Steven Austad

Well, I also think there's an individualization of this that we're missing. To me, health is a state of your physical being that you can do the things you like to do. Therefore, if you like to climb mountains, your health span is going to be different than if you like to play golf, for instance. And a lot of this is personal.

Well, I also think there's an individualization of this that we're missing. To me, health is a state of your physical being that you can do the things you like to do. Therefore, if you like to climb mountains, your health span is going to be different than if you like to play golf, for instance. And a lot of this is personal.

If you can't run a marathon anymore, some people will say, oh, my health is... And we never pay attention to the mental health piece, at least the biologists don't.

If you can't run a marathon anymore, some people will say, oh, my health is... And we never pay attention to the mental health piece, at least the biologists don't.

So I've got a different take on this. I actually think that this is a very good time for aging research funding. And that's not because of what's going on at the NIA. but it's what's going on in the private sector. There's more and more money. There's even interest now in big pharma. That was very spotty in the past.

So I've got a different take on this. I actually think that this is a very good time for aging research funding. And that's not because of what's going on at the NIA. but it's what's going on in the private sector. There's more and more money. There's even interest now in big pharma. That was very spotty in the past.

So I think if we focused entirely on the National Institute on Aging, we would get a false impression of what the funding climate is in the field now. And I think we need to take advantage of that. Got to make sure that it doesn't get captured by the people who are doing the flashy but bad science.

So I think if we focused entirely on the National Institute on Aging, we would get a false impression of what the funding climate is in the field now. And I think we need to take advantage of that. Got to make sure that it doesn't get captured by the people who are doing the flashy but bad science.

It's to preserve and enhance human health. I mean, it's basically the same thing that we do that we're supposed to be doing.

It's to preserve and enhance human health. I mean, it's basically the same thing that we do that we're supposed to be doing.

I think this is because we think about health all wrong. We think, let's wait to get cancer and see what we can do about it. That's what cancer biologists do. You have cancer, okay, how can we better treat that? Or could we have diagnosed it earlier?

I think this is because we think about health all wrong. We think, let's wait to get cancer and see what we can do about it. That's what cancer biologists do. You have cancer, okay, how can we better treat that? Or could we have diagnosed it earlier?

What Rich is saying and what we can know how to do in lots of model organs, it prevents you from getting cancer, delay it for a considerable amount of time. That's a little bit harder to study if you're a cancer biologist because you want to see the cancer before you can study it.

What Rich is saying and what we can know how to do in lots of model organs, it prevents you from getting cancer, delay it for a considerable amount of time. That's a little bit harder to study if you're a cancer biologist because you want to see the cancer before you can study it.

I think that's why we need aging biologists rather than people focused on certain disease to come and try to use what we do. If we prevented the cancers, they'd be out of the job.

I think that's why we need aging biologists rather than people focused on certain disease to come and try to use what we do. If we prevented the cancers, they'd be out of the job.

I agree, but I think we have that idea for marketing purposes, not for scientific purposes. And the idea is, well, the money goes to diseases. Let's call aging a disease, because I think what we're trying to do is we're trying to treat aging as if it were a disease, even though I would agree with both of you. I don't think it's a disease.

I agree, but I think we have that idea for marketing purposes, not for scientific purposes. And the idea is, well, the money goes to diseases. Let's call aging a disease, because I think what we're trying to do is we're trying to treat aging as if it were a disease, even though I would agree with both of you. I don't think it's a disease.

I think that destroys the word disease if we include aging in it. But I think there was a reason that suddenly this came because you thought, oh, maybe this will get Congress to pay attention.

I think that destroys the word disease if we include aging in it. But I think there was a reason that suddenly this came because you thought, oh, maybe this will get Congress to pay attention.

On the ride over here, Rich and I were talking about that. I don't believe there is one thing as biological age. I think there is potentially an age of your heart, an age of your liver, an age of your lungs, an age of your brain. But I don't see why we wouldn't simply call it health.

On the ride over here, Rich and I were talking about that. I don't believe there is one thing as biological age. I think there is potentially an age of your heart, an age of your liver, an age of your lungs, an age of your brain. But I don't see why we wouldn't simply call it health.

