Increasing Healthy Human Lifespan, Laura Deming of The Longevity Fund | Transcription

Transcription for the video titled "Increasing Healthy Human Lifespan, Laura Deming of The Longevity Fund".

1970-01-01T05:45:47.000Z

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Introduction To Longevity Research

Why focus on longevity now? (00:00)

Solar, why now in terms of longevity? What's happened to make you raise a fund and start investing in research in companies? Yeah, so we think this is an insanely important part of the story because if you were Aristotle and you were trying to start longevity fund, you would have a terrible time. It'd be like the worst idea. And so timing is super important. Why now for the first time in 2000, 3000 years of the correct time to work on longevity? To us, a lot of that comes back to tooling and what's available for us to use. You know, prior to the 1900s, if you wanted to impact biology, you know, maybe you should have been a physicist. You know, worked on optics, helped make the first microscope and like Robert Hook, a physicist, you know, discovers the cell. So, you know, there's so much that comes from physics and other disciplines into biology to push it forward. But then I think in the 1900s, something kind of fascinating happens, which is that for the first time, there's kind of this acceleration of tooling, right, x-rays, NMR, all these things, you know, the cathode very too discovered mass spectrometry. But you know, by this guy trying to find a massive electron, which is so cool. And so all these physics tools start, you know, coming online, but also more biology-driven tools. And so really, I think, you know, and we can get into this more specifically in the earlier time, but kind of what's excited us is just seeing the tools available to characterize, like life become available for the first time ever, right? You know, for all millennia, you had Darwin and like Mendel talk about genetics and like there was no knowledge of what was actually going on at the ground truth level. And in 1953, for the first time, you have like the link between molecular biology and like we're looking at microscopes and like genetics and like this, you know, sort of concept of fredity, which is just super exciting. And what caused you to jump in? Well, I mean, a, I think it was born in like a very lucky time, right?


Discussion On Longevity

How did Laura get started in longevity? (01:50)

Which I think you always have to be, you know, sort of cautious or like, I guess like a little bit concerned if you believe that about yourself, right? Like, why now? Like, you know, should it really be the lucky time? But then I think also, you know, as a kid, or a just like had a lot of relatives that were, you know, sort of aging and that was, you know, very striking, but also, you know, really wanted to solve cancer. And I remember talking to my dad about this and I was like, oh, like, I want to solve cancer. And it's like, well, you know, cancer is just a subset of aging. So if you want to solve cancer, you just like, you know, solve aging and like take care of all these other things as well. And that just ain't that coupled with kind of like hanging off my grammar. So like, that's just gonna make sense to me as a kid. I was like, okay, well, like, yeah, guess I'll go solve aging then. Like, that's the biggest problem. Because cancer is not the number one cause of death in the US, right? It's heart disease. Right. Well, you know, if you look at all the age-like diseases, you know, past this certain point are driving kind of like the majority of sort of natural deaths, so to speak. So, you know, like, you know, once we got rid of infectious disease, like, it really became the case like aging, which wasn't previously like necessarily the biggest issue sort of like rose to the forefront. Yeah. And so that kind of, I mean, this sort of just, I think made sense to like a small trials that that was important. Huh. And so why raise a fund rather than, you know, just go for curing cancer?


Why raise a fund? (03:00)

So the thinking at the time was, you know, possibly in a good way, like, emperor has no clothes like extremely simplistic. Like, you have to understand, so I was at MIT and I was like a sophomore. Yeah. And I was also 16. And I had like maybe a thousand dollars in my bank account. And so like, you know, knowledge about like the financial industry, like we're also below, my dad had been a public investor. So I kind of knew a lot about like the idea of investing in things like that. That was a generally good thing to do. And I'd worked in like aging labs for maybe four years. And I think the striking thing was just like there, there was just like no money to like make drugs. And it's kind of hard, you know, like when you're in a lab, you just have like no idea what's going on in the outside world. And so I would like ask venture capitalists, like, I, you know, call up a few in the phone book, like, you know, a few responded and so like, have these like brand conversations and just be like, you know, I'm just a curious student. He like, tell me more about like how this industry works. Like, you know, are you funding aging therapeutics? And like, none of them had heard of like aging therapeutics. They're kind of like Asian therapeutics. Like, what did you say? And so that was just very striking that like, something that I personally believed, like on the technology, like not just like from a mission perspective, like on the technology side was like super exciting, was kind of generally not really like looked at a lot by these folks who are supposedly like the grace translators of technology. And then I think also, it kind of made sense, like, you know, the first ever mutation found to really extend world lifespan was in 1983. The next was like 1993. And so really, I feel it started about like 20, 30 years ago. It's like, kind of made sense. Like, if you think about like how long it feels like get traction, like become known, like, okay, there may be like, less than 100 good labs in this space. Maybe like people just like haven't had enough time on like the venture or like investment side to understand that this is like really cool and important. And so like, then it kind of made sense that like, you might want to start a find at that where the case like help more drugs kind of get started out of the space. So in other words, like the big pharmaceutical companies are not investing in these, they weren't at the time. So it's like five years ago, something? Yeah, seven years ago. Yeah. So things have really changed. You know, seven years ago, there were like maybe like three companies have been started or so that had like the aging brand on them. Yeah, there was like zero people on shit. Like arch ventures was one of you that were like taking risks. There was like maybe 10 million invested like that year in total in like the space, right? And like in the past four years, we've had like 10 billion plus. We now have like 200 companies per year. So it's just really changed. Like it's very, very striking to watch you go from like zero to like what it is today. Yeah, now it's totally a trend. Hopefully it sticks around. So you have not a million, but many questions for you. I think like top of the list for me is what you do personally. Yes, this is probably the most common question. And I think all my friends will always say that I answer this terribly because I, you know, I'm kind of like, you know, I come from a semi-scientific background.


What does Laura do personally for longevity? (05:30)

And so like we like to get like to the ground truth of things. And it's just really hard. Like there's just like a million. Like if you start reading mouse size longevity, like you will find mouse size that say like if you decrease, like they've done this like really cool experiment where you take fat and sugar and protein and you decrease the level of each of them to keep a total calorie intake the same, you can kind of test like which component of diet is like contributing to longevity. And they did this and they like did kind of like a full matrix and they'd like less than studies for each of like the different proportions. And what they found from that study in mice was that like decreasing protein was the number one kind of thing that increased longevity. And so from that you might infer that like maybe less protein is good, but at the same time it doesn't seem like, you know, maybe if you work out a lot that would be different. And so I've come to the conclusion that kind of like, you know, I have some thesis about like what is good and what is not good. But it just as a scientist, it's really hard to say that there's kind of like a good kind of like real kind of like hypothesis there. Okay. And so, so much are like not a lot of like like not just despite like reading probably more papers on this than like most people in the world. Yeah, it really is something where I don't see things that I think are extremely clear kind of like movers for longevity on like the diet level, obviously that like are confounded by other things. So what's your diet? Well, I've tried a variety of things. I think right now it's just kind of like the sort of like bare minimal like try to eat low sugar, personally trying low protein just because I think that is somewhat supported by kind of like literature. Yeah. And low protein is like a gram per kilogram per day. I think to sort of like not it's a good question is like what is the correct per person and also if you exercise. I actually once tried to calculate out if you exercise like how much protein would be required, like a person just like all of your mouse and action proteins. Yeah. And it's kind of fascinating. I think that there might actually be like up to 100 fold increase in power like in your muscles where like if they all fired at the same time and get like you know sort of a lot of power. But any but I mean, I just I don't have any strong recommendations on diet. Like I really like I read basically all the studies. Yeah. And I think maybe low protein, low sugar are both like instrument fasting seems to be like somewhat supported. Are you doing that? I've tried it. I think it's kind of hard to maintain if you like, you know, have a graduating sleep cycle. But yeah, I wish I had better recommendations for that for that area. Okay. And in terms of supplements, you doing anything? You know, there's a variety of people working with everything from AD plus all the way through to like Metformin for the kind of the more adventurous. I think that so we actually have a secret list at the fund of like on market drugs and things that we think based on like our like body of evidence might be having an impact on lifespan and we're monitoring them. Some of them, I personally think it would be like intriguing to take. We don't release that list just because we were afraid that if we did and kind of like somebody acted on it and kind of like didn't work out well for them that's like a terrible thing to do to like them. But we have a secret list of things that we think are like interesting. Okay. And I but I think we're then in D plus though, there's there's some evidence to like positive fact there. But we haven't seen great life in studies showing like a large increase in lifespan. So that'd be like my one concern there.


