a16z Podcast - The Biology of Aging: Introducing Bio Eats World (ep 1)

Episode Date: September 23, 2020

Welcome to the first episode of Bio Eats World, a brand new podcast all about how biology is technology. Bio is breaking out of the lab and clinic and into our daily lives -- on the verge of revolutionizing our world in ways we are only just beginning to imagine.In this episode, we talk all about the science of aging. Once a fringe field, aging research is now entering a new phase with the first clinical trials of aging-related drugs. As the entire field shifts into this moment of translation, what have we learned? What are the basic approaches to developing aging-related drugs? How is studying aging helping us understand diseases like cancer and Alzheimer’s -- and increasing the amount of time we are healthy -- today? In this conversation, Laura Deming, founder of The Longevity Fund; Kristen Fortney, co-founder of BioAge, a clinical-stage company focused on finding drugs to extend healthspan; Vijay Pande, general partner at a16z; and host Hanne Winarsky discuss the entire arc of aging science from one genetic tweak in a tiny worm to changing a whole paradigm of healthcare delivery.Be sure to subscribe to 'Bio Eats World' if you want to keep getting it (and please feel free to rate it as well). To learn more about the expanding a16z Podcast network, please visit a16z.com/podnetwork.

Hi, everyone. Welcome to the A6 and Z podcast. I'm Sonal, editor-in-chief at Andreessen Horowitz, and what follows is the very first episode in our new show, BioEats World, a podcast all about how biology is technology. The show covers healthcare, which we've covered a lot on this show, and which, of course, is top of mind right now, given the COVID crisis, but this show covers how we'll diagnose and manage all kinds of diseases, create new medicines and therapeutics, and access and deliver health care. But it also goes beyond health care because biology isn't everything. It's in the products we use daily, our food, our manufacturing processes, much more.

Bio, in other words, is eating the world. And since we believe that biology is where information technology was 50 years ago on the precipice of changing everything, that's why the name of the show is BioEats World. It is part of our expanding A6 and Z podcast network, which you can read more, more about at A6NZ.com slash pod network, and it's led by Hannah Wernarski, whose voice you have heard on this podcast for over three years now, and Lauren Richardson, who you've heard on Journal Club, which will also be moving to this new show feed. So please be sure to subscribe to BioEats World wherever you like to get your podcasts, and please feel free to rate it as well.

Hi, I'm Lauren. And I'm Hannah, and this is our first episode in the new podcast, BioEats World, where we talk all about how biology is breaking out of the lab and clinic and into our daily lives, and really on the verge of revolutionizing our entire world in ways we're only just beginning to imagine. So, Hannah, the title of this first episode is The Biology of Aging. What aspects of aging are we going to be discussing today? Well, really, we've been trying to dream up ways of slowing down aging for as long as we've been aging, right? But the field of studying aging as a science is pretty new. So in this episode, we look at the entire kind of biology of aging, what we've learned, what's reality, and what is translating into actually increasing our health span and potentially one day, possibly slow down aging.

What's health span and how is that different from lifespan? Your first thought when you think about studying aging might be how we might slow it down. But really the way a lot of people in the field think about it is increasing our health span, which is the amount of time that we live healthy. What's really interesting about this episode is it's about not just increasing health span and age span, but what we're learning about disease and particularly chronic age-related diseases that might help us be healthier today. Joining me for this conversation is Laura Deming, founder and partner of the longevity fund. Kristen Fortney, founder of BioAge, a clinical stage company focused on finding drugs that extend health span using machine learning, and Vijay, A16Z general partner on the bio fund. Were there any insights from this episode that changed the way you think about aging yourself? Yeah, well, I definitely enjoyed hearing about the drug already widely available that really might increase our lifespan.

