The $101 Million Race to Solve Longevity | Jamie Justice PhD

Dr. Jamie Justice is the Executive Director of XPRIZE Healthspan - a $101 million, 7-year global competition to extend human healthspan by developing therapies that restore muscle, cognitive, and immune function by 10 to 20 years in people over 50. She is also a leading geroscientist and Adjunct Professor at Wake Forest University School of Medicine.

In this episode, Jamie breaks down the science of aging, the geroscience hypothesis, what 744 competing teams are building, and why the next few years could fundamentally change how we age.

We discuss:
- Jamie's journey from art scholarship and sports therapy to becoming a leading geroscientist
- The legendary Tom Johnson vs. Lynn Hayflick debate: are aging genes real, or is it all entropy?
- Why aging isn't like an oil tanker wearing out - the role of repair mechanisms and emergent complexity
- Steve Austad's quote: "The number of theories is inversely proportional to our understanding of a thing"
- The hallmarks and pillars of aging - the framework that gave the field testable targets
- Geroscience: targeting aging itself rather than one disease at a time
- Why we keep hitting a ~30% lifespan extension wall in mice
- Rectangularizing the curve: healthspan equals lifespan
- The Austad-Olshansky bet on a 150-year-old human - and why Jamie thinks that person is probably alive today
- Longevity escape velocity: why Jamie doesn't touch that question
- XPRIZE Healthspan: $101M, 744 teams, clinical trials in humans over 50
- The competition structure: semifinalists, finalists in August 2026, winners in 2030
- What's winning: metabolism/nutrient sensing and immune-targeting therapies lead
- The surprise entries: reprogramming teams ready for human trials sooner than expected
- Circadian-based teams, functional food approaches, and one team proposing to study nuns
- The upcoming XPRIZE in ovarian health - why it matters for both sexes
- How population-level shifts require more than individual breakthroughs

Guest: Dr. Jamie Justice, Ph.D.
Executive Director, XPRIZE Healthspan | EVP, Health Domain, XPRIZE Foundation
Adjunct Professor, Wake Forest University School of Medicine
XPRIZE Healthspan: xprize.org/competitions/healthspan

Mentioned in this episode:
- Peter Diamandis - XPRIZE founder
- Steve Austad - The "Dos Equis man of m

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Transcript

Jamie’s Path From Art To Aging Science

SPEAKER_01 0:01

Hey Jamie, welcome to the program.

SPEAKER_00 0:04

Rob, thanks for having me.

SPEAKER_01 0:07

I'm so excited to talk about the HealthSpan X Prize and all the all the great work you're doing. Peter Diamondis is a as a friend has been on the been on this podcast. And uh and we we really want to dive in, dive into that. But maybe since since you haven't been on yet before, and um maybe take a moment and talk about before you became one of the one of the world's leading gyroscientists, and what was the spark or or moment or experience that pulled you from that from that early art scholarship and into physiology and and and and gyroscience?

SPEAKER_00 0:50

Yeah, well, great. Yes, you've got uh uh definitely some background for me there. That's great. Um yeah, started definitely didn't think I was gonna go into uh to this as a career, but um, you know, once I got started in, and I'd actually been working as an athlete and also um with sports teams as a on as a member of a sports team and as a therapist. And, you know, in that role, I worked with some young athletes. And then when in working in Boulder, I actually fell in and started working with a lot of masters athletes and just loved it, you know. So some of the goals changed, some of the things change, but really, you know, people wanted to optimize their health and their performance across the lifespan. I mean, this was a very common refrain. Um, and then started doing work, not just characterizing changes that happen, um, so in how we control our movement and our our bodies, how they change with age, but then started getting really involved in thinking about intervention. So, what can you do upstream that actually targets not one disease, but multiple? You know, how do we actually support the things that matter to people as we age, which is not just managing diseases that are chronic, but really how do we optimize our health, right? So the things that we can do to um to increase whether it's you know, masters, athletes trying to improve their cycling time, um, or people that are maybe a little bit lower on the functional scale that just want to make sure that they maintain their their brain and cognitive capacity so that they can continue to work, uh, can continue to volunteer, keep their um, you know, that they are able to function well enough, they can play with their grandkids, go for walks, stay independent. You know, that these are the things that um that were really meaningful. And so I, you know, I fell in love with the work, thought I was gonna go and stay more on the clinical side until I entered a lab and realized that that is that's my home. It was so working on the science, still working with people, still doing a lot of the trials work, but having a chance to work on teams and really build out some of the uh some of the science that underlie the treatments that go into practice or the treatments that change policy and how we think about how we think about aging and how we study it. Um and I'm, you know, just by nature, uh really curious. The the creative side that goes from art follows right into science. Those two go really well together. Um and I'm fairly dogged. And so one of the other things that makes a good scientist is resilience. You have to get used to things not working over and over and over again and really cherishing the moments when they do.

SPEAKER_01 3:24

Yeah, I mean, it's great to work both in the basic biology of aging and then the clinical translation and see it all. I mean, what an amazing time. You know, we'll obviously we'll talk about the just the revolution and longevity science that's happening, but even basic biology. I mean, I think of I referencing George Church's Lila project out of Boston with the the dark lab doing AI and running the experiments 24 hours a day and you know pipetting and you know all that. Yeah, it's yeah, can't help but accelerate things.

