a16z Podcast - a16z Podcast: The Science Of Extending Life

Episode Date: April 18, 2017

Is it real or science fiction to dream of being able to treat… getting old? In this episode, we discuss with Dr. Thomas Rando from Stanford (who directs the Glenn Center for the Biology of Aging), Kristen Fortney, CEO of BioAge, and a16z’s general partner Vijay Pande where we are in the field of “geroscience” — the idea of studying, well, aging itself, and aging as the root risk for all aging related disease. Far from science fiction, recent discoveries have given us a whole crop of promising breakthroughs to treat aging, such as parabiosis (young blood infused into old blood), senolytics, and rapamycin, and more. What we’re beginning to see is a fundamental shift away from the idea of searching for immortality and towards the idea of increasing "health span” — where prevention means much more than eating healthier or exercising more. Are we moving from Dx to Rx to — perhaps Px? What will it look like when anti-aging therapies actually begin to be delivered to us: small molecule or protein or an antibody — or something else entirely? A pill or a blood transfusion treatment? A vaccine for aging? And finally, what has to change — conceptually, scientifically, logistically, in regulation -- to get these therapies into the hands of all? The views expressed here are those of the individual AH Capital Management, L.L.C. (“a16z”) personnel quoted and are not the views of a16z or its affiliates. Certain information contained in here has been obtained from third-party sources, including from portfolio companies of funds managed by a16z. While taken from sources believed to be reliable, a16z has not independently verified such information and makes no representations about the enduring accuracy of the information or its appropriateness for a given situation. This content is provided for informational purposes only, and should not be relied upon as legal, business, investment, or tax advice. You should consult your own advisers as to those matters. References to any securities or digital assets are for illustrative purposes only, and do not constitute an investment recommendation or offer to provide investment advisory services. Furthermore, this content is not directed at nor intended for use by any investors or prospective investors, and may not under any circumstances be relied upon when making a decision to invest in any fund managed by a16z. (An offering to invest in an a16z fund will be made only by the private placement memorandum, subscription agreement, and other relevant documentation of any such fund and should be read in their entirety.) Any investments or portfolio companies mentioned, referred to, or described are not representative of all investments in vehicles managed by a16z, and there can be no assurance that the investments will be profitable or that other investments made in the future will have similar characteristics or results. A list of investments made by funds managed by Andreessen Horowitz (excluding investments and certain publicly traded cryptocurrencies/ digital assets for which the issuer has not provided permission for a16z to disclose publicly) is available at https://a16z.com/investments/. Charts and graphs provided within are for informational purposes solely and should not be relied upon when making any investment decision. Past performance is not indicative of future results. The content speaks only as of the date indicated. Any projections, estimates, forecasts, targets, prospects, and/or opinions expressed in these materials are subject to change without notice and may differ or be contrary to opinions expressed by others. Please see https://a16z.com/disclosures for additional important information.

The content here is for informational purposes only, should not be taken as legal business, tax, or investment advice, or be used to evaluate any investment or security and is not directed at any investors or potential investors in any A16Z fund. For more details, please see A16Z.com slash disclosures. Hi, and welcome to the A16Z podcast. I'm Hannah, and today we're talking about the science of life extension. Are we finally just around the corner from a treatment for getting old? In this episode, we talk about where we are in the field of geroscience, which is the study of aging itself and aging as a major risk factor for diseases. Sometimes the buzz makes it seem like this is about the search for immortality, but it's really about living a longer life of being healthy, our health span. We talk about all the anti-aging discoveries that look like they might translate into real treatment, how these therapies will be delivered to us, and what happens to society if

they do work. The first voice you'll hear is Dr. Thomas Randow from Stanford, who directs the Glenn Center for the Biology of Aging, then A16Z general partner Vijay Ponday, joined by Kristen Fortney, CEO of BioAge. So let's start off with a simple question. Where are we now? There's a big discrepancy between the notion of life extension and the notion of health span extension. And that's a big distinction in the field, right? Because life extension sounds like this issue of moving toward immortality. And in fact, really the field in terms of the biomedical field really focuses on taking what we learn from lifespan extension in model organisms, in worms and flies, and applying