In other words, I got one of these epigenetic age clocks done on me a while ago, but I didn't know what to make out of it. I thought, is this just flattery or did it really tell me something? You must've got a good result.

In other words, I got one of these epigenetic age clocks done on me a while ago, but I didn't know what to make out of it. I thought, is this just flattery or did it really tell me something? You must've got a good result.

That may be the point. The whole thing, right? So I'm dubious about some number that is different than, I know I'm in good health. For my age, I'm in very good health. So I knew that already. Now I have a number for it. I don't put much credence in that.

That may be the point. The whole thing, right? So I'm dubious about some number that is different than, I know I'm in good health. For my age, I'm in very good health. So I knew that already. Now I have a number for it. I don't put much credence in that.

Right.

Right.

It's a surprise to me that longevity has become so big because for a long time, we tried to move away from that in the aging field because we were worried that people were thinking of longevity as, well, we're going to keep frail, feeble, old people alive longer. That's what longevity meant. When really what we were trying to do is extend health.

It's a surprise to me that longevity has become so big because for a long time, we tried to move away from that in the aging field because we were worried that people were thinking of longevity as, well, we're going to keep frail, feeble, old people alive longer. That's what longevity meant. When really what we were trying to do is extend health.

But I think the big but here is that even if that's the case, they would not be as good as what Peter would predict after all the tests

But I think the big but here is that even if that's the case, they would not be as good as what Peter would predict after all the tests

So I'm kind of surprised, but I think it's because there are certain people of a certain age who've started to think about their own longevity. And then I think there's a whole new generation of tech entrepreneurs that really feel like this is a problem that will allow them to live healthily for several decades, at least longer than they are now. So I think it's a combination.

So I'm kind of surprised, but I think it's because there are certain people of a certain age who've started to think about their own longevity. And then I think there's a whole new generation of tech entrepreneurs that really feel like this is a problem that will allow them to live healthily for several decades, at least longer than they are now. So I think it's a combination.

It's a multi-generational thing. That kind of surprises me. And you haven't seen this before, to be clear.

It's a multi-generational thing. That kind of surprises me. And you haven't seen this before, to be clear.

No, 30 years ago, I would have said, let's not even say the word longevity. Let's say healthspan. But that's changed quite clearly as more and more people have been from the outside. They're sort of peeking in at the field. I don't think the people in the field itself have changed the way they talk that much, but the people eavesdropping on the field certainly have. Rich, is that your experience?

No, 30 years ago, I would have said, let's not even say the word longevity. Let's say healthspan. But that's changed quite clearly as more and more people have been from the outside. They're sort of peeking in at the field. I don't think the people in the field itself have changed the way they talk that much, but the people eavesdropping on the field certainly have. Rich, is that your experience?

Not completely arbitrary, because they had some reasons for being there. I don't think any of us would say that those 12 things are not involved in aging. But that's a very little interest of itself.

Not completely arbitrary, because they had some reasons for being there. I don't think any of us would say that those 12 things are not involved in aging. But that's a very little interest of itself.

We could do a game where we each name one and see who can't. See if we get to all 12.

We could do a game where we each name one and see who can't. See if we get to all 12.

But certainly in that list, I would not consider epigenetics as the key hallmark, assuming there are such things. I consider it to be an interesting list. It became... biblically sacrosanct almost immediately. And I've never understood why, but for some reason it did. So I'd agree with Rich.

But certainly in that list, I would not consider epigenetics as the key hallmark, assuming there are such things. I consider it to be an interesting list. It became... biblically sacrosanct almost immediately. And I've never understood why, but for some reason it did. So I'd agree with Rich.

Yeah.

Yeah.

And I think Matt brought up a really important point, and we scientists are to blame, is the way that research gets reviewed. For lazy reviewers, having these 12 hallmarks is really helpful. Oh, this has got one of the hallmarks in it. This must be good stuff. I do think reviewers need to be more open to new ideas and new approaches.