Aha Moment: Debating Why We Age

SPEAKER_00 4:00

Okay, one of the you know, one of the moments for me that the the aha's is you know, I was um still fairly young in my career, was doing work, was really asking a lot of questions around aging, um, and was working in a couple labs in Boulder. And I had the opportunity to go to a point counterpoint with two fundamental, you know, really basic scientists that really generated the field that we're in now. Um, one was Tom Johnson, who he did a lot of the early work, even around the time that Cynthia Kenyon was coming out and doing stuff with like finding genes that actually are implicated in aging, that if you can knock out a couple of genes like age one, DAF2, is that you can actually extend animal lifespan. And so he was doing all of this really intense work on what he called at the time Geronto genes. Um and so he presented, and then there was a counterpoint to him, um, who was a good friend of his and someone whose work I've always admired was Lynn Hayflick. And so Lynn Hayflick was a, you know, again, he is the telomere guy, right? So he found telomere's and he is a personality all on its own. And so, you know, you would think because of his work thinking about senescence and how cells age and they replicate until they don't, and has all this great background. But Lynn, if you knew him, he was uh he was what we call a second law of thermodynamics guy. So he thought aging was inevitable. There's nothing you can do about it, it's stochastic and random, and you get these stressors and the molecules break down, entropy is going to happen, and we're just gonna break down. And I'm sorry, there's no rhyme or reason the genes don't matter. And so to have these two guys go one after the other, both arguing with the pros and cons of their point, thinking about at a very fundamental level at the time as a, you know, as a budding scientist, like why do we age? What do we do about it? Thinking about interventions and hearing these two, you know, classic luminaries in the field just really go at it. Like that for me was a moment. I left that session and it was one of those, I just needed to go have home, have a lie down, and just sort of reboot, you know, is that I'd just been thinking about function of performance and the application of these things, but not like the really deep, deep thought work around the theories of aging. Why do we age? How do we age? And then once we really begin to understand that biology, then what do you do about it? And even in the absence of having a perfect understanding is that, you know, there are still approaches that can be used to try to maximize the health with which we live the years we have, you know, and that that might also have implications for lifespan as well. But really fascinating. And I would say that those are two arguments that I still don't think on the science side we have a great, very clear picture of, but they they continue to drive a lot of my uh my study and my interests.

SPEAKER_01 6:45

That's fascinating. Hold that thought. I want to dive into that in a moment. But before we leave your your your kind of your your journey and that and thinking about the the human side and your your work with with uh older adults, you know, the people, their stories, their hopes. Was there any particular single insight with that that that really shaped your your life's mission on this?

From Wear And Tear To Complex Systems

SPEAKER_00 7:08

You know, twofold. One was that was just again that curious, and just to be deeply, deeply curious about, you know, with thinking about why it as we age is also, you know, it's another part of a conversation as to why do we live. And I think, you know, that fundamentally that's a question I think we all uh we all engage with, or at least for me and a lot of my friends and and those around me, we talk about a lot. Um, but the two, one is very practical and I would say shallow. Um, and that is, you know, I had worked with young athletes and and younger adults doing studies on muscle fatigue and other stuff and performance. And I, you know, I myself am an endurance athlete and a mountain athlete. So those were questions that intrigued me. Um but then, you know, working on an undergraduate campus with young adults, you get really tired of um them not coming in, showing up for 8 a.m. lab visits, still drunk from the night before. Um, and you know, the talking about like marathon or cycle times, like where you're just shaving minutes or half seconds or, you know, stuff like that off of time. And it just wasn't as deeply meaningful. Um, and then I started having a couple of questions about fatigue and performance with aging. And um, and part of it again, so superficial. But the older adults in my first study um and that I started really working with in uh in laboratory and in clinical settings, they would show up on time, they were engaged. Um, I got pregnant when I was in grad school, and um, you know, my research subjects they threw a baby shower for me. I think my first took me out for coffee and banana bread. So it's like I had like these really deep personal relationships, and it was so enriching that it's like, you know, I just was like, that's it, I'm done forever. And if you work with animals as well, um, many of the animals, as they get older, they become much more docile, fun to work with, gentle. They don't bite, they don't do, you know. And so again, there was all these superficial reasons that was like, oh, aha, this is this is I, you know, again, I have to make a living and a life for myself that I want to actually be in for the rest of my career. And it was like, oh, this is way better. Not only is it intriguing, interesting, coming in at the right time scientifically, that hard questions were being asked. And then there was also, again, yeah, that component, right, where suddenly the idea that there might be therapies out there that could change how we age was not just um not just a thought experiment, um, but that there was getting getting to be some real scientific rigor behind them and evidence. And so for me, going into my training at that inflection point and going, oh, there's a career here. This isn't just sort of weirdos talking in the dark, you know, this isn't just sort of a fountain of youth that's um been written about in in classic literature. Like there's there's actually a science here that could make a difference in real life and in and now. Um, and you know, and the demographics behind it is that this is uh, you know, one of the most important things that we could work on, um, period.

SPEAKER_01 10:18

Yeah, this is such an exciting time, as you say, in in aging, longevity, whatever you call it, that research where it's suddenly really, really accelerating, exploding. Well, let's just take a moment. I mean, when I was growing up and early training, aging was just, it was felt to be wearing out, you know, uh stochastic decline, everything wears out, you know, my car wears out, my shoes wear out, I wear out. But people don't think of it that way anymore. What are some of the newer models for aging, or how do you think about aging and longevity?

Theories, Hallmarks, And Pillars Of Aging

SPEAKER_00 10:54

Great question. And so, you know, and again, it's not that that's not true, right? So there is still an accumulation of damage. This is just one of those a damage accumulation hypothesis. There still is this process of sort of maintenance and wearing out that, you know, all of that stuff that Lynn Haflick was saying about, you know, the the entropy of aging, uh, you know, all that's still real. But, you know, when we're thinking about aging as a human versus the aging of like a fleet of oil tankers, you know, oil tankers are not biologic, right? So they don't have these fundamental, these physiologic principles that we talk about, right? So um like things like homeostasis. So these are processes that are built into our cells and into our body where um, you know, we can restore systems. There are repair mechanisms. Um, and so there's always this delicate balance that's happening between our ability to repair and our ability to maintain and the damages that happen over time. So it's not that any one of those things is right or wrong, it's that they're all interacting together. And that as we go from these very molecular structures to cells, to tissues, to organs, to organisms, to even whole communities, because we know how we interact with others is also really important. Um, and so, you know, thinking about these at each of these levels is that what we have is an integration and that we have something we call emergent properties. And so that's a fancy word that just means that as things get more complex, we see new features and how things combine and interact. And that, you know, previously, I don't think we had a great way to manage complexity scientifically or clinically, right? Is that it's a lot easier to treat single diseases and single mechanisms. And so I think we we naturally get really overwhelmed. It's like sort of try to contemplate infinity or think about our universe. These concepts are so big. But as our data resources get better, as our as our work gets better, um, as we combine more people and networks and how we're doing the science behind it, is that I think that you know there really are opportunities to intervene even in complex systems.

