 Is this happening for a reason? Do our genes want us to, you know, age and die? Or is it just that they weren't able to somehow develop mechanisms for a longer period that they have developed up to now? And welcome back to another episode of Amir Approved. We've got a special guest today and his name is Yuri Dagan. He's a serial entrepreneur and expert in drug development and venture investments in biotechnology and pharmaceuticals. Since 2013, Yuri also serves as vice president of the Non-for-profit Foundation Science for Life Extension, whose goal is the popularization of the fight against age-related disease. Now, before we begin today's episode, a couple of house-cleaning notes. Number one, like always, if you're watching this on YouTube, make sure to subscribe and hit that bell notification button so you get all our brand new videos that come out every single week. And number two, guys and gals, if you are listening to this on iTunes, please head over to iTunes and leave a review. Every review helps. In fact, I'll be picking one to two lucky winners every single week to earn $20 in Bitcoin. Now, without further ado, please welcome Yuri. Thank you. Thanks for having me. How are you doing, man? All right, not too bad. It's been a while. I think it's been like a year and a half since I saw you. Yeah, yeah, yeah. It has, it has. So what's new in the field of life? Actually, life extension as a theme itself has picked up a lot. It has, yeah, and definitely a lot more investment coming in than a year and a half ago. Yeah, I think people are kind of waking up to the idea that it's a good thing to live longer and it's now that we have to like find technologies that will help us do that. So yeah, yeah, I think it's getting much better. Like if I look back at like even five years ago, it was considered somewhat like a fringe topic to be able to be doing research in aging, aging mechanisms. And like even scientists are saying that they were kind of like hiding it. Aging scientists, they were like, okay, I'm doing research on cancer. And people were like, yeah. And if they said I'm doing research on aging, they were like, why would you be trying to like live longer? Shouldn't we only have like an expected lifespan and natural to age and die? But now people are, I think, yeah, like they're waking up that, you know, dying sucks. Of course it does. Try to live as long as possible. Do you think the narrative, though, has changed? Because I know David Sinclair. Yes, he's definitely like popularizing this idea on Joe Rogan. I love it. I love it. Yeah, yeah, it's a good podcast. And like it's been like twice in the past. Twice in the past. And, you know, I've been following epigenetics and life extension for a long time. As you mentioned, like four or five years ago, it was fringe. And I was talking to people about epigenetics like, Epa, what are you talking about stem cells, huh? I'm like, just wait and see. The thing I like about David, though, is redefining aging as not aging as in goodbye, but aging as a disease. Right. That's a huge narrative shift. It is. And it's not even like fully accepted in the scientific circles. There's a huge debate even among gerontologists, whether it's okay to consider it as a disease. So even some gerontologists are saying that we should prolong life, saying, no, but aging is not a disease. And yeah, to me, I'm in agreement with David that it, disease is just something that you want to get rid of, right? And aging fully falls into that category. Although everybody has it, it's a disease that we're all born with. But it's, yeah, something which we should try to get rid of as quickly as possible. So in that sense, it's a disease. It's natural, yeah, but like a lot of natural things are bad. So, yeah, we should definitely call it a disease and get funding into. Yeah, give people example like viruses are natural. Yeah, exactly. So I'm going to get a virus and do your thing virus. I won't do nothing. I'm just going to chill here, relax while I wither away. Or like, yeah, I think Sam Harris said it best that like getting eaten by a bear is completely natural, but it's bad for you. So, you know, it's nothing more natural, but we should definitely. That's why I love the debate. It's natural. I'm like fucking poison ivy is natural. Yeah, that's right. You can rub that shit all over you. Yeah, that's right. Yeah, I think David also had this kind of issue come up and Joe Rogan's podcast and said, yeah, like natural is not a good enough justification to tolerate bad stuff. I mean, all we do as a civilization for the past thousands of years on natural, but trying to make our life better because, you know, natural is just not good enough. So right now, biologically speaking, we know that ourselves can roughly do like 120 years, something like