Transcript

Note to readers: Laura has provided some additional commentary in the transcript about some of the points discussed — these are marked as footnotes as included in the “Laura’s footnotes” section at the end of the transcript.

Cold open [00:00:00]

Laura Deming: Then the other would be a regulatory breakthrough, which is the first acceptance of efficacy data for a lifespan-extension drug in dogs that just occurred a couple of weeks ago.

Luisa, to be really clear, this is something that I thought was impossible, like, five years ago. And the company got it done in four.

Luisa Rodriguez: Wow.

Laura Deming: We’re really talking about something where, if you’re in the field… Literally, when this happened, I was in this exact office. I broke down, I screamed, ran into a conference room, started crying. Because you just can’t be in this field for 17 years — again, since I was a kid — and just dreaming of things like this that could happen, where you get mainstream consideration, even just rationally, of the data in the field. I mean, it’s really emotional to see that happen. And it’s so hard to convey to people outside the field how big of a milestone this is, and how much it’s going to impact I think a lot of things that come downstream. Even if this drug ends up failing for whatever other reason down the road, I think this regulatory milestone is a huge one for the field.

Luisa’s intro [00:00:58]

Luisa Rodriguez: Hi listeners, this is Luisa Rodriguez, one of the hosts of The 80,000 Hours Podcast.

Today’s guest is Laura Deming, a venture capitalist who funds companies working on anti-ageing and life-extension technology.

Before this interview, I had no idea how far along the field of life extension research already was — and I was pretty sceptical that extending life way longer than our current life expectancies was particularly plausible. I also had some pretty deeply ingrained intuitions about whether life extension would even be a good thing.

But Laura really convinced me that there are lots of reasons to think lifespan is remarkably malleable. For example, we can increase life expectancy in model organisms like mice a lot by doing really basic things like restricting their calories, making single genetic mutations, and giving existing drugs already approved to treat non-ageing-related illnesses. Yes, mice are pretty different from humans, but there are reasons to think that human lifespans might be malleable in similar ways.

So that kind of blew my mind. But we’ve actually made a bunch more scientific progress than that. For example, it’s plausible that there will be FDA-approved life-extension drugs for dogs as soon as 2025, which to me feels insane!

We talk about all of that, as well as:

• The case for ageing research.
• Reasons Laura doesn’t think the objections to trying to extend human life are convincing.
• Recent big wins in ageing research.
• Talent shortages and other bottlenecks in achieving lifespan extension.
• And plenty more.

Without further ado, I bring you Laura Deming.

The interview begins [00:03:04]

Luisa Rodriguez: Today I’m speaking with Laura Deming.

Laura grew up being homeschooled in New Zealand, but moved to the US when she was 12 to start graduate coursework at the University of California San Francisco.

There she visited the Kenyon Lab, which had increased the lifespan of the worm C. elegans by a factor of two using genetic engineering.

She then got into MIT to study physics at the eye-popping age of 14, but in 2011 dropped out of MIT to take a $100,000 Thiel Fellowship, and attempt to launch a venture capital firm focused on funding companies that could slow or prevent human ageing.

That project, which became The Longevity Fund, raised $4 million in its first fund, then $23 million for its second fund, and millions more since then. With that funding, Laura has invested in a range of projects like Unity Biotechnology, and given seed grants to young researchers and entrepreneurs.

Thanks for coming on the podcast, Laura.

Laura Deming: Thank you for having me.

The case for ending ageing [00:04:00]

Luisa Rodriguez: I hope to talk about why we think increasing human lifespan is even possible, and some of the advances in the longevity field you’re more excited about. But first, why are you working on ending ageing?

Laura Deming: The way I think about it personally is just kind of working on medicine rationally. Really, in my mind, we just at some point arbitrarily decided to start calling certain classes of symptoms “diseases,” and then also somewhat arbitrarily kind of cordoned off a subset of diseases that we could work on — and diseases related to older age don’t fall into that.

I actually think there’s a good reason for that. I think mentally, it’s quite hard to deal with questions around death, or the inevitability of death, or when one might die. So it’s actually quite stabilising to say, well, that’s just automatically going to happen. But unfortunately, this is very inefficient if this means that you end up not developing technology or medicines to address that.

Luisa Rodriguez: Yeah, that makes sense. Is the idea something like there are groups of symptoms that come with older age that historically we’ve not prioritised? I do have this feeling that symptoms at older age are kind of inevitable. And so the idea is like, we irrationally have been treating them as inevitable, but they’re not. We can actually just try to treat them as diseases or as symptoms that can be addressed, the way we do many other symptoms?

Laura Deming: Exactly. And let’s be clear: when I was a kid, I just assumed this was true. And if we were talking 100 years ago, that would have been a bad assumption — 100 years ago, maybe talking about treating those symptoms would have been as reasonable as talking about going to Mars in that decade: it’s maybe physically plausible, but probably not going to get there.

I think the thing that makes this relevant, and makes this a really important area to work on — specifically people who understand the field to work on; I think this is an incredibly important decade in the field — is the fact that we have technology now that demonstrably can change lifespan. Like we know, in mice, many different ways to increase lifespan. And it’s plausible that some of those technologies translate over to humans. So this means that, for the first time in all of human history, we have a pretty clear handle on the idea that lifespan is changeable — and this will be the decades in which we demonstrate, if it’s possible, that that translates to humans.

Now, we’re not going to live, I don’t think, like thousands of years more from therapies developed in the next decade. It’s not going to be very obvious. But the point is: scientifically, plausibly demonstrating that in humans is absolutely the most important thing we can do in the field in this lifetime in order to change this widely held belief that lifespan is somehow a fixed parameter and not changeable.

Luisa Rodriguez: Cool. Interesting. That actually makes me want to dive more into the kinds of increases in lifespan that we have seen so far that make us think that, actually, this is a thing to think about now — it is relevant; it is a thing that science can touch — because I suspect that many people’s biggest objection to anti-ageing work is that they think nothing useful can be done, and ageing is just like a part of life.

So maybe we should address that right off the bat: fundamentally, why do you believe it’s technically feasible to work on ending ageing?

Laura Deming: I could give multiple different lines of argument here, but it just obviously is. And I think that that should be the prior, and that proving that it isn’t should really be a pretty high burden of proof. Somehow we’re in this really weird world where that’s the default belief, and then you have to fight to somehow prove this thing, which I think is scientifically just more plausible.

So, a couple of different things. One is just there’s really no physical reason that demonstrates that this is impossible. You can talk about the second law all you want, but that applies to global, not local, systems. So we are a collection of 10²⁷ [to 10²⁸] atoms; it might be pretty hard, but the question is just: can we keep those in some configuration that resembles health? And there’s just no physical argument that that is impossible. So if anyone says something like that, I just think that they’re not thinking in a way that’s physically reasonable. It might be quite hard, but it’s definitely not physically impossible.

So then the question is: how hard is it? And fair point: up until the ’70s, I would have been like, damn, probably. I think as a kid, my youthful enthusiasm might not have translated as a practical adult into the same belief. I might have been like, really, if you look at what we have to work with, there’s just nothing that’s making anything live longer: lifespan empirically seems pretty fixed. And so while this might be physically possible, it seems practically impossible.

The really, really weird thing — and I honestly sometimes just kick myself for what decade I got to be born in — is this is the decade where we saw a bunch of things happen that were really surprising. And I can’t emphasise how surprising they are. Again, as a child, not knowing anything about biology, I kind of expected these things to potentially be true. But as an adult, knowing a lot more about the number of atoms that are working together to make us humans, it’s completely mind-blowing.

To just give one anecdote (and we can dive much more into different areas): In the 1980s and the 1990s, researchers zapped a bunch of tiny worms. These were worms that have like thousands of cells, compared to our trillions of cells. These worms have no blood, no bones. They’re just completely different from us. As big as your fingernail. They zapped them with rays that mutated them randomly. They found eventual worm mutants that lived longer — in some cases, about twofold longer than normal. And if you change the same gene [Note from LD: “Technically, a gene which functioned in the analogous pathway in mice.”] that was found in that screen in a mouse, the mouse lived longer. That is one of the most insane things I have ever heard.

Luisa Rodriguez: That is insane.

Laura Deming: Even if you cared about longevity and engineering longevity, that kind of single-gene control of lifespan and translation across the species barrier is insane. Now, I’m not arguing that that’s how we’ll live a very long time, through that single-gene type strategy. But just to give an example of what we see in the field, it shouldn’t be true. It really shouldn’t.

Luisa Rodriguez: Cool. Yeah, I do find that extremely mind-blowing already. But just to pause and stick with this fundamental question for another moment longer, I think I still am like, “What is ageing?” I have some sense that it’s things like our cells get worse at replicating, and sometimes there are diseases that cause end of life that are more likely to hit people when they’re older. But I think I still feel confused about the fundamental thing. Can you just talk a bit about what ageing is exactly?

Laura Deming: I think I can, but I want to object the question and say something else first. But I will answer your question.

Luisa Rodriguez: Sure.

Laura Deming: The thing that I want to say is I just don’t think about it that way. I mean, I do in many practical ways — you have to frame things that way in the context of drug development. But the question I care about is: What do I want to do? Like, when I’m 80, how strong do I want to be? OK, and then if I want to be that strong, how well do my muscles have to work? OK, and then if that’s true, what would they have to look like at the cellular level for that to be true? Then what do we have to do to make that happen? In my head, it’s much more about agency and what choice do I have over my health. And even if I live the same number of years, can I live as an 80-year-old running every day happily with my grandkids?

That’s much more the question in my mind than the scientific question — which is at the core of our field and very interesting, but different — of “What is ageing?” Now, the reason the “What is ageing?” question is hard is because we have a million different definitions and they’re all for different use cases. Ageing is partially programmed in many organisms that we see, and partially a random accumulation of damage. I think you can try and answer that question with: How much of it is programmed and how much of it is not programmed? You can answer it a lot of different ways.

But I really don’t care about… I mean, I care about the question — obviously a lot, with my whole life. But the question I really care about is: What do I want to be doing at what age and how well? And it’s really more of an engineering approach, almost, to then work backwards from that question to: What do we have to do to get there?

Luisa Rodriguez: Right. Just to make sure I’m totally understanding now, it’s like, I’m probably, hopefully going to live to be 80. There are a bunch of things about being 80 for many people that make their lives worse. And we’ve just accepted that those things are all going to happen to us in a way that we haven’t done for things like getting cancer when I’m 30. We’ve not accepted that we’re willing to either die prematurely or have a lower quality of life. No, we’re going to develop cures.