SPEAKER_01 13:03

Yeah, yeah. And I mean, certainly on a cellular level, human beings rejuvenate every generation, as Shinya Yamanaka showed with partial epigenetic reprogramming. That's right. What about the late Misha Blagoscone and his his ideas of hyperfunction theory and other people of that? Where is that in in uh aging science?

SPEAKER_00 13:24

Is that uh, still talked about, um, you know, still talked about. And so this is one of my other, there's a lot of, you know, I don't know whether we call them all out theories or hypotheses. So um, a dear friend and somebody that I keep on all of my advisory boards forever because he's just fabulous, Steve Ostad, I think he had uh, you know, something in one of his books once that was like um the the number of theories um is inversely proportional to our understanding of a thing. And so for aging, where there's like between three to five hundred theories of aging, means that we don't understand a whole whole lot. And I think that again goes back to that complexity. So that there are many competing theories. Some of them are really good, some of them um, you know, have gone perhaps out of fashion, but many of them have had uh sort of truisms within them. Um and so I believe, you know, some of what you're talking about, certainly they're still discussed. Uh David Sinclair and George Church have come out with some ones recently that are fairly compelling around some of these information theories about how things are passed. Um, there's a lot of work really, again, looking at sort of those diverging things about how if we can maintain our repair capacity or even rejuvenate and sort of, you know, where does that play in amid the myriad complexities and emergent properties and all of those things? And so it's like it's not that any one of them are true or not true. It's more of that how we look at them and pile them together, you know, sort of right back to that first conversation I had. It's not that Tom Johnson was wrong or right. He had discovered genes in animals that if you knock them out, they live longer. That is empirical, that is a truism. And then how does that sort of those Geronto genes play with the stochastic theory? It's not that either one's right or wrong. Um, in fact, they're both sort of arguing a common truth, is that they're both true. These are both principles that are both happening, is that we are our genes, we are our environment, and magnified over time, I know, and so that we're going to become more variable. And so there's more opportunity for these to interact. I think the complexity is fabulous.

SPEAKER_01 15:30

So it makes it interesting, that's for sure.

Geroscience vs. Treating Single Diseases

SPEAKER_00 15:36

But again, but it makes it more challenging, right? And so I think one of the drivers for the field where we all got really excited. Um, and so again, I was coming through just finishing um PhD work, starting postdoctoral work, really got engaged at the time when uh there was a paper that came out, the hallmarks of aging. And the uh the this the Jero science was really coined. That there were two schools of thought that came out around the same time, one called the Pillars of Aging, one called the hallmarks of aging, but they identified anywhere between seven to twelve different factors that could be tested in a lab that have translational potential. And so they became pillars or hallmarks based on three very simple observations. You know, one is that these were mechanisms that change over age, right? So they you can see them across chronologic age, they are age-dependent, very important. Two is that if you do something experimentally to um aggravate them or make them worse, turn them up in some way, um, is that the animals across species don't live as long, right? Or they have a poor quality of health. Um, and then three, if you do something to knock them down or or turn them off in some way, is it then you can extend lifespan and the quality of life and not just one but multiple species. I mean, these are fundamental findings. And the idea that they could find them, those first papers looked at a very short set of potential therapeutics that actually had some translational potential. So maybe they don't just work in yeast or in flies and in worms and maybe a few mice. You know, how many of these could you actually use and target in people? Um, and that you could, you know, really potentially fundamentally change our how we live and how we age. And so having, you know, again, looking at that list, you're like, all right, I got seven to eight things. Let's start targeting, you know, that I think from a scientific perspective was really compelling and got a lot of people engaged in the field, again, reinvigorated that field that maybe this isn't pseudoscience, maybe this isn't crazy, there's evidence, let's do it. Um, and then, you know, now carrying that into our modern, you know, concepts is again going back to all that stochastic stochasticity and complexity, is how do we keep that simple framework but allow for the complexity of aging, especially in longer lived species like humans or other? Um and so it's uh it's a delicate balance and it's one you know you have to keep the enthusiasm. There are targets. It is, there are some simple things that can be done and some simple targets. Um, but you have to balance that again with many of these interact, there are other features, there's things to do. It will get more complex and harder to do in humans than a lap mouse. That's fine.

SPEAKER_01 18:34

Yeah, I want to come back to the pillars and hallmarks. One last question about sort of gyroscience. Some people in geroscience are reframing aging, not as a disease, but as the sort of root driver of health decline, right? So for listeners who haven't heard that framing before, can you break down the difference between treating diseases of aging versus targeting aging itself?