Worm and mouse studies (08:45)

Okay. Cool. Because yeah, in the worm and mouse studies, there have been like, you know, 100% increase in lifespan, right? With certain. So, so worm studies, we've gotten up to 10 fold reported, you know, possibly more. That's by decreasing a gene product though. So that's kind of like if you want to go and take a gene therapy, or we had such a thing, you know, poly, you know, from birth, possibly like that would work. But probably they fact to be a lot smaller. In mice, we've got about it up to a twofold increase. And that was a combination of a mutation and restricting the total core intake of the mouse. Okay. Down to what? I don't remember for that study on average. I think people will do CR to about 30% of normal core intake. But it really varies. So if you take 40 different, and this is where it's complicated, you take 40 different genetically different strains of mice, and you change their diet in the same way, half full of shorter and half full of longer. And so, you know, I used to, as a kid, I was like, oh, you're like, there's a simple answer. Yeah. And I think that there is. But I think it is a lot more sort of reliant on genetics and other things than we'd like to think. Hmm. How long have your family members lived? How long have my family been lived? Great grandpa is still going. She's in her mid 90s. It's a good sign. Yes, exactly. So they've all lived, you know, about age 80 or above. So, you know, hopefully, how about yourself? How long is your family? 90. So, yeah, we'll see how it goes. I need it more than you. Right. Yeah. What would you say the number one health hack that you'd recommend to your audience would be?


Craig's personal habits (10:20)

I mean, well, I mean, I've done a little bit of blood work, so everything's kind of anecdotal and based on feel. But I was vegetarian for eight years. Oh, interesting. For environmental reasons. And then I realized that I had developed this entire vocabulary around cheating. So, for example, if I was traveling, it was like cultural meat. And it was allowed. And then, you know, if I was like, you know, over your house and like you made chicken or something, I'd be like, whatever, I'll have it. I see. And at the point, it was like twice a month. I was like, I'm not vegetarian anymore. So then I started eating more protein, but really just more eggs. And then I felt a lot better. But really, the main thing is sleep. I think, prior to that. Yeah, that makes sense. I will say that actually one thing that's interesting on the health span in front, I think people have this like intuition that when they feel better, that's a metric, that's a metric for something that's good for them. Yeah. And it's actually not true. So if you look like a lot, to some extent, like, you know, maybe you want to optimize like robust, very cheerful lifespan, in which case, like, like, tautologically it is. But most of the time, a lot of the time, when you see our mice or you do other things, like make them live longer, so a total number of years increases, they're not kind of like as happy on a day to day basis, like a little bit thinner, a little bit more of the larger, in some cases. So I think it's kind of like, you know, whenever someone says like, I really feel better, because I'm doing guys, I'm always like, Oh gosh, like, I wonder if that's like the correct thing, like, maybe maybe not hard to say. When people talk about health span, in my mind, it's very correlated to how I feel. Like, if I was going to do a caloric restriction and every day would suck for 90 years, I would opt out. I mean, I don't know if there's a drug, I, for instance, like, I know a lot of people who have experimented with like keto and other random diets, and they're caffeinated to the gills. Like, there's no energy. That's so funny. That's one thing you can do. Oh my gosh. Yeah, it's hilarious. Yeah. Yeah. So I don't know. But one thing I've been curious about, like, there seems to be relatively limited data on actual humans.


Human studies (12:15)

Yes. So how might someone set up a set? Is it even possible now? Or is everything so regulated? Well, so there is this fellow in your bar's life who's working on what's called the Tame Trial. And the point of that is to assay the effects of this drug, but for which is a very old diabetes drug, on sort of markers or biomarkers of aging that he has kind of like put forward. And the cost for that will be about $60 million. And if people do it, the idea would be, okay, well, here's our first pass at testing aging in humans. And so finally, we have some more data. The way that trial was sort of motivated was there was this kind of large finding that in hundreds of thousands of patients, or I think about actually 70,000 that population from kind of like a UK study, if you look retrospectively, people who hadn't taken that form for decades, they had apparently like a little bit better kind of health span. So they had less HLA disease, the diabetic sit on this drug, even then they're kind of like non-diabetic counterparts who were not taking that form in. And so I think, you know, hard to study is kind of like definitive evidence. But that kind of motivated all this sort of question asking of, you know, could we really nail down in humans a trial to like test, you know, mid form in particular? That said, you know, I think that, you know, a lot of biologists will really kind of, you know, say, oh, it's very important to test things in humans. And of course it is, if we could do that, we would be doing it kind of all over the place. But I think increasingly over the years, and maybe it's just like I started out in worm biology, I'm kind of like more and more excited about like the animal kingdom. Like, you know, the animal kingdom is just like absolutely awesome. Like we have one company in our, you know, current sort of, you know, sort of portfolio that's working on this. They're amazing, Yofana. But kind of like, it's like, there's such diversity of phenotypes, right? And like, how can we learn from other animals, supposed to just like, our lowly selves? Because like, you know, for example, there's naked mole rats and rats, like naked mole rats are pushing 30 on lifespan. Like we have no idea how long they live. Like, their mortality rate at 30 is not going up. So we're just like watching these guys, like waiting for them to start dying. And then like rats, which have like very similar physiology, live maybe like three to four years. And so what on earth is different between these two animals, right? Like, like that's just absolutely fascinating. I think that's also important because like, you know, you, a lot of like your physician mathematicians, and I used to be this way, like we're always worried what if there's like inherent like limitation on like the complexity level, like what if given a certain complex system, a certain rate of metabolism, like, you have to die because there's some kind of like, you know, sort of theory about like entropy increasing over time and that like, you know, must drive and just like too complex, like really intervene. But then like, you know, these animals are basically the same size, like have so like, so many other similarities, like it would just be very hard to maintain like that theory and also accept this kind of like large differential longevity. Yeah, absolutely. So someone asked a question that I thought was kind of funny. Yeah, here we go. So Mike asks, basically, do you think immortality is going to be achieved by curing all diseases?


Mica asks - Do you think immortality is going to be achieved by: 1. Curing all disease and stop aging so we could live with our own bodies forever 2. OR is going to be something like porting our brain, "mind" to a computer/robot? (15:00)

So in other words, like the forever or like what's gonna happen first, that or are we going to just upload our consciousness to a computer and live forever that way? I think that, so that that is a question that I used to get very interested in sort of like, well, you know, if you like care about this, like you'd be working on kind of like the biology. Yeah, where do you work? Yeah, exactly. I think so the way the way I kind of think about it, which is not a good answer, but it's kind of like a frame of rethinking about this question is I think about biology like a set of tools, right? So you can kind of see this in like the kind of like things that had become available recently for us to use to affect human health. What I mean by that is like, you know, prior to like, you know, the 1900s or like, even like just the 1980s, or maybe like the 1930s, like the first time you really put the marker, if you wanted to make a drug, it was like a small molecule, right? Like it was like, you got a plant, you found something from a plant that was useful, or you like put some salt on a wound, which we realized that's a bad idea. Don't do that. Not very not very good for sterility. There are things you would do. But then like, you know, in the in the 20th century, for the first time, we use like proteins, you know, insulin or antibodies created by like our own bodies, or you know, the bodies like the mice that like we kind of, you know, quote them in, to treat disease. And so we actually use something that came from life to treat, you know, kind of like living organism. We now just in the past kind of three years have like landmark approvals and viruses being used to like blow up cancer, literally like these are called oncolytic viruses. There's new drugs using genetic engineered cells. You've probably heard of, you know, CAR-T and kind of like this whole kind of, you know, ecology phenomenon, also stem cells being used. And so I think kind of like the final frontier of all of that, like use of kind of like by all these own system to do cool stuff is the brain understanding kind of like that system. But I think to lead up to that, you kind of will do so many things that maybe the case that like we kind of get there the same time. Right? So, you know, like that's like the final frontier. And we solve that kind of like along the way of also kind of like done enough work on the other tooling kind of fronts that we get to kind of like do a kind of, you know, maybe we don't solve kind of like lifespan itself, but like longevity is definitely impacted by kind of like the work up to that time. Right. Exactly. And do you sense that there's like a strong signal at this point as to what might be the way that we, you know, a bunch of people ask these questions, but like, you know, increasing lifespan like 20%. Like if you had to put money on it, obviously you literally put money on it.