And I think Matt brought up a really important point, and we scientists are to blame, is the way that research gets reviewed. For lazy reviewers, having these 12 hallmarks is really helpful. Oh, this has got one of the hallmarks in it. This must be good stuff. I do think reviewers need to be more open to new ideas and new approaches.

I mean, everybody knows that NIH grants are approved if they're incremental. If they're really breakthrough, they don't get approved. In fact, a very famous biologist, E.O. Wilson, told me years ago, he said, don't ever include your best ideas in a grant. They won't get funded. Do standard stuff. Save your best ideas for projects that you do on the side. That's one of the reasons I left academia.

I mean, everybody knows that NIH grants are approved if they're incremental. If they're really breakthrough, they don't get approved. In fact, a very famous biologist, E.O. Wilson, told me years ago, he said, don't ever include your best ideas in a grant. They won't get funded. Do standard stuff. Save your best ideas for projects that you do on the side. That's one of the reasons I left academia.

But it's a way to address causality. Yeah, but you might equally say, no, no, it's the mitochondria that have changed.

But it's a way to address causality. Yeah, but you might equally say, no, no, it's the mitochondria that have changed.

Yeah, or it's the glycated proteins. There's a ton of things in it. There's no reason in the world at this stage, I think, to actually give epigenetics primacy over anything else.

Yeah, or it's the glycated proteins. There's a ton of things in it. There's no reason in the world at this stage, I think, to actually give epigenetics primacy over anything else.

It's a hypothesis.

It's a hypothesis.

And I think this also illustrates why traditional disease-based medicine is not about the biology of aging. It's about something of the biology of aging itself. is distinct and it needs to be investigated in a different way. And we know that in the aging field, but the people in the cancer field and the cardiology field and the neurology field, I don't think they understand that.

And I think this also illustrates why traditional disease-based medicine is not about the biology of aging. It's about something of the biology of aging itself. is distinct and it needs to be investigated in a different way. And we know that in the aging field, but the people in the cancer field and the cardiology field and the neurology field, I don't think they understand that.

But I also think you're going to get a huge argument from anybody in the cardiology field, the neurology field. Or Alzheimer's. The Alzheimer's field. It's their money.

But I also think you're going to get a huge argument from anybody in the cardiology field, the neurology field. Or Alzheimer's. The Alzheimer's field. It's their money.

Despite... Massive spending. Massive spending. I was once in Congress trying to lobby with about six people from the Alzheimer's Association in the same room. I was totally ignored by staffers that were in there.

Despite... Massive spending. Massive spending. I was once in Congress trying to lobby with about six people from the Alzheimer's Association in the same room. I was totally ignored by staffers that were in there.

It's going to take a little while, but there's reason to be optimistic. And there's also the private sector is another reason, I think, to be optimistic. So let's go on record right now. I think when we, if we defeat Alzheimer's disease, it's going to be because of the biology of aging. It's not going to be because of the drugs that get rid of beta. Absolutely.

It's going to take a little while, but there's reason to be optimistic. And there's also the private sector is another reason, I think, to be optimistic. So let's go on record right now. I think when we, if we defeat Alzheimer's disease, it's going to be because of the biology of aging. It's not going to be because of the drugs that get rid of beta. Absolutely.

That's part of the XPRIZE HealthSpan challenge, of course. I think that that's a perfect example. Influenza pneumonia has never fallen out of the top 10 causes of death in the US. You know, it used to be number two, but still now it's number eight or nine. But it's always there because... you can't really do anything about the late-life immune dysfunction.

That's part of the XPRIZE HealthSpan challenge, of course. I think that that's a perfect example. Influenza pneumonia has never fallen out of the top 10 causes of death in the US. You know, it used to be number two, but still now it's number eight or nine. But it's always there because... you can't really do anything about the late-life immune dysfunction.

Well, I just heard that there are over 80 senolytic studies in early clinical trials.

Well, I just heard that there are over 80 senolytic studies in early clinical trials.

At some point in this, I had to bring this up, but let's imagine that Rich is incredibly successful at finding these things. That is a very, very long way from assuming that it's going to be the same in people. Most things that clinically work in mice do not work in people. It might be, and that would be wonderful, but I think ultimately we're going to have to find this for people.