SPEAKER_00 18:58

So this is a great, great point. And that there's a huge conversation about, you know, um uh about the interplay there. And so I am uh at what I consider the first of a generation of geroscientists, so that this is what I was trained in. It's what I was trained to do and how our approach and our thought process, right? And so that is it's simply that there that aging, that there is a biology first, um, that is of aging that's not uh specific to any one disease class. And within that biology is that it can be targeted to change the risk of not one, but many different diseases or functional capacity syndromes overall. Um, and so that's that geroscience hypothesis. And so whether we're looking at that as a single drug that can target many different diseases, or looking at these aging pathways as potential targets for multiple age related diseases. So again, it's just sort of a it's a slight difference, um, it's fairly minor. But it's one that becomes important just in how we approach drug development, testing, and commercial. And they're both terribly, terribly important. So they're both formed by this geoscience idea is that, you know, that there are these common mechanisms, common drivers, that um, you know, uh the the one of the key features of aging is that you'll develop not one but many. And so unless we begin to change our approach and our thought process to identifying those biologic properties that affect many diseases and functional ability, um, then we're simply replacing one disease with another. Um, people are going to die of something. And so, unless we change that fundamental risk factor, it's which disease we get that is a little bit more stochastic, not that we get a disease, right? And so it's it's that basal state process. Um, and so that's the geroscience idea. Um, and again, its relationship to disease and how you test it, it is that overall driver, but again, it does my we know one of my first trials um in 2015-2016 was actually looking at a drug that could target one of these hallmarks called cellular senescence. And we had xenolytics. And instead of just testing it at large in anybody, because these drugs have risks, is that you know, we really looked at it and that it was a feature that we thought could help unlock a really difficult to treat age-related disease, evidiopathic pulmonary fibrosis, as a contributing mechanism that was identified from the geroscience side. Um, and so we started our initial testing again in an age-related disease. And so it's disease and age, it's not that they're completely uncoupled, they're really tightly coupled. It's just that um our thought process and how we arrive either at therapeutic targets or in the approach to testing those therapeutics changes. Um, and the geroscience is really is that fundamental sort of that concept shift in how we change and how we approach.

Limits, Rectangularizing The Curve, And Cancer Risk

SPEAKER_01 22:05

Yeah, it's such an exciting time, like the work that Dave Sinclair is doing in Boston now with the partial epigenetic reprogramming, which arguably you're treating coupled diseases of aging in the eye by not necessarily targeting the disease itself, but by making the cells younger and rejuvenating them. And there's some, you know, there are arguments there, but the the idea is just rejuvenating cells, and you know, 30-year-olds don't have Alzheimer's disease, you know, if you can rejuvenate it, you know, so many it's such a such an exciting time. I mean, I'm the biggest fan of longevity, and you know, it's such an exciting time, and obviously, you know, you're you're excited by it. I what do you say to to critics who say, you know, you meant you referenced Cynthia Kenyon's work, you know, decades ago, or even even the interventionist testing program with rapamycin now in 2009-2016, where we get 30% improvement in mice, you know, it's amazing that you get anything. But the but then the question is, well, why are we still only seeing 30% improvement? Why don't we have mice that live five years or 10 years now? Why it's it we seem to get 30% with different interventions, whether it's de satinib or, you know, synolytics or other things. But why aren't we, why aren't why are we hitting that wall? Why don't we see dramatic improvements in long time? Oh my gosh.

SPEAKER_00 23:30

Yeah. So this has been actually a fundamental question across the field overall, is that we have not engineered immortality yet. And for for many of us in the field, like that's okay. You know, we start where we start, that's fine. Is that for most of us, immortality is not the goal? For a few, it is. I'll I'll let them do do their things. That's fine. So um for us, many of us, yeah, we do see this sort of um, you know, and it's not uncommon, right? Is that in most biologic systems there is uh, you know, whether you know we're looking at sort of uh mortality curves or others, that you're just trying to shrink or what we call rectangularize the function curve, right? So that you don't end up with sort of this long period of poor health and decrepitude, um, is that most of us are really focused on trying to extend the quality of function and health so that it's more coupled, so that you maintain your function closer until the point at which you pass. Um and yes, with many therapeutics, you know, is that there has been, at least animal models, you can show not an indefinite extension of either that function curve or pushing out that mortality curve where there is you're hitting more of that sort of limit. I think we're still trying to figure out what drives the limit. Um, most of the interventions when we say whether they're successful or not, is we're not necessarily, in very few cases, do we see maximum lifespan extension, meaning that you have the longest lived animal. In most cases, we're looking at the mean, right, or the median of that of that population is what can you do for the most to extend one way or the other, knowing that there's always going to be some diseases, especially in mice cancers, that knock them out early and others that that you can't there. And so there does seem to be again that that balance between what can we optimize genetics, environment, and therapies versus uh versus those really stochastic processes that seem to determine somewhere in that limit per species. Because there is a genetic driver that you do see this across species, a lot of it's tied to our body mass and our size. Uh, there's a lot of work that's gone into that, but that's not universal either. Uh, you know, there are other um other, if you're looking across species, um, of some that uh animals that we see what's called, you know, negligible senescence, which is really fascinating to study, right? And so the negligible senescence in an animal population just means that the their mortality risk isn't necessarily driven by their chronologic age. Like there are species of bats, for example, that have negligible senescence, that most of the things that wipe them out are cyclical and environmental. And we don't really know how long they would live on their own. You know, some of it's just that we haven't studied and so we're still figuring it out. Um, but others, I mean, there really are certain species that show that. And so the question is, is can can humans get there? So I think rather than saying immortality, is that can we get to a place of negligible senescence where our chronologic age isn't the determinant factor of when we are going to die, which is what we now see is that as we age, our increased risk of death. And it's not death by one disease, it's by any disease. And so we need to think of these things that target these any disease process that state. Um, and so, you know, so again, so for most of us, it's not perfectly immortality, but it's figuring out that unlock. And then I think, you know, that there might actually be some engineering prep principles that could be done, whether it's reprogramming or combinations that fundamentally change our repair capacity. Um, but anytime we're looking at repair capacity or proliferation, those are things that when we start messing with that machinery, we start sitting really close to cancer. And so, you know, back to that thing that kills most of the mice, you know, that still is a risk for us. And so as we're developing new therapies, I would say that's one of the areas we all look at really carefully. Um, is anything that changes sort of that cell proliferation, division, repair, is it the kissing cousin is possibly something that could be uncontrolled. Um and so um, and so it's it's figuring out the balance between those in an appropriate level.

