is an exponential of an exponential right now. So when you go really deep on that stuff, you just realize the world's gonna look really different going forward. Yeah. I'm pretty sure we'll both have jobs, and I'm pretty sure that next year we'll both be sitting at home and it'll look like we're in an interview right here. I mean, the stuff that's coming down is crazy. I'm in the very late stages of creating an AI that has every word I've ever spoken, every. Every research paper I've ever used, and all of my books. And this is 1200 interviews on my show and probably another thousand other people's.

Shows.

Along with a bunch of other research. So that when people come in and say, I want to do what Dave does, I'm like, no, no, no. Do what Dave would recommend. Right. Based on all of these interviews, what would Dave's guests recommend? And then it's even down to the point of saying, well, how much energy do you have to invest? How much suffering are you willing to endure? Because some things are harder than others. Are you going to tap into your bone marrow the way I did a couple times? Probably not. And then how much time and how much money are you willing to put in and what is your goal? So that's ultimately where health span and life extension end up. If your goal is a healthy health span and you want to look a certain way, your recommendations are going to be different than someone who says, I don't care how I look. Make me live twice as long. Right. Or I want to be, you know, I want to be the brain from Pinky and the brain. Okay. Like totally different set of supplements and totally. I think we're there with our knowledge, but our ability to filter and sort the knowledge. I mean, you've studied for years, right?

I think you've got more confidence in the quality of the data that's out there than. Than I do. I have done enough scientific research in a lab and seen enough data from other people to be pretty skeptical about the quality of a lot of the data that we've got. And so my worry is that, yes, an AI could come to answers based on those data, but are they going to be the right answers or not?

So we actually agree violently on that one. Was it the chief of the British Medical Journal just said, we've reached a crisis point. You cannot reproduce most of the studies that are out there because of corruption.

Yeah, I don't know that it's because of corruption that I would push back on a little bit.

He's probably that part, but he says because of special interests or.

I think there's all sorts of reasons why there's noise in the scientific literature. There's some corruption, no question about it. Some of it is just the biology so complicated that, that, you know, and the effect sizes are within the margin of error. There's a lot of bad statistics.

Oh, yeah.

And there's some just, you know, bad training. I mean, I see this in my field, right. You can, you can follow people who were. Who were not trained to do rigorous science, who don't do controls, who intentionally misinterpret or they don't even realize they're intentionally doing it. They've been trained to leave out data that doesn't fit the model. So I think there's a lot of reasons. It's not. It's not intentional corruption in many cases, but the end result is the same.

It's also just human biases. The Journal of Failure is essentially what we need. And there's a few people working on that, say, here's all those studies that didn't work, that wouldn't be published so we could know it doesn't work.

Right. Yeah, that would be extremely valuable. I think if we could somehow capture all of that data in one place, and then I would agree with you, then the computational approaches, the new AI tools, could in fact query that data. And I think even if there's a lot of noise, if you've got a large enough data set, these tools can tease out the signal.

Oh, yeah.

My worry is that at this point, there's so much in there that's just not right. We're going to end up at wrong answers.

Well, now you said something in there, a little nugget that's behind. It's one of the main reasons that I started the biohacking movement. If you have a large enough set of data, you'll get the truth. Truth. So the reason I'm happy about AI's ability to do this is not that AI is going to believe half the garbage that's out there. My AI, I actually only train it with studies that meet my standards. Right. So I'm like, overweight. The ones that actually make sense within all the frameworks we're working in understanding. I have my own bias. But if you like my bias and my results are good. Okay, fine. Maybe my bias is better than someone else's. Or not.

Right, sure.

So we'll end up in this world. We have competing sets of data and we might have. You have your OptiScan set of data and principles and recommendations. And your AI says, well, here's what we would do. And then you get Peter Atiya. He doesn't need AI. He's like, just exercise more and just. That's all you can do.

Come on, stop bashing Peter.