And so this is like, let’s not accept that we’re going to be potentially physically weaker, or even I guess that we’re going to have white hair. Let’s give ourselves the option to see if we can develop technologies that give us choices about how we spend our 80th year, and maybe our 90th and 100th.

Laura Deming: Exactly. It’s like making chronological age not a risk factor for health, essentially. It’s like if someone were smoking a lot and getting a type of cancer related to that, we might be like, well, maybe we should either try and decouple the relationship between smoking… We’d have some opinion on whether this was a good thing or not. But the fact that chronological age… it’s just rampantly ageist: we’re just like, chronological age just should lead to very much worse health. That’s the one category of risk factor that we kind of don’t care about, because it’s just how things are.

And I think there are very deep reasons why we historically have never questioned that. Because I think it’s a healthy thing to do psychologically when you can’t change it. It’s extremely healthy to have that reaction. But the problem is, when technology forces you to ask a new question, you have to face some of those biases and actually interrogate them a bit more rationally. I think that’s what’s literally occurring in society. We’re in the middle of the beginning stages of that, I think.

Luisa Rodriguez: Cool. That makes a bunch of sense to me now. When you talk about wanting to solve or end ageing, are you basically saying that you want to make humans immortal? Or is that not the thing?

Laura Deming: I would say I’m 29 now, and I started working in this field professionally when I was 12, on some level. And obviously my answer to that has completely changed over time. When I was a child, I was like, “I’m going to find the way for us all to live forever. And then my family will not die and I will be a hero, and that’s a good life.” I mean, god bless that version of myself, but it’s a very young take. Now, having seen a lot more stuff, I think I believe much more in agency over this question of how long we live and when we die.

Like, I can understand somebody who might be in a lot of pain that they feel… I can really understand and support things like DIGNITAS to the same extent that I would support longevity research. I don’t have any opinion on how long someone should live, but I do have an opinion on not accepting an evolved number of years. There’s no reason why this number of years that we currently have by default is the correct one by any parameter that we care about. It just happened to be the number of years that we got from a very different evolutionary environment than the one that we are in today.

It could plausibly be that everyone living 1,000 years is a great thing for society. Again, not claiming that we have a way to get there with current technologies, but I’m just saying there’s no reason why on the order of 70 to 80 years is like a constant, and this is the good number of years for people to live in a great society. I believe very strongly that questioning that is good.

Luisa Rodriguez: Yeah. I still hear voices in my head objecting for reasons we can get into. Something like, “But living to 1,000 will make your time on Earth less special.” I don’t know, something like that. And we can get into that, but I think your explanation does really speak to me. I feel very sold on, yeah, a life expectancy of 75 is arbitrary. It didn’t used to be 75. It used to be like 30 and then 40 and then 50. And I think it’s great that it’s 75 now and not 40. I’m glad we didn’t accept that 40 is just the natural age to die. So yeah, I feel broadly bought in. But let’s come back to some objections people might have in a second.

Staying with the basic case for this: Do you think about quantifying the benefits of reducing ageing? Is that a way you think about it, or not necessarily?

Laura Deming: In my mind, you have to understand that this has been my life for 17 years at this point — like, ever since I was a kid. So when I think about why, I wish that I could give a one-sentence, quick answer that’s my true reason for believing that. But really it’s 100 different things, and all of them feel extremely strong. So if it’s OK, I’ll just try and describe a subset of them.

Luisa Rodriguez: Great.

Laura Deming: I think the first, and the one that feels the most true to me because it was the first thing I ever felt, was just like, I think thinking about death or losing someone that you love… I mean, if I think about the strongest emotions I’ve ever felt, that’s really one of them. And I think we have a really deep human intuition about losing somebody. I think there are some deaths that might be good. Maybe someone is ready to die. They pass in a very peaceful way, and maybe there’s a human intuition that that’s good.

And I don’t actually have any disagreement with that thought, but I think many deaths are not good deaths. Many deaths involve a lot of pain and suffering at the end. One person I love is Satoshi Kon, who’s a famous animator. He made my favourite movie ever, Paprika, and he died quite young before he was able to finish his final film, which had this whole storyboard, and it may never be made — this huge, beautiful masterpiece that he was so excited to make. I don’t think that was a good death, and I don’t think that’s a death that Satoshi would have chosen for himself. And I think the grief that I feel when I consider that is a really important thing to listen to.

So again, I’m old enough now to not think that the goal here is to eliminate the concept of death from humanity. I think it’s one that we don’t know how to think about yet. But I do feel quite strongly that giving people the choice over how long they live is something that… or just kind of removing this thing that we all just have to deal with in a way that can sometimes feel quite bad is something I care about. And there’s a whole side quest there about suffering and whether it’s good or not. But I just think the idea that when you think about death, there’s something there that’s just a human intuition that’s worth listening to.

So when I was 12, that was the first thing that I think was just a guiding principle. As I got older, another thing that felt really clear to me was just that this was an area of society where there’s kind of a burgeoning thing that’s going to change here, that may be one of the most important transitions humanity has ever gone through. To be clear, I totally think that if we do some cool AI stuff, and that’s an important transition, that might be a more important one. Who knows? But I do think transitioning from limited, finite lifespans to a much more unbounded sort of feeling: to me, that’s one of the most interesting things society can do.

I think the thing that became clear to me working on this in my teens was that no one is thinking about this rationally, or almost no one is. I kind of assumed that people were when I was a kid, but I think that the technology is so new that it hasn’t really hit yet, and the reasons for changing beliefs around how likely this is going to be really haven’t hit yet. So I think often I just feel like this frantic person, trying to be like, “Hey, no, no, but really, this time something is happening that we need to pay attention to!”

So there’s just kind of this feeling of this is happening, but the more we delay it, the more bad things could happen to people who don’t get these technologies. There’s just this element of, there’s this huge thing that’s going to happen, and it’s just going to happen anyway, but we really need to be thoughtful about trying to make it happen well and happen sooner so that more people don’t suffer because they don’t have access to it.

Luisa Rodriguez: Right. Yeah. Were there other reasons?

Laura Deming: Maybe the last one, I think as I’ve gotten older, has moved to being much less of a fear-based reason — like, “Oh gosh, there’s this terrible thing that we need to avoid” — and much more excitement and possibility around the future. I would dearly love to understand as much mathematics as a Field Medalist, and I probably never will in my lifetime at the current pace. It would be so wonderful to have more time to be able to do those projects, to be able to build projects over very long timescales, to be with the ones you love and have relationships that last that long. I think it’s deeply scary on some level, but also just deeply interesting and fascinating to think about how that would feel. And there’s a sense of unbounded possibility.

Lastly: also, in game theory, I love how often a cooperative strategy is not effective if there’s some limited, finite known number of moves. But if the number of moves is unlimited and unknown, often it then switches over to be that you should be a cooperator, not a defector. And I’m very interested in how societies change in that context as well.

Luisa Rodriguez: Oh, I love that. There’s so much there. I find that just really inspiring. I know the kind of game theory that you’re talking about, and that is an extremely cool application of it that I never thought of. Just if humans have much, much, much longer lifespans, such that the gains they can get for getting multiple interactions with other humans could be much bigger because they’ve got much longer on Earth, then maybe society is just much more cooperative. Amazing.

What might the world look like if this all goes well? [00:21:57]

Luisa Rodriguez: OK, so that’s kind of the basic case, or the case that’s really compelled you. I’m wondering if you can paint a kind of realistic but optimistic vision for what it would look like for an ordinary listener, if this all goes well. So what products might come out at what times, and what impact would they have? That’s a lot of questions, so we can do them one at a time: What kinds of products should we be imagining?

Laura Deming: I can describe what I would have thought before ML stuff started kicking off, and then I would give the caveat that I have absolutely no idea what will happen in the world if that continues to progress at some rate. All of the predictions that I would make are based on timelines that don’t take those factors into account.

So the baseline prediction, in the next, let’s say, a couple of decades — aka therapies that would be available to us and would have efficacy a couple of decades out — you’re not going to see hundreds of years, a doubling of lifespan, plausibly even you won’t see decades added to life.

But there’s a couple of things that inspire me in the next few decades. One is giving people like age 50 or older just enormously more agency over their health and wellbeing. It’s very inspiring to me to think about someone starting a second career. I think folks have talked about why not get a PhD at any point in your life, or why not go become an amazing artist? Like, could Picasso arise at age 50 in a population?

I actually feel really angry about this. I think often people are like, “Older people don’t have good ideas; they’re just dumb.” The younger people somehow have a blank slate. And there’s some of that. But also, if you’re over age 50, you just have a lot more physical disabilities to deal with. Not a lot at that age, but you’re starting to feel the impact. You have to be much more mindful of your health. You can’t pull all-nighters. You have all of these just physical things going on that indeed make it much harder to come up with good new ideas and to pursue them amorously. There’s definitely maybe a blank-slate component, but also a real physical component.

So I would like to even the playing field for people of any age to have the most adventurous point of their lives, and to feel physically able to embrace that. I think there are real ways in which lack of energy can impact your ability to do great work. And it’d be really cool if, for example, everyone’s parents could have an incredible second career where they’re like your direct competitors in industry or something, or like amazing artists. So that’s one thing.

Luisa Rodriguez: Cool. I just really like the thought experiment of what would someone who is 60 years old do if they had their life as it was to that moment, but also now had the energy and physical strength of a 20-year-old. It does feel just completely different and non-obvious that what they do is retire. It seems like the world is then their oyster, and that seems amazing.

Laura Deming: Exactly. And it makes me really angry, actually, because I would never tell somebody who was physically disabled in some way that they couldn’t do something inherently. I feel actually pretty angry about us saying, “Because you’re over 50, you can’t think creatively.” I think that is also a very, very harmful and bad stereotype or something.

The other thing that I would say that’s coming in terms of ways that longevity will change the world in the next couple of decades is just social change. Like, we may plausibly have longevity drugs for dogs — as in drugs that say “lifespan extension” on the label, which we can talk about later. Those are not finally approved, but we may have those at some point in the next decade. I think we may also show for the first time that we can make drugs that make humans live longer — again, by very small amounts, but that we have control over that — in the next decade. And I think that will kind of kick off a process of social change around our approach to longevity that’s also quite interesting.

So by default, there were no huge revolutions in terms of “We’re all going to live forever; this is going to be amazing.” But in my mind, these are two things that are incredibly revolutionary, because they’re the seeds of things to come.

Luisa Rodriguez: Right. Is there anything that comes to mind to you for reasons this is super important, or ways people think about this incorrectly that we haven’t covered yet?