SPEAKER_01 27:45

Yeah, yeah. And that's the challenge, yeah, with with all the partial epigenetic reprograms, certainly get the rejuvenation without the yeah, right, which is that's why it's the partial and not the core OSKM factors from Yamanaka.

SPEAKER_00 28:00

That's right, because one of those is varicancer. We don't want varicancer, but especially when we're thinking about prevention.

SPEAKER_01 28:07

Yeah, so so the concept of squaring the curve is it's great. Health span equals lifespan, it's a square curve, and then you just you just check out, but it's it's interesting with the there with all the stochastic variation, statistical variation, there are still no five-year-old mice, and there are no humans that live to 123. You know, it's uh we just despite billions and billions of people, you think within the statistical noise it would be a broader spectrum, but it we seem to hit a wall there, I guess. And you know, sure, sure, yeah.

SPEAKER_00 28:42

And you know, and hopefully we'll see it in the in the lab and in the animals first, you know, and we we live a long time, humans do. So, you know, uh, I would say for for most of those, I would give it a yet. So we don't see them ever, is that we have not seen them yet.

SPEAKER_02 28:56

Right, right.

SPEAKER_00 28:57

I do very much ascribe to um, you know, so again, back to my one of my favorite. If you've not had Steve Ostead on this podcast, podcast listeners, if you've never heard of Steve Ostead, look the man up. He is um in my field. I I hope, I don't know if you'll listen to this. I hope so. I'm gonna embarrass him right now. In my mind, Steve Osted is the Dose Eckies man of modern gerosides. He's the most interesting man in the world. He's um, he's a lot of fun. He's a biologist and um has done field biology work and and and lab by, you know, he's wonderfully thoughtful. Um, you know, he's and I call him the Dose Eccles man. I think he's one of the few people I've been in just casual conversation with, and he's like, that reminds me of this time we were chased by hippos while kayaking down the mile. And it's like, you know, Jamie, I would love to be on an advisory board meeting next week, but I'm actually going to be studying the ring-tailed lemurs down in Madagascar. He was like, Oh, yeah, well, I got into science because I was once a lion tamer for the Hollywood studios and was mauled by one of my subjects. You did what?

SPEAKER_02 30:13

I love it.

Population Shifts And 150-Year Bets

SPEAKER_00 30:14

Yeah, so he very famously years ago with um with Jay Olshansky, who's um he's a demographer and an economist, and brilliant. I just love Jay as well. Two thought leaders in our field. Years ago, I think they were having an argument at a bar about this question of, you know, when are we going to have a 150-year-old human? And so this has been a constant question for our field ever since. They've put wager, they put money on it that's being held in an account now and it's accruing over time. So, and they're both of the opinion that they probably won't recap the winner to see, but they put it on that date. So at this date, Steve, and I ascribe to Steve's belief is that I, you know, um, in in the 90s when they made that wager, I think the first person to hit 150 is probably alive. You know, the question is, will the population um of, you know, will we have a population level shift that accompanies the individual? Um, and you know, and I think with with great advances, we might get there. Will it be me? Probably not. Maybe somebody younger than me that might be born now if we make some major advances. And I think we could get one. The challenge is the population shift, especially when we have all of this other noise and all of these public health factors that really do determine at a population level what's going to happen. And if we're going to create a real unlock both for commercial and for society and for individuals, is that we really do also need to look at that population level shift. Um, and so again, that population shift is important because we've already made one of the most dramatic population shifts ever for humanity or any animal species that we know of, right? Over the last 100 years, due to public health and simple measures, we now live over 30 years longer. We've already seen this and we do not know how to comprehend it because we simply live one lifetime at a time, right? And so it's difficult to comprehend that we're experiencing a population-level challenge of aging and opportunity that we've never been able to experience before. We are the first, we're pioneering how to live in an aging society. Um, and so I think with that, we have to come up with novel approaches and the time is now, or we're going to miss it, you know, is that we have both the challenge and the opportunity. And so, you know, again, this goes back to this is the challenge of our lifetime. There is nothing more exciting we could be doing is trying to figure out at a global level how do we age and how do we restructure our societies to adapt it.

Escape Velocity Skepticism And Practical Pathways

SPEAKER_01 32:50

I I want I want to dive into that also in the last few minutes. But before yeah, before we leave, before we leave that other point though, Pete Peter Diamondis and and uh Ray Kurzweil even more talk about longevity escape velocity and other people too. What's your take on that?

SPEAKER_00 33:06

Uh I I don't touch that one. Again, you know, that's one of those theoretical principles. I will I will sign up on the Jay and uh and Steve bet all day. I'll put a wager down for the individual. I think the individual for me is easier to conceptualize. And and I think 150, that for me is an effect size that is far beyond what we currently have in our practice right now. So that is going to require tools in an arsenal that does do not exist at this moment for clinical use.

SPEAKER_02 33:38

Yeah.

SPEAKER_00 33:39

And that's the distinction. Are they being developed? Do we have things in RD? Time will tell. We need to have the systems in order to test them. We need to change our regulatory pathways in order to adopt them. And we need to reconsider how we do our clinical practice in order to make them effective and actually implement them with real people. So those are huge, huge questions. I think the individual might be there. The longevity escape velocity, um, you know, I for me right now that is still a thought experiment. And it's one that I'm going to focus on sort of the practical mechanical problems and how do we how do we get this started and uh and how do we conceive of it? And uh we'll see what happens in the future. But I don't touch the uh the escape velocity question. Just not my driver. Not my driver.

SPEAKER_01 34:23

I'll sign up for 150. I'll take 150. Ask me again when I'm 149, if that's enough. That's it.