At some point in this, I had to bring this up, but let's imagine that Rich is incredibly successful at finding these things. That is a very, very long way from assuming that it's going to be the same in people. Most things that clinically work in mice do not work in people. It might be, and that would be wonderful, but I think ultimately we're going to have to find this for people.

And my thought is the kind of evaluation that you do routinely of your patient's If we took a group of 65-year-olds and we gave them a drug that we thought was an anti-aging drug and followed them the next five or six years doing these evaluations, I think you could probably safely say this is slowing aging or not slowing aging.

And my thought is the kind of evaluation that you do routinely of your patient's If we took a group of 65-year-olds and we gave them a drug that we thought was an anti-aging drug and followed them the next five or six years doing these evaluations, I think you could probably safely say this is slowing aging or not slowing aging.

So I don't think that it's going to be that easy to jump from mice to people in this.

So I don't think that it's going to be that easy to jump from mice to people in this.

That would be great. Let me just say that I think that people that study animals, myself included, always underestimate how well we can evaluate health in people with a very, very thorough evaluation because we don't do that.

That would be great. Let me just say that I think that people that study animals, myself included, always underestimate how well we can evaluate health in people with a very, very thorough evaluation because we don't do that.

This is something that, I mean, aren't there six or eight clinical trials going on right now?

This is something that, I mean, aren't there six or eight clinical trials going on right now?

Absolutely agree with that, Rich. And nobody's saying that 100% of things that work in mice do not work. But I think there's a critical difference for aging research, which is it takes four years. To do one of these and mice. And so if we have to do 40 to find one or two that work.

Absolutely agree with that, Rich. And nobody's saying that 100% of things that work in mice do not work. But I think there's a critical difference for aging research, which is it takes four years. To do one of these and mice. And so if we have to do 40 to find one or two that work.

Well, I don't know that we need that, to tell you the truth. So I went to the FDA to try to get them to approve a trial of metformin. And we didn't couch it in aging, because you're right, as soon as you mention aging, their eyes glaze over and they're not interested anymore. But we did it in terms of multimorbidity, and they were fine. They were fine with that.

Well, I don't know that we need that, to tell you the truth. So I went to the FDA to try to get them to approve a trial of metformin. And we didn't couch it in aging, because you're right, as soon as you mention aging, their eyes glaze over and they're not interested anymore. But we did it in terms of multimorbidity, and they were fine. They were fine with that.

Right. But the important thing I think about what Rich said is all the stuff that he pointed out could be easily done in humans. Wouldn't be hard to measure hearing.

Right. But the important thing I think about what Rich said is all the stuff that he pointed out could be easily done in humans. Wouldn't be hard to measure hearing.

I think here's where we get back into healthspan versus lifespan. The effect of exercise on longevity is pretty small. Its effect on quality of life is enormous.

I think here's where we get back into healthspan versus lifespan. The effect of exercise on longevity is pretty small. Its effect on quality of life is enormous.

Maybe it would, maybe it wouldn't. In mice. I'm very agnostic about what we can learn from exercising mice because mice are basically kept in a jail cell, something the size of a jail cell their entire life. If you took a bunch of people and put an exercise wheel in a jail cell that we'd use it, would that be the same?

Maybe it would, maybe it wouldn't. In mice. I'm very agnostic about what we can learn from exercising mice because mice are basically kept in a jail cell, something the size of a jail cell their entire life. If you took a bunch of people and put an exercise wheel in a jail cell that we'd use it, would that be the same?

Would that substitute for people that walk around, that go inside, that go outside, that go to the gym, that do this? It wouldn't substitute for all of it, no question. So to me, it's a very low level of exercise. If you didn't see anything from it, You wouldn't rule it out.

Would that substitute for people that walk around, that go inside, that go outside, that go to the gym, that do this? It wouldn't substitute for all of it, no question. So to me, it's a very low level of exercise. If you didn't see anything from it, You wouldn't rule it out.

Yeah, I think we need to find that out. They look good. I think there's two parts, though.