that. Well, some some cells already do like neurons. They're long lived in the, you know, like you're kind of like born with the neurons that you're going to die with, but other cells divide all the time like epithelial cells and they have very different lifespans. Like depending on their specialization, like cells have very differing lifespans. Some are like, yeah, very long lived like neurons and others or blood cells. They get renewed every like three months. Yeah, like, yeah. So, yeah, but I think cells are capable of living much, much longer like individual cells. Forget about like the cell lines, which could be immortal or like even our own, like the germ line that the line of sexual cells that we came out of is tracing back for billions of years to our common ancestors. So, yeah, it's not a problem for like the cell population to be supporting itself indefinitely. It's just like our organism just seems to have a very like narrowly defined lifespan for each species that, you know, you're kind of born with. And for each species, it depends on its place in the hierarchy of like its consumption. That's ecological niche where like the top predators live longer like we do or I don't know, lions, but like animals on the bottom of the pyramid for some reason are much for sure lived like mice who only get, you know, two and a half years to three years to live. So I think that's the enigma. That's the secret we have to kind of figure out what are the mechanisms that are making some animals live much longer than others. But do we know right now what's the mechanisms in humans that make us age? Well, not really. I mean, we know the hallmarks of aging. We know what goes wrong. I mean, we can see all this kind of systems start deteriorating at like a pretty young age, like starting with the immune system. The time it starts to involute like deteriorate at like 12 with the onset of puberty. It already starts to shrink. Other systems are only doing like starting to degrade at a long like higher age. Say your cardiovascular system is like 25, 30. That's when it goes down. Like that's why athletes usually retire by age 40 or some in some sports, even like like age 30 is the limit, the limit. Yeah. Yeah. But, you know, we see those processes, but we haven't gotten to the bottom of why they occur. What is it exactly? And how can we intervene to not have this occur? We're not there yet. We kind of see some patterns and we already, I think the field is coming to the realization that it's epigenetic processes that control these kind of changes in what happens to the systems. Like the gene expression is the mechanism that controls these changes. But, and we kind of at this point where we have some proof of concept interventions like the Yamanaka factors that I'm sure you want to talk about that seem to roll back the aging process. But we're not yet at a point where you can say, OK, like this is how aging works and this is how we can stop it. We're only like trying to like figure out like a jigsaw puzzle. Yeah. Yeah. I think yeah. It's like we're, you know, trying to like determine an elephant in like a dark room. We're just trying to see, is it an elephant or is it like a... Is there a consensus though on mutations of cells? I mean, there was the mutation theory of aging was pretty popular like maybe a decade or two ago. But there's definitely mutations happening and in different types of cells at different speeds. But scientists just can't, they were trying to see if mutations are the biggest driver, that they could be the causal role in aging but they just don't seem to be. I mean, different tissues have different mutational load and different animals that have very different lifespans have very similar levels of mutations. So kind of that alone tells us that, you know, that's not really the answer. But mutations occur and they definitely play some role and it seems that at some point our bodies are kind of toning down the ability of our cells to first of all detect mutations and second of all to deal with them. I mean, and that's at that point, that's when cancer starts to like skyrocket. Which is my debate I tell people, like if we can live longer, like that's the first piece of the domino that you're everything, like as you age, as your body starts, honestly, let's say slowing down, you have a high propensity to get cancer. And depending on your life, so all these other factors, right? But if you can kind of extend your telomeres and keep the health of the reproductions of yourself. So, you know, the copying of the DNA is 100% data dense as opposed to like, oh, it's like a photocopy analogy, right? First one's good, second one's like, yeah, 90%, third one's like, then you're down the line like, what the fuck is this? Yeah, it's definitely like how mutations occur that, you