SPEAKER_00 34:30

That's it. Yep, yep, yeah. But even still within that, is that my my main focus, my main driver is given that we have already shifted, is that how do we first maximize the years? And that, you know, and I'm still am, there's a lot of question about can you extend lifespan without extending health span? So if you fundamentally do change your health span, you would expect a change in your all-cost mortality as well, your mortality risk. And if you do that over aggregated over a population, you will eventually have a population shift. Um, you know, but the the challenge is, of course, is how do you how do you build that in a systemic global fashion that overcomes things like um you know drinking water and other things that could cause pandemics and um and some of the very social factors, you know, whether it's seeing the opioid epidemic, which is very real, um, and balancing against um, you know, other population level shifts of suicide risk, which is of course increasing, um, is that there are many reasons that we die, some of which are driven by aging. Um, right now we've shifted our population that many of them are, and we need to grapple with that first, and then we'll deal with the longevity part later.

SPEAKER_01 35:47

Well, you're in a great position to look at this as you now lead the the X Prize health span, an audacious 101 million dollar competition with a mission to extend quality human years. So so tell us, what's the big the big audacious goal here and how does this differ from other longevity efforts?

Inside The Healthspan XPRIZE: Rules And Stakes

SPEAKER_00 36:10

Oh, holy smokes! So this is huge. Um, this is a$101 million global competition to extend human health span. And health span, as we define it, is that we're requiring for the first time that teams run clinical trials. So again, this is not in mice, this is not in worms, this is what can you do in people, not people who are young in these huge prevention trials, but what you can do in people right now who are over the age of 50, um, that you can restore their muscle, cognitive, and immune function. Not one, not two, all three. So that you change fundamentally some functional status about how they are able to adapt and function in the world. And it's not to attenuate the declines. They have to you have to improve it by 10, 15, or 20 years in order to win the grand prize. Um, so it is uh, yeah, it's a lot of money. Yeah, it's gotten a lot of attention. It's a seven-year prize we launched in 2023, um, and we will um announce our winners in 2030. Our teams are not left out on their own. We do a lot of work with the teams, a lot of framework building and and matchmaking. Um, this past year we uh we closed our our initial registration round um and we named our top 100 qualified teams as semifinalists, um, and we awarded the top 40 teams a certain monetary amount. So we do give some of that 101, we break it up and we give it over time so that we can incentivize some of the winners. And we also host with those uh investor summits and chances for people who are interested in getting involved in this space a chance to meet the teams. And again, those teams are a little bit of everywhere. We had at the end of 2024 over 600 teams that registered to compete globally. Um, we've kept our registration open, even though the teams are in semifinals. We're now at over 744 teams as the uh as of last week. Um, so again, we still have teams coming in who think they have the right idea, the right approach. And the teams that are coming in, we have everything uh we awarded for our top 40 semifinalists. We awarded everything from a high school team from Malaysia. Um, I just came back from Tokyo. We had some outstanding teams from Japan, both academic and industry. Um, we have teams coming in at Harvard who are running excellent trials with really novel therapeutics. We have teams that are coming in doing repurposed drugs that might already be in the market right now. Um, thinking of like metripamycin, which we've already mentioned, metformin. Um, we see other antiretroviral therapies that are being used. Um, of course, the GLP1 agonists are getting a lot of attention right now as well. Um, and so you know, we allow our teams to do new repurpose. We have gene therapies, we have immunotherapies, we have cell therapies, we have plasma-based therapies. The exciting part is that we don't know which one will win. We don't know if it's going to be a company or an academic or a university. It could be a small startup, it might be a publicly traded pharma company. We just democratize the science. We give people frameworks that they and milestones they have to achieve. Um, our teams right now in the semifinal stage are out showing us that they can get into clinic. So they have to test their therapeutic in at least five people, and they have to submit the results from that early stage trial in April of this year. Our judges reconvene, they look at the Data, they look at their applications, and they're going to identify the top 10 teams that they think have the greatest potential to restore muscle cognitive and immune function in older adults in one-year trials. So this is not a minor ask. No one is going to win by accident. Um, you know, and and in fact, I think getting to the finals, being one of those top 10 teams, means you have one. So for the teams that are thinking of competing, it means that they have an idea that is compelling enough that these independent judges who are international experts from across different disciplines have said, yes, that is an idea worth testing. Those teams, when they go out and test, we have a common data coordinating center. We have a central lab who will be announced next month, but we're working with them really closely right now. We'll be adding biomarkers to each of those functional performance assessments. We'll have an opportunity to test and evaluate different clocks that are being developed using blood-based testing. We're hoping to add wearable and digital monitoring. And so that there'll be a whole set of data that comes at the end of these trials so that we'll, yes, announce a winner, but the real winner is going to be who can use this largest data set ever from trials across people using common data elements and protocols. And we're going to get the next generation of what might work based on the solutions that come in now.

SPEAKER_01 41:26

And the the the 10 that you select, um, so those are those are chosen not on results yet, but basically a panel says these are the most promising, correct?

Selecting The Finalists And Measuring Impact

SPEAKER_00 41:36

That's where we came in the first time. The next round, they will be results-based. They have to be in trials, they have to show that they can affect function or health, at least a biomarker of it, an early signal or indicator that crosses not one but multiple systems. So that's going to be hard. So this is one of those factors we're talking about with aging that's so important. It's not one disease, it's not one mechanism, it's not one function. And so looking at what we call this plurality of effect is what really will give our judges the confidence that this can be used. Some of the factors our judges will be looking at that that are more um that are not as demonstration-based is that they're also going to be looking at scalability and access, right? So if you have a solution that can only be used in a few people, is it going to give the magnitude of result on the back end? Um, or, you know, we're thinking primarily on impact of population, but there's also a commercial component, right? And so, you know, if you can scale this in a way, does this company, if it is a company, have something that could be have a scale and commercial impact so that it can be used at the end of a trial? Could somebody pick this up and actually engage with it? Could a clinician prescribe this, whether it's lifestyle or drug-based? You know, um, how will it be used in the most people? Is it maybe it has a slightly lesser effect, but has an outsized impact at the end of trial? They're really going to be looking at that as well. So those are some of more of the qualitative aspects in addition to the quantitative. Did you affect multiple systems?