And I also loved hearing about what the difference between Benadryl and Unisom is. So we start with a little bit of a history of the field, talk about where it's come and where we are today. So where actually are we in the biology of aging today? There's been a big surge of talk even over the past few years about what the science of longevity is how it's developed. But where are we actually today? Mortality is like this thing that philosophers opined for millennia, but yet the biology of aging seems new. Right. New and so far as it's new that anything actually works, I guess, right? One of the earliest discoveries in aging research that goes back decades is that if you could severely restrict food intake in animals,

calorie restriction, they would live substantially longer. But it's only been fairly recently that we may be able actually intervene and actually impact how long a mammal can live. And one of the interventions that was first shown to work in mammals is his parabiosis, exposing old mice to young blood. And that really was first discovered 50 years ago. The major acceleration came during the 1990s, the 2000s, and it's mostly attributable to the first finding, you know, Cynthia Kenyon, Gary Revka, and Tom Hughes, that you could delete a single gene in the worms, the elegance, and double its lifespan.

Everyone thought aging, so complicated. You know, how are we going to have a dramatic impact on aging when it's really all these different systems and processes that are going wrong simultaneously. And then, you know, wow, wait a minute, this one tweak, and then suddenly this massive difference in lifespan. So a lot of invertebrate geneticists went into the fields and mapped out all these longevity genes that impact worms, flies and yeast, which is awesome.

But now, you know, which of those translate to humans? Those are the ones that matter for translation. Coming back to kind of the history of the field, you kind of have these really, you know, sort of highly advanced intellectuals going to the field and kind of losing a lot of their momentum forward. practically. Noble laureates like Ellie Machinkov, claiming that gut bacteria kind of control aging, and maybe that's coming back around now in some areas of current biology, but back then

it's not as well supported. It's only recently they started to have the traction in the field to make specific discoveries. That period of time was just so critical to the field's birth. Cynthia Kenyon, when she was making these first studies, was told, you'll fall off the face of the earth, literally, if you pursue this research and you do the study. And if you look at her first paper, she was the lead author because no grad student was willing in her lab to do the work. was such a controversial first step to take as a young principal investigator, that was how unexpected it was, that people really thought that it would be the end of your career to kind of go into this field, and it just kind of started it anew. They didn't even want to touch it.

Yeah, exactly. Worse than unexpected, like bad science. So can we talk about what that traction actually is looking like right now? What is the most promising traction? I think one thing that we feel really strongly is this is the critical decade. Patients are for the first time receiving drugs that were developed in the context of aging biology. And it's fascinating to watch as these first clinical trials occur, where companies are actually developing drugs. And when that first patient gets an actual clinical benefit, we're going to see, you know, people actually affected by these kind of ideas that have percolated in the field for decades. One of the kind of examples of this that's most sort of prominent in the field is a trial testing, a drug called metformin

in the elderly. And so it's actually looking at all-cause mortality, not just a specific disease as an endpoint. Metformin itself, you know, is this drug which retrospectively has been shown to be somewhat correlated to a decreased mortality. And for example, diabetic patients, well, it was discovered just by analyzing health records, right? Which itself is kind of fun. Which itself is like, yeah, that's a great way to find sort of repurpose drugs. Who's living longer? Exactly.

Yeah, so it's one of these drugs that millions of people have been taking for decades. You can actually go back in time and ask the question, you know, are people who are on metformin living longer, and they are. And that's kind of amazing. So that's sort of where the whole hypothesis for this compound came from that's now being tested in the clinic, which is so exciting. I've got to go get me in. Other key approaches.