Most likely strategies to increase lifespan (17:15)

Yes. Like what would be the most likely thing to take off? The most likely thing to take off in the next 50 years. So here's how we think about it. Like we have extremely strong confidence that it's possible to impact lifespan between like, you know, three months to maybe 10 years. Yeah. And you know, obviously like, you know, different probabilities with what we have to in fact, we're pretty sure that there are some things in the clinic already or on the market that with some probability are impacting lifespan. Right. Okay. Life span seems to be very malleable. You know, to a small degree, I think the larger question is like, well, you know, A, how many of those can you like put together to like get kind of the maximal impact from like that first wave? And then B, our thesis is that none of those things will be sufficient on their own to result in like an engineered lifespan. So you have this first way of things like kind of work, but like they're kind of limited, like they have kind of like a maybe like 60% and that's like the max. So then the question is like, how can you like go above that? And we think that really all comes back to tooling. So that's where I don't know if I'm, you know, we're Aristotle or kind of like we're like Newton or like maybe like in the best case scenario, we're like Einstein or like, you know, of someone today and in the realm of physics in terms like going to the moon, like you've tried to go to the moon and kind of like 600 is a little bit hard, more recently, maybe a little bit easier. But like, I think that's where we have we have some hope and optimism, or we're not as confident that there are things today that we'd point you to say, that's going to result in kind of like unbounded engineered ability to kind of like impact longevity. And that's why we also really care about about tools when we think about like investing in this space, not just kind of the first wave of like awesome therapies that'll be available sooner, but like maybe aren't just kind of like, engineerable. Right. So you're kind of hedging if this is still foundational stage. Right. Exactly. I think we'd love to think that it is. And like, yeah, like 1953, my argument for foundational stage would be like, this is the first time ever in history that we have the link between genetics and microbiology. Like that happened in 1953. That's pretty landmark. Maybe it's been 70 years, like what happened in seven, you know, couldn't just have happened like right after 1953. But I think that'd be the argument for like, that's why today makes sense from like engineering perspective. Okay. And then ethically, you know, Ryan Hoover asked like about the ethics of longevity. Another Jack Fernandez asked like, people want to actually want to live longer.


Ryan Hoover asks - Ask about the ethics of longevity. Jack J. Fernandes asks - Do people actually want to live longer? (19:25)

Right. Do you have strong opinions on this? Or you are stepping back? So we get asked about this all the time. And it was funny because when I started the fun, I never thought that people would ask those questions. Yeah, you thought it was assumed. Well, because the reason we started the fun was like, cure like things like cancer and Alzheimer's. And so like from our perspective, like, you know, like you would never ask like, is it good to cure cancer? Like no one would ever ask that question that I've heard it or maybe some people would. But then we realized that like when people think longevity, they think about it as different than those things. And so I think like, you know, from our perspective, like that, I just, you know, I think it makes sense to cure cat like these as if we can. And so we definitely wanted to do that. And so like, you know, we would never deviate from kind of our mission. I think, you know, from a broader scale, it's kind of like two camps, like, do you want to be like malthusian? And you're thinking of like, you know, the world is like a bounded place, like, you know, it's really like limited resources or like kind of like David Deutschian, like, you know, like, you know, like, you know, we're on, you know, spaceship earth, but like, no, we're not actually like, let's go and like, spoiler cause, I wasn't kind of like unlimited resources, you know, like, energy is like an all matter. I think like just like kind of like from a like, philosophical standpoint, I'm more on the kind of ladder sort of camp. I just like that kind of viewpoint a little bit better. But yeah, I think to us, like, just the like the rational philosophy of what he really was, let's curate play diseases. How do you do that? You work on aging? Hmm. And yeah, maybe they're multiple universes where we I'm trying to get David on the podcast. I met him one time when he talked about it. And really, yeah, yeah, would you have to like go to him and his house? That's what I did when I met him. That would be the best interview ever. Yeah, he did run with Sam Harris. It was kind of cool. Oh my gosh. But really like in terms of having an actual opinion on this, so there was a cool one on the ethics Mike asked, how would immortality change society? Wouldn't we become more complacent since we have to quote forever to do things? Wouldn't that diminish our rate of innovation?


Mica asks - How would immortality change society? Wouldn't we become more complacent? Since we have "forever" to do things wouldn't that diminish our rate of innovation? And since less new individuals are being created we would have access to less new ideas. We would just stop creating new Newtons, Einsteins, Mozarts… (21:20)

And since less new individuals are being created, we would have less access to new ideas. In other words, like, there are fewer newtons, fewer einsens and sort of this is like, yeah, why the the basic income or one of the basic income arguments, right? We allow for these people to succeed. Well, so I think there are two implicit assumptions there. One is that we understand how people are motivated and that their motivation stems from this feeling that like they will die. Yeah. I think number two is this idea that like people have an innate kind of rate of loss of new ideas of age kind of innate like loss of openness. And so I think, you know, addressing both those on the first point, but I don't think they're kind of all questions. I don't, I just, I don't think that that's true person. Like, I don't think that like I'm motivated to do things because like I know that I'm going to die. Like, I think that, you know, perhaps everyone else is, and this is just kind of like a personal thing. But I think I'm motivated by many things like curiosity, competition, sort of like, you know, personal growth kind of like wanting to be like better next year than like, you know, was today kind of like a sense of mission and importance, kind of like, you know, it's important to go do certain things. And, and, and, you know, I think if you ask most people, you know, maybe they'd have different answers, but I just, you know, I'm curious of like death really is like the core kind of like motivator to do things. Everyone in the world like that. That's one thing. And my result in few people wanting to go to war, which might be called Maddock if you kind of like want more war and more soldiers, or not if you would like less war, like that interesting thing. But I think for that question, I just, I don't, I don't agree that we really understand like the core motivation of everyone on this planet, and that that is by its sort of definition, the, the fear of death. I think the other thing that's interesting is sort of to the second point, the question of like loss of ideas with age, you know, there is a lot of like just cognitive like change with age, which is very fascinating, right? And sort of like, you know, biologically, you do change. And like, you know, part of what we like really want to do, you know, is impact aging, but like a large part of it, like we can just make a cognitive enhancer, you were like sharp until you're nine, and then you, you know, dropped. Like that would be equally like that to us would be like an awesome product in of itself, like just cognitive enhancement, like alone would be great. And so I think, I think actually people kind of like under counting the value potentially, you know, if you're a Newton, absolutely brilliant, and you help develop a field and maintain your 20 year old openness and kind of like fluidity for 100 years, all with you to age 90. Yeah, like what insane kind of ideas would Newton be coming up with at age 90? Yeah, like with that kind of openness, the counter argument there was like, well, he would just go and do alchemy. And so then you have like, you know, young Newton being great, and then like old Newton, like doing alchemy, they'll kind of carry argument is like, well, maybe alchemy like caused a decline in thinking because like he was sniffing too much mercury. So everyone can carry. Yeah, you almost won an argument for like outsider scientists who don't get discovered until they die. And then they have like 100 years of portfolio. Right. And then they're also just, I mean, like so many people, like, you know, some incredible physicists at Stanford who are still amazing and coming with extremely, all these, like, you know, Hawking publishing on like black holes and entropy, right? Like this final paper, like on this completely novel, fascinating field. And like, was that like, you know, was he declining? Would we like talking to kind of like step aside for like the younger generation? Like can't we have both, I guess would be a question. Interesting. So would you be a proponent of like, you know, giving the entire like somewhat like Florida in the water, putting like provigil in the water? I think that I'm never a fan of things that don't involve individual choice.


