This year’s J.P. Morgan Healthcare Conference (“the largest and most informative healthcare investment symposium in the industry, bringing together industry leaders, emerging fast-growth companies, innovative technology creators, and members of the investment community”) included a breakout session entitled “Extending Human Lifespan,” sponsored by BIOAGE and Felicis Ventures.
The centerpiece of the event was a panel discussion among five luminaries of the aging field: an academic researcher, a startup founder (who was an academic researcher herself not too long ago), and the principals of not one but two venture firms actively investing in the sector. The author of a bestselling book on longevity moderated the conversation. (I’ll introduce all of them below.)
The session, held in a lovely room in San Francisco’s Contemporary Jewish Museum was attended by a diverse audience of more than a hundred people, ranging from scientists to startup founders to venture capitalists. The conversations and networking both before and after were electric—I’ve been to a lot of events like this in my life but I’ve never seen quite so many people run out of business cards in the space of an hour.
I’ll let the participants speak for themselves in the transcript, but I wanted to note an important point that was apparent as soon as we walked into the room: the title’s unabashed commitment to extension of lifespan per se (the number of years we are alive) rather than healthspan (the number of years that we are free of disease). Although healthspan extension is a noble goal, the term is sometimes a bit of a dodge, enabling the speaker to defer questions about the merit or broader ramifications of pursuing lifespan extension as an end in itself. I consider the selected title to be further evidence of the mainstreaming of anti-aging sentiment as technology edges ever closer to delivering products capable of meaningfully slowing aging itself.
In the text below, ellipses indicate sequences that could not be accurately transcribed. Text has undergone minor editing for clarity and flow.
Sonia Arrison (moderator): Welcome, and thank you for being here. I know that some of you know some of us, but maybe not all of you know all of us. So I thought I was start of the panel off by asking the panelists to say who you are, what your company does or your, research is (briefly), and why you care about longevity. So let's start with Simon.
Simon Melov: I'm an investigator at the Buck Institute for Research on Aging, which is just about an hour north of here. And I'm also the newly minted CEO of a brand new startup funded by YC called Gerostate Alpha.
Sonia Arrison: Why do you care about longevity?
Simon Melov: Ever since I was a little kid, I have been interested in the biology of aging, trying , to understand why it happens, what we can do to attenuate it. Currently, the best methods for slowing aging are stuff which is familiar to everyone in this audience: You all know: Eat right, exercise regularly, and sleep a lot. It's not a very satisfying message. So that's why I started Gerostate Alpha.
Kristen Fortney: I'm the founder and CEO of BioAge, and just like Simon I'd cared about aging for most of my life... I come from a more computational background; I did my PhD at the University of Toronto and my postdoc at Stanford, where I applied AI and systems biology to map out pathways influencing aging. After my postdoc I founded BioAge, just a little over 3 years ago now. We're about 20 people now...
Aydin Senkut: My interest in aging is from a personal perspective... From an investor perspective, it's probably the largest area...in terms of people and bringing meaning to their lives. I can't think of a more important area. Well, interestingly enough, now that we have this amazing event and this is the second year, but like five or 10 years ago, it was probably hard to fill a single table in this room, but now we have investors, we have companies, we have funds that are dedicated to longevity, let alone these amazing scientists and companies and founders — these are amazing things. And I'm just proud to be part of that journey.
“If evolution gave you modular switches to control aging, why would you not want to flip them?”
Laura Deming: Hi, I'm Laura. I run Longevity VC; we're a venture fund focused on longevity companies as well as Age1, an accelerator. To answer the question of why I'm fascinated by this space, it's probably: if evolution gave you modular switches to control aging, why would you not want to flip them?
Sonia Arrison: These are all great answers. So here's a question directed at you. Longevity has been an atypical space for VCs, and obviously you're interested in it, but why now? Like why is Felicis suddenly getting interested in the longevity space?
Aydin Senkut: I think one of the things we do as a venture firm—we're a little bit unique, in the sense that we like to invest in particular areas of consumer enterprise, but also frontier technologies. I think health is the one place where we can see technology have amazing impact, and the physical health and all the obvious stuff there's already been a lot of progression, but I think longevity has been discounted for a long time a more academic area, but the way that I was thinking about in very simple terms, is that we already have people living to 90, 100, 120 years old.
So a lot of people say, well, this is like science fiction—take people who are 80 and make them live to 200. However, even if you look at the real truth today, we do have someone who lived to be 120 but it's one in a million, one in a hundred million. What if all of these approaches had worked, and that number went from 1 in a million to one in a hundred thousand, or one in ten thousand? That would have a hugely positive impact on society. Because right now we are trying to take all of our productive resources and basically spend it on people in their last six months or last year of their lives, trying to fix them or extend their lives when they are the most broken. …
“Right now we are spending all our productive resources on people in their last six months or last year of their lives, trying to extend their lives when they are the most broken.”
