- 18 hours ago
"Longevity science is entering a new phase, as advances in biology begin to translate into real clinical applications, from targeting the mechanisms of aging to preventing age-related diseases.
In this fireside chat, Joan Mannick shares a front-line perspective on turning scientific breakthroughs into viable treatments, and which approaches show the most promise to extend healthspan. Beyond the science, the conversation explores what it will take to scale these advances: overcoming scientific, regulatory, and economic barriers, and ensuring that longer, healthier lives are accessible to all."
In this fireside chat, Joan Mannick shares a front-line perspective on turning scientific breakthroughs into viable treatments, and which approaches show the most promise to extend healthspan. Beyond the science, the conversation explores what it will take to scale these advances: overcoming scientific, regulatory, and economic barriers, and ensuring that longer, healthier lives are accessible to all."
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TechTranscript
00:10Well, good morning. Welcome back. Thank you so much for being with us. I'm very excited
00:14to be hosting this session with Dr. Joan Manik. She is the chief medical officer and head
00:22of product development at Aaltos Lab. You all know what the topic is, how we're going
00:26to live forever. No, I'm just joking. Dr. Joan would not let me say it that way. But the
00:32first question I had for her when I first met her was, is it too late for people like
00:36me or people like us? How far away are we from this promise of longevity? So the very, very
00:43first question that I had for you was kind of twofold. What is this longevity talk all
00:50about? Is it too late for me? So welcome, everybody. I think most of us think longevity isn't about
01:02just living longer. It's about living healthier longer. And I think there is sort of an acceleration
01:09in the science and actually clinical work being done in this field. So I would say in the next
01:1710 years, we'll have our first drug-approved, I'm guessing, that we'll be targeting aging biology
01:23and at least improving parts of why we age and how we can keep healthier. So it's not too late
01:34for you.
01:35Okay, so now that we got this out of the way, I have actual good questions for you, Dr. Joan.
01:40So we think about longevity, and I think there's many misconceptions about it. So let's first not
01:49define it in a very sort of boring way, but what isn't longevity and what is longevity when we talk
01:55about it from a scientific medical perspective? Yeah, so I think one way to think about what happens
02:03as we get older is we lose some sort of buffer capacity we had when we were young. So you
02:12can be
02:12born with genetic mutations that are going to give you Alzheimer's disease or cancer, and you are
02:19perfectly fine when you're young despite having these mutations because you have something to buffer
02:25against the damage they cause. And I think what happens as we get older is we lose that buffer and
02:33trying to define what is the buffer we're losing as we age and how can we replenish it so that
02:41we can
02:41stay older and healthy is kind of the basis for the longevity field. You know, so when you say older
02:50and healthy, so really is for that, you know, maybe 20, 30 years at the end of our lifetime, right?
02:57Between our 60s, 70s, 80s. Is it about better quality of life at that part of our timeline or
03:05is it really just reversing aging altogether? I think what's feasible is that we can age in a lot
03:14healthier state than we're currently doing. I think there are multiple organ systems whose function declines
03:23and we've just assumed this has to happen and I don't think it does have to happen. I think we
03:30can
03:30keep organ systems healthier much longer than we have been accustomed to living with so that we'll
03:38live a much better quality of life, not necessarily a longer quality of life, but a life in our 70s
03:45and
03:4680s and 90s and 90s where we can get on planes and walk around cities and enjoy grandchildren and
03:53things that are sort of taken away right now from a lot of older adults.
03:57So, you know, when I asked you what isn't, I was immediately thinking, doing a little bit of, you know,
04:03my own research. When you Google and you look things online, the first few things that come out when you
04:10search for longevity is peptides, all sorts of junk out there. So, tell me a little bit the
04:19difference between the work you're doing, you're leading in Altos Labs and what's really out there.
04:26Yeah, so right now there has nothing that's been proven to extend lifespan or healthspan except
04:37exercise, reasonable diet, sleep. So, anybody selling something saying this is extending your
04:45healthspan or lifespan, it just isn't true. There's no data to support that yet.
04:50It's not to say that this data couldn't be generated, but it just doesn't exist. So, I would
04:57really caution people not to take peptides until there's placebo-controlled data in people who are
05:04healthy, that they're actually doing something good beyond placebo.