Cognitive enhancement (24:30)

So anything that like would be sort of a coercive or kind of like enforcement than like no, but I mean, so like if everyone looks like it, sign up for it, then like, I do think that, you know, there's like all this fascinating work on like cognitive enhancement, like just starting to come out today. And that's a story. We've seen a lot of companies that were super excited about the HAFSTU, kind of like, you know, making your neurons kind of like make more scientists like increasingly, they're like rates of division or, you know, hypothetically, I think that aerosol but contentious. But you know, like that to us is kind of like, that's part of longevity. I mean, if we just had a pill for like cognitive enhancement, you know, that that that in itself would be like, absolutely wonderful. Yeah, yeah. I mean, everything I've tried, it's yeah, it works. There are some times where you get this feeling that you're, you know, you're really good at like your crush and email, but you're not the most creative. And you're just like sweating the whole day. Not coming up with the deep thoughts. Yeah. It's actually fast. And remember this book on daily habits? No. I would actually recommend, I think you might like it. The daily habits of mostly writers and artists.


Daily habits (25:30)

Okay. But it's super fascinating because the details can like how they live their life. And it's just extremely variable. But the most common thing is that they all wake up and go to sleep. They have a very certain routine. And when they wake up, do you work and go to sleep? I'm already on that cycle. Yeah. I mean, what a thing I have found is that my, my mornings are just much more valuable than my evenings, especially in the middle of the day. Like I'm just kind of useless. So I just work at it like two in the afternoon. I'm curious why that is like it's either biological or psychological, right? Sort of like, you know, you get like too much loaded into your brain and you don't want to think or it'd be really fast thing if sleep played a key role there. It would sort of like sleep does something biologically and props psychologically that like somehow induces like an optimal state like right when you wake up. But yeah, have you tried it like sleeping in the middle of the day and then just getting back to work? I have, but that's an interesting idea. Yeah. I'm curious what that would do. Possible interest. Yeah, I'm so curious about cognitive enhancement. We did a podcast with Rosalind Watts who is an Imperial about psychedelics. Oh, that's awesome. I mean, it's very similar. Actually, her research with Robin Carhart Harris at Imperial is in Michael Pollan's book. Oh, interesting. No, I've heard so much about it though. It's really great. But I mean, it's kind of like cognitive enhancement in a very broad sense in terms of like trying to break you out of your old habits and like have more confidence. Increase openness and yeah, exactly. And so are you taking anything to like any in the new Tropic sense? No, I think I don't even do caffeine because the general thought is like try to win yourself off of everything kind of like if you can perform great there than like perhaps someday like they'll be a safe job that comes on market. That's worth trying. Yeah, I also like I like Marcus Rillis like Stosas was like the idea of kind of like, you know, none of the necessary things but like maybe there's an application of that philosophy now I think about it. Yeah, some part of that just makes me angry. Like I just like I want to, well, it's like it all, you know, kind of like the caloric I'm I don't know, I'm a dichotomy. Like it's it's all stretched apart because I'm very much a creature of habit. Okay. That being said, I like caloric restriction, not having like a beer with my friends, like all of this stuff. I just like don't I'm not doing it. I'd rather I'd rather work out an extra time but then but then some people say like that's bad for your heart, right? You know, like you can't win. You can't win. Yeah. So I don't know. I feel like in some ways it's like the devil I know and I just avoid other vices like texting while driving and smoking. That's interesting. Hmm. Hmm. What is like the thing that you do that you're the most proud of? Like the habit that is like hard for you to maintain that you nevertheless are kind of like quite happy to like be able to do. I mean, exercise is no problem because I go crazy without doing it. Right. I think what's consistently the hardest to maintain is giving energy to the side projects that are creatively demanding. Oh, that's interesting because I this is what I didn't expect. I used to work for myself and I work at YC and obviously and there are obviously like you have so much energy in the day and obviously you can like push harder and get worked on and like be more disciplined but I found that like there are certain side project ideas that are just kind of like too much to even think about. Oh, interesting. So I'm yeah, like when I when I make progress on that, I'm very happy with myself because the side projects that are like, you know, I've like made like little sass tools and stuff and that's cool but it's definitely not the hardest thing. And what like allows you to make progress on those projects? Just internal motivation, like wanting to do it. I think the what's always helpful is just imagine imagine yourself in 10 years and like look back. Oh, interesting. And then just use that as a metric for like what you want to, would you be proud of yourself for having done that? That seems like someone like the business framework of like, you know, when you're 60 and you kind of look back on your life. Yeah, that's interesting. But then but it's dude, it's like who's to say what's going to lead to the next thing that's great. So like, you know, all right. So before we did the podcast, like I was talking about working at the onion, right? Right. And now I'm here. Yeah. And you're like, that's not a standard trajectory. Right. So you can't really say authoritatively, like the best way to spend your time is X. But when I when I was a kid, someone said to me, like before you start working on something, think about what winning looks like. And that's kind of a framework for projects for me. Oh, that's interesting. But I don't know. That's a personal thing. What other like hacks and motivations like do you have in your arsenal? I just don't spend time with people that annoy me or like stress me out. Okay. Yeah, that's a positive thing. I am never busy, but I am fine using that excuse. Oh, you're never busy. I always have time for my friends. And like the things I really want to do. And I just cut everything else out. So I don't know how about you. That makes hacks and motivations. I think it's like always trying to keep the baseline pretty, pretty low, like kind of, you know, like, yeah, like, I think like you can control like your output, but you can't really control like how the world responds. So it's kind of like, if you're just like, all right, if I do good output, then like that's great. And then like however the world responds, like can control it. But like, like being really happy when you do stuff that you can control is I think probably the biggest, like mental hack for, because I mean, you usually just can't control. It's so hard. Because you're you're still pretty. How with you? Uh, 24. Yeah, yeah. So I remember when I just moved out here, I am. How old were you then? Uh, 23, 3? Oh, interesting. And you just come out of college? Or? Yeah. So what happened was, um, I was in New York for college, and then I lived there for like a couple years afterwards. And my girlfriend and I split up and I was like, I'd always wanted to live in California. And New York was just like, I was just like grinding at me. And so I just moved out here. Oh, just then. Wow. Which has been cool. And so when I did you have a job or something, we just like moved out. So the onion moved from New York to Chicago and almost everyone left. And so I started accompanying with my friends. And we were doing these hackathons where developers and comedians made stuff together. And it's like, it was a total not startup, total small business. Super fun. Yeah. And we did one with Twitter. And so I moved out here for that thinking I would be out here for like months. And now it's like, whatever, six years later. But what about California was like so different for you that you had to stay here? Well, I love doing the outdoor stuff, for sure. Okay. But it's a trade. I don't know. Everyone wants to talk shit both ways. And it's totally a trade. Culturally, it's not the same thing as New York. But then if you're working in like tech, this is where or entertainment stuff, I mean, New York's kind of mix. But there's LA. It just seems so much so much more professional. Not in like the polished sense. But like, everyone is like, most people are here. And that's cool. That was cool to me. Like going to these like, you know, coffee shops and seeing, you know, this person that I only seen on the internet before. And I was like, man, all this shit's happening here. That's interesting. But I don't know. How do you think these have changed? I'm also sorry. I don't want to like to. But how do you change like in the past seven years? Or I guess, has it been seven years for you or something like that? Yeah. What has been the biggest thing that's changed? Like, I either both positive or negatively or neutrally.