approaches that we haven't touched on yet that we should be describing as this new field kind of evolves. There's also a restore bio, which, you know, was testing a molecule that's similar to repomycin, and that was for respiratory tract infections in the elderly. That trial did not work when trying to try fide replicate in a phase three, but if that had replicated, that would have been one of the more big sort of examples. There are some sort of drugs in the clinical sort of landscape today that are for metabolic disease, so things like natural diabetes or obesity, which when you overexpress these proteins and mice, make the mice of longer. So there's this key, link between like things that we already are using to treat metabolic disease in the clinic and kind of

what might actually impact lifespan. So that's the connection with metformin? Metformin impacts cancer deaths too. So again, it's like a broader aging related mechanism. Yeah. Okay, that's interesting. One way that we try to classify these companies is in three generations. One is focusing on traditional pathways. So things that might affect, for example, insulin signaling in the body. And those are kind of known targets that people are drugging with existing modalities. The second would be trying to screen for novel targets using platforms that are high throughput and kind of either novel model organisms or kind of novel kind of in vitro or kind of in vivo screens. The third would be to actually target damage directly where you're

not saying there's an evolved pathway that we're knocking up or down, you're rather saying there's a set of damage accumulated, and that's what kind of going after in a more engineered fashion. So, you know, for example, targeting what are called senescent cells, so cells that get kind of old and decrepit with age. The idea of zombie cells, right? There's damage that builds up in the lysosome of each cell called lipofusin. And that is an aging-related type of damage, which when targeted, may be relevant to these neurod disorders that people are kind of starting to work on. So there's three different, you know, just small examples of clinical sort of work being done, but for age-related diseases.

It's like three different frameworks, basically. Well, the question, right, for the first generation of companies is what's the low-hanging fruit? If something is very well-conserved through invertebrates up to mammals, probably it's going to do something in humans too, right? So M-Toror is a very interesting target. That said, the genes that are the most important for invertebrates are probably not the most important ones for humans, right? So I think a lot of those new pathways have yet to be discovered and will have much higher impact on longevity phenotypes as well. And damage, I guess, also is sort of going directly to the major, you know, causes of disease. So I think those all make sense as approaches.

I mean, it's so unexplored now therapeutically, right? Even those drugs that have a very mild impact on longevity are, I think going to be incredibly meaningful. I think that's a really important consideration as well. And what do you call mild, like 10% increase in? Yeah, like a few percent increase. increase in lifespan. Rapamycin is probably the most well-validated drug for extending mouse lifespan, right? But, you know, the amount of compounds that were tested to that level of scientific rigor is about 30 compounds. They put 30 drugs into mice, you know, did 30

random experiments, right? And one of them, you know, boosted lifespan by 14%. So I think there's going to be tons of things that have much higher effect than rapamycin. Getting back to thinking about just the biology of it, it's, is there any other trend for the Why now? Is it just finally people like Cynthia Kenyon being brave enough to sort of help create the field? Are there any other sort of confluence of things coming in here? Mapping out every single molecule in a blood sample, in a human blood sample, proteins, metabolites, whatever we can get our hands on, and seeing which of those predict living a long healthy lifespan and going after those that are causal. Even five years ago, really, the technologies

that we're using didn't exist. Kristen, you really kind of changed my thinking here. When we first met, You were talking about biomarkers for longevity and how important those were and to be able to test our hypotheses in human, and that's where it all counts. And so kind of when you had pointed out that this was the key problem, I think that was such a big watershed for the field of if we just make a fast, easy, cheap, reliable biomarker for aging, that's really going to change the whole field in a way that is more than just kind of getting one pathway to market. The biomarker thing is actually very interesting because let's make an analogy. We have cholesterol as a biomarker for heart disease. And because there's such a causal relationship between cholesterol and heart disease, you don't have to run a trial waiting for people. people to die of heart disease. And that's huge. And especially also you can measure it. You can see small changes go up and down. You have something that's not binary dead or alive. You have

something that has a lot of nuance to it. And so having biomarkers is both really useful, but I think somewhat reflects just the maturation of the space, too. Is there another approach where we're all aging differently and we need to understand things on an individual level in terms of what our aging type is that different systems age in different ways? It's the same as with any biomarker, right? Or with cancer. You can like personalize the hell. of it and say you've got, you know, these weird mutations and therefore you're part of this special subtype, right? And I kind of think that personalized medicine is where you go after you've sort of exhausted the things that are going to work for a broader population. I mean, as we