Laura Deming: I think there’s been, again, nothing more compelling to me than really spending a lot of time — my whole life, really — with the question of why is it that most people would not agree that this is an interesting thing to work on. And I think I just feel very passionately that the reason is not good enough. I feel very passionately that longevity should be the default kind of assumption, and that there should be really good reasons for slowing or stopping progress on things that decrease suffering or give people more agency over how long they live.

I think that this is just incredible. In my mind, there’s nothing that we care about more than these things, but we live in a society where it’s inverted — where you default think that there should be some hard limit on these things that we really care about, and that it’s bad to question this. And I just really care about a world where we invert that, and instead that you have to have a really good reason not to give people more years of healthy life.

Reasons not to work on ageing research [00:27:25]

Luisa Rodriguez: Yeah, let’s talk about some of those objections that people will have. I guess many people suppose that folks would have progressively less fulfilling lives on the margin as they lived longer, or that it would demotivate people to live forever. Sometimes people say something along the lines of, “Death gives life meaning.” And I have some part of me that has that feeling. What’s your reaction to that?

Laura Deming: Oh, yeah. I mean, I can for sure promise you that no medicine is going to give you immortality. That’s something I can 100% guarantee you. So what we’re not talking about here, which I think is maybe one of the most important distinctions to make, is eliminating death. No medicine can give you that, and that’s not on the table. What we’re talking about instead is agency over how long you live, and I guess some more agency over when you might die from natural causes. Again, the base rate of accidents equals even if medicine cured all your other problems, you’d still have to work pretty hard, and it would be a continuing process. So just to be clear: there’s no magic button that we’re going to create that’s going to fix that problem.

Luisa Rodriguez: Right. How about just this feeling less fulfilled in your 400th year relative to your 200th? I can imagine you making two arguments. One is like, well, then you can choose to die at any point; we can make that an option. Or I can imagine you making the argument that’s like, we don’t know what it’s like to live to 400. Maybe it’s actually freaking great, and assuming that we’re going to be bored with life by 400 is assuming something that we just really can’t know.

Laura Deming: Yeah. I feel like there’s the answer I should give, and there’s the answer I want to give.

The answer that I feel like I should give is kind of what you said: if you don’t like it, then you don’t have to stick around, but also probably good to have the option. I think an answer that I should give is that that’s not a good enough reason, frankly: that might be true for you, that one might be a little bit bored, but that is absolutely not a good enough reason not to develop medicines that could save lives. It just definitely doesn’t even begin to pass the cut.

So if you want to make an argument against that, or against spending a lot of time and energy doing that, the reason needs to be a lot better than “We might be a bit bored of society.” I take that very seriously, to be clear. I think even living to age 30 is actually difficult. There’s a lot of stuff you go through in life, and life is hard, but I just think we’re not going to stop medical progress because of these specific… I don’t think they’re good enough objections.

But then the other thing I want to say is just like, I totally empathise with that point of view. Again, even living a normal lifespan, you encounter grief and hardship and boredom, and these things are all part of our experience. But I just want to be optimistic about the idea that you can grow, and the idea that there’s so much to explore and so much to see, and that we should try to make a world that we would want to live in. I can’t argue that life is worth living, but I can say that I think we should try to make it worth living and to act towards that. And I think this is in line with that value. So it’s like, can you fix all social problems? Totally not. But should you try, and should you act as though you perhaps can go in that direction? I just personally believe that you should.

Luisa Rodriguez: Yeah, I find that really compelling. Turning to another objection: some people might have environmental concerns about a growing population, if we stopped dying at the rate we do now. How much does that worry you, personally?

Laura Deming: I think there’s a lot of population stuff that is going to be an issue if we have longevity technology or not on some level. We really don’t know how reproduction rates would change, whether they would drop dramatically. And you do, I think, see that trend a lot. Maybe we would prefer to have more young people than older people.

This is something that I think about a lot. But personally, having tried to work on a hard problem for 17 years, this has really been something that’s taken a while. I’m just like, you really don’t know how to solve things until you try, but you really shouldn’t just assume that you can’t find a good way to address a problem.

And in this context, let’s say we stayed on this planet forever, I really think there are a lot of ways that technology can help us think about how to solve these problems. Again, they are very complicated and difficult and the technology is bad, but there’s definitely no reason why… I think the reason is still not good enough. To me, I’m thinking about someone that I love, like someone in my family, and I’m like, the reason for me not to try everything that I can to help give them this… The idea of a problem that we’re not sure that we can solve, but we might be able to, in my mind, that’s just something that we have to try and figure out.

I feel really passionately that I wouldn’t withhold a medicine from somebody that I love because of the potential of the future problem that we think is quite difficult but isn’t obviously insolvable. While at the same time, I acknowledge that maybe the world will be overall worse if we try to do this. I really, having worked on a hard problem for 17 years, know how hard it is to even solve that problem. And I think what you’re talking about on a social level is a much larger problem.

Luisa Rodriguez: Yeah, it makes a lot of sense to me. It’s just like, again, there’s a very naturally instinctive feeling about this particular medical intervention that’s extending life. But like you said, we don’t not try to save people’s lives. Right now, if someone is 30 and has cancer, we try to save them, even if that is going to mean the population continues to grow and then we have to solve population growth somehow.

Laura Deming: Yeah. I think the answer that I should give is that there are probably technical solutions to a lot of the problems that people pose. And I think it’s very plausible that we can address them in ways that make society better. But the answer that I feel is honest is just that I think we should fight for every life that doesn’t want to go. I mean, I just really feel it quite strongly, and there’s nothing that I’ve ever… That’s a core value that I guess I have personally, and I think everyone deserves to live in the way that they want. I just think it’s such a core human thing.

Luisa Rodriguez: Yeah, I think that lands really well with me, and I imagine it will land well with others.

Maybe this one’s a bit out of left field, but another objection you might encounter, at least in some circles, is that you might not actually think that humans will remain biological, fleshy humans for so long — if we develop the capability to upload our brains and live as digital people, for example — so anti-ageing technology might become obsolete relatively fast. Does that sound plausible to you? Does that sound like a reason not to work on this?

Laura Deming: Oh, yeah. In the past couple of years I spent a lot of time grappling with these questions personally. Because it’s a real question, right? If that were true, I’d just be like, “Great. I guess those guys will figure it out. We’re good on the biology.” Biology is pretty hard, so no reason to keep working on it, unless for fun, if you don’t have to.

But I think the core problem for me is you’ve really got to be sure. I think as humans, we have this feeling that continuous identity is pretty great. A lot of our beliefs in everything is kind of built around that as a core — and everything that deviates from that, you kind of have to be pretty sure of a philosophical position to commit to it. So let’s say I did destructive uploading, and maybe I’m like 99% sure — but just in case there’s some reality to continuity of consciousness that we just hadn’t philosophically figured out yet, I’d really hate to give up the ghost before we’d done that.

So, in my mind, longevity is always this thing of “just in case”: maybe before we make all these transitions, we should just live long enough that we can get philosophically wise enough that we can figure a lot of this stuff out — and then, heck, why not do whatever? But am I going to commit to a theory of consciousness now? Definitely a lot of people might be, but I certainly wouldn’t. I think there’s a question of, What is humanity? What are we as humans? What’s special about us? We have no idea what the answer to that is. And so it’s just like, why not stick around long enough to figure that out before you make a big transition?

Luisa Rodriguez: So just to make sure that everyone can follow, is the idea there in particular that, for example, if we did develop what we thought was the capability to upload brains, some people think that uploading your brain to something digital would be in some ways not a stable transition from you, as you are now, to something that’s also you, but like, whatever in the cloud. Is that the worry? And you’re like, “Maybe it will be me, and maybe I’ll feel like me, and maybe I’ll just go on living my life, but I won’t have a body that sometimes breaks. But I don’t want to bet my life or many other people’s lives on that being the way philosophy turns out.”

Laura Deming: Yeah. I can give more of a framework for the different approaches before stating that view again. Basically, the question of longevity is related to the question of what you care about preserving. And I’d say most people in society default believe that something about some continuity of consciousness is important. The idea of sleeping sometimes makes this a question, or the idea of anaesthesia can kind of question what do we really mean by that, but there’s something about the continuity of consciousness. Like, I just want to keep existing as me. That seems to be what most people care about.

There is a subset of other people — who are maybe either Buddhist, or really into uploading or some other way of thinking about just information as identity — who might say, “I really just care about what I would do otherwise still existing, or the information that I am still existing and propagating.” This kind of comes back to the Parfit thought experiment of: If I could make a copy of myself that went to Mars, because I want to go to Mars, but I’d have to kill my current self immediately after I made that copy, would I do that? And these are people who would say, yes, they would do that.

Luisa Rodriguez: Yeah, this is one of my favourite thought experiments.

Laura Deming: Exactly. And it’s actually interesting: I think personally I’ve flipped to kind of be more in that camp. I used to be very much in the former camp. So it’s been weird working on longevity and being like, well, but maybe it’s just the continuity thing is not so important.

And then the last thing is people who are maybe in between, where they think, “OK, maybe we could upload ourselves, but there’s some continuity that we think is still important. So if we could, let’s say, gradually swap out neurons with cyber components, or just very gradually kind of transition our brains, there’s something about the continuity there that’s important to preserving something.”

Again, I’m not an expert in this field, but those are different ways that you can think about what you want to preserve. Now, the reason that I still work in longevity, literally, even though I’ve switched over to default believing that I would do the Parfit thought experiment, is just in case. I don’t know. I’m 29, have been thinking about this for a couple of years, decided this thing might be true — but would I want this version of myself to make that decision? Or a much older version of myself who had some more time to think about the question? These are really big things to commit your life to. And I think it kind of seems like one might be true, but we’re not really sure.

Luisa Rodriguez: Yeah, it’s one thing for me to be like, this is a fun thought experiment. I feel like I would totally… I don’t know. If you told me that yes, it’s guaranteed that when you make a copy of yourself on Mars, all of the memories, all of the preferences I have are all going to be copied so perfectly that I feel like I am just exactly myself on Mars… It’s one thing to think about that thought experiment and be like, “Yeah, I’m pretty sure that will just feel like basically me waking up, or maybe I just won’t even notice. And I’m fine letting my Earth-self die if that’s what has to happen to make that copy.” It’s another thing to be like, “I’m going to decide not to pursue research that will help end ageing for human physical bodies, because I think probably that kind of philosophy experiment is plausible and shakes out that way, and my personal view is that I think maybe I would still be myself.”