Technology & Entrepreneurship In Labs

Tech environment changes in the past 5-10 years (33:50)

In myself or in the environment that you've seen from like, oh, yeah, that's super easy. Yeah. Tech is completely vilified. That's been the biggest. Oh, interesting. Yeah. Yeah. I mean, it's like, if it's not this next election, it's the one afterwards, like tech is the evil thing. Interesting. And what did you see what drove that or kind of? Um, well, in some ways, it's like an incredible amount of wealth being accrued to a small amount of people. They're young. And I think their amount of power is just off putting to so many folks, obviously with the Facebook thing and like, like, you're like, you have like the person to vilify. It just feels like the new banker to me. And that's the, that's been the shift. Like not a great precedence. And I don't know. Because have you noticed anything? Um, honestly, I think it's kind of like in bio is just, you know, 200 of his attention to bio. Like we're just all the way over here kind of like, you know, working on things that take a really long time are very like hard and expensive. And so people like, oh, you know, they're still over there, like still working on drugs. And so I don't, I don't think it's as much. And they're like very few weirdly there, very few billionaires in biotech. I think this is something that was very striking to me when I first came out. I was sort of like, I was looking for people who were amazing and also I made like a lot of capital and buy because like those are people who like wouldn't be successful and like know how to build business as well. At least was my thought. And there were very few of them. A lot of them were in VC who had invested in these companies. I was like, where are the founders not getting the capital that like, how does that equation work? Um, and then I think, uh, one of them was like a, a former salesman. And it's like the most informative meeting I ever had about sales, he was just like, cause I was front-end, I was like, how do you sell a business or an idea? I'm like, you know, you know, from MIT, it's like, you know, complicated, like, we had a textbook about it. And like, right. And he was like, you just sit the person down and tell them what to do. I was like, okay. Now I think I understand how this like whole area of like life, you know, how to communicate a little bit better than I did previously. Yeah, it's so funny. Yeah, I really hope more of these companies, I mean, they're, they are popping up already. Like you've seen longevity biotech. Um, and if there is any kind of lull, in the ecosystem, it's just going to be like fertile ground. I think there was like, there's, there's been historically a lack of like founder different companies. Yeah. And like, obviously the fine environment has changed to make it like more likely to happen, like the next couple of years. Yeah. But it's just so striking. Like it really is different when you have like, cause you, like, I think people look at like the wealth created and tech and in biotech. It's like really see the distribution, you know, going so much more to venture capital, I think than to founders. And that was just, that's been like, really, those are really weird things kind of like observable, like first coming here was sort of like, why is that the case? Do you have different terms than normal BC funds? Well, I mean, I, for, for our funds. Yeah. I mean, if that's like a strong opinion you have, like what are, what are your terms? Yeah. Like, well, my definition, like, you know, we have H1, so, you know, so much, what, what you folks are working on, like, you know, that, that's founder driven, that's like, you know, and sort of trying to get people, you know, sort of leg up and, and promote kind of like grad students, postdocs as the founders, grads, the company, and like, not try to replace them. Yeah. I guess like, like kind of some other firms, which I think is a, you know, a fair strategy, if like, that's, you know, sort of, you know, something that, that's been your bulwark for like decades, but, I mean, I think marketers would say, it's similar to what's happened in software, like, you know, you had this first wave of kind of like, professional managers, you're kind of like a swingback to technologists, you kind of like, swing back to the middle of kind of like, now we'd like some more managers, please, but like, you know, still technologists are kind of driving the show. And I think it might be kind of like, midway through that, we're kind of like, we've had like, the managers period for a long time, we might have more technologists, and then like, maybe kind of like swing back to the middle. That's like a pretty simple pattern match. Like, you know, who knows what really happened in the future? Yeah, because the, that's interesting, if it's a trailing thing from software, because you probably know, yeah. So what's happened now is like, maybe 10 years ago, or when YC started, it was incredibly rare for you to be able to just like pitch an idea. Exactly. Yes. You can easily do that. But more importantly, you can, I mean, I hear crazy numbers from people leaving college and going to work at Facebook, or big companies. And then I think that's like, overall, probably bad for the ecosystem, because like, it encourages this like, extreme risk aversion. Right. And I think the likelihood of lifestyle inflation and never starting something is high. But think about, so what enabled YC, right? AWS, from the outside, a huge part of it, right? Like, the first ever ability driven by tooling to kind of spin something up really cheaply. And I think in bio, and it's like, what everyone talks about, it's really like, you know, there really was this point where like, you know, dropping costs of sequencing has been occurring over the past like, you know, 18 years, but really up until like the past three or four years, you could not get $1,000 genome, right? Like that is a recent phenomenon. And so like, what argument would be like, you know, look at like, luminous revenues, you know, like today, it's absolutely crazy how someone they are, like, Intel's revenues, like right in the 1970s, or like, like the parallel there is like, extremely, and this is, you know, a friend of mine, and made to like, notice this, but kind of like, there's just like, this real history, probably between like the enabler's technology, that we kind of see, you know, in kind of like one segment, and they kind of like, what's happening in bio today? And who knows what will happen in the future, but there is an interesting parallel there. Huh. Huh. Would you think there are people in labs? Well, actually, like what percentage of people working in labs, you think want to start companies?


What percentage of people in labs want to start companies? (39:00)

So this is the fascinating thing. So we were, we were curious about this, because if you look at the amount of funding that's available on the venture side to go into biotech in the past couple of years, it's insanely, I mean, it's double tripled in the past couple years alone. But the number of companies funded has stayed fairly constant. And so we're just looking at this, like, what the heck is happening here, right? And what's happened is like the number on the top end of like, the median hasn't even changed. It's like the top end of core, like the top quote on companies are getting more capital per company. So it's like, all this capital has come from LPs, because you've seen like, you know, the, the NASDAQ bio index, you know, go from like stagnant, you know, up until 2011, like, monotonically increasing, or it's different from a small dip. And then like, where do you put all this capital? There are no more companies to invest in. And so we were like, why are more people not starting companies? We went and talked like 100 grad students and postdocs. And the answer they gave us was like absolutely striking. It was like most of them. So it may be like, you know, 10% of our reputation risk, like they didn't want to leave fail and then go back. 80% had never thought about the idea of starting to come up. Like they just were not aware that there was, you know, a possibility. And so you could argue, okay, maybe that's like they're not entrepreneurial. But you know, if you think about like, you know, in the 80s or the 90s, like, would you have gone as a CS student and Stanford like started something maybe, like maybe you'd have a lot higher of a barrier or bar to doing that, right? I mean, that's part of why she started living that process easier. And so I think really well, since it's a lack of education, you know, and kind of like just availability of options to these people, which like, makes you so angry, right? Like, you know, like, you should never be forced or kind of like convince you something that you don't want to or that's not good for you. But you should be aware of your options, like, how are all these smart people not aware of like all the possibilities that are out there for them? I mean, it's, but I think the saddest slash funniest one I've heard is when someone often in like a hard science, like lab or background, they learn about why I see and then think that we're just giving them loans. And they're like, Oh, no, I can never do that. Yeah, which is like, I mean, I don't know. If you had no exposure to this, like, why wouldn't you think that? I mean, like, and all of these myths exist. But I think the education thing is a good point for the most part, people don't even know. That's absolutely crazy. Yeah, so you should talk about your, I mean, you have, dude, you have so many questions.


Pioneer (41:15)

But you should also maybe mention your project, Daniel, if because that's wrong. Yes. Yes. Yeah. So super excited. So my friend Daniel Groves started this really, really awesome sort of project called Pioneer. And what Pioneer is, is it's trying to find like the lost Einstein's of the world. I think it's like an awesome tagline. And you know, I think Danny has a fascinating background in that like he, you know, was kind of on track, drawing like the Israeli army and then, you know, uploaded a kind of application to YC. And you know, like basically like his whole life changed after like one flight out here, and in meeting with like, you know, Paul Graham and go sort of like this, you know, he's now this incredibly successful person, but kind of like, you know, would he have had the same chance if not for like a lucky, you know, I think his dad forged him like an article about what I see like that was how I found out about it, right? Really? I don't know. I think that's one of the one that you mentioned. So it's like, there's this coincidence that kind of drove his journey. And so the question is like, you know, how many people are out there that like this small intervention could like, you know, drastically have like a different life course. And so Pioneer, or Pioneer dot app is this place where if you're anybody in the world and you have a project you want to work on, you can apply anything anywhere from kind of like, I want to have more my high school friends do like science stuff all the way through to like, I'm 80 and I finally want to write my novel. And you know, there's this thing called the Pioneer tournament where people work for about 30 days, kind of, you know, do their projects and kind of like the community votes like on their kind of like most kind of, you know, favorite people. And then kind of based on that, at the end, you know, a set of people are selected to like be flown to San Francisco, they receive about like a $5,000 grant. And they kind of like join the Pioneer community, which is kind of like this, you know, set of really ambitious outsiders trying to change the world. And so I understand this because like, you know, my personal story was coming from New Zealand at age 12, you know, based on like a random email I sent to like a professor here. And it was the first thing later percent like someone who was on a phone number and she responded. But if she had responded and like that luck hadn't occurred and like, you know, where would I be? I have no idea. And so that's why I think it just like, Pioneer is so exciting because it might help a lot. And everyone who's listening, like, you should definitely apply Pioneer on app. You know, I think it unlocks so much potential. Like everyone in the world who like could be doing awesome things. I think it's so cool. Yeah, just enabling people to like have the confidence thing has been the biggest surprise for me at YC. Oh, interesting. I think a huge unspoken part of why YC is successful is that it gives people the confidence to do their thing.