Yeah, I think we need to find that out. They look good. I think there's two parts, though.

And it clearly has neurological effects. There's effects on addiction. The dementia connection is not inconceivable. It's crossing the blood-brain barrier. Right, right.

And it clearly has neurological effects. There's effects on addiction. The dementia connection is not inconceivable. It's crossing the blood-brain barrier. Right, right.

And these are going to be mice that are an incredible amount of stress from all the handling, the injections.

And these are going to be mice that are an incredible amount of stress from all the handling, the injections.

Do we know if terzapatide, for instance, if we're given to people of normal body weight, do they also lose 15% of their body weight?

Do we know if terzapatide, for instance, if we're given to people of normal body weight, do they also lose 15% of their body weight?

Not 3.8? No, 38. That's analysis by Andrew Scott, his British economist. That's bigger than I would have guessed.

Not 3.8? No, 38. That's analysis by Andrew Scott, his British economist. That's bigger than I would have guessed.

You know, the things that drive aging.

You know, the things that drive aging.

Can I push back a little on what Rich said about healthspan versus lifespan? Several papers have come out recently showing that the gap between healthspan and lifespan in people is actually increasing, and it's increasing the fastest in the United States, and it's increasing faster among women than men. So in humans, this is a very real gap and it's a growing gap.

Can I push back a little on what Rich said about healthspan versus lifespan? Several papers have come out recently showing that the gap between healthspan and lifespan in people is actually increasing, and it's increasing the fastest in the United States, and it's increasing faster among women than men. So in humans, this is a very real gap and it's a growing gap.

So can I give a counter example? Because there's good experimental data that these things can be at least partially eliminated. And when you do that, there's an improvement in health. And this has been done both in a genetic treatment, which genetically, which they prime these cells to be genetically killed. And it's also been done with drugs, not with fisetin, I hasten to say.

So can I give a counter example? Because there's good experimental data that these things can be at least partially eliminated. And when you do that, there's an improvement in health. And this has been done both in a genetic treatment, which genetically, which they prime these cells to be genetically killed. And it's also been done with drugs, not with fisetin, I hasten to say.

So I think there's strong evidence that getting rid of these P16 positive cells, which is really what it's all based on, can have an improvement in health and in longevity.

So I think there's strong evidence that getting rid of these P16 positive cells, which is really what it's all based on, can have an improvement in health and in longevity.

Yeah, yeah, yeah, yeah.

Yeah, yeah, yeah, yeah.

Okay.

Okay.

A long time.

A long time.

And I mean, in the published papers, they do show a reduction in P16 positive cells. And you're saying you couldn't replicate that in your lab.

And I mean, in the published papers, they do show a reduction in P16 positive cells. And you're saying you couldn't replicate that in your lab.

And I think one of the advantages of the kind of geroscience, the stuff that we do, is that Richard's right. We don't see this in our experimental systems. So this, to me, emphasizes the fact that we need to change the focus. I think one of the reasons that the gap exists is we're getting better and better and better.

And I think one of the advantages of the kind of geroscience, the stuff that we do, is that Richard's right. We don't see this in our experimental systems. So this, to me, emphasizes the fact that we need to change the focus. I think one of the reasons that the gap exists is we're getting better and better and better.

So the NIH has just put about $600 million into a network of researchers to study cell senescence. And I'm on the advisory group for that. And to the extent that Rich is saying these are many, many different things all pretending to be the same thing. That's clearly true. But they're coming up with bigger and bigger and broader definitions of what a senescent cell is.

So the NIH has just put about $600 million into a network of researchers to study cell senescence. And I'm on the advisory group for that. And to the extent that Rich is saying these are many, many different things all pretending to be the same thing. That's clearly true. But they're coming up with bigger and bigger and broader definitions of what a senescent cell is.

But on the other hand, they're also coming up with more and more interesting things that those senescent cells do, either in tissue culture, which I don't put much, or in mice. I don't think the NIH would put that kind of money into something if they didn't feel there was a valid basis... I think part of this is we're calling it senescence.