05:13So, so far when it comes to the science of things, what have we been able to prove scientifically about
05:22lifespan? So, we know in every pre-clinical species study to date, not in humans, that if you target
05:31specific biologic pathways, lifespan and healthspan are extended. And these species span billions of
05:39years of evolution, so we know there are going to be biologic pathways we can target that will
05:46likely extend human healthspan and lifespan. But exactly how to do it, what older adult population
05:56would benefit? All of that has to be worked out and it hasn't yet been done.
06:03So, tell me a little bit about the work you do day to day. Sort of, I heard the word
06:08epigenetic last
06:09time I talked to you. What does that mean?
06:13So, I mentioned that buffer capacity that we lose when we're young. And no one really understands what it
06:21is we've lost that makes us get sick when we get older and not when we're younger.
06:26And one of the best ways that we found to restore that buffer capacity is with some factors called
06:35Yamanaka factors. And there are four of them. And it's when they were discovered because when a 40-year-old
06:46sperm inseminates a 40-year-old egg, the resulting baby has an age of zero. Now, 40 years of aging
06:56of
06:56the egg and the sperm are wiped away. And what wipes away that age is Yamanaka factors. And when you
07:04look
07:04in cells, those Yamanaka factors restore this youthful buffer capacity, at least on a cellular level,
07:12that's lost as cells age and as we age. So, these Yamanaka factors are resetting
07:20marks on our DNA that regulate gene expression. And so, they're not safe to use or systemically
07:30right now because they have side effects, but they sort of elucidate a biology that we can tap into
07:37to sort of not only live longer, but actually potentially reverse aging-related conditions
07:44by restoring this buffer capacity.
07:46So, when I hear about the Yamanaka factors, to me, it sounds like science fiction.
07:51And I wanted to realistically ask you, how far away are we from getting to that point? I know you're
07:59working on this at Altos Labs. Is this a 10-year, 20-year? What does the success look like?
08:04Well, what's exciting is a company called Life Biosciences, I used to work with them,
08:09has actually now started a clinical trial of Yamanaka factors in the eye to restore vision
08:16in glaucoma patients. This works in mice. It remains to be determined if it's going to work in humans,
08:23but it's that first step to start to translate what could be a game-changing biology in preclinical
08:32species to humans. Well, we're in an AI-friendly crowd and a tech-friendly crowd here. Do you believe
08:41the technology, the way it's accelerating today, how does that help the work that you're doing?
08:47So, AI is just critical in this field because aging is so complicated. And in order to understand it,
08:57you have to take so much data from cells, from in vivo models, from humans, and start deconvoluting
09:07what is happening when we age. Or even things like, what is happening with a Yamanaka factor that is
09:15turning an age 40 egg and sperm into an age 0 embryo. And it's really complicated. And there's no way,
09:26or we can't easily do this sort of deconvolution without AI. How are you concretely using AI right
09:35now to do that? So there's a, at Altos, there's a whole institute of computation which is all AI.
09:43And it not only is sort of digesting reams and reams and reams of data, but it's also creating
09:53virtual cells. And it's looking through reams and reams and reams of data for what are the right
10:00targets we should be going after for aging-related conditions, which humans might be the right humans
10:10to target, and which are the clinical trials that are most likely to succeed, all sorts of things.
10:17It sounds to me that this is very laborious, very lengthy in time. No matter how much AI you use
10:25or
10:25tech you use, it's still going to take a very long time. Talk to me a little bit about,
10:32are there any shortcuts to this? What would, could we do it faster?
10:39Yeah, I think it is long, but if you're smart and you take one step at a time and break
10:48down this
10:49very complicated process into things that are a little simpler and manageable, that we can start
10:55getting our first drugs there. You know, you don't have to say, oh, our first drug is going to
11:03stop every aging-related disease and have us live 20 more years. If we could even delay one aging-related
11:10condition like Alzheimer's, that could keep healthcare systems from going insolvent. I mean,
11:16would just be a huge advance. Joanne, I asked you this before. Is this a rich people thing? Like,
11:24will this, will other people, will the entire world be able at some point to benefit from these kinds of
11:30longevity research and discovery? Yeah, absolutely. So even in, you know, developing countries,
11:41there is a huge burden of aging-related diseases now that are crippling healthcare systems. So
11:47metabolic disease, obesity, hypertension, heart disease. And these, again, can all be targeted
11:54by going after fundamental aging biology. So this shouldn't just be a, you know, first world,
12:03western rich country benefit. It's going to benefit if we do it right, global economies.