Confidence (43:35)

Right. And they're often like, I mean, sometimes it's insider, you know, like, tracked, like I went to Stanford, whatever. But sometimes it's like total outsider people. And it works out. And I think that like, yeah, man, without systems that give people that that little extra push, a lot of people will never do it. Ah, interesting. It is kind of intuitive. Yeah. I mean, it's crazy. Like, because I do these office hours occasionally with people who are interested in applying, right? And they're awesome. They're great. And all it takes is like that one meeting where you're just like, you're good enough. You can do it. And that's it. That's so awesome. And then they apply. Huh. It's crazy. Interesting. Yeah. I mean, I think one of the fascinating things that the data is going to run into is sort of like, how do you give that to like, how do you scale that feeling of like transmitting confidence? It was like, you know, it's yeah, it's non-trivial. Well, you asked me about podcasts before we started, right? And so this is like a crazy side effect of podcasting because it makes you feel and the thing, it makes you feel like you know someone really well. But the reality is you kind of do. And so that relationship of someone as like, whatever, just like friend or mentor or whatever is enough to be like, oh, like, I kind of get this, I can be myself with them. And I can kind of just like express whatever I want to do. But then there are totally like weird elements for me. Like, I'll be like in the bathroom at demo day, literally, I'll be in the bathroom or demo day and like someone like tapped me on the back and be like, oh man, I like to podcast, like, cool, not now. That's so funny. Do people feel like they know you from hearing so many of your conversations with others and kind of like, how you think about the world?


Podcasting (45:30)

I guess like, because you said that one thing that you find fascinating is like how other people think about the world. But I guess like the way that you ask questions must give some information about how you build models or a few systems. Or how stupid I am. Yeah, no, I mean, I don't talk a ton about myself. I mean, I do, but yeah, people get the sense and I was actually thinking about talking to my friend about this this morning of like, what is it about the how am I different on the podcast versus in real life? Because there's like some dislike for both of us, right? There's like going to be some dissonance there. And I'm curious about like, how to best merge the two. And I haven't figured it out yet because I actually don't know what the gap is. So you don't know what your I mean, I was I was about to text him and I didn't and yeah, because I mean, you seem pretty kind of like on the surface similar, but yeah, I guess it would be hard to know without one period of off to me to listen to it before. No, just the conversation, like our 50 minute conversation before we started then kind of like, oh, right. But I guess it basically is the same thing. Yeah, maybe. Huh, interesting. Yeah, I don't know. It'd be better if you were more like the person that you like, is you like long? Like, yeah, like what authenticity do you think would, like, would bring like that? Like, you don't have kind of now curious. So in some ways, I'm just selfishly interested in like making it something that feels more like me. And it's my thing. Right. You're always curious about like gains, you know, what can make the show better? Right. And when I think about the podcast that I like, you know, things like broken stuff like that. I mean, I mean, like, that's not fringe, but I imagine and this is again, like projecting because I've never hung out with them. I imagine that it's like very close to what hanging out with the person is like, and then when I watch the podcast and me sometimes, I can tell that I'm nervous or not as like, I don't know, natural as normal. Do you think it's the environment? Like if you, if you made this, like, feel like you're living in that, if you slightly different or, um, yeah, it's possible. Yeah, it's totally, I mean, I think one thing that would be beneficial is like, hang, I mean, you're, this is, you know, you're great. So it's like very chilled. It's very easy. Yeah. But sometimes like, uh, hanging out with someone beforehand. Oh, I see. So if you have a conversation and then it just continues into. Yeah. And the, uh, my desire to keep it like on topic can make it less natural than it could be. Right. That makes sense. Yeah. You know what I mean? Yeah. Cause you always come back to like one thing, but then maybe like that's not actually the, the organic way that it would have gone. Right. Because I mean, like what actually this would be a good test because I'll put this one out and people like, dude, what the fuck are you doing? Stay on topic with the longevity stuff. Yeah. I don't know. Yeah. That'll be interesting. I don't know. It's stuff. Cause you're, are you a podcast person? I actually am not. It's like, I really only do books and papers.


Choosing media to consume (48:50)

Cause podcasts are kind of annoying. Like you can't fast forward through them easily and kind of like use your eyes, like figure out if like they were transcribed, then I might read them, but yeah, which you can, some do, we do, but not everyone. But then I also feel like I don't, I think there's like something about. Deeping to call it. Like, you know, because everyone doesn't need to the same podcasts and you go and like spend the same amount of time reading like full on like the Greeks, like kind of, you know, like what, what the cities was thinking. You might have like very outdated information that's like not very informed, you know, about today, but you also might like, I guess get a similar feel for how somebody was, but have it be like more de-correlated and therefore ideally kind of like more sort of like, maybe give you like a better viewpoint than normal. I think you should. I think it's all like, I mean, dude, the amount of times I've heard people reference sapiens or Charlie Munger is like, I just can't deal. I mean, they're great. They're awesome ideas, whatever, but like, everyone's consuming the same media. Yeah, and I think it's interesting because like if you, if you don't and you try to understand it from first principles, which I think like first principles itself being like kind of like, I think that is often cited as like the good thing, but maybe not fully understood, like quite different. Like I think one thing with people really is like, you know, math and science often are like more artistic than they are kind of like logical, but like everyone's trying to like frame things like the kind of logical process. Yeah, well, because it's, I think a counterintuitive thing is that you, well, I mean, it's obvious when you say it out loud, to pursue an idea in math or science, you have to be inspired to pursue it because you don't know if it's true beforehand. Exactly. No, it's so crazy. Like, I think it's fascinating. You look at Newton, right? Like Newton spent, he had like this amazing year when he was 21, he like just covers all these things, and then he goes into like alchemy in the Bible. And you're like, what? Like, where does that come from? But I think part of it is like the kind, I mean, obviously, it's like logical and analytical and like is these like books were like so curious. But I think also like he has to kind of like a little bit like a mysticism, like this is kind of these weird aspects of it's like a little bit artistic. And we kind of like, we forget that we're like, oh yeah, like scientists are kind of like robots. But they're really, yeah, they're really not. Definitely not. Definitely not. All right, so let's actually get some of these questions. So which ones appealed to you? Because we have so many. I think the ones that are like factual are just like the research questions probably. All right, let's do that. So maybe we should rip through because I'm genuinely interested in a lot of these. And I read your longevity FAQ, which is awesome. And it's very like Tim Urban, WapotY style. And maybe it's the drawings that got me. Yeah. But that was cool. Well, yeah. Yeah, that must have taken a lot of work. I was like, you know, just drawing in the kind of like axes and then like three lines was, yeah, it was hard. So, Sam Batesh asks, do you think there's going to be another step function change in human life span?