that to humans, to mammals, to make them healthier, not to make them live forever. And so it's a dichotomy between the goal being extending life versus the goal being extending health, which might secondarily lead people as a population to live longer. That's an important distinction because so much experimentation goes into lifespan extension in animals, but really the translation is making people healthier, longer. Yes, they may live a little longer, but what we really want to do is have them live longer in a state of better health and a much shorter period of disability at the end of life. Because what's the point of living longer if you don't?

If you're unhealthy, exactly. It's not impossible to imagine instead of that curing all disease would be harder than curing one disease or multiple diseases with the idea that when you have an antibiotic, it in high doses will kill bacteria in the petri dish. But in your body, is it really killing the bacteria or is it simply weakening them such that then your immune system kicks in? And so it's about your immune system more than it is about the drugs. Is this really something different than health care and affecting human health? I would see as the natural next step. I think about life extension very much as the ultimate endpoint for improving health care.

and why we're doing this in the first place. So can you describe to us some of the recent science that you think is really exciting? Because it's felt like for a long time we're sort of right around the corner from a major breakthrough. Are we now or is that still to come? Certainly in the field of aging across, say, the decades, there's a pivot happening now that I think is really remarkable. It's changed a lot in the last two decades and then every five years you see another big

increment in terms of not only our knowledge, but how we approach this. I would say that the conceptual change that's happened over the last 10 years is this notion, quote, of geroscience. And that is this idea that if we can understand the process of aging and if we can do something about it, if we could intervene with a pill or an intervention, and we could actually slow the process of aging, the consequence of that would be the delay and onset of all age-related diseases, conceptually theoretically. So if that's true, that really changes the way we think about health because this is preventive health in a way that's not been imagined before. And how is that different from how we used to think about it and approach it? The field of aging has only reached that kind of mechanistic intervention stage in the last recent years. Having said that, this idea of caloric restriction extending lifespan has been around since the 30s. However, that has just always been in the background.

People have mostly described aging and described age-related. it changes. It's really been since the, really discovery of individual genes and individual drugs that can extend lifespan, that's changed that from kind of a conceptual field of here's what happens when we age that describes it to something we can do something about. But those studies usually are on model organisms. Almost all. Almost all. Well, they're getting closer is the point, I think. To me, the exciting point was that in the 1990s, in the early 2000s, we found a lot of interventions, single gene interventions or drugs. that extend life in yeast or in flies or in worms.

A lot of progress was made in invertebrates, and that's because you can knock out every single gene, you know, in a worm and see what happens. You can't do that in humans. And really, it's only been the last decade where there have been some successes in mammals, right? There's rapamycin and mice. There's senescent cell clearance in mice. So we're getting closer and closer to humans, which I think is what's really exciting about the state of the field right now.

The field has focused in academia on invertebrate models because they're sort of more attractable. they have shorter lifespans, but because of sort of new genomic technologies, we can actually finally directly study human aging, which is going to be most relevant to extending our health spans, which is also a fairly recent innovation. Well, actually, could you go into that a little more? I mean, that part actually is super interesting because, you know, just naively, I think a lot people would think if you're trying to understand life extension or health extension for 10 years, that would be a very difficult study to do in under 10 years.