SPEAKER_01 43:16

And going forward, I'm sorry. I'm sorry. Please. I was saying going forward between now and 2030, um, will it just be the 10, the 10 finalists, or will the 700 still be able to proceed?

SPEAKER_00 43:30

So what does that look like? 700 can they'll have to put in their finals application, show us that they're ready. Um, if the judges approve them as like a we didn't award you, but you have a great idea, if they're approved for it, they can continue, but they have to pay their own way. So the 10 that go in, one of the value ads, right? We award them$1 million to help offset some of the costs, but we also provide them all of the biomarkers, the frameworks, the protocols, the data center. All of that is part of a package that they're given. Um, and that it's not given. They have to work for it and they but they get to use it, but without additional cost. So additional teams can choose to come in until it's simply they just don't have time to run a one-year study. Um, and so they're allowed to come in late. They can still engage, they can choose to buy in, but it just that will have more of a financial cost for them that will make it more challenging, but they're certainly allowed.

SPEAKER_01 44:27

Well, out of these 700 applicants, what what were some of the wildest, most unexpected ones that you any of you could talk about just that you didn't see coming?

Scale, Access, And Trial Infrastructure

SPEAKER_00 44:38

We can have a whole hour. I have seen, oh my gosh, I have to tell you, I have seen really excellent ideas. I mean, just some absolutely outstanding science of things that I was like, wow, I never saw that coming. Oh, I didn't think we were that close. You know, thinking about reprogramming, you know, when we first put these applications out, our judges were really excited about some of these reprogramming applications, but going like, you know, gosh, they're only in cells and in and in animals right now. I don't think they're gonna make the jump to humans, but please, please get there. And now we're starting to have some people come knock on our door and say, actually, no, we're ready for clinical trials now. And and so that to me is a little bit breathtaking, is to show how close we are in some of these therapies that even a year ago we thought were out of reach. Um, and so that's really exciting. Um, starting to see some combinations come in that are really thoughtful. And I think that for me is also really heartening is start it's starting to see people wake up to the approach to which they're doing testing and combinations of, you know, how are we using biomarkers and monitoring to actually personalize our approaches? How do we figure out those combinations and what's working? Um, and and starting to see some really thoughtful approaches of whether they're using AI or just really thoughtful algorithms and how they're applying. I love to see it. I think that's going to be a huge unlock for the field. It's not just what, but how and who. And so I think that that's going to be uh, and I was really excited to see that and some of the approach. Um, other things um were uh lifestyle-based, you know, it's great, really cool, very, very simple things that could be done, whether it's circadian-based, we had a totally circadian-based team out of the Sulk that was like gorgeous study. And their data was shocking that if you just and the management of common diseases change the timing and do some behavioral stuff, and that they showed some biomarker work and some and some health outcome data that were like, God, I don't know what that's gonna do in the finals for our improvement category. But showing what they're showing, and maybe it's just a prevention and public health thing, but my goodness, dramatic. And so those were some things that for me, again, on the really exciting side, some immunotherapies, some novel therapies, some packages. And then on the terrible side, I was just as charmed. We had some of the worst ideas for human health. I mean and uh, you know, that there is, and I think that that's also part of the field, right? Is that this is a really big point, and I think it's one for science in general. But um, you know, when it comes to human health, is that we have to um be aware of some of the risks, but also embracing, right? Is that I don't always know on paper. To me, it looks like snake oil, but we have to allow people the opportunity to join the dialogue and to figure out how to test it rigorously and transparently. And so rather than do it a lot of things where we kick people out, which we did have to exclude some people from competition because there were some ideas that looked truly unsafe. Um but by and large, many of them are like, well, I guess you know, if it's not going to be a major risk, my goodness, go test it. Who am I to say? And that we'll just see. Um, and then we had some others that were just genuinely just hilarious. So um yeah, I'm trying to think of how to uh how to give a couple of those away without identifiers. Everything from uh one that we we lovingly called the Anna Nicole Smith application was somebody who decided to, I don't know if you're aware of like the heterochronic parabiosis is a term in the field where you pair young blood to old blood. So they were keeping that heterochronic theme. Um, but how do we say they created a dating app?

SPEAKER_02 48:33

I love it, really creative.

SPEAKER_00 48:36

Yeah. And so um, you know, that was one of those. I think I just I laughed myself silly. But I mean, but they had proposed a whole trial with it of like, you know, but this is how you'll do the control groups and how you'll do the other, you know, and it's like, well, I don't think they're ever gonna get that past an ethics board, but I love it.

SPEAKER_01 48:57

Well, we're we're almost out of time here. I I know so in April, this is super exciting. You're gonna name the 10 10 finalists, is that right?

Surprising Entries: From Reprogramming To Circadian Hacks

SPEAKER_00 49:05

Oh, yeah. So the applications are due in April. So finish their really early stage studies. At least five people, they have to submit the data and a finals application to tell us that they're they're ready to go through. Those are due April 13th of 2026. Our judges will review them in June. We'll notify the teams in June, so as soon as we can after we have that there, the judge's verdict. Um, and then we'll have the award ceremony and the big public release will be on August 13th. Or August 13th. Oh, nice. Sorry about that. Yeah. So there's a little bit of a staggered delay because we have to, for global competition, give the teams time to purchase their flights to make it for the P the press release and and all of that.

SPEAKER_01 49:50

Yeah. Do you do you anticipate that 10 is gonna be like one will dominate like all mitochondrial transplantation or parabiosis or partial epigenet reprogramming, or do you see it more as a it'll be a blend of many different things and who knows?