Laura Deming: Yeah. What I would say is, if no one was working on uploading, I would be sad for sure. But I think the allocation of effort is kind of… Maybe the uploading folks would hate me for saying this, but I think it’s a little bit of an easier problem than keeping 10²⁷ atoms roughly in the correct configuration over hundreds of years. So I’m kind of fine with spending a lot of time on the latter still, even given uploading, because I think that it’s the default safest thing to do — and then maybe once you’re really sure, you can do the other thing.

Luisa Rodriguez: Right. OK, another objection: AI and ML advances might help us figure out much faster ways to do scientific research. Should we just focus on AI for now and defer applications like anti-ageing research to a time when AI can just do most of the work?

Laura Deming: Yeah. Welcome to my life. There was a period in the last couple of years where I was thinking about this every day. And I think there’s always a question of, are you doing something just because of sunk cost? And to be honest, working in this field is extremely hard. So maybe it’s like, it’d be great to take a vacation from it

But I think there’s a couple of things. There’s a lot of questions about what’s going on in the human existence, and what is it about this thing that we think we want to preserve, that we have no clue about. And I think there’s a world where we just never answer those questions, and skip over them, and then maybe lose some of the most important things that we treasure as humans. Maybe AI systems will take over everything and then have some objective value function that determines what happens. But at least to the degree at which society still matters in that world, I think society really needs to get on board with what happens here for it to happen.

And I think 90% of the battle of longevity is actually social — just kind of changing an old perception that’s just about to be updated. I think that really individuals matter a lot to that right now. It kind of feels like we’re at the beginning stages of, like, IVF — where maybe a few people made a big difference to women’s reproductive health down the line. But would an AI system care that much about a woman’s reproductive system? These are human values that we’re figuring out. It’s really the case that I think the people who build the most important companies in this space, or research projects in this space in the next decades, will determine a lot about how society looks in this respect, even independent of ML progress.

Luisa Rodriguez: OK, let’s move to what I suspect is people’s biggest objection to anti-ageing work, which is that they think that nothing useful can be done, and ageing is just an inevitable part of life. Why do you believe it’s technically feasible?

Laura Deming: I’m just going to give a long answer to this question, because in my mind, this is one of the biggest things.

So number one, just to kind of set the stage: when I was a kid, one of the things that convinced me that this was a plausible thing to work on was I used to believe that everyone lived to be exactly the same age. Like, I used to think that everyone lived to be 10 years old, and then they all died at exactly 10 years old. Because obviously there must be some order to the world, right? There’s some reason why we all died at a certain age. I remember being so shocked to learn that actually people die at different ages, and that also we do not know why.

At its heart, this kind of illustrates, you know, again, if everyone lived exactly some amount of time and then died at exactly the same time, maybe I’d be a little bit less convinced that this was a plausible parameter to vary. But this is already a variable parameter in various research in genetics and environment — so proof positive, genetics and environment do determine to some extent how long we live, number one. And environment is something that, again, we could change.

Then number two: we are just some number of atoms that need to be in the correct configuration. And that’s an argument that only works on universal timescales. Maybe we can’t change all those atoms, but it’s just that there’s no physical reason why it’s not possible.

And then number three: we’ve made mice live like 60% longer than normal with single genetic mutations That’s one of the most mind-blowing things I’ve ever heard in all of biology. And nothing that you could have ever said to convince me theoretically — before that empirical discovery — as someone in biology, would have ever convinced me that was true before seeing that fact. So just factually, stuff is happening that we have no idea what it is, but it’s like lifespan is just really easy to change in a lot of animals.

I think the core thing that people are asking when they ask that is like, “Great, so we can change it a bit today, but do we have the tools to live a lot longer?” And the answer is: heck no, we definitely do not have those tools today. Those are the things that we’re trying to build. And by default, I think progress on biology might result in those tools in hundreds of years — again, excepting progress in ML — but that’s not nothing. And I think that the more that we irrationally allocate effort today, the less that we’ll have those tools quickly in the future. So it still really matters to get things right today.

Luisa Rodriguez: Yeah. The last point about the fact that we can actually already influence lifespan in a number of animals is the thing I personally found most mind-blowing when looking into this. I actually think most people don’t know that we can influence lifespan a little bit in some animals. So maybe we could talk about that a bit.

Things that make mice live longer [00:44:12]

Luisa Rodriguez: On your website, you have this incredible list of 95 things that make mice live longer — quite a lot longer, in some cases.¹ I want to mention a few of them, so that people get the idea that not only do some of these increase lifespan significantly, but some of them are also drugs already approved for use in humans for various diseases today.

So for example, removing senescent cells increases mice lifespan [to] 135%. Could you say more about that — what are senescent cells and what removing them entails?

Laura Deming: Sure. I would say this is a field that we don’t yet know translates to humans, so we don’t yet know if this work will be relevant to humans. And also, I think there’s a lot of caveats around the work that’s been done in mice. I’m just caveatting because you want to do that when you’re a scientist.

But basically, a subset of your cells might accumulate quite a bit more damage, or have very specific phenotypes that are bad with age. And they seem to both themselves not be quite healthy enough, but maybe also make the environment around them a little bit unhealthy. If you just target these cells in particular, and eliminate them with genetic tools in mice, you can make the mice a lot healthier during an aged part of life.²

Honestly, these results were very surprising to me. Like, the first results in this field were in accelerated aged mice — so mice that were artificially aged — and I was like, “OK, fine. Whatever. Maybe that works there, but it won’t translate.” And you just keep seeing, I think, benefits. There’s a lot of caveats to this. I think this feels like working out how important senescent cells are in human-relevant indications. So we still don’t know how important they are there.

But this is a weird one, where ageing keeps doing these things, where no one is like, “This should work.” Everyone is like, “This is the weirdest thing that should work.” To give an example — which I think everyone is talking about now, so probably a lot of your listeners actually have heard of this one: more recently, this lab expressed a set of factors which kind of cause cancer³ sometimes and reprogram cells in a very extreme way, just cyclically in mice, and allowed them to have these health benefits. Just stuff that no one in their right mind would look at and be like, “Yes, that’s probably going to result in longer-lived, healthy mice,” seems to affect ageing in ways that we really wouldn’t have expected.⁴

I’m just trying to say, look, no one is arguing that from first principles, you should believe that eliminating old cells, or reprogramming cells developmentally, across the whole mouse in a really extreme way is going to make them live longer. But just weirdly, when we try crazy stuff like this, it seems to actually work some subset of the time. And again, no claim it’ll translate to humans. But again, this is empirical data. I’m always like, this is weird that it’s happening, and I don’t believe these results; it just shouldn’t be true that this is working.

Luisa Rodriguez: Right. But it’s this proof of concept. Whether or not it actually works in humans, it’s like lifespan is actually just a malleable thing. And when we poke around with some things that seem to be associated with lifespan, sometimes they actually just affect lifespan. And that’s insane.

Laura Deming: Exactly. And there are use studies⁵ where you can just mutate a fraction of genes in an organism: yes, some of them just make the thing live longer. It’s not actually that hard to find genes that, if you change them, make an organism live longer.

Again, this doesn’t mean that they’re going to live unbounded longer; it doesn’t mean immortality or like thousands of years. But lifespan is really not that hard to change as a parameter, just empirically.

Luisa Rodriguez: Yeah, I want to drive that home by going through a few more examples. So, giving mice the drugs rapamycin and metformin increases their lifespan [to] 110% and 106%, respectively. And I think these are drugs that are approved for humans. Do we have any idea why these increase lifespan in mice?

Laura Deming: Oh, we have a bunch of theories. We have theories out the wazoo. But this is just like some guy went to the island of Rapa Nui, dug up some soil, found this compound rapamycin. Randomly, it was kind of associated with pathways that caused longevity and increased lifespan. And there’s so many different reasons why that I could say buzzwords for, but my personal opinion is that we really don’t know yet.

Basically, there seem to be a few central genetic axes or pathways that a lot of these treatments hit. For example, I mentioned a worm mutation that’s kind of on the insulin IGF-1 axis. It was discovered in worms. That translated to mice, also works in flies. And that’s just a central genetic pathway that maybe a bunch of different things impinge on it. In a similar way, there’s something around mTOR and nutrient sensing that we think is kind of a central pathway that a lot of things are impinging on. So I think typically we want to be able to try to group these interventions into categories — but I would make no claim that we understand how they work in some really fundamental way.

Luisa Rodriguez: OK, and we’re actually going to talk about how some of those groups of pathways that we’ve learned over time do seem really related to ageing, and that maybe we can affect through different technologies or through different drugs.

But maybe just a few more examples before we get there. Do you have a personal favourite example from the list? Is there a particular thing that has increased lifespan in some animal that has stuck with you?

Laura Deming: I think this might be on the list. Methionine restriction is really interesting to me.⁶ I think a lot of people have heard of the idea of caloric restriction — where you eat less — quite a bit less; often like 30% less than you would normally — and get a corresponding increase in lifespan. This is actually the opposite of what I think people originally expected to see. They expected that you’d eat less and you’d be more unhealthy. But what’s interesting is you can also just try and restrict specific components of diet and get maybe a similar effect. I’m not sure if the effect is actually that same magnitude. But let’s say you just restrict one amino acid — like methionine, for example, which is at the beginning of all proteins, I think — you see a quite large increase in lifespan just from that as well.

So I’m very fascinated by this question of: if we could just make little enzymes that shoot up the methionine in our food, would we be able to eat quite a bit, but also have the benefit? I don’t think it’s a plausible thing to do, but it’s a very interesting finding that it might not actually be as much the total number of calories you eat as the dietary components. But again, this is an evolving field, and what I’m saying might not be something that everyone would agree with.

Luisa Rodriguez: Sure. But it does seem true that reducing that particular part of a protein does have this lifespan-increasing effect. That part is somewhat studied. Maybe it’s not robustly studied, but there’s some evidence for it.

Laura Deming: Yeah. And it is where the frustration comes in if you’re in the field, because a lot of people will be like, “Caloric restriction doesn’t count, because you’re just decreasing the total amount of stuff the organism does. And so it’s just kind of a normal…” But then you look at a lot of what’s going on, and it’s like, no, this is a very complex pathway that’s responding to changes in nutrient content and doing a lot of very complex things. So it’s not like we’re just slowing everything down.

I mean, I think you can make that argument, for example, maybe with temperature. It’s actually interesting in worms: if you increase temperature, they live a bit shorter; if you decrease temperature, they live a little bit longer. So it’s like they’re literally slowing stuff down. Literally, that is what is happening.

Luisa Rodriguez: Wow.