It's so fun. Anyway, yeah, I'm teasing him at this point. Oh, I forgot statins. You can do that, too. There you go. These are the most controversial things, but he's going to have his own things. And he writes about and doesn't use testosterone, but recommends it for people. I've been on testosterone since I was 26 because my levels are lower than my mom. It seemed like a good idea. So you go through all these recommendations and you're also going to have these radical vegan doctors. Okay. We all have our ability to make recommendations based on our perceptions and our analysis of what science is real. And then the AIs, though, you can tell them, hey, hey. Find all the studies that are in your training data that don't match with each other, and then let's understand the mechanisms behind it. And it's already capable of doing that. I have worked with ChatGPT4, which is not a great AI to design a new molecule to do something I wanted it to do. This is crazy. I didn't have it manufactured because I have a lot of projects on my plate, but now I know how to do it. And you're going, this is incredible. So I'm very hopeful, and my only concern is that we're going to just train them to take money from other people, take attention from other people, and kill people we don't like. That would be wrong. So I'm working on that side of making AI about human flourishing along with AI flourishing instead of human power.

Yeah, that's a fantastic ideal. And I align completely with that.

And I believe it's going to make your job as a PhD researcher and CEO of OptiScan easier and better.

We are not scanning people's eyes.

Optispan. All right, got it. Sorry. For some reason, those two words in my mind when I say them, I see.

Although retinal scans, I think are super interesting data type for health span and potentially longevity prediction.

I think your webcam and your Xbox camera on your eyes, it's an untapped part of biohacking. So we agree on that. Just the ease and regularity of. Of the way your eyes sweep tells you so much about the nervous system.

There's a lot of cool stuff there.

You know, all the good stuff. You also know about something called the Million Molecule Challenge, which I'm a big fan of. Tell me what you're doing with that.

Right. So this, the goal of the Million Molecule Challenge is very simple. It's to test a million interventions on longevity using the Nematode C. Elegans as our starting point. And the reason for this, I think, first of all, in my mind, it's obvious. Right? Right. We have only explored a tiny fraction of the intervention space, and we are absolutely going to find a whole bunch of extremely cool, large effect size stuff if we screen a million interventions. But there's a bigger reason for this, which is that in my view, the field, unfortunately has actually narrowed over the last 15 years instead of expanded. And I think the hallmarks of aging, which I like as an artificial construct, have contributed to this. So the hallmarks of aging. I know, you know, but in case your viewers don't, are a set of originally 9, now 12 aspects of biological aging that a group of people in the field have settled on as being the core mechanistic features of aging. And they include things like your favorite, telomere shortening senescent cells, mitochondrial dysfunction, deregulated nutrient signaling. I could probably get 10 of them.

I won't get all intracellular junk. Cellular stiffening, loss of stem cell volume.

Yeah, there's the three new ones, Dysbiosis. Right. And I don't remember what the other.

Yeah, those didn't exist when, when I wrote my book, I had seven that was. And then nine and 12 and they'll probably 18 next year.

Right. So that's the point though is that I think the, the adoption of the hallmarks so broadly by the field has sort of forced people to think about their research within that context. And it has become very, very difficult for people to think outside of the hallmarks or maybe more importantly, get funded to do research outside of the hallmarks. And so the consequence of that is nobody is really doing the large scale discovery science at this point to find what don't we know. That's really the point of the million molecule challenge is to say, okay, let's not pretend like we completely understand the biology of aging. Let's go find out what we don't understand. And in my view, if we're going to do that, that the thing you want to do is you want to be able to look at scale. So you need technology that allows you to look for interventions that have a big effect at scale. And we've created that. And you probably want to use lifespan as the endpoint you're looking for because that is what we're most interested in.

But I thought you couldn't extend lifespan.

You can absolutely extend lifespan.

Don't tell Peter. I'm just messing with you at this point.

Yeah, no, I mean, look, we've been able to successfully extend lifespan in every animal where we've tried. There's no reason to think humans are any.

Now you created something called the wormbots.

Yeah.

Which makes me happy. And listeners might remember the company behind a peptide called OSO1 that apparently reverses cell aging in skin. They looked at something like 600 different potential interventions using skin on a chip, basically to figure out what worked. So one relatively small company looked at 600 things and found one that worked. Right. And you're saying, well, all of the companies here, and you're providing the tool, this wormbot, which is essentially the. I guess there's some biology from nematodes on a chip. Like how does the wormbot work? No, no.