Yeah, I completely agree with you. If we have any putative intervention that we think is going to extend, and mouse or human lifespan, how do we actually test that without waiting decades? And I think that we finally have the opportunity to build real biomarkers using genomic data. So we can sort of measure something in your blood that tells you what your biological age is. And then after a drug or some other intervention, measure it to see if it's improved. So we can sort of really accelerate these discoveries. So I've always been very interested in biomarkers as surrogate endpoints. And these technologies are just coming out now. And I think they're really going to accelerate

progress to find new therapies for human aging. Yeah. I'm especially excited about that approach because that gets to not your sort of chronological age, but your degree of healthiness, which is what we really care about. Exactly. And I think, you know, the idea of having biomarkers is going to accelerate this field enormously. I mean, currently the notion of using drugs in humans is underway, but the ideas you take a lot of people, you watch them for a long time, and you watch the onset of age-related

diseases. But even, you know, even looking for the onset of disease as opposed to looking for the end of their life, you're still talking decades. So if we could have a marker that over year to year could predict the rate of aging and slowing that aging, we would have a much better handle on how effective any treatment we have would be. From the pop culture perspective, like choleric restriction, this idea of old blood and new blood, some of the actual science has roots in old ideas and some of it is based in completely new. ideas. Can you break those down a little bit so that we know what we're kind of looking at? There's a lot of mythology. Yeah. It's very difficult. I mean, so there are a lot of ideas that are

out there. Now, this idea of old blood and young blood actually comes from our work from, you know, early 2000s. Having said that, this idea has been around in the mythology for centuries. Since like the 17th century. Exactly. So, you know, so they were right somehow. But so what do we really know about that? What we really know these days is that it does seem that if you know, infuse components of a blood from a young animal into an old animal, it actually can revert some of the aging phenotypes from an old state to a younger state, which is something quite different because that's really reversing aging as opposed to slowing aging. But that's what we know. We don't know, like, how much it would take. We don't know, you know, where this mythology came

from. I don't even know. I don't even know how this came about. But it turns out to be quite accurate in terms of thinking that really what I think the idea is that there are circulating factors in the blood that are very promoting of youthfulness in the young individuals, young mice, young humans. And the older we get, the more in the blood are factors that suppress that youthfulness or promote aging. We'd love to know what those are, and we'd love to be able to use those to develop interventions that would actually either slow or maybe even to some extent revert the aging

phenotypes. And it speaks to the predictive capability of those biomarkers. Absolutely. You can actually not just use that for DX, but RX means that there really is something there. That's right. What are some of the other approaches that you're keeping an eye on at the moment that seem particularly fertile for extending the health span of a life? Yeah, there's a few different things that have shown promise in mammalian systems. So there's a paribiosis, as Tom discussed, which is his expertise. There's also senescent cells. So when you're cells when you're older, a lot of your cells, you know, after they've replicated a bunch of times, they get sick and one of two things can happen. They can apatose or they can senes,

which is a sort of state of permanent growth arrest where they become actively toxic and they recruit your immune system. And there was this hypothesis for decades in the literature that these senescent cells were actively bad for you. And if you could just destroy them, that would be better. And that was really sort of tested for the first time in a really strong paper that came out just over a year ago from the Mayo Clinic and the Buck Institute. It was a big collaboration. And they showed that if you killed senescent cells in a mouse, you could boost lifespan by 30%. And that's a very hard result to achieve in a mouse. So that's really exciting. The search is on for drugs that can kill senescent cells in these animals. And that should

translate to humans as well. It's a really sort of mechanistic hypothesis for aging. It speaks to one question I have, which is, what would this look like? Would this look like a small molecule that actually would, if you take it every day as some sort of supplement, would help your aging? I mean, what do you think the technology is going to lead to in terms of the short term versus long term? Well, I think in the case of that technology, which is called senolytics, lysing senescent cells, it would be, and it is being pursued as a small molecule treatment. Now, what we really don't know is, can you take these for a long time? What are the downsides of killing all your senescent cells? There's some indication that senescent cells can actually

be beneficial. You might not need to, though, right? If it's just, you know, building up. Right. You can just accumulate, you know, take them, take it once a month, take, we don't know this. But that definitely is a small molecule approach. And so it has the flavor of a therapy that could be turned turned into a pill. The plasma coming from the paribiosis work, that idea of plasma infusions, you know, actually can be done, but it's much more invasive. You have to inject plasma to people. We really don't know, we don't know this at all in terms of lifespan or health span. humans. Right. Do not try this at home. Do not try this at home. But what we know, what we see that translating to is, is a protein therapy. You know, is a component of the blood that

might be a protein. It could be something else, but that one could take or even an antibody treatment to neutralize an aging factor. You might want to get rid of something in the blood as opposed to add something. So both of those are feasible. They're in line with, you know, major selling drugs around the world, proteins or antibodies. So one can envision a non-small molecule, a non-pill approach that might also have that kind of benefit. I can imagine science fiction story right now because you can develop an antigen for that antibody. And now you have a vaccine for aging.