discussed earlier, there are already mechanisms of aging conserved across species, you know, from yeast to us. So certainly there are also really potent mechanisms of aging that are conserved across humans. We're focused on targeting those first, looking at the commonalities first. But certainly, you know, for certain individuals, there will be particularities to how they age that you could also, treat differently in different people. When we're talking about changing paradigms, it's not just a scientific paradigm or even a clinical paradigm, but it's a healthcare delivery paradigm as well. Now there is this opportunity to say, given that knowledge, what can we do against existing therapeutic areas, existing disease? We don't have to talk about founding of youth. We're talking

about learning new biology, learning new targets that can directly go into a clinical trial for a new disease. And I suspect that could be a very interesting sort of initial area, initial application. So it's like what can learning about aging actually do to make you healthier right now in the age you're actually in? Or it actually can help you cure a disease that you have. What is that connection? Can we just spell that out? Yeah. And there's a couple variants of this.

One variant would be an aging related disease, like run nurse disease, these diseases where you age rapidly. That's kind of an obvious one. But maybe what's less obvious is other diseases like could we be talking cancer, could we be talking Alzheimer's, could we, you know, what are the possibilities? It's all of those, right? I mean, age is the single biggest risk factor for those diseases. Like, 20-year-olds do not get Alzheimer's. And we cannot cure Alzheimer's today, and it's therapeutically, it's been a disaster. Everything has failed in the clinic thus far.

And part of that is probably because we're studying it in the wrong way. I mean, when we're testing drugs in animal models, mice don't get Alzheimer's, and young animals do not get Alzheimer's at all. Alzheimer's disease, cancer, heart disease, and stroke. We have to study these diseases in the context of aging. And that I think is a new perspective. If you think about just the biology of Alzheimer's, it's not even clear what's going on. Like even which protein?

Is it a beta? Is it tau? Is Alzheimer? And a beta aggregation problem? Is it a fibril problem? Is it a tautopathy? Like, even the field can't even agree on the biology. Even targeting a fibril or targeting tautopathy, it's not a traditional pocket that you get a small

molecule to go into. If you have something where the current drug design methods don't work, it seems like applying the current drug design methods is not the right thing to do. This feels like the type of radical shift that could have an impact and still keep us in small molecule land. When we think about this, then actually the translation part is pretty straightforward. Because I think the beauty of what we're talking about here is the current healthcare system won't have to change. Interesting. That basically we have indications. And as Kristen mentioned, like not just any indications, but the biggest killers that we have to deal with. Huge amount of need. Yeah, huge amount of need.

And Alzheimer's, where there's at least to date, no drug at all. I'm curious, like, you could have a patient with the early signs of Alzheimer's, like, you know, with MCI, mild cognitive inhibition. Could you reverse a phenotype? Or could you just delay a phenotype? I think that is the whole promise and the practical approach as well, right? That really, if you have a drug in hand that treats aging fundamentally, it should treat several different diseases.

And yes, we can work within the existing medical system. With the one caveat, I don't think an aging drug is going to be a great drug for metastatic cancer, You know, right? Stage four is probably too far. Yeah, and sort of how far is too far. And really, these targets will probably have their most potential when they're used in a preventative fashion. And of course, that's not something that the existing system can deal with. But I do think that early disease like MCI, you can at least halt progression, which would be massive, you know, and potentially reverse it with some of these mechanisms.