12:13So demystify this for me, because again, when I, you know, consulted my friend Google,
12:19and I looked into longevity, longevity was a man's world. And there's hacks, and there's all sorts of
12:29interesting things that people are doing to hack aging. Do you think it will ever become the kind
12:37of mainstream? I'm thinking, economically, I agree with you, right? There's, the whole world is your
12:42market. But will it ever reach that kind of a point where it becomes more than just a privileged few?
12:49Absolutely. I mean, it's, aging, if you can target it, the impact it will have on
13:00healthcare is going to be the same as targeting obesity. And the drugs that we develop need to be,
13:09have a cost that's low enough, because it's, you know, something that everyone in the world
13:14experiences aging. But if you can target this aging and keep people healthier longer, the cost benefit
13:20to every government will actually be positive. But it's critical to keep the cost down of the
13:27therapies so that it is available to everybody. And do you think there's an economic imperative
13:33to that? I was thinking, who is right now, besides the United States, doing research on this? Because
13:38it's, as I said, it's not just laborious and time consuming, but it's also a very expensive endeavor.
13:44Who else is working on it? Yeah, we need investment. I mean, Altos Labs is lucky. It has wonderful
13:53funders. But there's so much work that needs to be done. And it needs to be done at a high,
13:59sophisticated level. I think there are a lot of biotech companies with really inexperienced
14:05management team. And it's hard to develop a drug period. But to develop drugs for something this
14:11complicated is really difficult. So getting more experienced management teams, more sophisticated
14:18investors who can help the management teams is going to be really important. And then, of course,
14:24if we could have more government support, it will be really beneficial.
14:29Why would government care to invest in something like this? I can see from my, you know, private
14:34sector approach, I want the whole world to be my client, right? There's 8 billion people, 9 billion
14:41people. Why would the government care about that? Do you want more people to live forever?
14:47Right. So it's not living forever. The cost of people aging with multiple comorbidities is
14:54bankrupting healthcare systems, and it's going to get worse. And I can just talk about Alzheimer's
15:01disease. It's going to be crushing for most healthcare systems. In the US, I think it's going to be over
15:08a trillion dollars in the next decade of costs, or maybe it's two decades. And so if we can just
15:17delay
15:18the onset of some of these diseases so that we can live healthier and then die quickly and not sort
15:26of
15:27drag on with dementia, it actually will keep not just the US healthcare system, but many healthcare
15:34systems from becoming insolvent. So it's a cost benefit analysis, what you're saying. Right.
15:40And how does that actually work? Well, I think if you look at the economics, and I think governments
15:47will look at it, it would prevent them, their healthcare systems from becoming insolvent. If they
15:54do, if this is the cost of the drug, and this is the savings of delaying something like Alzheimer's
16:00disease by three years, there's a huge savings for the government. And now we see aging populations
16:08in certain regions of the world. What does that look like? How does that make the work you're
16:15doing more urgent? Yeah, as the population ages globally, there's just going to be right now more
16:23and more chronic diseases that always occur as we get older that are going to cost the healthcare
16:30systems more and more money. Do you think there will be a moment, you mentioned obesity drugs earlier,
16:37and the last few years we've seen those have become more and more available. And they've changed the
16:44equation quite a bit on managing comorbidities that you were talking about. Do you see such a moment
16:51happening for the longevity health side of things? Absolutely. I think first we have to develop
16:59drugs that work with, you know, rigorous placebo controlled trials. But if we can develop drugs
17:06that do delay or even reverse some of these chronic diseases that are crushing, with crushing healthcare
17:13costs, it will have an enormous impact, like the GOP ones. Enormous. And how far are we from there? Like,
17:23I know I've asked you before, and I'm very specific about it. What does the timeline look like? And where
17:29are you in the timeline? So I think it's actually feasible to do this in the next 10 years. I
17:37think there are going
17:39to be drugs coming into the clinic with really novel mechanisms of action that are going to be
17:47targeting fundamental aging biology and could get approved to delay aging related conditions in the
17:56next 10 years. Joan, what got you into this work? What makes you excited to wake up every day and
18:05do the work
18:05you do? Sure. So I was actually in academic medicine and I ran a basic science lab and I saw
18:13patients
18:14and I was in my lab reading, I think it was Nature, and there was an editorial by Cynthia Kenyon.
18:23And she said, if you mutate one gene in a worm, that doubles the lifespan of the worm.