Well, there's an idea. I would love to talk about, you know, the role of data. Because it's not just right about finding the molecule and the protein. It's also about how we process the knowledge. Yeah, I mean, it's a whole feel in itself. sense. How are modern technologies outside of biology having impact here? For instance, computation, data science, machine learning. Is that playing any sort of role? Yeah, I think that's playing a very large role. If you want to understand human aging, you have to use non-invasive technologies

that can monitor people throughout their lives. And that's, that basically means genomics. That means transcriptomes, RNA. That means looking at all the protein levels in your blood, looking at the metabolites in your blood. So I think that those new technologies that sort of let study human aging in some ways for the first time. Did they accelerate it? I mean, are we still in a position where we have to actually watch people age over, you know, decades to know whether something is working? Yeah, so two answers to that.

First, there is a way around that. So you can work with, there are fortunately a lot of sort of forward-looking biobanks, often in European countries, that have old human samples in the freezer, complete with electronic health records. So you can go and get those samples and you can query them with new modern technologies and you can integrate that with health records and say, can I predict on the basis of a combination of things I can measure in blood, you know, who's going to live for 10 years versus who's going to live for 20 years? And what were those samples taken for? What was the context of this bank? Yeah. Lots of these biobanks, you know, it was, they had the exact right idea. They thought that new technologies will be able to, you know, this will be useful in the future. So we're going to start storing it now.

Wow. Yeah. Yeah. So we work with a lot of those and I'm pretty excited about that. And the second answer to that question is that I think that aside from accelerating research into human aging, it's also accelerating research into mammalian aging in general. Because even with mice, if you want to see if a drug makes a mouse live longer, you do, that's a three and a half year experiment. The National Cancer Institute, the total number of drugs they've given to mice to see if they cure mouse cancer is over 110,000. The number of drugs the National Institute on Aging is given to mice. to see if they live longer is 30. So, you know, basically zero. Even though they've only tested 30, there's already been one success. Rapamycin that came out of that, which is a very exciting discovery. Basically, the first molecule that came out of this large-scale program, they started to feed it to mice at middle age, and they found that the mice that got the rapamycin lived about 30% longer than the mice that didn't.

And it delayed the onset of pretty much every bad age-related phenotype or disease. So it's something that if it worked that way in humans, we'd all love to take. There's, of course, safety issues. There's toxicity issues. It's never that easy. But this is exactly the kind of therapy that we're looking for. And I think there's going to be a lot of other success stories. Once we have a system for evaluating many more drugs than 30.

So I think there's a lot of low-hanging fruit there. What is intriguing about the ability to get this information from blood, whether we're talking about markers or we're talking about the ability for this to be therapeutics, is this is something where we can be dealing with the science of this now. in an age where a lot of this is perhaps often been more speculative and uncertain for whether it's really useful. That's the part that I think makes me think there's something different in what we're seeing today. So if this time is different, we're going to start seeing a whole bunch of new businesses and startups in the space. What is it like to start a business up in this area? What's it like to enter in the scene from the business side? You're dealing with a lot of very entrenched incumbents, a lot of different interests and invested parties.