But on the other hand, they're also coming up with more and more interesting things that those senescent cells do, either in tissue culture, which I don't put much, or in mice. I don't think the NIH would put that kind of money into something if they didn't feel there was a valid basis... I think part of this is we're calling it senescence.

And I think none of us, to me, that's stolen a really good word out of the vocabulary because senescence just means aging. And it used to be you could talk about calendar aging, you could talk about senescence, which is what we now think of as aging. Now you can't use this anymore because anytime you do, they think you're talking about these cells. Is this what they call the zombie cell?

And I think none of us, to me, that's stolen a really good word out of the vocabulary because senescence just means aging. And it used to be you could talk about calendar aging, you could talk about senescence, which is what we now think of as aging. Now you can't use this anymore because anytime you do, they think you're talking about these cells. Is this what they call the zombie cell?

I keep forgetting.

I keep forgetting.

Yeah, but even neurons, they're not considering senescent neurons, and neurons are post-mitotic.

Yeah, but even neurons, they're not considering senescent neurons, and neurons are post-mitotic.

No, that's right.

No, that's right.

at treating heart disease and cancer and all these things and keeping people alive when they wouldn't have been alive 10 years ago. But this is a really important factor, I think, about thinking of public health globally.

at treating heart disease and cancer and all these things and keeping people alive when they wouldn't have been alive 10 years ago. But this is a really important factor, I think, about thinking of public health globally.

And they discuss this a lot in the senect... Because even the SASP, even these things that are oozing out of the cells, varies quite a bit depending on the nature of the cell.

And they discuss this a lot in the senect... Because even the SASP, even these things that are oozing out of the cells, varies quite a bit depending on the nature of the cell.

But I mean, people are aware of these complications and are studying these complications. Now it seems to me that it's the terminology that you object to. And I can appreciate that.

But I mean, people are aware of these complications and are studying these complications. Now it seems to me that it's the terminology that you object to. And I can appreciate that.

That's a good idea. I'm all for it. No, no, no. We've actually, so a group of us who are lobbying Congress have actually asked the NIH to tell us exactly this. How much work in geroscience is going on in all these other institutes? Of course, they're going to have some motivation to minimize that or maximize it or something, but at least it will give us an idea.

That's a good idea. I'm all for it. No, no, no. We've actually, so a group of us who are lobbying Congress have actually asked the NIH to tell us exactly this. How much work in geroscience is going on in all these other institutes? Of course, they're going to have some motivation to minimize that or maximize it or something, but at least it will give us an idea.

Right now, we have no idea how much of the NCI budget is going to this or NIDDK or anything else. They already have produced a report that told us how much they were spending in the NIA, but we already knew that. We wanted to know how much they're spending in the other institutes.

Right now, we have no idea how much of the NCI budget is going to this or NIDDK or anything else. They already have produced a report that told us how much they were spending in the NIA, but we already knew that. We wanted to know how much they're spending in the other institutes.

And I think that's an important point, that if we target aging, we're doing something different. Yeah. with the way that medicine is operating now, which is targeting individual diseases after they occur.

And I think that's an important point, that if we target aging, we're doing something different. Yeah. with the way that medicine is operating now, which is targeting individual diseases after they occur.

I think it's very promising. I'm skeptical because I'm always skeptical in the absence of evidence, but the observational evidence, ignoring the Bannister paper, just the consistency of the observational data that it reduces dementia, cancer, cardiovascular disease, suggests to me there's enough smoke there to look to see if there's fire or not.

I think it's very promising. I'm skeptical because I'm always skeptical in the absence of evidence, but the observational evidence, ignoring the Bannister paper, just the consistency of the observational data that it reduces dementia, cancer, cardiovascular disease, suggests to me there's enough smoke there to look to see if there's fire or not.

But sorry, Steve, you're saying it does all of those things in diabetics. Well, most of the studies have been done in diabetics. Absolutely. And how much of that is just because you're curing the diabetes is an open question.

But sorry, Steve, you're saying it does all of those things in diabetics. Well, most of the studies have been done in diabetics. Absolutely. And how much of that is just because you're curing the diabetes is an open question.