18:31And so I thought, fine. Okay, you double the lifespan of the worm. It's not dying of something that normally
18:37dies of. But what she said in the editorial, she goes, this shows that organisms have the capacity
18:44to live much longer than they normally do. And that one phrase that she wrote, as a physician who was,
18:52I was an infectious disease physician, so I was trying to keep
18:55people in intensive care units alive another week or another month by getting rid of their bad
19:02infections. And the idea that that wasn't even touching the surface of what medicine could do
19:09and that potentially humans could live much longer than they normally do, I found it threw the whole
19:17medical field on its head. And I love that. And so after that, I started getting interested in this whole
19:25biology.
19:28I got very comfortable. Do you think
19:34that you will ever go away from this work and try to do something else?
19:43Maybe when I retire, but I love it. So no, this is like, it's really hard. It's really risky.
19:49And it's going to be really transformative. And that's my thing. I love that.
19:54I've never asked you about the risk. What are some of the unintended consequences or risks that you
19:59think might happen here?
20:01So I think the risk is more, it's so new, so complicated, so transformative, if we get this
20:12right, that it's really likely we're going to fail multiple times before we hit. And we just can't be
20:21scared of failing and just make sure we design the clinical trials and the experiments so that we
20:27learn and can iterate and can get there. But because it's so new and high risk, it's like a, it's
20:34a
20:34little bit of a, you can't be scared when you go into this field.
20:40And it's very audacious the way you've always talked about this, which I find fascinating.
20:47You talk about productive failure, like we're going to fail a few times before we get it right.
20:52Do you feel that investors, governments, the tolerance for that kind of risk and failure
20:58is there with you?
21:01Yeah, it's a great question. I think this is one of those investments that you have to be
21:08evergreen, you need evergreen investors who understand that they're in it for the long run,
21:14that they're going to, it's going to be a bumpy ride. But when it hits, it's going to be enormous.
21:21But the investors have to be able to tolerate some failure, brushing themselves off and keeping
21:30going and being resilient.
21:32You know, I once asked you, like, what happens, you know, when something goes wrong, like,
21:38and it goes to market, like, how careful do you have to be with, with a drug or a,
21:45you know, a therapy like this? What goes wrong, when it really goes wrong, goes into market?
21:52Right. So, you know, the reason I actually like healthcare
21:58regulators is they minimize the chance that something's going to go really wrong by requiring
22:05big safety databases, placebo-controlled trials, because anything targeting biology
22:12is going to have a side effect. If it doesn't have a side effect, it's probably not doing anything.
22:18And this is why I think where things can really go wrong are when they get to market without
22:25regulatory approval, like the supplements, the peptides, because you have no idea what the side
22:33effects really are. And so, because there haven't been any placebo, big placebo-controlled trials
22:40with safety databases acquired.
22:43So, as consumers, as end users, what would you advise we do, especially because what you're saying,
22:5210 years is a short timeline in the grand scheme of things, especially with the, the acceleration
22:58that's happening with tech. What is it that, as consumers, we should be wary about? Because,
23:03for lack of a better term, this market is flourishing in a good or bad way.
23:08Yeah, again, I would just be very wary of taking supplements right now, taking peptides right now.
23:17There isn't any data. There's one Nestle trial of a cocoa extract where there actually is placebo-controlled,
23:25well-powered data that it can decrease cardiovascular events. That one, I think, is fine. But in general,
23:33I'd just be very cautious. Everybody's free to take what they want. I don't take
23:37anything because I haven't seen the data to prove that the risks, the benefits outweigh the risks.
23:46So, all of these examples that you see online, you don't think that they're legitimate?
23:51I don't think, I think we just don't know. So, that's why, again, if there's a real biology,
23:58then there's a side effect. And I don't know what the risk benefits are of any of this.
24:02I'm listening to you, Dr. Joe.
24:07But, you know, we have less than a minute left, so I wanted to leave everyone with a bit of
24:11a more
24:13optimistic view.
24:18You know, when I first met you, everything sounded to me like science fiction. I told you that a couple
24:22of times. Do you really think that in the next 10 years, we'll be able to be at a GLP
24:27-1 level where
24:28we are going to be able to say there's these diseases that are making us live a very difficult
24:36life in the last 20 years of our lives and they're going to be completely eradicated?
24:41No, I don't think every chronic disease will be eradicated in the next 10 years, but I think
24:47we'll get one major one, like the GLP-1s are getting obesity. I would bet that by targeting aging
24:56biology, we'll get one big chronic disease delayed that we couldn't delay before in a new way.
25:05Which one do you hope that's going to be?
25:09I'm going to take the fifth on that one.
25:13Thank you so much, Dr. Joan. Thank you to all for being here.
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