SPEAKER_00 50:04

That's the one. I think we're gonna see a blend is that you know, we didn't give our judges any clear instructions to give this breakdown of approaches, but it naturally fell out that way, where we had about a quarter of these multi-domain, like clinics that are, you know, doing that combined approach, really thoughtful with the lifestyle intervention. Um, we had about a quarter of teams that were going after functional foods, nutraceutical supplements. Um, we had about a quarter of teams that were doing drugs, and it was almost perfectly split between repurposed drugs and novel drugs. About a quarter of our teams were doing biologics. Um, and the biologics, I mean, we saw the breadth uh within that as I went through and I did a really deep dive on where our teams are coming in and who's winning. And I'm telling you, the winning is is split, is that we're really seeing everything from um, you know, again, cell therapies, plasma-based therapies, um, uh gene therapies and RNA-based therapeutics. We had some uh protein-based novel immunotherapies. We see a little bit of everything. And when I took another deep dive and looked overall what mechanisms are being targeted the most, is that I mean that we really had two nodes. And I would say that this is actually borne out within the animal literature as well, is that there are two big drivers that if you target them, you you see uh fairly consistent improvements in in longevity. And so these are around these nodes of um metabolism, right? So nutrient sensing and metabolism, these are anything from your rapamycin to your GLP1s to your um to uh uh you know that there's there's uh you know anything sort of in the acarbose, insulin signaling, yeah, I'm sure insulin signaling, all of that. So that lives in a bucket. Um your other bucket that we saw really well represented in the teams were things that um were either immune targeting or had immune effects. Um, some of them were immune-based therapies. So, you know, actually engineering your immune cells, like a CAR T cell-based therapy or a vaccine or something. But either way, there were these immune targeting areas or had effects really primarily around inflammation and immunosinescence. And so those are the two poles that I saw the strongest. Um, outside of that, other areas that were adjacent and often related because all of these are interconnected. Of course, we saw a few epigenetic reprogramming. As I mentioned, most of those were really early, uh, but now they might come in. Um, mitochondrial therapies for sure. So mitochondrial targeted peptides, um, mitochondrial targeted antioxidants, uh, mitochondrial transplant. We saw a couple of really compelling um applications come in there. Um, and again, mitochondria and metabolism and energy sensing and inflammation, they all are together. So they're not independent of one another, right? It's just what gets targeted for the primary mechanism. Um, we still did see some senolytics and um and xenotherapeutics. So these are things that target senescent cells for clearance. Um, of course, those are also related to immune and and to other areas. Um, that for me, I we actually saw fewer of those than I anticipated. So about 10 years ago, senolytics were like all the rage. Everyone was doing synolytics for about five to 10 years, me being one of them, you know, is that we we put a lot there on that very rare cell type. Um, I would say that I think that that has gone um out of vogue just a little bit. And we certainly saw that as a trend in the applications that came in. People are using them, but typically in combinations. So more of those therapies that were algorithm-based on your rather than using that as the singular or primary. And so we'll just see how that plays out in the finals as well. Um, what were some other areas? We saw a little bit of everything, but I would say those are right now some of the dominant polls for mechanisms.

SPEAKER_01 53:52

Well, I want I want to be respectful of your time, Jamie. You've given us anything we didn't cover that you'd like to like to touch on before we wrap up here?

What Will Win: Metabolism And Immunity Lead

SPEAKER_00 54:01

Yeah, I'm just gonna go really quick. One of the things within this competition, right, is that we're mandating that our teams go after and they have to do testing that applies to both men and women. So the the trials are for both sexes. One of the other really big um conversations in the field right now, both within aging, within health in general, within society at large, is sex differences. And so, what therapies might preferentially target or affect males or females, the same or different? Um, and how do we begin to um to leverage some of those differences to find uh refined and personalized approaches for health and novel therapeutic development? And so, you know, knowing that this is a really big area, um something else we're doing at XPRIZE, in addition to HealthSpan, is we do these prize competitions and we fundraise to do prizes to overcome major barriers using this competition model. Um, one of the competitions in development is around ovarian health. And so this is one so how do we monitor and how do you begin to intervene in ways to improve ovarian health across the lifespan as an unlock for solutions not just for women, but again, can tell us, give us a lot of information about personalization and new approaches that can be used for both sexes. Um, so that for us is a really big unlock. So if any of your listeners are interested in that, um, either because they have ovaries or they love someone with ovaries, um, please have them follow along because again, it's uh it's really acknowledging that that is an organ system that has far more impact beyond baby making, um is that the organ is important for systemic health. And so we're trying to create that as an unlock for for health across the lifespan. Um, so that's one area, please follow along. Um, if you love other crazy ideas in uh in science and health and biomedicine, uh reach out. We do prize concept ideas that come out all the time. Um, we have a call for ideas coming up this spring. So if you have a crazy idea in the biotech biomedicine space, you're like, man, I've been hitting my head against this. A prize or putting a prize purse out there, it serves as a carrot on the stick to get the society at large and scientists to chase after it and break down that barrier to get through. Um and that's uh that's the business that we're in is you know strategic philanthropy for good to solve our greatest challenges. Um so um encourage anybody who's interested, please follow along. You can find us at xprize.org. Um, and I encourage you to reach out.

SPEAKER_01 56:43

Yeah, it's such a such a great model uh for the the whole XPRIZE and the XPRIZE Health that you're in you're in charge of. Uh it has potential to do so much, so much good uh for for for all of us. Uh well thanks thanks so much, Jamie. Really, really appreciate it. We'll put the link in the show notes and everything, but uh thanks for being with us today and we'll pray for snow here.

SPEAKER_00 57:07

Yeah, thank you. Colorado needs it.

SPEAKER_01 57:12

Definitely. All right. Well, hopefully, we'll have you back. This is such an exciting time. Everyone's gonna stay tuned. We'll and uh and see see how this develops in the next few months. Some some really exciting things will be announced, I'm sure.

SPEAKER_00 57:27

Yeah, absolutely. And Rob, we often have events in and around the LA area. So invite you or your listeners to anything that we're doing with XPRIZE. Thanks.

SPEAKER_01 57:34

Great. We'll we'll keep we'll we'll uh we'll publicize them when they happen. Thank you.

SPEAKER_00 57:39

All right, thank you so much, Rob.