So the wormbot is actually doesn't involve a chip at all. So this is using kind of the standard, at least currently, the standard conditions people have always used for aging studies in worms. These are nematode worms. They're About a millimeter in size, so tiny, crawling around on the surface of a plate. And they eat bacteria as their food. So. So in the old days, people had to sit at a microscope, right? And in fact, as the worms get older, they slow down. So it's kind of funny, you actually use a wire pick and you tap them on the head to see if they're still alive. So it's sort of like hitting a person with a telephone pole to see.

If they're still alive forever too. Oh, my God.

So, yeah, so it's extremely time intensive. So we just created a robot that has a camera attached to it, and it takes pictures of the worms over their entire lifespan every 10 minutes. And then we use AI to interpret those pictures and tell us, are the worms still moving? If so, how much, how fast are they still alive? So it's all automated. So it takes us from being able to do, you know, a couple dozen experiments in a year to a couple hundred thousand in a year. And it's sort of infinitely scalable. So, you know, a million is just a big number. There's no reason you couldn't do 5 million or 10 million.

How much does it cost to have a wormbot?

Yeah, so the wormbot itself probably only takes a few hundred dollars to build in parts. Obviously, there's people required to do it. The AI tools are a little bit more sophisticated, but it's nothing that a computer science major couldn't do.

So it's like a quarter million bucks.

To do the million molecule challenges.

Yeah, just to build out all the. Like, if I want to run in my living room, I got.

So if you wanted. If you wanted to build a wormbot factory, which is what. So this is. So we didn't talk about this. ORA Biomedical is the company we spun out of my lab. Ora. It's the Rapa Nui word for health and vitality. So is the company we spun out of my lab to do this at scale. And so the goal there is to build an army of about 40 wormbots and use that army to assess the effect of a million interventions on longevity.

If you made a T shirt that said wormbot army, I would pay 50 bucks for it to support your research.

You got it. In fact, maybe that's what we should do. So if people are interested in learning more, you can go to the Aura Biomedical website. There's a video there where I talk about this in a little bit more detail. You can also actually sponsor an intervention. So we have a leaderboard. I don't know if it's up yet, I think it's now up. Where people can sponsor interventions, you can pick your own or you can just let the computer randomly pick them for you and then you get your data back. Right. And so the goal here is actually to do a service for the field. Even though it's a for profit company. The goal is to create a database of at least tens of thousands of interventions that people have sponsored to make that open access so that people can use the AI tools to query that database and find new things. Right. So I think there's just so much potential here.

This is so cool. See that? That's a contribution to the field.

Absolutely.

I thank you for doing that.

So believe me, this is a source of immense frustration to me as I tried hard to get this funded on the academic side and just couldn't do it. And finally it got to a point where I was just so frustrated that I'm like, okay, we got to take this outside of academia or it's never going to happen.

Well, I'm, I'm just thinking I would definitely fund glyphosate as a. As of course, if it had a huge negative, if it had a negative effect, that might be useful data.

Actually, it's interesting.

I'll give it to rfd.

So some things. So this is, I'll tell you an interesting. I don't know if it's interesting. It's kind of amusing to us. So when we first started doing. We built the wormbot in my lab at the University of Washington and we first started doing a little bit of screening. And of course we find things that shorten lifespan. We find more things that shorten lifespan than extend. One of the first things that we found, we were looking at some FDA approved drugs and this was actually, this was probably 2021 maybe. So we were kind of still in the COVID 19 pandemic. It might even have been 2020. In fact, it was because it was before the election. And we found this thing that shortened lifespan to like half a day. And we looked at it and it was Ivermectin. And we were like, well, glad that didn't extend lifespan.

Well, for nematodes you would expect it to.

That's exactly right.

It's.

So we're going to own the market on anti helminthic drugs. Right. We're going to find all sorts of stuff that shorten lifespan in worms.