Well, and the reversal is what, I think, gets everyone excited. Definitely. But even if you could just slow down, in Alzheimer's slowing down could still be very, very, very. very valuable. Yeah, it would still be disease modifying. Yeah. And then you could have a real endpoint against that. So it's interesting, you're saying almost that like the biggest hurdle is getting the biology of aging in its approach of its own. And then once you can get the right targets, then you can sort of slot into the existing system and keep moving. I think there's so much about the science, the biology of aging that has been validated, that now has opened the door to now

treating these as targets. And actually, you know, the funny thing is you could like just identify that target, toss it over the fence to your favorite pharma, and it would slot in to the same type of programs that they would be running right now. It doesn't require a radical sort of re-envisioning of pharma to make this happen. Moreover, I think, you know, if you look at the history of pharma, it goes through waves of new technologies, and maybe it's an interesting question, when or if longevity becomes that hot new trend. And I suspect that in order for that to happen, you have to have to have one or two clinical trials that have showed this works, and then it probably just catches fire. I'd want to amplify one thing Kristen said that I think went by relatively

quickly. That is very, very important, is that these compounds, if they are truly going after the biology of aging, will be useful in multiple indications. At first, that sounds magical, but they're actually precedents for this for existing compounds. So that alone is interesting that they're already precedents. Can you compare an example that? I mean, so my favorite stupid one is actually Benadryl and Unisom. So actually, it's the exact same drug. If you go to the pharmacy, Often, they just happen to be on opposite size of the aisle. And actually, when sold as a sleeping pill, it costs a lot more than as an end- I've never noticed that.

Is that true? It's the exact same compound, exact same dose. And if you ever take banjoil for allergies, you get very sleepy. So that's a simple example. They're better examples in other diseases. Humera, for example, is one of the ones. That's a great example. Humera is like, what, five or six indications?

That's right. I think even more in like the world's most valuable drug as well, right? Yeah, yeah. But this is a little different. I think in that one, you just happen to like. They're similar. There's similar diseases. They're more similar.

So in the Humery case, it's similar diseases. In the Benadry case, it happens to make you sleepy. And it's almost like taking advantage of the side effect. This is something fundamentally different. This is something where actually the sort of way to save all these diseases is to slow down aging. And that's why it has such broad impact. So is it oversimplifying it to say aging as a kind of root cause of all these diseases? Or is that?

Or an amplifier of the disease. Or a causal driver. A causal driver, yeah. Well, look at immune aging, right? I mean, your immune system declines horribly with age. You don't respond as well to vaccines. You're more likely to get incredibly sick when you do get, you know, the flu or a cold. And that affects everything in your whole body that makes everything worse.

From a pure basing point of view, it is a causal driver, right? There you go. Just a mathematical statistical point of view. By definition. And then that makes it a very natural philosophical way to think about it. One of the hypotheses about why we have genetic pathways that control aging is that we've evolved those for a reason that there's a benefit to living longer enough to have kids in a different environment. And it really wouldn't do you well to live longer and be sick, right? You want to have

ways to impact all your health that pushes back all diseases. Otherwise, kind of you just get dead of a different thing kind of earlier. And so that's kind of perhaps why it'd be plausible to, you know, believe that there'd be sort of all disease sort of efficacy for these kind of anti-aging therapeutics. Actually, in that, what is the evolutionary selection for aging or lack of aging. Because you could see that once you've given birth to children or maybe gotten them to grandchildren, like there's, then you have no purpose, right? I mean, you're done. Like, from an evolutionary point of view. And you've, let's say, diminished purpose from a purely sort of cold evolutionary point of view, but you're still taking up resources. If you have a certain

fixed mortality rate year over year, if that's actually much higher than it is today in our developed society, your probability of being dead at any one point in time in your life is actually gets pretty high, even independent of aging over time. And so if there are any things that benefit you when you're young that might be harmful to you older, or just kind of many things that accumulate randomly, past the point at which you're likely to be dead from other non-aging causes, they might accumulate. And so now that we have actually the ability to live long enough to potentially have benefited from the number of years, there's been no selective pressure potentially to kind of live sort of longer in that sort of period of life. One of the things that I'm