What are some of the challenges and how do businesses begin to navigate them? Yeah, that's an excellent point. Like, you know, biotech companies, drug discovery companies have a lot of challenges to face. And I think there's even more in the case of an aging company, because even if we do discover another repomycin, another drug that slows aging, then what's the FDA indication for that. How do we get that approved as a therapy? So, again, we can sort of look back and see what happened with rapamycin, right? And there are pharmaceuticals companies that are trying to work with, they call them rappelogs. They're sort of chemical analogs of rapamycin.

and they're basically just sort of throwing them against various age-related diseases to see what sticks, because that's how you get therapy approved at the FDA. You have to have a particular disease indication. And a drug that slows aging when you give it to healthy people isn't necessarily going to be the best therapy for someone who's already very sick. So that's sort of a unique challenge that we're facing. There's a tame trial. So that's the trial for using this drug metformin, which is a commonly used drug for diabetes, but has also been shown to extend lifespan and model organisms.

And lots of Americans are on it. And there's epidemiologic data, which is associative. It doesn't prove causal fact that metformin treatment actually does enhance lifespan, especially of people who have diabetes. So the notion is maybe everyone will live longer if they take the metformin. So especially in people who have diabetes, but also in people who do not. Well, I'm saying epidemiologic data is that. So there's no epidemiologic data on people who don't have diabetes who take metformin because

they're not on it. Because it doesn't happen. Right. So, but the question is because it happens. healthy animals, and in some humans, maybe it happens in all humans. So the trial is to give a subset of patients who are healthy metformin, and as we were saying before, watch for the onset of age-related diseases over a long time period with the idea that if it works in this kind of geroscience way, you know, treating aging to treat all diseases, all of these diseases will

come on later in this group of patients on metformin versus those not on metformin. And part of the real fundamental shift here is usually one would think treating two diseases or three diseases is much harder than one. But this perspective is by attacking the central aspect that's common to all, you can address many diseases at once. That's right. So it's really not treating three diseases. It's really, the notion is that, as you said, it's preventing. The notion is that aging, well, the concept that's out there is aging is the major risk factor for all of these diseases. heart disease, cancer, Alzheimer's disease, and that if we understood why older people get all

of these diseases, and we could get at that fundamental mechanism, we could, in theory, delay all of these diseases. I don't know what the right Latin is, but, you know, there's DX and RX, we should have PX or something like that. Right, exactly. Just a new class of how we think about this. Well, yeah, in some ways, it might be an easier problem, right? Like if someone presents with late stage lung cancer, fixing that, drugs to fix that, that's really hard.

You know, it's you come in your very damaged system. But what we know from these mouse trials of drugs that delay aging, you can intervene when the system is still mostly working and you can just sort of nudge it in the right direction and delay the onset of all these debilities. So that's what excites me. So it's trying to get at the root cause, right? All of these approaches are getting at the root cause, not all the symptoms and diseases that are associated with it. So how does that tie back into your conceptual framing of it as increasing health span? Yeah. I mean, it is increasing health span because obviously you avoid these age-related diseases by staying young.

I think this fundamental shift of towards prevention being more than just eat less or exercise. Prevention meaning what? Yeah. So prevention meaning like potential small molecules or other types of things we would consider as therapeutics, but for the disease being aging itself in some sense. And that's going to take a shift. There's going to have to be a shift in how we think about it from a regulatory point of view, how we think about it from a clinical point of view. Part of, I think the challenge here is not just the science, but shifting that mindset. I mean, I think that's really important. What Chris was saying before about this notion of FDA regulations is going to have to change because there's no way right now that any drug is going to be approved for treatment of healthy people.

And is that because of the time, because it takes so long or is it? No, it's just the historical context. I mean, I remember, so probably 15 years ago, I was talking about our work to a company, a big pharma company about this idea, which, you know, it was way ahead of the time back then because we really didn't have even the. the knowledge of this, but this idea that one could potentially treat aging. And I wouldn't say they laughed me out of the room, but at the end of the day, the answer was, that will never happen because it will have to be as safe as water. Wow. Because it will never be approved to give a drug to healthy people, unless it's as safe as water. And the premise of that is because you don't want to mess up. Right. Things can only go wrong. Essentially, right. And you don't, we would have no trial basis to say over the course of, you know, decades that it works. You're still healthy.