Laura Deming: There’s just all this weird stuff where I think people tend to have very simplistic ideas — where it’s like it’s just something where we’re slowing down some overall metabolic rate, and that explains all of the longevity stuff, so therefore it’s all kind of under the same umbrella and not that important. But I really want to argue for: no, there’s an incredibly complex set of pathways that are responding here, that are being tapped into when you see these effects. Again, just increasing the wonder factor of that this works at all is quite unbelievable.

Luisa Rodriguez: Cool. Just to make sure I understand: when you decrease calories, some organisms seem to live longer. And to echo what you’ve already said, that’s surprising, because I think the original study was like, “Let’s see if, when you starve mice, they die earlier. That’s kind of interesting because some people don’t have enough to eat. So let’s see what the health effects of that are.” And then, to their surprise, mice actually lived longer. And that was in itself just a very surprising result.

Then the objection is that that’s just because, the thing I’m picturing is like if you were to slow your heart down, you’d get the same number of heartbeats over your lifetime, but you’d be able to do fewer things because you’d be constricted by a heart that couldn’t speed up to run or something. The basic idea is you’re just slowing down all of the processes in a body by giving it less food — and that does prolong life, but that’s not a very useful or exciting prolonging of life, because the mouse is just going to be sitting around conserving calories because it’s starving. Is that kind of the objection?

Laura Deming: Yeah. Well, I think also people are kind of like, “I can see why that’s true.” Or they’re like, “That’s kind of obvious to me why it would be true.” I want to be like, no, your body is a robot. Literally, when you look at cells, and you look at what’s in cells, it’s a bunch of tiny little robots running around. And this is what you’re built of, and they’re all working together in this really complex way to cause these effects. It’s not as simple as you would think.

Luisa Rodriguez: Right.

Laura Deming: But one last point that I want to make, because I think it’s important for folks to understand, is what we’re talking about with all of this — everything on my website, everything we’re talking about — this is not going to get us to thousands of years, et cetera. What we’re talking about are the only things that we know about now that in the next couple of decades could get us the first longevity therapy.

But the point is that there’s a bunch of other stuff that we’re not talking about, because it’s way crazier and hard to reason about. The things we’re talking about, they’re just kind of proof points that this is plausible at all, that I think are very surprising. I don’t want to imply that they are the things that will get us a lot more years of life. They’re just the only things on the table for the next couple of decades right now.

Luisa Rodriguez: Yeah. OK, so we’re not going to live to 400 by restricting our calories, but it’s evidence that, again, lifespan is malleable.

Laura Deming: Right. Maybe to state the point as clearly as I can: no one is arguing that we’re going to live to 200 with small molecules targeting single genes. It’s just insane that that’s even on the table, that we’re even talking about that even for a couple of years of life. That that’s a strategy we could use blows my mind.

Parabiosis, changing the brain, and organ replacement can increase lifespan [00:54:25]

Luisa Rodriguez: Cool. Yeah. Let’s pivot from that, actually, to talking more about the science behind this research. You’ve written about nine major areas of ageing research. And we’ve got time to talk about some of them, but not all of them — but because I just find the list so mind-blowing already, I wanted to list the things that we’re not going to talk about, so that if anyone’s interested, they can go read up on them.

We’ve already talked about caloric restriction, but basically a range of evidence suggests that eating less in a variety of ways can make you live longer.

• There’s insulin, or insulin-like growth factor, because apparently genetic pathways related to growth and insulin signalling are linked to ageing.
• Autophagy is a thing I’ve never heard about, but it’s apparently the part of the cell that recycles all of the waste and junk that accumulates within a cell. That deteriorates with age, and so helping that system do its job better might increase lifespan.
• The reproductive system apparently is involved. It sounds like removing the ability to reproduce can increase lifespan. For example, removing a worm’s gonads can increase lifespan by 60%, which is mind-blowing.
• Mitochondria might be related. These are the powerhouses of the cell, and apparently mitochondrial mutations impact lifespan.
• And then finally, a thing that I don’t totally understand called “sirtuins” add tags to the structural protein balls that DNA wraps around. And apparently these regulate ageing.

And I would love to talk about every single one of those, because they are fascinating, but that would take hours and hours and hours, or days. So a few that I found particularly interesting were parabiosis, changing the brain itself, and actually, if there are any of the things that we’ve already talked about that you think are super interesting, we could talk about that as well.

Luisa Rodriguez: But maybe we start with parabiosis, which is where you literally join together two organisms — in the case of ageing research, usually two organisms of different ages — so that they share their circulatory systems, so all their blood kind of flows out of one, into the other, and then back again. What’s interesting about parabiosis for ageing research?

Laura Deming: This is the one that always is like the lightning rod of the field, I would say. I think of all the things that I would bet are going to be a huge deal, it’s not in my top 10 to be. Or, it’s no longer.

Luisa Rodriguez: Oh, OK. Interesting.

Laura Deming: Just to give an example of the kind of crazy stuff that you see showing up in longevity: if you take two mice, and you stitch together their vasculature between an old mouse and young mouse — such as they’re just kind of frankensteined onto each other — you see health benefits in many ways to the older mouse, and in some ways, health problems in the younger mouse. Just thinking about that for five minutes, it’s like, number one, who came up with that experiment? And then number two, the fact that that works at all — and that’s despite the fact that these mice are sutured together; like, their sides are kind of connected, so you can imagine there’s a lot of health problems that come along with that — is quite surprising.

And I’m not an expert in this field — or any of these fields, really — but I think you can see a little bit of a similar effect from just plasma injection. So even if you don’t suture together the two mice, I think you can still see some positive benefit from just plasma injection.

There’s a way of talking about this field that’s very fun. But there’s something I really want to say, which is just that I now view it very differently: I have a very different frame of thinking about it, which is all about interventions and what we can do. I think what you see in that list, and what a lot of ageing literature is about, is just all the different data points of areas that we can maybe explore. But then pragmatically, if you want to do something in the field, I think it’s all about the tools that we have at our disposal to affect human biology.

So from that lens, there’s a couple of different frames that I want to mention. One is length scale. As humans, we’re maybe on a metre length scale. And there’s this question of what length scale are you intervening at, and how many tools do we have to do that well? You can maybe jump the length scale down like five orders of magnitude to a cell, and think about replacing cells, or making things that target cells, that overall just change cell state. You can think about going to a protein and trying to find things that either make a protein better or make it do something in a cell.

But really the exciting thing about modern biology is how many more tools we have to do this, which I think is the number one contributor to our ability to make any kind of progress towards human therapeutics at all, compared to 10 years ago. Because you have to understand, when you look at these mouse studies, we can do all sorts of things with mice that we are absolutely not going to do with humans anytime soon. We can change their genes, every cell in their body from birth. And often, if you look at these studies, that’s what you’re doing. There are a few where you’re giving drugs, but often you’re just changing genes and cells.

But in humans, it’s all about what can you do? And really, we’re in a completely unprecedented, exciting time. Because for most of our human existence, we were just like grinding up plants, and then that’s what we had to give somebody. Then we figured out how to get chemicals to be more sort of pure. In the ’70s, we started being able to take proteins and have bacteria make them and then use those proteins as therapies. And they’re enormous. You go from like a 100-atom molecule to a 100,000-atom molecule. You can sure as heck do a lot more with that huge thing, which really is a robot. If you really think about what you’re looking at there, it’s like this huge robot. And now, we can take whole cells, program them with extraordinarily complex mechanisms, and inject them into people and expect them to do things like, for example, go after cancers. Oh my gosh, that’s amazing. We can repurpose viruses.

So the point I want to make is that I think there’s a really fun way to go through ageing literature — which I enjoy and love — which is spending a lot of time on all these data points that we have. Then when you switch over to the question of, “What are we going to do?,” the thing that I spend a lot of time, most of my time, actually, feeling really excited about, is just the number of tools at our disposal for changing human biology — many of which are only on market or in the clinic as of the past couple of decades, and only really plausible to work on, like gene therapy in a really general way, much more recently. Like you see companies assuming that gene therapies will work for certain tissues now getting started: that would have been laughed out of the room decades ago.

And so I think that’s the heart of, when you’re an operator in this field, trying to make drugs, like what you spend most of your time kind of focused on. And then the question becomes, OK, of all the different genes that have been screened in longevity on this list, can I just pick three? You do a lot of thinking about the biology, but you really have to have a modality that you could use to apply that — because you can’t just take a gene and make it different in every cell in the human body from scratch in a human. Yet. Or anytime in the next decade, probably.

Luisa Rodriguez: OK, let’s talk about changing the brain itself. What does changing the brain have to do with ageing? How can it help?

Laura Deming: Again, I want to be clear that I cite a lot of papers that I’d say are really exciting, but I think this is a field that’s still very young. Again, scientist caveat: none of what I’m saying will obviously translate to humans with 100% certainty. There’s just some genes that we’ve discovered, generally, you have this story that this gene is helping an organism live longer, or the protein that it makes by doing something in every cell in your body that’s helping every cell. So this is pretty good. And it’s just kind of weird when sometimes you only express it in the brain or knock it out, and that also increases lifespan. It kind of makes sense, because maybe the brain is some limiter, but it’s just kind of weird.

There’s also ways in which, for example, the brain can regulate temperature, and if you just change the brain to do that, then you get maybe a little bit of extra licence. I just always thought that was so weird and interesting. How much is your brain telling your body how long it can live? Obviously not 100%, but there’s definitely a nontrivial amount where you can do brain-specific things. There were a lot of papers a while ago that were doing brain-specific knockouts of certain genes and seeing effects. And again, this might just be due to things being secreted or like signal that are causing specific effects. But the fact that there is some systemic kind of signal, or way in which the brain is controlling longevity, is really interesting. It is just super interesting.

Luisa Rodriguez: Yeah, the fact that if you try to convince the brain that the temperature is actually higher or lower than it is, that that affects longevity… So it’s not like a physical thing, where heat or cold negatively affect cells in your body. It’s just like your brain is like, “Depending how hot or cold it is, I’m going to decide to send signals that translate to me living less long or longer,” which is just really weird. Do you think that this is a promising area? Would you be excited about interventions that try to convince your brain of something that seems to make it tell the body to live longer or less long?

Laura Deming: Well, again, this comes back to rubber meets the road in drug development. If I had to convince all the cells of any organ to do something, I sure as heck would not probably pick the brain because you have to get therapy in there. If you were saying the liver, I’d be like, oh my god, yes please. If we can just convince the liver of something with a given therapy, I’m all over that. But the brain is a very tricky beast. This could change in the future. So no, actually, I would prefer not to have to convince the brain of something if I can. I would prefer literally any other organ, probably, than the brain.⁷ Maybe there’s an exception to that, but yeah.