know, the more copies you make, the higher the chance that you're going to make an error in something that matters. Because of course, you know, DNA, like only like 10% of it in each cell is like protein coding. Yes. What actually matters. But yeah, down to some level of, you can tolerate it's like some level of mutations where nothing really changes in the cell. It's still operating as if, you know, nothing really bad happened. But at some point, if you do it long enough, play that kind of Russian roulette long enough, you're going to get mutations. And that's the kind of current thinking of like the driver mutation theory of cancer that you need like a few driver mutations to occur in a single cell simultaneously and that's when the cell becomes cancerous. And I mean, yes, the longer you live, the higher your risk of getting cancer. But it's just the question is, why do some animals get cancer much sooner than others? For a mouse, it takes it like two and a half years to develop cancer and die. Or elephants even like don't seem to get cancer in their lives at all. At all, yeah. Or at much, much lower rates and whales too. I mean, they're mammals too. They're closely related. They can live 200 years without cancer. And they're huge, right? They're like a million times bigger than a human. So obviously we understand that genes have certain mechanisms that they could use to, you know, not have cancer. But for some reason, we haven't developed them or maybe they're only active up to a point in our life, maybe post reproduction, after which they just seem to be toning down. And, you know, that's the big question. There's another debate in the gerontology field. Is this happening for a reason? Do our genes want us to, you know, age and die? Or is it just that they weren't able to somehow develop mechanisms for a longer period that they have developed up to now? Same debate can be for cancer. Why does cancer even exist? Yeah, exactly. There has to be some reason that exists. Yeah. Well, I mean, I guess in biology everything is kind of viewed for the lens of evolution. And it's obviously... To preserve energy, though, for looking at nature. I guess it could be, yeah. I mean, one of the reasons that it's, I mean, it's good for the species or the evolution of the species may be because it helps them kind of die and clear the way for the new generation or it increases the turnover of generations and it helps, like, adaptability of the species so that if the environment changes there's enough generational turnover to make sure that the species doesn't die out. Right? Because, you know, if you live long enough and you don't have enough turnover and you might not be as adaptable as your competitors who can adapt much faster. And that's one of the theories that, you know, what could be why aging could have evolved, like what is the benefit of aging to not an individual, but to a species. And this kind of turns... It comes back to, like, group selection and whether, you know, selection operates at a level of species or does it only operate at a level of individuals? And, of course, there's, I mean, I'm of the view that there's definitely some group selection and it operates at different levels of, like, the fractal levels of, you know, organism and cells and down to, like, single, yeah, yeah single nucleotides, single genes. I always tell people, it's kind of a mind fuck for them and, like, you realize, like, we have this thing called the mitochondria that has its own set of DNA. Like, what? I'm like, yeah, dude. Yeah. Circular DNA. Huh? I'm like, yeah. And we still really don't know too much. The history of, like, how did it come there? Did we evolve it? Did we co-evolve? Did it, like, take us over? Like, I don't know. Yeah, it's actually a good point because there's some, like, fringe or non-fringe opinion that maybe it's the mitochondria that are, like, really the hosts of the organism who are just doing their bidding and because, I mean, they're much more successful than us if you view it through the lens of how many DNA copies they have around, like, in the biosphere. There's much more mitochondria, DNA in you than, like, genes. There's a good count for that. Power Sex Suicide by Power Sex. Yeah, this book is good. You might know the author too. Here it is right here. Power Sex Suicide. Nick Lane. Haven't heard. Yeah, he tries to, he's a, like, science journalist and he goes through, like, the history and he talks about that thing too. It's like, the mitochondria take us over because back then, like, we looked at, like, the atmosphere and, like, through carbon dating, there was more hydrogen, you know, the oxygen-hydrogen levels. It was, like, could it be or just a big host for this? Yeah, yeah, it's definitely worth considering that that could have, at least that's could