You're still healthy. So it would take a very long time. Now, again, that mindset is shifting that, that I think, you know, now the notion is maybe we can treat healthy people in a preventive way. And it doesn't have to be as safe as water has to be very safe. But that's the big change. How do you see it starting to shift a little bit? Well, even this tame trial being discussed and being presented to the FDA and the FDA discussing it is already a major step forward. I mean, that would not have happened 10 years ago. So I think the caveats and the constraints are being loosened and we're moving that in that direction. We're not there. We'll see how this first trial goes. Yeah, I'm really excited by the tame trial and by what they're doing.

I think there's a lot that we can do in parallel to like companies in this space, what we have to do basically is choose a particular disease indication, get approved for that disease indication and then hopefully be used more broadly. Oh, interesting. It's almost like an artificial specification. That's right. So everyone would like sort of a story like statins, which basically are an aging drug now. The indication is, oh, you're over 40, have some statins. Or the metformin, right? Well, but statins are actually approved. Right. Right. Used as an aging drug in practice, right? So that's sort of the path that we would like to take with any sort of therapy that we'd like to take forward. So there is still the hope that even though it gets

approved for a narrow indication, it can be used more widely when people realize what the benefits are and when it's, you know, been through the process. I think one of the challenges for the companies will be picking the indication. Yes. I think that that will be a major challenge because it could fail in certain indications and you could throw the baby out with the bathwater. And I think that will be a major advance that the company on the corporate side will make in terms of identifying indications that become kind of the standard for

if you have an anti-aging drug or aging prevention slowing drug, test it in these conditions. If it works, then you may be on to something. So can you pick multiple ones? And are there certain ones that tend to crop up over and over again? Or it's just right now it's just a free for all of it. Well, yeah, part of it is just the question of choosing the best regulatory path, right? I mean, the regulatory path for some therapies is better than others. Like even if we came up with a drug that we thought slowed aging tomorrow and I thought it would be wonderful for diabetes. I probably wouldn't want to go out and pay for a diabetes trial, right? That's a very competitive space. You need a huge expensive trial with lots of people. So that was sort of a poor choice of indication if your goal is really just sort of to get it through the process, right? So you actually want to choose smaller indications that you think are still going to be relevant. And this is actually common even in other areas that even for like cancer and drugs, they'll pick an indication for a cancer worst that would be first in class, even if the drug could be helpful more broadly.

And so this is a game plan that at least is well known. A familiar pattern. So what you talked a little bit about this, but what might it look like? Is it most likely to be a pill? Are there other or will it be, I don't want to go there like a blood transfusion? You know, what do you think it might look like? And who will it be for first? You know, I mean, is it really only the province of sort of the elite and wealthy in the beginning? Or is it how, how will this, how will we actually start to see this being delivered to us if we do?

Well, it's a, it's a good question. It's a big question. So let me just say, first of all, that the company based on the kind of this work of the blood transfusions is currently conducting a trial of delivering plasma from young individuals to patients with early onset Alzheimer's disease. so it's in trial and we don't know if it'll work yet but but so in theory in a short time plasma infusions for certain diseases might be as might be a treatment now who's going to get it is going to be a major economic issue because will insurance companies pay for it will they not pay for it if they don't it will be limited to people who can afford it and that would be a tragedy so these will end up being i think basically societal issues that will have to be worked out

as to who's going to pay for these things if they're effective. Now, will it be a protein, will it be a drug? All of these are being pursued. Which ones will get their first, I think, is, or will they be all of them? Yeah, I suspect there will be many different approaches. The small molecule ones will eventually go off patent. And so then they will be generics and be very inexpensive. That's right.