But what if this was like some kind of vaccination when people had a chance to age a lot slower or be in much better shape in their seventies, as they were when they were at age seven. How can you not be excited about it? I'm excited about it as a parent, I'm excited about it as a son. As an investor, I can't think of a more important part of society where that could have impact...and I think this is not only a great mission, but you can create a great commercial company like Google, Amazon, all these companies worth close to a trillion dollars. In my mind, the next Google, the next Facebook could be in this space.
Sonia Arrison: Laura, do you have something to add to that? I see you nodding your head.
Laura Deming: I'm completely agreeing! The only thing I'd add is, I started Longevity not to start a venture fund to make maximal profit, but rather to help aging advance, and the way to do that at the time in 2011 was to start a venture fund, because there was no funding in the space. And what we thought about it was, if you flipped back to 1973, what would you do to help make oncology maximally move faster? You'd start Genentech. So I think that's kind of the same — Cynthia [Kenyon] came out with her first research on aging in the 1990s, but there was never a Genentech moment. So we're like, let's catalyze one now.
Sonia Arrison: So here we are, on the front lines of aging research, and a burning question for me—I would love an answer to this—is, what's the lowest hanging fruit in this area? I'm curious to see what the scientists' answers are versus the investors' answers, but—what are we going to get to first?
Kristen Fortney: I think the lowest-hanging fruit is those things that have already worked in model animals, where we see them work over and over again. There's a long list of those things, starting with rapamycin. They first published that result in 2009, and resTORbio did their Phase IIb clinical trial successfully just a few months ago. That's really gone all the way from basic academic discovery through to translation, and there's a long list of those things that have been shown over and over again to make mice live longer—and those are ready for translation now.
Sonia Arrison: Anyone else? Low hanging fruit?
“Whenever you have a new energy source like oil, it completely transforms economies. I feel like data is the new oil.”
Aydin Senkut: One thing to add...one of the amazing things is, like Laura was mentioning, is also the fact that Kristen can start BioAge today. I don't know if she could start BioAge 20 years ago, maybe not even 10 years ago.... Today...a company like BioAge, with very few people, can come in and actually find these data in biobanks, and apply AI and machine learning to it. So I think in some ways it's like a golden age–whenever you have a new energy source like oil, it completely transforms economies. I feel like data is the new oil. Now, it can truly impact areas like longevity, where instead of being like science fiction, could be a real science...and that's a reason why we think this potential is real.
Simon Melov: Yeah, just following up on that, your comment about five years ago, 10 years ago. That's absolutely true, and I think actually we're in this transition fuel, which is being fueled by breakthroughs in technology which are broadly applicable to much of biology. Even 18 months ago, we couldn't be doing single-cell experiments, which people are doing routinely in the lab—not so routine, still, but it's still being done at a high level. And so, technology, like most areas of biology, has fueled this impetus to create many, many, many small companies all of which are trying to tackle aspects of the same problem, which is aging. There's going to be a lot of bad ideas, but the same was true of the dot-com era. And there's going to be, probably, many right answers—there's no clear correct answer at this point.
Sonia Arrison: I want Laura to answer this question too, but I have a quick-follow-on following. So, is biotech still moving? I remember seeing a chart where it was moving faster than Moore's law. Are advances is still happening that quickly. Do you see them happening that quickly?
“There's going to be a lot of bad ideas, but the same was true of the dot-com era. And there's going to be, probably, many right answers—there's no clear correct answer at this point.”
Simon Melov: You only have to look at the explosion of journals to believe that that's true. Either people are making a lot of money on crappy science in journals, or there's actually legitimate work and there's so much of it that the journals are just exploding. It's extremely difficult to keep pace with the technology at this point in time—you have to be a voracious reader—and keep pace with all of these breakthroughs, any one of which you can specialize in.
Sonia Arrison: Wow. It's like, good news, bad news, right? . How do you keep up? But it's great. Okay. Low-hanging fruit. Laura, you're up.
Laura Deming: I just want to echo Simon's point, which is... [someone] brought up a great point, which was, people might ask, why couldn't you find longevity genes in the 1920s? Well, you couldn't isolate genes in the 1920s; cloning didn't happen until the seventies and eighties. And so when you see the first longevity experiments occur in the 1990s, about a decade or two after you get the technological ability that leads to the breakthrough. And I think that Simon's point is really important, in that it that answers the question "why now?" by saying, well, the tooling is here and it never was before.