have how it started, right? Like, mitochondria were using, like, they were a parasite because you can see it all the time, like, big animals being used by, like, small parasites. Whoever's, if you're listening to this or watching this, if you, like, just go to YouTube and this isn't for, like, the squeamish. Yeah, like, the ants? Yeah, yeah, yeah. Yeah, so there's a fungi. Yeah. Yeah, so type of, like, fungi control ants. Yeah, yeah, yeah. It's crazy. So the ant, it changes the biochemistry in the neurons of the ant. It's pretty much, the fungi controls the ant. The ant climbs a little tree branch and the fungi pretty much pops out of the ant and the ant jumps in suicide and through, while the ant jumps, the fungi spreads because they're spores and propagates. I'm, like, fucking nature. Yeah, and there's, like, another example of some other, I think, ants that they, once they're infected, they get to, like, climb to some, yeah, like, high branch and so that, like, a bird eats it and then it poops out. The poop, yeah, yeah, yeah. The bacteria or something, yeah. So, I mean, yeah, examples of this kind of parasitism are down, so they could have been what mitochondria did to, like, the big cell that they... Because for me, when I look at, like, longevity, you know, we've got to ask ourselves and we're just in the early days of this, right? Yeah, absolutely. Absolutely. You know, we look at things that play a factor in human health or proper healthy DNA copying. We look at the mitochondrial health, right? You know, without the mitochondria, we die, it creates ATP, we need it to live. Then we look at our telomeres, right? We have certain enzymes, like telomerase enzyme that can determine the length. And that's another question, why is it enzyme active only in certain cells? Yes. But on others, if telomeres are, like, so important and they do seem to be, you know, when you need them, our body knows how to elongate them using telomerase. But for some reason in other cells, it just doesn't. No, but there's also... Incorrect me if I'm wrong here, but there's also cancer, the hijacks. Yeah, I know. I know. People say, like, they use the argument, why do you need telomeres at all? Why do they shorten at all? And the argument is, so that prevents cancer. But of course, cancer can, like, turns on telomerase. Yes. Or there's, like, other alternative ways it can... Because the reason I bring this up, when I read about this, I'm like, well, if cancer can turn it on to extend it, we'll allow it when we figure out what it's doing. Exactly. Yeah, I know. And then there's another, like, theory that maybe cancer is trying to, like, escape aging and for, like, in a very selfish way. Just those cells that are like, I don't want to, like, play by your rules. That's my theory. You want me to die, why should I die? You die, and I'm just going to propagate. I have a sentient theory of cells. Hmm, okay. I think cells, I think you're right from a fractal. I think you can go from a geometric perspective, like, all the way from up to down, down to up. Each cell, and even, like, the organelles and everything inside, are sentient. And so you have, let's say, like this cell. Okay. And it, I'll say evolves into a cancer cell. Yeah, well, it does evolve. Yeah, I mean, that's all, like. And the reason why it's evolving, it's like, Amir, your rest of your body sucks, because I'm an early detection system, because I know what's going on. That's right. I'm like, I don't want to die, because I sense what's happening. I'm going to hijack this, evolve, so I can protect myself. Yeah. Even, like, without being sentient, it could be, like, evolutionary driven to, like, do its thing so it survives for longer, or is more successful in, like, an evolutionary sense of making more copies of itself. And, yeah, that's interesting. Like, maybe it's, like, you mentioned that you think, like, we're in simulations from, like, that perspective is kind of, like, has its own, like, sentient, like, outside of this kind of reality in other, like, in whatever is outside this simulation. Well, like, my other thing... ...programmed out the cells are... The reason why I bring that up is, I look at, like, cycles. Right. And so, let's say we go back, even, like, before Homo sapiens, like, lineage, ape lineage, or even beyond that, like, we can go down to single-cellier organisms since we evolved from multi-cellier, and here we are, right, the building blocks. Let's say we're looking at, like, you know, one of our predecessors, like, Homo erectus or something like that. And it gets cancer. And it dies. Now, back in the day, and I might be wrong, we just don't know, I'm pretty sure they didn't have caskets and all that stuff, you know? Yeah, well, they might have buried their, like, throwing them off. Yeah, yeah, yeah. But