Right. But which is why you have to do the study.

Right. But which is why you have to do the study.

Where is TAME in the world of... TAME is in a very preliminary state. There's now enough money to get it started. It has not enrolled anything yet? It's enrolling right now. Previously, they didn't want to start it until they had enough money to do the whole thing. It's been impossible to get that. There's now a small amount of money, enough to get it started at a small scale.

Where is TAME in the world of... TAME is in a very preliminary state. There's now enough money to get it started. It has not enrolled anything yet? It's enrolling right now. Previously, they didn't want to start it until they had enough money to do the whole thing. It's been impossible to get that. There's now a small amount of money, enough to get it started at a small scale.

with the hope that that will start the pot rolling. But yeah, it's been around for eight years now. And I was in on the original discussion about, do we do rapamycin? Do we do metformin? And it was all about cost and safety. That was the whole thing. I went in strongly advocating for rapamycin. I came out saying, okay, there are these cost issues.

with the hope that that will start the pot rolling. But yeah, it's been around for eight years now. And I was in on the original discussion about, do we do rapamycin? Do we do metformin? And it was all about cost and safety. That was the whole thing. I went in strongly advocating for rapamycin. I came out saying, okay, there are these cost issues.

And I think it was important because when we went to the FDA, we didn't want them to think that we were trying to make a bunch of money with this trial. And nobody's going to get rich from Metformin.

And I think it was important because when we went to the FDA, we didn't want them to think that we were trying to make a bunch of money with this trial. And nobody's going to get rich from Metformin.

Well, we know it has a target in the mitochondria, complex one. It inhibits. We know it affects. But in which cells? Well. That's my point. Like it's not in the muscle. That's the question. And we also know that it activates AMPK. But those mechanisms are probably related. This is why Nir points at two of the hallmarks. Yeah. I just have to tell you this. But here's the interesting thing.

Well, we know it has a target in the mitochondria, complex one. It inhibits. We know it affects. But in which cells? Well. That's my point. Like it's not in the muscle. That's the question. And we also know that it activates AMPK. But those mechanisms are probably related. This is why Nir points at two of the hallmarks. Yeah. I just have to tell you this. But here's the interesting thing.

A good friend of ours, George Martin, who died a couple of years ago, once went through and cataloged all the human diseases he could and tried to look at the similarities of their phenotypic changes relative to what happens with normal aging. He came up with diabetes as having the most similarities to accelerated aging of any of the groups that he looked at, which

A good friend of ours, George Martin, who died a couple of years ago, once went through and cataloged all the human diseases he could and tried to look at the similarities of their phenotypic changes relative to what happens with normal aging. He came up with diabetes as having the most similarities to accelerated aging of any of the groups that he looked at, which

My intuition is that it might work. I don't have a strong opinion. There's enough suggestive evidence that I think it's worth a trial. I think that if we wait until we figure out exactly what each drug does in each cell type, it will take us forever to get any therapies. And in medicine, there have been many, many advances that came about before we understood the mechanistic underpinning.

My intuition is that it might work. I don't have a strong opinion. There's enough suggestive evidence that I think it's worth a trial. I think that if we wait until we figure out exactly what each drug does in each cell type, it will take us forever to get any therapies. And in medicine, there have been many, many advances that came about before we understood the mechanistic underpinning.

And if there's enough suggestive evidence and there's not a lot of side effects that Suggests me that it's worth digging into now because the benefits are so enormous. Like we said, one year, healthy aging, $38 trillion. That should talk to Congress and nothing else does.

And if there's enough suggestive evidence and there's not a lot of side effects that Suggests me that it's worth digging into now because the benefits are so enormous. Like we said, one year, healthy aging, $38 trillion. That should talk to Congress and nothing else does.

In the dog study, you're using a slow-release formulation.

In the dog study, you're using a slow-release formulation.

Well, the current state of evidence, I'm skeptical. It's one of those things that makes a great deal of conceptual sense, but the evidence at this point is not very compelling. And we have the ITP evidence that is, I think, the strongest.