Potential Innovations In Life Span Extension

Sam Betesh asks - The last thing that led to a step function change in average life span was germ theory. What new areas of research might provide the next step function change? (51:55)

Since you know, germ theory. What's the next one? I think this is a super fascinating question and time to be alive. Because like, you know, you know, it really, it's fascinating. You look back and kind of like, you know, germ theory is like such a huge breakthrough. I think, but one thing I think is lost also is like there's another breakthrough that's similar related, which is that like life comes from life. Yeah. Because like, for all history, we think that like, there's spontaneous generation of life, like literally up into like, you know, right about that time. And then this year is like, nope, nope, like, you know, these germs are coming in like through the like the neck of the pipe. It's not. And so, you know, that and that was a huge breakthrough. And then, you know, obviously Darwin, kind of like, you know, also important. I think the thing that we kind of have an intuition will be important in longevity that most people are kind of not paying attention to is like what it, it's going to sound way too philosophical. But really, when you get into it, I think it's the important thing. What does it mean to be alive? And at what point are you kind of differentiating between like the germ line, which is kind of like your reproductive cells, and the zone, which is kind of like your kind of, you know, skin tissue, because there is a immortal line of kind of like living kind of things that has been replicating since like our first ancestor, right? Transmit it through our germ line. When I have a kid, that kid does not come out and like, how the same amount of aging that I do when I have it, it is kind of like brand new, right? And like, how the heck does that happen? And how do you fit that kind of paradigm? And if you take, for example, a bacterium, now there are some bacterium that do asymmetrically divide and like possibly have some form of aging, but kind of like, you know, do you look at a bacterium and think like that, that thing is aging, maybe, maybe not. And so what is it about multularity and kind of like our germ line and the differentiating between the two that's caused us to kind of evolve or start this kind of like aging phenomenon? And given that, is it natural? Or can we think about how our desire to kind of like live longer ourselves fits into kind of like that differentiation? Because you know, nature has already solved for kind of like living forever on some level, right on the cell level. And so kind of what is it about, yeah, our so much that like is so different? And are there any things that we can repurpose and use, you know, for that? And so I think that that area is going to be super super fascinating. And then I'm also just broadly in love with the question like, what is life, right? Kind of like that's so interesting, like, you know, shorting germ like the 1930s kind of like writing this fascinating track, like bringing like Maxwell work and others in. And so that, you know, that and kind of the people thinking about that, like, you know, sort of Germany and England, you know, MIT are just absolutely incredible in their work. That that's probably sort of a longer answer, like, you know, we just think like, I love this question. So like, you know, we spend so much time thinking about like the practicalities, but kind of like the higher level order of like, what would be the actual breakthrough? I think that like that, that are just like really interesting. Sort of tangent, you mentioned, yeah, giving birth, is someone working? Or I mean, I assume someone, but like, are people working on extending fertility windows if you extend health spend?


Extending fertility windows (54:45)

Because that seems like, you know, if you could live forever, right? As a dude, like, I can just opt out, right? Like, I'm not gonna have kids or I'm not gonna like, in my mind, that's the real issue, right? It's like allocating time. Yeah, you know, so if we say you work aggressively until you're 30, or 35 or whenever, and then you have kids, like all of a sudden you have to take care of this thing, or it will die. Right. So being able to push that till you're 60 seems like really valuable. Yeah. Well, so we think that's that's, that is an, so I don't want to say fasting too many times, so it really is a fasting area. Because, you know, there are some animals, many in fact, where like, you know, you have some octopi that lay their eggs, and then their mouth disappears, and they're like sitting on their eggs, and like literally human suicide. And if you reverse like, langelar action, like gives rise to that, they just keep on living. And so to give programs in essence, all over the animal kingdom, and like, we're, you know, at 3% are humans, and so we say, oh, that doesn't happen to us, but you think about menopause, right? Like, a woman, like, what is that? That is a clocked, acute onset, a kind of loss of health, right? Not just fertility, like many other things, you get fat distribution, you know, like, you know, bone loss acutely at the time of menopause. So many of the things get, like, a lot worse in a clocked fashion. You're gonna look at other animals, like, oh, we're all like that, you know, but really, are we that different? And so that area is just, and there even some hormones that we're looking into right now that are involved in that process that we think are super fasting for longevity. And so I think like that area is just, yeah, it's really, really interesting. So what, yeah, I mean, is it more, I imagine it's more likely for it to be an artificial womb than re-engineering humans, but maybe that's inaccurate. I think the artificial womb, it's not one that we naturally look at, because it's sort of like not, you know, if you solve that problem, when it's just like, solved longevity problem. Right. But I think there's actually, you know, that would be cool. But like, even just thinking about like, what is menopause, right? Because like, you know, why is it so timed? Like, what is the clock that like turns on? And if we like turned off that clock, like, would it push backward? Is there some kind of natural? And there's some like, obvious answers for that. But I, you know, it just, it really is, and you think about like, how did evolution decide like that was the correct time. So that, I think that it was like, yeah, really interesting. That's awesome. All right. Jason Troy asks, what's the percentage of longevity attributable to lifestyle choices versus genetics, and the progress of technology and influencing both?


Jason Choi asks - What % of longevity is attributable to lifestyle choices vs genetics and the progress of technology in influencing both. (57:00)

Oh, interesting. So there's a recent paper that actually came out, Superfasting by this guy, Yannith Ehrlich in science. And what it did was they have a public database of heredity. So basically, like, a family tree, unfortunately doesn't have actual genomic data for each person. But you have a lot of lifespan data. So age, birth and, and sort of death dates, many generations back. And so you can ask, what is the kind of like, um, heritability of longevity? You know, if your parents lived longer, are you also likely to have longer? And I think prior to that, we had about a 25% heritability kind of figure. I think that dropped to like about 11%. I could be off on this figure, but I think that paper was about 11%. Could be wrong. And so that, I think that's kind of the current statement from the field is that like, that's, you know, our prior, like percentage, a longevity of people to genetics, I think that underestimates the potential of packaging and like, you know, do you have kind of like, you know, mutants that are like long lived in the population? No. And so maybe, you know, I think it doesn't tell you like how much genes could be changed in flint longevity. But yeah, about 11% would be like the current estimate from the field. Okay. Thank you. Fatih asks, is blood transfusion? So this is parabiosis.


Fatih asks - is blood transfusion a thing or just a hoax (58:15)

Is it a thing or just a hoax? Oh gosh, no, the blood boy question. Oh, yeah, I know. The blood boys are like, they fall around everywhere we go. We were asked about the blood boys. So one thing that's fascinating, right, is like, sorry, fascinating all the time. If you go back and ask, what are the first ever things discovered to impact longevity? You know, the tools that we had prior to 1950 did not allow us to do genetics. They did not, or on the molecular level, they did not, did not allow us to do like any of the things that we now kind of become longevity. The one thing that you know, Alkskarelle in 1912 gets an Nobel Prize for sewing blood vessels together. And so what is one of the things that is tried in the early half, like the 20th century? Because like, that's the only thing that we have the tools to do. It's like literally, you know, like you're sewing loves together between a young and old mouse. Yeah. And that does appear to have positive impacts. You know, there are three or four nature and science papers that have come out recently showing, you know, there's some positive impact on kind of like the function of the brain, some positive impact on function on the heart, someone muscle. So we do see positive impacts. I haven't seen to date a really good longevity study. So I think we've seen a lot of evidence of like age related kind of phenotypes getting better. But I personally have not seen a study that like really, you know, makes me super excited about kind of like the number of extra years. Lots of stuff to like indicate that might be the case if done correctly, but just I actually haven't seen that study, you know, like sort of done yet. There's been some studies published like in the mid 1900s about peribiosis that I think I might have cited that kind of indicated an extension, but they're kind of like really replicated properly to really believe that. And so I think that, you know, there's probably some impact on lifespan. Like, I don't think we have that well characterized yet. Hmm. Okay. So true, like not a hoax, but not a hoax, but I think people really over focused on that because it's such an easy story to tell. Right? Like, vampires, vampires, vampires, like 60 different things that make, you know, excellent longer and like, you have to look at, you know, but people don't want to hear about like Daphne's and receptor, like the one here about like vampires. Yeah. No, I mean, it's just like, like kind of what I was saying before about like tech being seen as black and white, like sort of like everything people just want the pill. Oh, actually, I wanted to talk about Rapa Mison.


Rapamycin (01:00:20)

Yeah. So my friend, Nicola wrote a New York article about it. Oh, awesome. And I'm like, I'm slightly terrified. But can you can you just break it down? So Rapa Mison is this is this really, really interesting drug discovered on Rapa Nui, the aisle in a social sample, as many, many drugs were. And you know, kind of what it does is many things. But I think one thing that's been focused on is an impact on what's called M-Tor, which is a protein that's part of kind of two different complexes of proteins. And so, you know, the problem for Rapa Mison is it has a lot of kind of like side effects, right? It's originally developed, like, you know, maybe immune suppressant in one use. And so do you really want to be taking that like, you know, continuously? Probably not. There's a lot of doctors, you know, if you ask kind of like a subset of kind of people who specialize in crazy things that might actually work in longevity, if you then will say like, pull strap of Mison's or taking Rapa Mison and very kind of, you know, cute doses, but then like on a schedule, not continuously, is a good thing. Yeah. And I think that like, we don't see that like being disproven or like implausible, just kind of like, it is, I think, a risky endeavor on some level. One thing I would say is, you know, we, there are several companies trying to develop much safer versions that do the same things like have the positive benefit, like don't have like all the other kind of like, sort of negative negative effects. And so I personally just kind of like wait until those like get a little bit farther along. But I mean, Rapa Mison is kind of a reporter. I think the other fascinating thing is like, I don't think we have a great feeling for what the max is on the life mix, because that's possible with Rapa Mison. Yeah. Like the question is like, if you dose it up, like what's the maximum dose and how much at what point you start to get like decreasing returns in longevity, it's not clear that we've actually hit that barrier quite well. That's the other fascinating like sort of thing. Interesting. What about, um, I've heard people taking testosterone and like that is debated over like, maybe it increases health span, but it actually might shorten lifespan.