the actual flesh, you know, the carbon and all that, touched the ground, it was in the ground. So the cell goes back into the ground. And maybe there's some process in there that we still don't know today, you know? Because we just don't know that gets recycled somehow back into this ecosystem. It's still alive somehow, I don't know. I have no idea. It's just one of my thinkings ahead in the past. I'm like, there has to be a reason why. You know what I mean? It's like, it's preparing, it knows, it's going away, so it's figuring the body will collapse, it decay, the body will decay back to Earth, and it goes back into soil somehow, and somehow some part of the recycling system, I don't know. It's just like, because I always ask, like, why? It's like, yes, it's a fact that we have cancer here, and you know, it's fucking horrible to have, but there's a fundamental evolutionary reason that exists. Yeah, I mean, yeah, cancers are, like, they're very diverse, but yeah, they're called cancer, so of course there are, like, many types of cancers, and yeah, they have very differing mechanisms by which they get to this kind of, like, they discover or invent this kind of rebellion against the body and just try to propagate as much as possible. Of course, eventually, it does lead to their demise, so they're not, I guess, that sentient. No, that's my thing. I don't know if it does actually lead them to their demise. Like, through the decay, I don't know how long it takes for a body to decay, but, you know, it's back in the earth, it decays. So you think there will be, like, living, free living, even though the body decays, the cancer cells are able to sustain themselves? Yes, or, or, we talked about this before, there's no free will, so it's already pre-programmed the simulation for this cell to do its thing because it needs to fulfill a role to fit into another piece of the cog. Right, I mean, from the perspective of, like, determinism, for sure, they're like, nothing else could have occurred, like, if it's pre-determined, that, you know, that cell was predestined to become the cancer cell. But, I mean, yeah, not in some kind of, like, grand design, but just, you know, that's how, like, the sequence of events that, you know, you look at the past, you know, leads you to the future. And this, or, I mean, to the present, I mean, this is the same as on a grand scheme of things in a block-time universe that's going to occur. Yeah. That cell is, you know, yeah, like, that's what's going to happen. So what have we found today that, in science, both on the cutting edge and both more and more coming into, what have we found that actually might contribute to us living longer? At this point, I mean, there's some things that are kind of on the cusp, on the horizon, that just might make it to the clinic in the next five years, like synolytics, I'm sure you've heard of those, like, they're trying to clear the senescent cells that we have, and this theory was developed, like, I think, in the past five to ten years, like, senescent cells being one of the drivers of aging. And so the idea is, if we get rid of them, if we get rid of those senescent, bad cells that are poisoning the organism, maybe we can, you know, prolong lifespan. And they have demonstrated this in mice that, yeah, like, if you clear senescent cells, those mice seem to be living longer, living healthier, not by much, but like, maybe 20 to 30%, which, you know, for mice that's not huge, but it's something. So they're having some clinical trials right now of these senolytics, and if those are successful, then, you know, within, you know, five years. So how does that mechanism work? So how are they administrating this therapy and what's it doing? Well, there are different kinds of senolytics, and some are, you just take a pill, like, there's, like, anti-cancer pills, there's injections, you can just inject it, and they're, like, one of the clinical trials is the arthritis trial, also the arthritis in the knee, and they inject it into the, like, the cartilage. Well, what is it? What are they injecting? It's one of the molecules, it's proprietary, like this. That's a proprietary molecule, I got you. Yeah, it's a proprietary molecule, and they're studying that as, like, preferentially targeting those senescent cells. Normal cells, but it's only killing those bad cells that we want to kill. So it's kind of cell or aggressively, I don't want to say aggressively, but when I was simulating, recreating autophagy. Pretty much, yeah. I mean, ideally, those cells should have, like, committed suicide, self-destruct, but they don't, and that's why, like, cancer cells, and actually senescent cells, there's a theory that those are kind of pre-cancer cells that were recognized that they have some kind of problem and they just stop dividing, but