Kristen Fortney: Just to add onto that, I think that while all this technology and data science is driving all of biotech, I feel like the effects are especially keen and especially felt in aging because really uniquely in the 1990s, early 2000s, we were really good at characterizing aging in invertebrates in worms and yeast and flies, and making those animals live longer. And really only in the late 2000s, starting to look at mammalian genes. Rapamycin was one of the first ones that made mice live longer (reproducibly). And I think that because aging is so complex, we really should be studying human aging in humans rather than invertebrates, because there are a lot of things that are particular to humans. And you need these new modalities like AI in order to do that.
Sonia Arrison: That was going to be my next question actually. So, what about the mammalian models? Are we focusing too much on that? Is that really translatable? What are your thoughts on that?
“Because aging is so complex, we really should be studying human aging in humans.”
Kristen Fortney: On mammalian models in general? Yeah, I mean this is sort of true in biotech more broadly, right?. For the most part the mouse is the model organism is used because if you're developing therapy you have to test it out in live animals and see what happens. But there are going to be limitations there, because mice age very differently from us—like, mice in the lab all die of cancer and we die of a much more complex spectrum of diseases. So there's gonna be a lot of things that are relevant to mouse aging and are less relevant to human aging.
Simon Melov: I think these systems have their place in different pipelines. So, if you want to work on very a specific pathology of aging in humans, then you need a model system which can recapitulate that. That might be mice, maybe not. There are a whole variety of different tools, and when you're trying to dissect aging, it's very difficult to identify pathways and targets which are relevant to human aging biology in humans unless you have gigantic data sets —many of which are available now in a variety of different ways. But I want to put in an advertisement for the invertebrate organisms. We're not over invertebrate organisms yet. In terms of screens, they're unparalleled. You can't do survival screens in mice.
Kristen Fortney: I completely agree with you. You can't do genome-wide experiment in humans or mice.
Simon Melov: ...There's different systems you use in different paradigms.
because aging is so complex, we really should be studying human aging in humans rather than invertebrates, because there are a lot of things that are particular to humans.
“Longevity is so complex that no one company is going to win it all.”
Aydin Senkut: One quick investor perspective. I don't know if you guys will agree with this, but in most other markets, there is this concept of zero sum. Google is the leading advertising provider; Facebook is the leading social network. There is not really that much oxygen left for the number two company... But to Simon and Kristen's point, what's interesting about longevity is that it's so complex that it's not going to be one company that is going to win it all, and that is one of the exciting things. It's the reason why we're so excited to be part of this journey. You know, there's BioAge, there are other approaches taking different parts of the body, and we can all help in different ways because the way that people age and our bodies start decaying is not just one thing. And so I think it is like an ecosystem. And the other interesting thing is, not only is it really exciting to see so much interest in so many companies, incubators and funds. All the governments in the world will start to care about it because if you're reading The Economist or the New York Times, one of the biggest trends is the rapid decline of fertility and birth rate. So we have a rapidly aging society but they're not in good shape; there aren't enough young people to work and make enough income to be able take care of those people. Not only that, but those aging people, because we're not catching up with aging technology, are essentially getting sick, and we're spending all of our money to take care of the sick...So these are very interesting times.
Sonia Arrison: So, we've talked about where things were, and where things are. But what happens if everything goes right, which is a huge if. What are we talking about in 10 years or 20 years? How do you see the future? I know it's a big question.
“I think the dramatic breakthroughs are going to come suddenly, and they're going to come fast, and we're not going to be ready for them.”
Simon Melov: We never hear this question. Where are we going to be? The stock answer a scientist will give you: five years. It's always five years; it just slides off into the future. But speaking on a point that Kristen made earlier, we're already in this transition zone, where we're not talking about give years. resTORbio, as Kristen pointed out, has three successful clinical trials under their belt. That target was identified in invertebrates, translated to mice, then translated to people. So that story is going to be repeated over and over again. I think that the more interesting question is, how far are we going to go in short period of time. There are going to be an expanding range of indications put forward by a variety of different entities—biotech, big pharma—and ultimately people will start targeting aging itself, as opposed to some of these approaches, which to some extent are a little bit serendipitous, but the targeting of aging is going to result in dramatic breakthroughs. We're still in the stage of incremental improving healthspan a little bit, improving this indication or that indication, but I think the dramatic breakthroughs are going to come suddenly, and they're going to come fast, and we're not going to be ready for them.
Sonia Arrison: ...Anybody else want to address the question of what does it look like with success?
Kristen Fortney: Yeah. resTORbio isn't the only one. Unity also just started a Phase I of their anti-senescence drug, and we think metformin is also an anti-aging drug, so what if all three of those are approved, and we start taking the combination. People could already be doing that in ten years....