Testosterone (01:02:05)

No, we, we had a lot of, you know, there's a lot of people like, we're in a low T society. There's also, I think a lot of people think growth hormone, um, you know, for longevity. Yeah. And when I first, when I first saw that in a kind of like an airplane magazine, I was furious because like in worms, if you deep, if you like knock out the analog of growth hormone and receptor, they live longer and in, you know, mice like Dorf mice are the long lived mice and like within a species, not, you know, between species, but within a species, you know, being small, I was actually a correlate with kind of like longevity. Um, but I think, you know, one thing there is like maybe taking growth hormone makes an 80 year old feel a lot better. It's kind of like a health span optimization. So back to that kind of like, you know, do you feel better like that results along lifespan? But I don't think that's a great thing obviously to do for kind of like actual lifespan in general. Because to clarify, it can, uh, increase or encourage like cancer or cell growth? Um, I mean, there's this positive minor thing there, but I think for the most part, there's a not fully defined complexing link pathway. Um, that seems to kind of be quite related to longevity that was first discovered in worms and then kind of like all scary, wise humans, like there's a subset of Dorfs, for example, um, who appear to compare to their relatives, suffer much less cancer and metabolic disease. Um, and that correlates with what you expect from mice. Like if you mutate mice to be Dorfs, they live about 60% longer than normal, like 60% percent. Pretty non trivial. So how much shorter would you be if you can live 60% longer? I'm not quantity. I don't know. I'm not like 10% obviously, but like, you know, between a 50 and 70, but, but, but I, or 80, I'm not actually sure for, for, for those mice how much more they were quantitatively, but I think the interesting thing is you can actually possibly decorulate like the being smaller with the effect. So it's like not, not just like a size, it's like a similar thing as well. Would you make that trade? If you're like, one foot tall, the trade is positive. So the idea is like you can, you can decouple like the being small of like longevity benefits. Oh, I know, but I'm asking you a would you rather? Would I make that trade? Uh, yeah, probably. Probably. Uh, so Aubrey de Grey, another like kind of famous longevity person. Uh, someone asked about them.


Discussion On Organ And Tissue Replacement

Chris asks - Aubrey De Grey, IIRC, mentioned a number of times that we might, in the future, replace organs and tissues with new organic ones before they fail. Is this actually a reasonable idea, or is it more likely that we'll replace them with synthetic ones, if we replace them at all? (01:04:15)

So Chris asks, he's mentioned several times about replacing organs with new organic ones before they fail. Is that a reasonable idea or would they more likely be replaced with synthetic ones? Oh, interesting. I think so this is an area that we're still building are like maybe too late to be like seven years and still thesis building. Yeah. Um, but it, I, you know, I think there, there's so many things that have to go right for that to become like the obvious thing to do. Um, you know, I mean, in some ways is like the oldest version of aging, right? And that like, you know, back to our friend Alex Carell and his Nobel Prize, but like, you know, he is doing the first ever kind of like sewing of kind of like the organs and kind of like, let's get it, you know, little if you read his paper, it's like, let's just grab this like dog, kidding. Like we'll take this one from this other dog and like, you know, plug it in. And he's just, and you're like, wow, that's the early 1900s. So in a sense, what Aubrey's proposing is the oldest, most kind of like worked on idea. But then, you know, I, I think we also, we just haven't seen that done well on the rejuvenation front a lot recently. And I think I don't, you know, I think we're still full understanding, you know, there's some things where like, if you get an organ for somebody who's had cancer, for example, there's like a small rest, like 10 years later, you might also incur like some kind of negative events. Um, it just thinks like that. I think we're still understanding kind of how to, how to weigh those, those risks. But I think it's fascinating. So it's a surprising fact that it is, you know, sounds the most futuristic, but it's actually the most kind of like old method of kind of like considering working in the space. Right. Well, you're just like, take the part out, put it another right to go. Yeah. All right. So I have a very important question. So Micah said you did a cookie diet.


Is that true? Yes. Yeah. How did that go? Um, I think it was pretty informative in that, you know, again, I would recommend any way to like go eat just cookies, but. Were these like fancy health food cookies? No, no. So the reason I did it was my friend had claimed that he had only eaten whipped cream and bacon for a month. And that this was possible. Of course it's possible. Yeah. Right. But then he was like, but I actually feel pretty good too. And I thought that it was whole BS and that he probably, I mean, he's a very smart and like, you know, conscious person. I was like, well, like either he's like very different than I really thought he was, or that's possible to do. And so I wanted to test it. And so I tried that. And I was like, well, you actually kind of can and you kind of feel fine. Um, so I'm just like curious if you took any random thing, like any random food object, like just ate that for a month, like what would happen? Um, and the cookie diet like worked very well. But I just, I for the long term, it seemed like probably not a good idea. So switching off of that, like a lower sugar diet is probably a good idea. Did you, were you doing blood tests or is all by feel? No, no, I should have done blood tests. That's funny. Yeah, there was this, um, well known long distance hiker named Andrew Skurka. Oh, okay. A bunch of blogs and stuff. And he's, uh, pretty well known for having kind of extreme, like he just has a diet that can take anything, it seems like. So he was like, interesting. I think for a while it was just like Snickers and Pringles, something like that. That sounds great. Yeah, I mean, I guess if you have enough toothpaste, like on the Pacific Crest Trail, you're fine. Yeah. You have to kind of word it though, like, like how much worse that would be than like one example is right. I think that like a lot of people eating meat, maybe the worst part of it is that if your animal is stressed, like had like a lot of the incorrect type of hormone directly before like being killed, but actually like a more important thing, like whether you're eating meat or not to sort of like what the kind of like minor things are that we don't think about like the axes that aren't like explicit, like what like what those are, but yeah, hard to say. Hard to say. Cool. All right. My last question is, are you seriously not doing anything really weird?


Laura'S Diet Approach In Longevity

Is Laura actually not doing anything strange in her diet? (01:07:45)

There's like no pills. There's no weird food. There's no crazy fasting. Um, I mean, I think that like apart from trying to use a cookie diet, so it was one thing that I was trying to do for a while was like I was trying to like quite a bit understand, you know, because we're just like black boxes and like you intake some number of calories and like you should be able to calculate like where are they all go? Like how many are necessary to like eat each day? Like from first principles, like figure out kind of like what an awful diet would be. I tried to do that for muscle. So I was like, like how many proteins should we eat 30 minutes after working out? The first problem was it's really hard. Like why three minutes after working out is the correct amount of time. No idea because sort of like, you know, our cells are expanding at a period of time. Like it's hard to, you know, figure out. Um, also just got really down in the weeds of like how many amino acids would be required to like replace certain things. And, and I think I came out of that just kind of like very convinced like a lot of things that like people talk about the high level like wrong and like probably theoretically still like a like in a lower level. And that like, I shouldn't have the time to kind of like really think about doing that for like a full diet. And so I think at this point, until I have like, you know, maybe a full year to kind of like go back and understand that whole area better. Um, it's kind of like just, you know, the obvious thing is because history is probably like a good teacher for like, you know, baseline health. Nice. All right. If someone wants to learn more about you, where should they go? Yes. Um, so we run Long Jovity Fund, uh, and I'm just, uh, Laura at Long Jovity.PC and anyone can reach out and we love to talk to you. Cool. Thanks for coming in. Awesome. Thank you for having me. Thank you. You You


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