they also, instead of killing themselves for some reason, stick around. And so the idea is that, just like we target cancer, we can target those cells, and hopefully, you know, if there's some kind of burden of those cells in the organism just causing it to age. So oral injection, it's a proprietary molecule, the cell absorbs the molecule and stimulates autophagy. Yeah, I think it's... I'm not sure about, like, the exact mechanism by which they kill them, but yeah, I think they induce apoptosis. Yeah, I think that the cell just commits suicide, essentially, or maybe they use the immune system to, like, to kill ourselves. At the end of the day, they're just doing house cleaning. Pretty much, yeah. And the idea is that, you know, in place of those bad cells that they kill, there's just going to be some nice cells, good cells that are like stem cells replenish that kind of tissue with good cells, and they'll prevent aging or some kind of, like, health decline or extend health span for a long period. And, you know, that's on the horizon and, I mean, it won't, you know, make us immortal or really produce huge rejuvenation benefits because we see in mice it's only, like, a minor, like, minor in terms of, like, life span. Maybe it's increasing by 20%. But it's, at least it's something because at this point we're, like, to answer your question, and this is a very long-winded answer, we don't really have anything that we can use right now extend our life span significantly or even, like, buy, like, a measurable, like, say, five years, we don't really have anything. Yeah, nothing's there, right? I mean, we have these kind of lifestyle things that we know that if we don't do them, we can, like, shorten our life span. If we smoke, if we're obese, yeah, drink too much alcohol. We know, like, the person who does all this bad stuff versus the person who does all the good stuff and, say, exercises and, like, goes to the sauna or whatever, like, difference in life span is, like, maybe 14 to 15 years and, like, a couple of studies that looked at lifestyle effects on life span. The quality of life, though, is different. Yeah, exactly. Well, you can choose. If you really, like, you know, a good glass of wine, you can, like, okay, I'll trade that for, like, three years. Yeah. If you smoke, okay, you can take that. I always said if there was a consensus and somehow crazy studies came out, the coffee will, like, kill me by five years and, like, I'm gonna give a fuck. Yeah. Although, thankfully, it's the opposite. It actually seems to have some kind of idea. It's good. It all depends. I think it depends on your liver enzymes. Like, you can run a 23 and me and look at your, like, the genetic data and you can see how, kind of, some people, like, fast metabolizers, slow metabolizers, you know, the, so it's, for me, it's like, I just fucking love coffee. Yeah, I know. Same here. So it's actually, like, always good to find a study that supports whatever you're already doing is that's a good thing to do. Especially for, like, a lot, there's very interesting studies on, like, a tangent, like coffee and prostate cancer for men. Really? Yeah. Yeah, but, yeah, they said that there's, like, an association, a small one with people who drink coffee that they have a small increase in the lifespan and, you know, like, lower mortality and, you know, like, cancer racism. Antioxidant, chlorogenic acids inside of it. But, so, we have that in, let's talk about the Yamanaka factors. All right. It's my favorite topic. First of all, what are they? Well, Yamanaka factors are, like, the transcription factors of this guy, Yamanaka, Yamanaka discovered back in, like, 2006. He was basically looking at things that can rewind a cell back into embryonic state. And he was looking at, like, a panel of 24 different genetic factors. Like, a transcription factor is just, like, a genetic mechanism that goes inside, like, the nucleus and, like, changes gene expression, changes what genes are turned on and off and can do, like, a massive kind of remodeling of a cell. And it turned out that those four, if you use them together, they do not just, you know, massive remodeling. They can actually bring it back to embryonic state where that cell can now, again, become anything you want in the body. Because, you know, what is so special about, like, an embryonic stem cell that it can turn into pretty much any cell in your body. They thought, yeah, before that, before Yamanaka, they thought that this is, like, a one-way street that you cannot come back. Your skin cell cannot be back, like, turned back into an embryo, right? They thought it's, like, the waterfall, the one-direction model where, yeah, it just kind of rolls down and can't get back up. And Yamanaka, like, turned it all on his head and said, no, you actually