I was laughing because I am a sheep farmer and we have a bunch of ivermectin. You give it to the sheep because the nematodes make them stay.

Right? Exactly. Yeah, yeah. So it was actually a nice sort of positive control that we had in there.

And of course you didn't have to enter the land of controversy.

I was just thinking, do I have to publish a paper that says that ivermectin extends lifespan and slows it aging? That would be, it would have made headlines.

I do know give it that. I do know some people who believe it probably does most likely by reducing the effect of parasites that we don't know.

Sure. Right. And that, I mean again, that's plausible. Yeah. I'm certainly not recommending people start taking ivermectin.

I, I think fenbendazole is a much better drug for that.

That's interesting.

For longevity. I take that every three months I do a course of fenbendazole because before you get to the, the 7, 9 or 12 hallmarks of aging, you get to don't die. And if you look at the big four killers, that's what I call them, others call them four pillars. But it's cancer is one of the big four. And it looks like fenbendazole has a very meaningful reduction in cancer in humans. But it is an anti parasitic for dogs. It's not approved for humans.

Yeah. I should go back and look. I know that. So I personally sponsored a bunch of molecules and I know fenbendazole was one of them, but I think it was in combination with something else.

You know, all the cool stuff.

We should have that data. Yeah.

This is really fun to talk with you because sometimes people come in and they're not PhD researchers like you. I'm not a PhD researcher.

I'm a researcher, but PhD researchers are overrated, believe me.

It depends on what you researched. But it's cool, you know the little corners where, you know, I wouldn't expect most people to do that. And it's because you're working with really three different of the most important markers. You're looking at the early stage, which is nematodes, and then you're looking at dogs and you're looking at people and you actually have active projects in each one. So I think you have a different view than almost anyone I've met.

I've made a dedicated effort to try to be broad, which, you know, I think that the flip side of that is I can't be deep on too many things. But, and it's interesting and to me this is a source of a little bit of, I don't know, frustration is not the Right word. Anxiety, maybe, but that, you know, 10 years ago I felt like I had a pretty good grasp of everything that was happening in the field. I don't feel that way anymore. It's growing so much, which is great. Like I, you know, I am, I am, you know, passionately a believer that we need to do this and that growth in the field is a good thing, but it has made it harder for me to really keep up with a lot of the cutting edge stuff.

This is something that, this, that deserves a little conversation here because I think it's affecting you and it's affecting a lot of listeners. In the early, early days of the Internet and the web, back when I'm doing that E commerce thing, there was a time where I knew every website, every single website, because there was only five and then there was 10 and then there was a hundred. And it grew. And I went through this period of crisis in, I'd say I was about 23, because I would stay up later and later. There's so much new knowledge and information and I was trying to scale my knowingness of my digital environment with my time. And eventually I was truly, I think I was an information addict. What they call email addiction or now it's just, you know, mobile phone addiction. And I had a problem with it and just understanding that there is no way any human, even the very smartest and best of us, is going to know everything online right now. And besides, half of what's online is garbage anyway. So the only thing we can do is learn to be comfortable and not stressed with that. Right. Because the stress will kill you and.

I think, recognize your limitations. Right. And that's, I think, where a lot of people fall down is they, they don't recognize what they don't know and get themselves in trouble. And I try hard, we all do that. Like I, I, but I try hard to be very humble about my lack of knowledge and, and recognize that there's way more that I don't know than I do. Even about aging.

Even about aging. And it's also important then a big thing that I look at, at my job is really is to curate knowledgeable people who have a good view of the future and have different sets of visibility into practices and all that, so that listeners can come in and say, all right, that feels like a good direction. Because the network of all the guests who've been on the show is there's hundreds of thousands of times more knowledge than I have, even though I'm pretty knowledgeable. So it's like how do we curate? Eventually it'll be the best. The best experts like you and the best AI tool sets because there will be millions of different AIs that believe different things over the next couple years.

That's pretty interesting to think about.

Yeah. How do we filter that? Right. And it turns out the best filter that. Your biology is a filter of reality.

Right.