But biologically, it’s very interesting. And so maybe what you could ask is: is the brain secreting something or causing to be secreted or signalled that I can mimic or create that will recreate that effect? Without having to actually recreate what happened in this experiment — which is to change a single gene in all the cells of the brain from birth in a mouse model.

Luisa Rodriguez: Right. Are there any research areas or these categories that we haven’t talked about yet that you think are especially interesting?

Laura Deming: It’s a good question. There’s a whole category that’s hard to talk about, because I think no one in the field has any idea how it will play out or work, which is this idea of, can you replace whole organs? Like, if an organ is so old, can you replace it with a younger version? And that’s a way to help. And it’s not at all feasible, I think, in some sense today to do that broadly, because there’s a lot of complications in organ transplant, et cetera. But I just want to flag that it’s insane that organ transplant is a thing that exists. We take organs from someone who has passed, and just put them into somebody else. The fact that as a medical procedure works at all always blows my mind.

So there’s enough complications now that it’s not an actually good intervention. But I think everyone in the field sometimes is just like, “We’re doing all this complicated biology with small molecules and proteins and all these metabolic pathways. What if we could just swap it out?”

Luisa Rodriguez: Right.

Laura Deming: And it’s not clear that you can’t. It’s just, I think, figuring out how to deal with the immune consequences of that. It’s quite unclear how to do that well. Obviously, the brain, you can’t swap that one out, probably. There would be other places in you that determine identity. How would you do that? It’s a whole separate question.

Luisa Rodriguez: That’s a fun one.

Laura Deming: But that’s an interesting one. Yeah.

Luisa Rodriguez: OK, cool. So the idea is like, we’ve talked about a lot of tiny, small things — like taking out cells that are especially old and struggling to replicate as they should — but one idea is just to go more macro, and be like, there are a bunch of damaged cells in the liver. We do liver transplants for people whose livers are failing when they’re younger. We could just take a young person’s liver, put it in an older person, and that solves all of the problems that came with ageing for that person.

So there are all these pathways. They’re all kind of unique and mind-blowing. I’m curious if we’re going to get far just by doing a bunch of individual therapies like this, where each one makes people live, I don’t know, a couple of years longer? Or do we need some very comprehensive package to avoid only stopping the ageing processes, and then people just die in a different way?

Laura Deming: This is the thing I would just continue to say: I think any one small molecule or protein therapy is maybe going to get you a couple of years max. I think a decade would be amazing. But again, I’ve been a grump about a lot of stuff, and I get surprised by a lot of stuff, but that would be amazing.

One last thing I’d say also — which is a recent thing that I’ve been a huge grump about, and really thought was dumb for the longest time, but I guess I see the rationale a bit more now than I used to — is this idea that I mentioned previously of reprogramming all your cells, or at least partially reprogramming them. If you think about it, old people create kids who are young. What? What is going on there? This tiny cell that was in this older person is really young, and then it just keeps happening. And so there’s like this immortal lineage of cells that have been doing that since billions of years ago. So what’s up with that? And is that something that we can take advantage of to then have all of our cells rejuvenate?

Now, there’s a question, there’s a caveat there, where I’m always like, well, but what if the cell just divides a lot? The damage just aggregates. So this is a question I have about how much we can really localise that to one cell, versus spread across a bunch of cells. But that said, that’s an area that I’ve been a huge grump about, but I think I’m kind of coming around on a little bit.

Luisa Rodriguez: Cool. So the fact that human bodies, or many animals’ bodies, have just kind of solved the problem of specific cells decaying over time is amazing. And we can just try to learn how it’s done that for reproductive cells, and then see if there’s anything applicable in other areas of the body?

Laura Deming: Exactly. If there are these factors that professionally turn cells into very young cells — that have been chugging along for essentially as long as humans have been around, successfully — gosh, maybe we should take advantage of that. And isn’t that interesting that there’s this proof point that that’s happened for so long? It just kind of makes you really change your perspective, I think, about what’s plausible in longevity in a way.

Luisa Rodriguez: Yeah, that’s a great point. So you seem to come at this whole project from a very kind of engineering mindset, where you see the human body as a bunch of systems, and you just kind of want to tinker with them and make them more robust and kind of replace the faulty parts so that they last longer. Is that kind of right? Do you want to say more about that?

Laura Deming: Yeah. I would say the way I think about the field is that there’s these two really beautiful things, and they’re coming together for the first time. So it’s like this really fun synthesis of two different points of view, and often people will fall into one camp or the other.

The first camp is like there’s something jiggly: we poke at it, we see if it lives longer, and then whatever we poked, we’ll just investigate that enough to translate to humans. And that’s honestly most of the field to date. I think that’s kind of how most of the scientific community thinks about things.

And there’s this other perspective which is like, wow, the human body is like 10²⁷, 10²⁸ atoms. Let’s go figure out what a healthy configuration of those looks like, and then try and change systems at whatever level we can in terms of our tools in order to get towards that configuration. And obviously, it’s not possible to literally have a map of those atoms and hold that configuration in your mind. But I think it’s quite a powerful point of view that really, this is a physically determined system, and you can really think about it. It’s not possible to think about biology logically in many ways, but it is in a few ways, and you should sure as heck try and reason from those.

I think really in this century, in biology, is these two points of view kind of converging. I mean, we can actually look at a cell and see a lot of things in it directly. We can directly digitise blocks of matter, like nanoscale resolution — which is totally extraordinary and a very recent thing. So it’s sort of like, for the first time, we can actually look at the systems that we’re trying to change, and that just gives us a much more granular picture. And this is a century where I think we’re integrating these two points of view.

Luisa Rodriguez: Yeah. That is exciting and inspiring. I’m curious, why do you think biology is mostly so illogical, and why is this an exception? Why is this a place where we get to look at it logically?

Laura Deming: I think there’s two points of view on this. One is that there might be beautiful general laws of nature, kind of like Newton’s laws. I always love thinking about this: are there Newton’s laws for biology that we could find? We definitely have not found those yet, if they’re there. So there’s a few laws that we can kind of hold in our heads, that give us simple, beautiful ways to reason about these systems. That said, physics exists, has done a bunch of really cool stuff, figuring out how atoms move.

And again, this is the first century that we’re entering where we actually can look at the stuff that we’re trying to solve. When I grew up, reading biology textbooks was always very confusing, like shapes and triangles that were bumping together, and somehow they’re supposed to tell me how a cell worked. But instead, now when one thinks about biology, it’s like one thinks about floating in a cell surrounded by 10¹³ molecules that are jiggling around.⁸ And you can see the exact protein structures, because we actually know what they look like in many cases. And this just gives you a very different perspective on how to reason about these systems.

I can’t tell you what small molecule will cure Alzheimer’s, but I can tell you that if I have a protein, I can literally imagine the shape of the protein in one’s head, or look at it on a screen, and then think about what a lock and key might look like for that protein, and then actually just test whether that works. And that’s a very satisfying action to be able to take.⁹

Big wins the field of ageing research [01:11:40]

Luisa Rodriguez: Cool. Yeah, that’s amazing. I want to come back to some of the particular new technologies that we have that make that kind of stuff more possible than it’s ever been.

But first, I want to zoom out and just talk about the state of the ageing field: how things are going so far, and what the main bottlenecks are. Just to start kind of open-ended, is there a big scientific win that we’ve had in the last few years that is already public so that you can talk about?

Laura Deming: It’s a great question. I think there’s two big wins that we’ve had recently — with the caveats that we’re still seeing how these will play out, and we definitely don’t know how they’ll impact human health yet.

So one that I’ve been pretty resistant to, but I think I’m coming around on is reprogramming — which is just this idea that an old person can create a young child, and whatever biological process helps cells do that is something that we can take advantage of for human health. Again, we have no human therapeutics that really do this, and there’s a lot of reasons why it might not translate, but it’s just weird and cool that in mice, we can just turn this pathway on and see that they have age-related health benefits. This is just a weird and cool thing that I think the field is starting to metabolise.

Then the other would be a regulatory breakthrough, which is the first acceptance of efficacy data for a lifespan-extension drug in dogs that just occurred a couple of weeks ago. I really can’t emphasise how exciting this is. Again, this is not an approved drug: there’s still safety, manufacturing. And once the drug is approved, it’ll need to go through a conditional confirmatory trial. So there’s all these many ways in which the drug still needs to jump some hurdles, and those hurdles could definitely fail. But it’s extremely exciting that the regulatory bodies are even considering this kind of pathway. So I think the field is just kind of starting to metabolise that as well.

Luisa Rodriguez: That’s amazing. So the concept is reprogramming, and it’s basically an old person can produce a young child, and there’s some way in which you can tap into that pathway to extend lifespan. Is that right?

Laura Deming: So the core concepts here are as follows: it would be so great to be able to take an old cell — let’s say a skin cell from your body — and turn it into a kind of cell that can do anything it wants, or turn into anything it wants. And this one guy, Yamanaka, he was just like, I’m going to guess that this set of maybe 20 to 30 different proteins could be things that if we express them in a cell, they’ll lead to that regeneration or reprogramming process. Just tried some stuff and then found four things that do this. And this is amazing. I think it led to his great success later.

But no one in their right mind was like, “Obviously, then if we just take those same factors and express them in every cell in a mouse’s body, that mouse will have effects that look like they’re having some resilience to ageing or doing better in an ageing context.” I certainly would never make that connection, because it’s too simplistic. But yet when this was tried, indeed you do see positive effects of expressing these factors. And it’s weird, too, because if you express them the wrong way, the mouse can get cancer, and so you have to be careful on how you express them. But it’s just an example of a really simple idea that someone tried that actually worked. And I bet a bunch of biologists would have totally scoffed at it in isolation of the few papers where this is shown to be an interesting thing.

Luisa Rodriguez: Yeah. OK, let’s talk about this other one. So for context, Loyal is a company that works on life-extension drugs for dogs. One of these drugs draws on the fact that large and giant breed dogs have average life expectancies that are only half that of the smallest dog breeds, and targets the biological mechanisms that are thought to cause this lifespan disparity.

And it has gotten at least a step toward regulatory approval from the FDA in the United States. Can you say more about that?

Laura Deming: I think honestly the core step is them just making the bet that if they tried to compile evidence from the literature about the ageing field, and present it in a way that they think is just scientifically fair to the CVM [Center for Veterinary Medicine] branch of the FDA, that they would actually consider this literature and take it seriously, and consider lifespan extension as a claim.

I mean, I think it was a risk, and it took an act of imagination to make that step. And I think it was great credit to the FDA or CVM’s part that they actually considered this indication. Luisa, to be really clear, this is something that I thought was impossible, like, five years ago. And the company got it done in four.