Well, the current state of evidence, I'm skeptical. It's one of those things that makes a great deal of conceptual sense, but the evidence at this point is not very compelling. And we have the ITP evidence that is, I think, the strongest.

Yes. Yeah. Okay. Just to make it clear. I assumed that people knew that. I guess I should

Yes. Yeah. Okay. Just to make it clear. I assumed that people knew that. I guess I should

I think NAD is a very, very interesting molecule. And I don't think we could throw out manipulating NAD as something that could be important for aging. I just don't think the evidence is there at this point.

I think NAD is a very, very interesting molecule. And I don't think we could throw out manipulating NAD as something that could be important for aging. I just don't think the evidence is there at this point.

impact your life? Yeah. I think this is an incredibly interesting question and it really deserves to be investigated in detail because if it's true, it's a real game changer because we do transfusions. I mean, this is not exotic medicine. I think we very much need to know whether this works the same way in people. And also it would be nice to know how much of it is due to the

impact your life? Yeah. I think this is an incredibly interesting question and it really deserves to be investigated in detail because if it's true, it's a real game changer because we do transfusions. I mean, this is not exotic medicine. I think we very much need to know whether this works the same way in people. And also it would be nice to know how much of it is due to the

What's in the young blood versus how much of it is getting rid of the old blood. But the evidence from mice is very, very compelling.

What's in the young blood versus how much of it is getting rid of the old blood. But the evidence from mice is very, very compelling.

that the products that ended up in the circulation of humans was a very different nature than in mice. The number of things that differ between humans and mice and blood would be enormous. So pinning it down would be. But I think there probably is some reason to suspect that it may work. I'm very impressed.

that the products that ended up in the circulation of humans was a very different nature than in mice. The number of things that differ between humans and mice and blood would be enormous. So pinning it down would be. But I think there probably is some reason to suspect that it may work. I'm very impressed.

Right. And it may not work in young people. but it may work in older people. I think there's a lot of drugs that could affect aging that because young people haven't aged as much might not have minimal effect, but you give it to somebody 50 years later might have a big effect.

Right. And it may not work in young people. but it may work in older people. I think there's a lot of drugs that could affect aging that because young people haven't aged as much might not have minimal effect, but you give it to somebody 50 years later might have a big effect.

Well, on the other hand, if it has a positive effect, I don't think it really matters. That's something to be investigated later. My thought is it's not simple. It's not one thing. It's not GDF 11 for sure. If it were simple, there's enough people looking at it, they would have figured it out. My guess is it's some combination. If there's something there, there's some combination.

Well, on the other hand, if it has a positive effect, I don't think it really matters. That's something to be investigated later. My thought is it's not simple. It's not one thing. It's not GDF 11 for sure. If it were simple, there's enough people looking at it, they would have figured it out. My guess is it's some combination. If there's something there, there's some combination.

I mean, why can't you do both?

I mean, why can't you do both?

My thought is we still wouldn't be using anesthesia if we had to wait until we figured out how it worked.

My thought is we still wouldn't be using anesthesia if we had to wait until we figured out how it worked.

We don't know now. Yeah, we don't. If it's young blood is good, old blood is bad, or some combination, we would automatically, if we only did the plasmapheresis, we would only be testing part of that.

We don't know now. Yeah, we don't. If it's young blood is good, old blood is bad, or some combination, we would automatically, if we only did the plasmapheresis, we would only be testing part of that.

It just seems to me that- I agree.

It just seems to me that- I agree.

I think it would be good to invite Vadim Gladyshev, because I think even though I disagree with some of what he says, I think he always has something interesting to say.

I think it would be good to invite Vadim Gladyshev, because I think even though I disagree with some of what he says, I think he always has something interesting to say.

I think in a year from now, I think there's going to be a lot of new stuff. That's what's new in aging research. Rate of progress.

I think in a year from now, I think there's going to be a lot of new stuff. That's what's new in aging research. Rate of progress.

Yeah. I would second that. That's an excellent idea.

Yeah. I would second that. That's an excellent idea.

Thank you. It was fun. A lot of fun.

Thank you. It was fun. A lot of fun.