can. You can any cell that has a nucleus can turn back into, like, embryonic cell. And, again, you can create an embryo. Like, you can create your own clones from your skin cells or whatever, and you have that kind of cell, which is a scary prospect, but that's beyond... So this is kind of, like, so this would be kind of similar to, like, stem cells where... Yeah, yeah. It's even, like, a more, even more different stem cell. Correct. It's an embryonic stem cell. So theoretically I can draw my blood, theoretically. Yeah. Apply through the therapy of stimulating the Yamanaka factors into my drawn blood. Let those cells then go back to a younger version of it. Right. And then re-inject it into me. Well, that's one of the ways. Yeah, you can create stem cells out of those, or you can take your own stem cells and kind of rejuvenate them using Yamanaka factors. Kind of roll it back. How we stimulate the Yamanaka factors? Well, you have to kind of get them into the cell. You have to either get the genes for these factors into the cell and get the cell to start, you know, creating proteins from those genes, the actual transcription factors, or you can get the actual proteins, the Yamanaka factors into the cell. Of course, usually the easier way is to do the gene thing, because we have a lot of instruments that can insert needed genes. What could be used on this? CRISPR is, yeah, it's one of the ways, but I mean, they have kind of AAVs, that then associate viruses that do, like, or are you specialized for this, for gene delivery? I mean, CRISPR is more used for, like, cutting stuff, and you still need... They're good to RNA, cut it out for you. Yeah, pretty much, yeah. And so, yeah, once you get those genes into the cell, and if you activate them, they can roll back the cell back to this kind of pluripotent state. And with that, they rejuvenate it in the process. So, if it was, like, a 100-year-old skin cell that he had, with all these kind of problems that a 100-year-old cell exhibits, like, I don't know, like, misfolded proteins, or reduced mitochondrial efficiency, mitochondrial function, if you induce Yamanaka factors, roll it back to the pluripotent state, and then create another, again, make it induce it to become a skin cell again, that new skin cell will be completely rejuvenated. They have normal, young levels of mitochondrial function, all the misfolded proteins. So, where we are today with the research for this? Like, this seems to be like... It's happening. Yeah, I mean, of course, on the cellular level, creating pluripotent stem cells, they've been researching it as soon as in 2006 Yamanaka published this paper, but what just recently scientists in the aging field realized that you can use this in vivo, like, in the animal, if you activate those factors just, you know, in the right dosage, then you can rejuvenate the animal itself, like, systemically, and make the animal live longer, which is, I think, that's the groundbreaking thing, because it's one thing to just, you know, take cells. So, they've done this? Yeah, they have. Rats? It was a transgenic mouse line so they haven't been able to do this in normally aged mice, which is kind of where the field stands right now. This is like the next milestone we need to accomplish. We need to take these factors and make a normally aging mice that usually lives like two and a half years rather than like, I don't know, three months and make it live longer, as long as possible. And this milestone is still to be accomplished. But the proof of concept that was shown in 2016, this paper out of Solke Institute by Ocampo, it showed that you can use this kind of gene therapy in our bodies inducing Yamanaka factors to prolong lifespan. And this dovetails very well with the idea that aging is an epigenetically controlled process because, you know, Yamanaka factors, that's what they're doing. They're kind of rewinding the epigenetic clock backwards to the, you know, time zero where it's embryonic cell, which has, by definition, H0, epigenic H0. And luckily, this rewinding process is gradual and, you know, we're just, it didn't have to be. It could have been a binary thing where, you know, cell is an old cell, skin cell, and somehow it's rolled back into embryonic cell, but not in a gradual way. But luckily it is a gradual process where if we kind of cut off this kind of re-programming process just in time so the cell still remains a skin cell we can gain the rejuvenation aspect without losing the kind of cell identity. And this is important because that's the kind of danger right now of this process that when cells are taking too far, they lose their identity as a skin cell. They become kind of this kind of lost in the no-man's land where they're not yet at an embryonic cell, this kind of in-between thing. Then you can get