Note: As part of her work with The Longevity Fund, Laura Deming is the lead investor in Loyal.

Luisa Rodriguez: Wow.

Laura Deming: We’re really talking about something where, if you’re in the field… Literally, when this happened, I was in this exact office. I broke down, I screamed, ran into a conference room, started crying. Because you just can’t be in this field for 17 years — again, since I was a kid — and just dreaming of things like this that could happen, where you get mainstream consideration, even just rationally, of the data in the field. I mean, it’s really emotional to see that happen. And it’s so hard to convey to people outside the field how big of a milestone this is, and how much it’s going to impact I think a lot of things that come downstream. Even if this drug ends up failing for whatever other reason down the road, I think this regulatory milestone is a huge one for the field.

Luisa Rodriguez: Amazing. And I just actually personally love the product. It’s life extension for dogs. And as someone who has a new puppy, I desperately want this puppy to live forever. And obviously that’s not going to happen, but it feels like maybe a slightly easier sell. People love their dogs, and it’s less counterintuitive to them that it’s not obviously good for dogs to live longer than it is for humans, bizarrely.

Laura Deming: I think what you said is really interesting, where you’re like, it’s immediate to you that you’d want your puppy to live forever. Or you’re like, of course this beautiful thing. But then when you think about it for yourself, maybe it’s like that’d be a bit selfish, or maybe it’s a bit much. And I think there’s something beautiful about how we always want for others what we feel like we can’t, you know…

Luisa Rodriguez: Yeah, exactly.

Talent shortages and other bottlenecks for ageing research [01:17:36]

Luisa Rodriguez: OK, let’s talk about this report that you contributed to that talks about lots of bottlenecks for ageing research, and outlines 12 key challenges. I’m going to see if we can get through about half of them. We might not actually make it through that many, but we’re going to try.

The top need, according to this report, is accelerating the path to market for ageing drugs. Can you explain what the challenge is there?

Laura Deming: Yeah. This is something I think is so interesting. One hypothesis that I have — and again, to be clear, this is just a strong belief; it’s like a strong intuition I have from being in this field for a long time; it’s something a lot of people share, but you can argue a lot with this — is that the next big milestone the field should aim for, and has a chance to hit in the coming decades, is showing that a therapeutic can extend lifespan in a human. And the reason that’s important is just no one thinks that you can do that. I think some part of the field thinks that you can do that.

Again, to be clear, this is not a large lifespan extension; this could be the most marginal. But basically just getting a huge number of people — enough to actually show any even monthslong-to-significant extension — just to be able to show that we can change biology in humans in a way that does affect lifespan.

But just kind of showing what we already know, in a sense: the question of how you do that is enormously difficult. It could be that there are no drugs out there that do this currently. It could be that there are drugs on the market that people are doing today that are already doing this that we just haven’t measured. And so the strategic questions around figuring out how to build companies or orgs that do that is by far the hardest strategic and scientific question that a founder could face this decade. But I think the best founders will go towards figuring that out.

Luisa Rodriguez: Yeah, that makes sense. Is part of the problem that when you do trials, and you want to show evidence that your drug works on something, for things like cardiovascular disease we’ve ended up with blood pressure as this interim metric. That’s something that we can track, and we can do a trial that’s months long, and work out whether the impact on blood pressure is good enough that we expect a certain impact on cardiovascular disease. But it seems really hard to generate the kind of evidence a regulatory body would want on something like, “We tried to follow a group of people for decades and figure out if they lived longer relative to the control group.” How do you even get the kind of relevant evidence that would make regulatory bodies be able to evaluate ageing interventions?

Laura Deming: There’s lots of interesting approaches to that question. One is trying to just find generic biomarkers that aren’t even functionally obviously relevant to health, but seem to be highly correlated with and possibly causal of longevity. Again, quite hard in humans, because the level of evidence you might need to confirm that those are potentially causally related would be quite high potentially.

There’s things you can say, like, maybe I don’t want to lose function. Let’s say that I get a bunch of physiological proxies for things that get worse with age that I wouldn’t want to have get worse, and I just measure how those change. And then I say, I just assume that if these change, then maybe the drug will change lifespan. I don’t think I am that tied to this drug having to move, for example, maximum lifespan in the first iteration. It’s more just strong evidence of affecting the ageing process in humans, in a way that we could predict in advance. So that’s also interesting.

Luisa Rodriguez: So another major priority is better understanding the ageing brain. Does the work you’d like to see here differ from more traditional research into dementia and similar diseases?

Laura Deming: It does, actually. Parts of more traditional dementia research do look at differences between young and old brains. A lot of these studies are nontrivial to do. For example, getting old mice is a whole thing. If you’ve ever tried to just order old mice online, someone has to keep a colony of mice around for a long time to get them to age long enough. So it’s actually kind of tough to just get access to that as a resource, so that means the burden to do an old-to-young comparison study might be higher. I just feel like there’s a lot we don’t know about how old and young brains differ because of just very practical issues.

And the fact that if you look at the budget of the National Institutes for Health, the majority of money going towards ageing is very allocated towards things like Alzheimer’s. And it’s actually, I think, kind of a science funding question or problem. I’ll see a lot of professors who don’t really care about Alzheimer’s inherently who reframe their whole research agenda to have an Alzheimer’s angle. And what do you do if you do that? Well, maybe you order an Alzheimer’s transgenic mouse, and maybe it’s not a great model, but you just test your thing in it.

So it’s hard to emphasise how much just having a tagline of something being a disease affects all research, and it’s very pervasive. This is not to say that Alzheimer’s research is at all not something that we should spend a lot of money on. It’s just that I think the fact that ageing doesn’t have similar, for example, funding weight, and doesn’t have similar advocacy leads to just a lot of these inefficiencies.

Luisa Rodriguez: Yeah, that’s really a shame. What is a project that you would like to see done here? Is there any way to get better access to aged mice?

Laura Deming: Yeah, better access to aged mice. Just making them more available to researchers is one thing. Actually, better access to aged human tissue is a huge issue. Many people pass want to donate their tissue, and just the process to logistically get access to human neural tissue is really quite complex. And often, tissue you’ll get access to has aged for like two to three days post mortem. So what are you going to do with tissues that have been sitting out for days? And really, what are you going to infer from that about human health, analysing it?

So in many ways, it’s just kind of tough to actually ask the question, “What’s here?” And then, “What’s in old stuff and what’s in young stuff?” Just logistically. It’s not that there’s one specific study. It’s literally just a body of work that characterises that a lot better than we have, where we can address all these operational challenges to getting that data.

Luisa Rodriguez: Yeah. One approach to solving brain ageing that I read about while reading your work for this interview is creating new brain cells like neurons or glia, which are the immune cells of the brain, and using them to replace old ones. How promising does that seem to you?

Laura Deming: It’s a good question. I’m not an expert in that field. One thing I really love about a lot of this research is it kind of forces us to ask questions about the nature of identity. So if this was changing the nature of identity, how would we even know in a mouse model? I think those questions are so interesting.

And what I will say is that it’s not as crazy as it may seem. We are able to do cell therapies where external cells engraft and grow. So we know a lot of this stuff is possible in theory. It’s just a question of what fraction of the brain could we then gradually replace? And how would that affect the identity of the animal or the behaviour of the animal? And those are still open questions in the literature.

Luisa Rodriguez: OK, we literally know that we’ve been able to — in mice, maybe? — transplant brain tissue into a mouse brain and have it exist and be part of that animal’s brain. But then the open questions are: how much could we actually do that, and that mouse still be that mouse, in the way we care about, or at least we definitely would care about it in humans? And then also, just biologically, how far does that kind of grafting go successfully?

Laura Deming: Exactly. If synapses are being formed, what does that really mean? And what are the identities of these cells? But I think that people often feel inhibited thinking about biology because they’re like, “Oh, it’s so complicated. I don’t really know what…” It’s like, if you just think of the dumbest thing that you would do to fix any problem, and you actually wonder: if you just did that thing, what would happen? Sometimes you really can just try a very simple thing. And a lot of interesting results have come from just that approach, I think.

Luisa Rodriguez: Yeah. Something I had no idea about was the fact that, unlike humans, songbirds and turtles can continuously generate new brain cells throughout their lives. Given that humans can’t do this, and the ageing brain is a huge bottleneck to solving ageing in humans, do songbirds and turtles seem worth studying? Or does that seem a bit far-fetched to you?

Laura Deming: There’s so many inefficiencies in research, it’s really cool to find new ones. I think one is the diversity of organisms that haven’t been studied for reasons that are just kind of logistic. Songbirds and turtles are studied.¹⁰ For example, a friend was just telling me the other day that slices of turtle brains can be more resistant to certain types of treatments because they’re more stress-resistant in certain ways.

But let’s say you’re a grad student showing up to a lab for the first time, and you need to get a PhD. And there’s this model organism that you know scientifically has some interesting properties, but you could just order mice from Jackson Lab — and why wouldn’t you, to grind out a study on an indication that everyone cares about and they can get grants for? I think it’s a big inefficiency where great model organisms aren’t studied as much as they should be.

Luisa Rodriguez: Yeah. Another priority is around replacing damaged tissues and organs. I think this basically refers to making it easier to access organ transplants. Is that right, or am I missing a piece?

Laura Deming: I think it falls into a couple of categories, but my understanding of the biggest bottleneck in that field currently is just that, right now, an organ transplant is not something that you would sign up for casually or on a lark. It’s a huge, invasive surgery, and it can have quite complicated downstream effects.

Luisa Rodriguez: OK. Another bottleneck is talent. It sounds like, in some ways, this field is growing massively. There’s been something like a 70x increase in funding in the last decade, but talent is still a major bottleneck. Why is that?

Laura Deming: It’s so exciting to be in the field right now, because you have to understand, when I first entered the field a couple of decades ago, it felt like there was a small cluster of people who all had this kind of shared secret, and they were all hanging out together, but you know, it just felt a little like a Dungeons & Dragons club or something. It was a very isolated ingroup.

And now, I meet people who, since they were like a kid, have wanted to work on this and have been reading about it. And we have so much more online now, and so much more education about how to start a biotech company or different areas of longevity. And to meet someone who’s like 18, has spent five years already kind of loading all that stuff, it’s honestly just mind-blowingly cool.

So I think this is maybe one of the first generations where we’ll have a combination of both highly mission-oriented and educated founders with a high degree of competence and pragmatism, and then also the existence and support of a community that can actually help them actualise that.