always just curious about is, what don't we know now that we need to know? Because the problem with biology is that it is just so complicated. Longedity and aging biology seems to be amongst the most complicated. That's the thing that I'm always wondering about as what is going to be the big surprise or the big curveball and what can we learn from it. That's a really good point, right? Because I think we're all waiting for the first clinical trial to be successful. And that's going to be so important for the field, right? For pharma companies that traditionally don't work in this area to really get confidence and excitement around it. But yeah, there's so much risk associated with bringing these first mechanisms forward and figuring out the indication path. I mean, you can even have a good

mechanism, but have, you know, defining these indications for the first time. Of course, we're going to get it wrong the first few times. There's so much to figure out because it's really such a new field. Okay, so we've talked about the explosion of the field of the study of the science, the biology of aging. And then we've talked a little bit about what that brings us actually right now in terms of understanding biology and disease. But where do we meet resistance again, where we try to get this into the health system that exists today as a kind of preventative medicine. What does that look like in terms of the end goal being a healthier life, a longer life, a longer health span?

I think that's a great question because you've got this therapy in hand. You think it's actually slowing down aging. And yes, you can work with the existing health care system and layer on indications one at a time. But really, you're not getting to the whole aging population as quickly as you can, right? And what could that path look like in the future? So biomarkers is one route, right? I mean, maybe people are still pre-disease, but they're frail.

They're sort of functional and molecular biomarkers that predict they're going to be sick soon. Again, like statins. Like statins. Exactly like statins. Statins will, you know, sort of does handle a biomarker. Yeah. With the hope that's done prophylactically to avoid disease. People often say that people don't want to pay for prevention, but we do pay for statins. You know, there's this old joke that plumbers have saved more lives than doctors.

And that's this point about sanitation is just. been this fundamental sort of floor for just for human health. And then I think the next level up in my mind is getting rid of the Fritos and no disrespect to Frito-Lay or about to go or minimizing the Fritos, you know, as much as I do like them. That's what comes to mind. I mean, basically, no one should have type two diabetes. I mean, that's another version of sanitation. And so now the question is, could you imagine like the with longevity biology in hand where you have these biomarkers no one should have these aging-related diseases or maybe nobody should have disease before the age of blank and that blank goes from like 60 to 70 to 80 to 90 and onward.

That's right. Perhaps what we really just need is something to have this rock solid biomarker that the clinicians are convinced is an issue. And then you have therapeutics that can help you manage to that biomarker. At least there's a paradigm for that. Well, exactly. But any therapy that really delayed aging that really delayed aging, that really delayed the onset of disease would save a tremendous amount of money. And you know, and you can put a number on that and you can justify a certain cost. It shouldn't be that hard. I think that's where it comes back to

this is the decade, because this is the first time that we're going to see trials actually looking at all-cause mortality with therapies that are already on market today. And we're going to see the impact of those readouts. That's never been something that's ever been done before. That's truly different from any other time in history. And that's the proof we need to get the system to really start recognizing it that way. One would hope. That doesn't move parts in mind. So that's a great point. I'm wondering, like, what would be the analogy? Like, are we at, like, First Lipitor kind of thing? We're looking, because then, then there's been, what, four generations of statins since then. Before then, actually, that model didn't even exist.

It means you kind of farmed, responding to, like, the first watermark trial with a shift in paradigm, and that kind of occurring potentially as a result of views. But, yeah. For the field, too, right? I mean, we're now at the point where several of these hypotheses are being tested clinically. We're going to have to wait. Well, we really get the human proof of concept for the idea. And then once that data comes in, I think that's going to be huge.

Osteoporosis is a really good example too, right? It didn't used to be considered a disease, but there's sort of markers of, you know, your bones get weaker as you age, and that predisposes you to really severe outcomes and events. And now it's recognized as one, and now there are drugs and there's a way forward, and payers were convinced, right? So there are case studies, I think, that we can follow. Where it's kind of flipped, the understanding has flipped and how to approach it. And the mentality towards it is.