But years from now, right? I mean, we're talking about longevity, so. We'll all have plenty of time to be generic. So, yeah, but realistically, like, you know, it may take some, the patent, windows are not that big anymore, you know, by the time they get past clinical trials. So, you know, it wouldn't take that long. And so I think that would be one thing. I think the protein therapeutics is much more. Yeah, I guess I'm expecting small molecules to come first because that's what pharma is used to. You know, that's what we have all the models to make that

work. And the space of chemicals has been so unexplored. So I think there are going to be other repomycin's other metformins that become available in the next few years. And just from a kind of a step back point of view, from an economic point of view, if it turned out there were treatments that delayed the onset of age-related diseases. When you think of the cost savings, this would be globally, governments would be lining up to get these treatments. So it would, you know, again, this is assuming this all works and this is effective, there would be a huge incentive on the public side, on the government side, to institute treatments

to preserve health. It needs to be thought of in a different way in that it's, you know, more akin to like seatbelts and airbags. That's right. fluoride in the water. Fluorite in the water is a great metaphor. But there is also a cost to, I mean, say we did all add 40 years to our lives, you know, which would be amazing. But you have a generation then on the planet that's hanging around for much longer using resources and food supply.

Retirement gets pushed back 40 years. No, that's because of 40 productive years. Oh, interesting. Actually, you could see the other way around that when you're 70, if you're youthful and 70, the amount of information expertise you've gathered. and to apply that in a way that had the energy of a 30-year-old. You know, I often wish I knew now what I knew when I was 20 and all the things I could do. I imagine now making that really possible. That's true.

But I think the point you raise is an important one, which is how does society change if we add 40 years to life? It would have to change. You know, it's interesting because really over the last century plus we've doubled human life expectancy. Right. Already. Already. Already doubled. But all of those extra years have been added at the end. So we still get married at the same time, have kids, retire. That's all stayed exactly the same. And now we have these. And what we don't want to do as a society is just keep adding them on at the end. Because I think there really has to be this global shift, even as we're extending lifespan just by what is happening naturally. The interesting thing about this is that if it really is extending health, you could imagine that the age in which women can bear children could be extended out. That would be a very different world.

that would have a huge impact in terms of women in the workforce and their ability to have children and so on. It could have fundamental implications in very, very positive ways. I mean, to be human is to be finite, right? And we think about our very humanity in these terms. And what does it mean when you, when we, when we open that end, how we think about humanity, full stop? We're still not talking about infinity. There's a big difference in 40 in infinity. Right. Not immortal. Or 100 in infinity. So I think it doesn't fundamentally. redefine that. I think, you know, it ends up being much more of a demographic issue. And if you, if you look at the extension of lifespan, obviously, in developed countries, that has been

paralleled by a decrease in fertility. Right. So, you know, if this were about population explosion, that would be one thing. But in fact, populations are shrinking because birth rates are going down in a lot of developed countries. So there really is already this huge demographic shift going on. We are living longer. We're having fewer children. That's changing the nature of society. And that's continuing. And then if we add on top of that even longer life, that just puts more pressure, I think, on society to adapt to that kind of changing demographic. We adapt very slowly to changing demographics. We like our institutions. We like when we go to school. We like when we start jobs. We like retirement 65. Those are very much, you know, they're rooted in very old-fashioned

demographics. So there's a very slow process for society to catch up with these kind of demographic changes. To some extent, we can sort of already go and see what that would be. I mean, I think the near-term therapies are going to add, say, 10 to 20 years, and there are groups of people now who have exceptional longevity, which is a heritable genetic trait. There are families that are enriched for this. And 10 to 20 good years. Well, exactly. They're like, like, cha-cha.

Yeah. Yeah. Who are like doing those viral videos. There's a famous family, and all five siblings live to be over 100, and they were still working into their, you know, hundreds and still mentally there into their hundreds and still physically active. So we know that this can exist. And we sort of know what it will look like from studying these long-loaded populations.

And I think that's what we all want, longer life without increased stability. It's already been getting longer and longer. And I do think you would, I mean, you would live your life totally differently. Very differently. Okay. Well, thank you for joining us on the A16D podcast. Great. Thank you.

Thanks. Great.