We just published an interview: Laura Deming on the science that could keep us healthy in our 80s and beyond. Listen on Spotify or click through for other audio options, the transcript, and related links. Below are the episode summary and some key excerpts.
Episode summary
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?
- Laura Deming
In today’s episode, host Luisa Rodriguez speaks to Laura Deming — founder of The Longevity Fund — about the challenge of ending ageing.
They cover:
- How lifespan is surprisingly easy to manipulate in animals, which suggests human longevity could be increased too.
- Why we irrationally accept age-related health decline as inevitable.
- The engineering mindset Laura takes to solving the problem of ageing.
- Laura’s thoughts on how ending ageing is primarily a social challenge, not a scientific one.
- The recent exciting regulatory breakthrough for an anti-ageing drug for dogs.
- Laura’s vision for how increased longevity could positively transform society by giving humans agency over when and how they age.
- Why this decade may be the most important decade ever for making progress on anti-ageing research.
- The beauty and fascination of biology, which makes it such a compelling field to work in.
- And plenty more.
Producer and editor: Keiran Harris
Audio Engineering Lead: Ben Cordell
Technical editing: Simon Monsour and Milo McGuire
Additional content editing: Katy Moore and Luisa Rodriguez
Transcriptions: Katy Moore
Highlights
Why work on longevity
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.
Why we think it's feasible to end 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 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.
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.
But won't life get boring?
Luisa Rodriguez: 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.
Longevity progress over the next few decades
Laura Deming: 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.
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.
Surprising things that make mice live longer
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. 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 by 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.
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 cancer 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.
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 studies 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.