Laura Deming: One thing that Kristen and BioAge noted early on was the need for biomarkers and being able to measure interventions. So I think a hilarious case ten years from now is that everyone's going to live longer and they're unware of it, like they're on a medication that is relevant to aging but they don't know it... And so I think that's the fascinating question. Will it be case that we've not solved the problem, but made advances, and just be kind of sitting around unaware or unable to measure that.
Sonia Arrison: You mentioned tackling aging, versus right now I feel like we're still in this model of tackling the diseases of aging. And there's all these questions that surround that, in terms of, will FDA ever consider aging as a disease? Are we ever gonna get there, and does it even matter? Should they be separated like that? Like the diseases of aging versus aging, or are they all in the same bucket? What are your thoughts on that?
Simon Melov: This is a question which is often discussed within the aging community and is slowly starting to seep out into the regulatory area. For example, Nir Barzilai and his colleagues, who are proposing using a very well tolerated compound like metformin as a multi syndrome agent to address many aspects of aging simultaneously. That argument has been had with the FDA, and they appear to be quite receptive to it. It does open up a whole bag of worms about how you measure all the different impacts, and it does fly in the face of conventional pharma thinking in the sense that you want a drug to be very specific to one tissue, one target, and you don't want it to affect other things. In fact, if you were able to reduce heart disease as well as Alzheimer's disease simultaneously, that might kill your drug pipeline, which is kind of crazy from the perspective of an ever-expanding aging population and the incidence of all these things going up. So it is going to require a sea change, in terms of both the regulatory bodies as well as the researchers, to begin to think about aging as the single biggest risk factor for all disease There's no question it is—you can point to a handful of exceptions: infectious diseases, childhood diseases—but the vast majority of billable disease is aging. So when you begin to treat that as a problem, then maybe the pipelines will open in terms of investment in new companies, and so on.
“The challenge from a company perspective is that right now we can't measure aging very well.”
Kristen Fortney: The challenge from a company perspective is that right now we can't measure aging very well, and the ways that have been proposed would require really massive clinical trials—and so you really want to spend $40,000,000 on your Phase II when you don't have to... And this is very much on my mind right now as well, because we have our first drug, which if everything goes well will be in people in a couple of years, and I wish aging were an indication, but it would have to be one where even in a small number of people in a short period of time you can see an effect...and I don't think we're there yet...
Sonia Arrison: Do you think that model will ever break down, the way that it is now? I feel like at some point it's going to break, but the question is when, and what's going to break it?
Aydin Senkut: ...Parkinson's and cancer don't happen overnight. It might take 20 years. But then in the last year or last two years it accelerates, and that's when all the physical symptoms start manifesting. So the problem, though is that that's when people are most urgently caring about cures, so we're always spending all our efforts on the 'last mile' in this case, and I'm thinking of longevity as almost like a vaccination... What if all of a sudden we could say, well, if you could just do this, rather than an 80 percent chance of cancer, you've got a two percent change. And if we could get to that point where we can quantify that impact I think everybody, including the payers, the health systems, the governments will have to care about it...because if you don't, you have to spend 20x the money, which is money that no one has. And so like I think if we can re-educate people and it could be re-understood in a way where that's the real impact, that's why it's so important for the ecosystem to work, for these companies to succeed, I think it's going to change people's approach.
“The idea of ‘longevity’ or ‘aging’ sounds too general. If you were to…make it a properly named disease, that would allow a broader-based approach.”
Laura Deming: I think it might be partially a naming thing. Like, arthritis is the inflammation of the joints. But the idea of longevity or aging sounds too general. If you were to call it "aging-itis", or you were to make it a properly named disease, that would allow a broader-based approach. If you look at a lot of the diseases we treat today, they're not well-characterized. In fact, a lot of them are far less characterized than aging: they're hard to pin down, organ-specific, we don't know what causes them. For example, IPF - "idiopathic" means "we don't know what causes it," and it's in the disease name! And so the question is, what's the new disease name for aging?
Sonia Arrison: Okay, good. We can take that away and start thinking about what the new name is going to be.
Kristen Fortney: I was forgetting, but resTORbio is creatively going after aging. They're looking at a number of respiratory infections as a measure of immunosenescence in their clinical trial. It is short term, but it is pointing at more general aging mechanisms, which I think is really interesting.
(At this point, the speakers turned the floor over to the audience for questions…but didn’t turn over the microphone, so much of the discussion could not be recorded and therefore was not transcribed. Rest assured that it was fascinating.)
Disclaimer: Hourglass receives financial support from Longevity Fund, which exercises no control over its content.