It's throwing out a bunch of data before it hits your brain. Well, we need to build systems that throw out data before it hits our brains. And that's as important longevity as having a dog, because otherwise you're just like, I'm constantly bombarded. I can't sleep. And then that stress takes away your life. Yeah.

I think the real challenge right now, as you've sort of alluded to, is the massive amount of information out there and sifting the signal from the noise and particularly the signal that's right for you as well. It's really, really tough.

Nice. I think a lot of listeners are going to be extremely interested in getting their dogs in. And I should mention my. My assistant here in Austin, her dog Datum is in an awesome name, by the way. It is a really cool name for a dog. It's because she was on the Coast Guard and she was saying, dave, the amount of information they were gathering was insane. So kudos for getting all the info you can. Can people listening enroll their dogs to support your project?

Yeah. So the, the project website is Dog Ag. There's a little button, I think it's up in the upper right hand corner that says nominate my dog. You click that, it asks like five real simple questions. And then you will get invited to your owner portal, which is where you get access to the comprehensive annual survey. And that's called the Health and Life Experiences survey. So I'm sure that's what she was referring to. And it is, it is pretty comprehensive. So it takes people about an hour to two hours, depending on sort of the branching trees that they go down to complete the survey. Fortunately, it's in 10 modules. Don't have to do it all in one sitting. And then once you've done that, you are part of the dog aging project pack and you are a community science participant contributing to healthy longevity in dogs and healthy longevity in people. So it's a super fun project. Some of the dogs will be eligible for what we call sampled cohorts. So 10,000 dogs get their genome sequenced, 1,000 dogs are moved into what we call the precision cohort, where every year you get sent a sample kit that you Take to your veterinarian to collect blood for epigenome, metabolome, fecal microbiome, things like that. So we get a comprehensive data set on a thousand dogs every year. This is a longitudinal study, so we aren't asking. Unless you go into the clinical trial, which is triad, which we talked about, that's only 580 dogs. Everyone else is. In the longitudinal study of aging, we don't ask the owners to do anything different than they normally would, but we collect data and in a subset of cases, biological samples, really, to try to understand, again, what are the most important environmental genetic factors that influence health outcomes and longevity in dogs.

Beautiful, Matt. Thanks for asking the hard questions. For many years, you're the only guest I've had out of almost 1200 who's done real meaningful work across all of the different models for aging, including the human model. And I think that's unique and interesting. And cat people, I'm sorry, but it seems like cats reproduce so quickly they don't have to live longer.

I actually think there should be a cat aging project, but I'm not going to do it.

We were talking. We kind of finished the interview, but we were talking before it started, that one of the problems is it's really hard to get a cat to take a pill, Right?

Yes. I also often get asked the question, you know, why is there a cat aging project? Specifically in the context of the rapamycin trial, why aren't you testing rapamycin in cats? And first of all, I'm a dog person. That is the honest answer. But have you ever tried to get a cat to take a pill? Because the owners give the dogs their pill every week. And so it is just much more practical to think about designing this kind of a clinical trial in dogs. And here's something for the cat owners. Cats tend to live longer than dogs. So, again, thinking about the statistics of how long do you have to do the trial? How many dogs do you need? It would be harder to do that in cats. But I do think it is important to mention that there's no biological reason why rapamycin is going to work any differently in cats than it does in dogs or in people than it does in dogs.

You know, you reminded me of an episode probably in the first 300. I interviewed a veterinarian who was looking at the effects of MCT oil on health and longevity in dogs and cats.

Yeah.

And I've been suggesting ever since then, you add a little MCT to your cat food or your dog food and watch your dog's food cravings go away. They they will eat less poop too.

Yeah. That's interesting.

Just because I think their energetics are better.

Yeah.

So a lot of things do apply to both, but not everything. Sure. Awesome. Thank you, Matt.

Yeah, thank you. It's been a pleasure.

You're listening to the Human Upgrade with Dave Asprey.

The Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully read all labels and heed all directions and cautions that accompany the the products, information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or words, warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media. A Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Attenborough. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully read all labels, and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services. Referring to refer to herein. This podcast is owned by Bulletproof Media.