Yeah. So where are we in the hype cycle, would you say? Yeah, aging and biotech generally, like, it's shifted in the last few years to be, a lot more accessible with, I would say, like low upfront capital, right? So first of all, the data sets that my company relies on. We were, for the first couple years,

a data company, you know, like with people with laptops vastly cheaper than biology. Even if we were doing biology, now there are incubator spaces. Now there are CROs like Wooshee that can do all your chemistry outsourced. So I think the barrier to entry for biotech

has gotten a lot lower and really enabled a lot of these new and exciting ways to work on targets and therapies. and 2011, 2013, there were so few companies that, like, just having enough money to finance those companies in the space was the limiting thing. Now, I think there's actually enough money just even from the past couple of years to fund the good ideas and the good people. And so when an entrepreneur comes to us and says, hey, like, I want to make a lot, this is a common thing, make a lot of money,

and then put it back into biotech. It's like, no, no, no, if you're actually good entrepreneur, please start a company. That's what we need more of. Start a company if you want to impact the space. We lack people. So, I mean, Kristen, one thing I'm just fascinated by is, you know, you were one of the first to really go out there and do a couple things. One was say we need biomarkers for aging, but also just built an aging company at all. I mean, there were very, very few aging companies when you started. What have been the sort of easier and harder things that you've encountered as result of that focus? I mean, it's new, right? So everyone, I think, understands that it's riskier, I guess, than if you have, you know, another company for Nash, another company for cancer,

where everybody knows exactly how that's going to go from discovery through validation, through your clinical trial design, through your reimbursement. There's a lot of uncertainties because the space is so new. But related to that, there's also so much opportunity. I would say that there's more awareness now that these drugs are in trials. There's more, I would say, also appetite for novel mechanisms now that the usual approaches are not working. So I think it's, the landscape has changed a lot, not just, you know, at the startup level, but in terms of like big biotech as well. Well, there's, you know, one sort of just common question for any founder sort of in the biopharmacide, when you can do many things, what do you do first? You know,

How do you pick a therapeutic area? That's probably one of the hardest questions an entrepreneur has to deal with. Yes, there's no sort of clear, well-trodden path, but that means that we also have the opportunity to really optimize and build something new. We're trying to design our first clinical trials. So should it be for an age-related disease? Should it be for something closer to aging? Again, uncertainty plus opportunity, right? And trading those two things off and making a bet, right?

We're really focused right now on just getting more people to be longevity founders. You know, early 2010s, it was lack of capital. Like, there's just no money in the space right now. The big baldneck is founders. And we've seen many amazing companies built by both grad students directly out of their kind of Ph.D. But also people coming from software engineering managerial positions. And a lot of these people self-select out of the population. They say, I can't start a longevity company because I don't fit the profile of a brilliant scientist founder or a kind of traditional investment banker type.

But, you know, they make incredible founders. And there's just a huge population of folks out there who I think should be sorting companies. So just to double down on the idea that, like, if you want to really impact longevity, start a company, that is like exactly what we need right now. What are the other types of founders that you tend to see coming into the field, you know, in this new field? The founders in this space typically combine a couple of things. They either are biologists who have embraced, you know, machine learning or other areas or even people that are coming from the tech side that are learning the biology.

It's a really unusual time where you can actually learn both. Maybe you've learned both from the beginning, but actually it almost feels like it's never too late because you can. pick up both sides, but that if you can capture both sides, I think you'll have a huge advantage. A non-traditional founder for us would be someone that is coming maybe from the pure pharma side. And we haven't seen that yet, but I suspect they're coming. I mean, Kristen's nodding her head. And I suspect they're coming either to be founders or as, you know, CSOs and that they maybe become some of the key employees for these companies. So the culture and the

talent landscape changing too, evolving and interesting. That's it for the biology of aging. And thanks so much for joining us on BioEats World. If you'd like to hear more about all the ways biology is technology, please subscribe to the A16Z Bio Newsletter at A16Z.com slash newsletter. And of course, subscribe to BioEats World anywhere you listen to podcasts.