Luisa Rodriguez: That’s really cool. I wonder if because maybe this field has a very sci-fi vibe to it, it’s hard to get talent where people who are kind of altruistic, and want to work in biotech or bio or medicine or something, are like, “But not ageing. I don’t know, it’s too weird. That’s for edgy, weird people who are trying to make immortal humans. That’s not for me.” Does that ever feel like it comes up, or do you have a sense that there are some people feeling that way?

Laura Deming: Well, I’d say there’s a couple of things at play. One is like a disgust reaction to incoherent people, where I think a field like this attracts some fraction of very high-quality work and some fraction of people who are not doing high-quality work. I think that you can feel when a field has competence or something. And I think the ageing field has a lot of competence, but also has a lot of noise, and that can cause just a lot of kind of force field around it.

I think that’s changed a lot. There’s now just an enormous number of great labs in this space that are very obviously, objectively competent. But that’s a hard one. I think it’s just not a thing that’s in the water. I am in this field because I grew up disconnected from every social kind of system you could imagine: homeschooled in a house by myself with a futuristic kind of milieu. And it just was obvious that this was a thing that you could do.

Luisa Rodriguez: Right. You were just a child wondering about death and why we’ve arbitrarily chosen 70 as the age to die.

Laura Deming: Yeah, exactly. I think our house also had a lot of just pro-science memes, and it was just very much in the air, and most people just don’t grow up with that. I think if something is not in the air, you have to fight hard to find it — but then it probably is one of those things that has a lot of impact, because no one else would have found it. And so that’s definitely why I think ageing is so underworked on.

Luisa Rodriguez: Yeah. So maybe for people thinking about whether they’d want to enter this career or not: knowing that yes, there’s some noise, and yes, there’s some stereotype or vibe of it being weird and sci-fi, but actually, there’s just clearly a lot of really excellent science, and people founding legitimate, powerful things.

Laura Deming: I think what I’m describing are a lot of really hard things, right? It’s like you’re trying to make this big social change, or trying to develop a drug. And developing a drug is an extremely difficult enterprise. You create a molecule that has on the order of hundreds of atoms; you freeze its design; you test it in 10-year iteration cycles. This is not something that anyone in their right mind who enjoys doing things quickly or efficiently would do. So there’s this question of, well, why would you work in this field?

I think there’s a couple of things that I want to say about the beauty of biology, and the joy of it, that I really think it’s one of the coolest things you could do. And so one perspective on that is just that the way you learn biology in school isn’t what it really feels like. When you’re thinking about biology properly, you should be thinking as though you’re like a little molecule floating in a cell,¹¹ and you’re looking around, like figuring out what to do. And again, the really beautiful thing is we now know what parts of the cell look like, so you can imagine yourself in this alien world — floating around, deciding where to go, deciding what proteins to hang out with.

When you look inside of a cell, you see little robots. I don’t know if you’ve seen Big Hero 6, but there’s a scene where Hiro, the main character, is building these little nanobots in his garage. And the really cool thing that you get to do in biology is you get to work with thousands of nanobots¹² that have been created over millennia, or much longer than that, and you can play with them and manipulate them, and you can do it kind of rationally in many contexts. Like when you look in a cell, you see proteins literally walking around — like they’ll literally have little legs, and just be like walking around or carrying big bags of molecules from one part of the cell to another. And this is all at your disposal.

And the point I want to make about timing is that this is new. This is new stuff. This is not something that we had in the early 1900s. Our ability to copy-paste DNA really started ramping up in the ’70s, and many of the most exciting tools that we have — like cell therapies, gene therapies — are only coming into their prime now. And when I say cell or gene therapy, what I mean is I’m taking a literal cell — like a whole complex city of tiny robots that work together normally to keep you alive that we barely understand — and I’m making rational changes to it, adding new robots that I’ve created with my own hands in a Microsoft Word document somewhere. I was like copy-pasting letters in order to make it do something — like, for example, eliminate a cancer cell. That’s just one of the most extraordinary things that humanity has ever done.

And I think if you like operations, you should work in this field, maybe in an operational context, and enjoy that. But if you love science, if you really get a kick out of it, there’s just so much here that truly wasn’t here 50 years ago. And it’s like this is the time where it’s all being figured out.

And this integration that I was mentioning of these ageing viewpoints — of we just poke something and we see what happens versus from the ground up, or we understand a lot about how the system works — that integration is happening now. And that’s why it’s so exciting to work in this field. Not just because you should because it’s impactful — which I definitely personally feel — but also very strongly because it’s one of the most beautiful things you could spend your time or your mental energy calculating. So I want to make the case for the beauty of biology as well as the impact of it.

Luisa Rodriguez: That was beautiful. Anything else you’d want to say to people considering moving into this field?

Laura Deming: I mean, this is probably common to other areas of impact, but just as kind of a word of caution to those considering working in the field, I think it can be stressful or hard in a variety of ways. So just to be honest about that, I really think at its core, a question I keep coming back to is, why would you work on longevity? If you care about impact, why is it rational to work on longevity? I think a lot of it comes down to if there’s a belief that is not yet shared by the full population but only a small set of people have, that would cause the whole population to act differently, to me, that’s the core of the reason. The reason to really personally spend time on it is just like this inefficiency.

But the problem is, if only a small set of people believe something, it can really feel quite hard to advocate for that, or interact with a population that doesn’t have that belief. It’s quite jarring. This is one of the most fundamental topics in the world, our relationship with death and inevitability, and having any agency over that is extremely scary and weird. I just want to make the case that it’s a very weird field to work in, because I think you have to be really thoughtful and careful with yourself and with others, in how you respectfully talk about this stuff and navigate it, in addition to also building companies and thinking about drug development and all these other things.

Luisa Rodriguez: Yeah. Nice. I’m curious if you personally think about your own death very much. Does it feel far away or scary, or does it feel like your work on this is kind of detached from your own mortality?

Laura Deming: Yeah, it’s a question that I think about every day, and have for a long time. I guess when I think about people I love, it’s also a pretty active topic. I’d say personally, working in this field I think has given me maybe a much more peaceful relationship to my own death. I don’t believe that I’ll necessarily live some unbounded number of years, because even if you solved every logical problem like we talked about, there’s still accidents and such. I don’t know. I guess just because I’ve had to think about it for so long, it doesn’t seem that scary anymore. It just kind of seems like something that could happen.

Something I’m grateful for that comes from working in this field is that I think people often think that if you work in this field, you have this weird blind side to death, where it’s like death is universally bad. But I think if you work in it long enough, you just have to really sit with that as a concept. And it’s hard to describe, but it really changes your relationship with it in an interesting way.

Luisa Rodriguez: That’s really fascinating, thank you for sharing. OK, one final question: if you could solve one scientific mystery in your lifetime, what’s your pick?

Laura Deming: Definitely “What is life?” Definitely that’s the one that I’m curious about.

Luisa Rodriguez: Can you say more about what you even mean by “What is life?”?

Laura Deming: I mean, there’s obviously something going on, right? You know, living things, you can predict so much about them. We barely know how or why we’re multicellular, and we don’t have any idea why that’s true. Bacteria talk to each other in so many different ways. We don’t know why or what they’re saying, really, or what’s going on there. And I just feel like it’s this huge field that we don’t understand at all, and it’s so exciting.

Luisa Rodriguez: Cool. My guest today has been Laura Deming. Thank you so much for coming on.

Laura Deming: Cool. Thank you.

Luisa’s outro [01:36:37]

Luisa Rodriguez: All right, The 80,000 Hours Podcast is produced and edited by Keiran Harris.

The audio engineering team is led by Ben Cordell, with mastering and technical editing by Milo McGuire.

Full transcripts and an extensive collection of links to learn more are available on our site, and put together as always by Katy Moore.

Thanks for joining, talk to you again soon.

Laura’s footnotes

1. This was a set of studies I pulled to illustrate the diversity of approaches and the sheer number of things that have been reported to increase lifespan, but often a fair fraction of papers don’t replicate and so it’s plausible that only a subset of these will stand the test of time – what I meant to illustrate was the diversity of approaches, and how common it can be to get a positive readout, but I realize I’ve failed to stress the replication point historically (I do think it’s fair to say at this point that we can reproducibly intervene to increase mouse lifespan, in large part due to the excellent work of the NIA ITP program)
2. This is a complex field and the question of what a senescent cell is feels increasingly unclear to me (in part due to conversations with friends who did their academic training in the field) – I think it will take a while to answer these questions, and we may be incorrect about some of the simple ways we first thought about about this biology.
3. What I meant by this is overexpressing these factors seems likely to pose a risk when it comes to cancer.
4. To be clear, I wasn’t implying here that the Ocampo paper cited was in WT mice (it wasn’t, it was in progeric mice) – rather, I meant this literally (if you were to make a list of things that seemed relevant to the question, reprogramming sure wouldn’t have been on mine). A colleague recently published a teardown of the first paper to link reprogramming to WT lifespan extension, which might be interesting to readers.
5. In this study, I think ~238 out of 4698 (so ~5%) single-gene deletion strains screened showed increase replicative lifespan. To caveat, replicative lifespan is an interesting measure but might not capture things that i.e. a chronological lifespan screen would – I just thought it was interesting that sort of fair fractions of genes screened do impact this.
6. To be clear, this was kind of a random idea I happened to be thinking about that day b/c our team had recently done a review of the literature on caloric restriction, and I haven’t done a feasibility or reproducibility check on this – I just think it’s funny that we keep knocking out random dietary components or having mice just eat one kind of thing and seeing lifespan effects. And that it’s not obviously just caloric effects, that there seems to be some signaling aspect to it. I’d honestly feel bad though if anyone took methionine restriction super seriously just because I happened to mention it.
7. One caveat to this is that the brain has a bunch of sensory inputs, and I think it’s really cool and fun to think about how modulating those might have some effect (obviously a very, very complex function, but it’s fun to think about).
8. I might be off one or more orders of magnitude here, depending on the kind of cell (they vary a lot in size), this is also molecules not atoms so depending on how you’d make that distinction.
9. Apologies to all the structure-guided drug developers to whom this is a grossly simplistic and ‘we can’t do that anywhere near perfectly yet’ take on a field that is not just, uh, fitting shapes together.
10. I was making kind of a tangential point here about diversity of model organisms, and don’t mean to imply that songbirds and turtles aren’t studied today with robust communities and fields.
11. Or like a cell itself! Hanging out in a milieu with all of its friends, motoring around, swapping messages encoded in genetic information, popping viruses back and forth 🙂
12. I mean this literally – objects built out of nanoscale components, acting on about that scale, that literally often look like (complex and mildly chaotic) robots just padding about the cell dragging things from one place to another.