all kinds of problems and that's why animal dies. They develop these teratomas. Like cancerous tumors from this process and this is what we need to iron out. We need to make this process safe so that there's no side effects and then, of course, efficacious so that it extends lifespan by significant amounts. But it's very exciting because all of the signs are pointing that if we learn to control the epigenetic process of aging then we can periodically rewind this epigenetic clock and this is another thing. This was revolutionized the field of aging research, the discovery of the epigenetic clock that we have in our bodies. It was like in 2013 and even before that there was the most famous scientist was Steve Horvath. I'm pretty sure you've heard of him of developing this epigenetic clock of aging. It was discovered that everybody a person of a certain age has a very similar level of specific genes like their epigenetic levels of these genes are the same which was kind of weird. Why would our bodies develop in such a predictable way? Because initially we thought that aging is like a stochastic process and by that definition all these epigenetic settings should diverge. You shouldn't be able to take two random people of the same age and have the same levels of certain genes being expressed. It was discovered that there is actually a subset of genes that change in a very predictable way so that you could take a cell from anybody without knowing their age and just using these analysis of epigenetic patterns you're able to say how old the person is. In a cellular age. Not just one type of tissue but there's a universal epigenetic clock that you could take like your blood and then its epigenetic clock will correlate with your neurons and this is very odd because it's very different cells Neuron is as old as your you are, right? Because you had it from being an embryo but blood cells renew all the time but at the epigenetic clock level the clock is showing the same time and this is very strange because it's showing that there is some kind of coordinated program in an epigenetic program that hopefully will decipher one day and be able to hack. It doesn't come as a surprise, you know the famous fly studies you look at like BMO clock and all the circadian clocks we know our body functions on clocks. Of course and yeah to people who are not like deep into biology it seems like common sense that of course there's some kind of program because we have life stages we know that at a certain age puberty starts and everybody about same age goes through it and then at another age like for women there's menopause and it's also pretty much predetermined at a certain age so our body does keep some kind of clock of course there's a circadian clock we want to go to sleep at a certain time and of course it seems like common sense that the same kind of clock could be used to internally needs to be synchronized could be used for aging as well but for biologists it was for some reason it was a surprise that there could be some kind of coordinate process that is tied to aging and even after say like even after your reproductive age stops even after that it's also synchronized which you know this kind of goes against the dogma that we only evolved up to the level of when reproduction stops and after that mutations go wild and things should diverge in our bodies because that won't be passed to our progeny because we won't have any more progeny but no even after reproduction stops for some reason there's a lot of coordinated processes that occur at very similar rates in different people and this is odd it kind of points to there being some kind of synchronization between what happens to people during aging and I think it's a manifestation of an aging program that hopefully we're just around the corner of being able to decipher and do something about it so what are things people can do currently today even though it might increase a couple of years but what kind of therapies can we do well it goes back to the lifestyle therapies there really isn't a metformin trial it's starting because there's some circumstantial evidence that it could be prolonging lifespan by just a little bit unhealthy people it goes back to diabetics because metformin is a diabetic drug and they kind of notice that people on it, the diabetics on it for some reason lived longer than their healthy counterparts, people of the same age but who didn't have diabetes they were dying sooner than these guys who were supposedly less healthy so they weren't metformin and they were out living their peers of the same age so it became like a biohackers drug of course biohacking is a very loosely defined term in Russia it's used for people who just do self experimentation in the West it's used as people who do gene therapy in their garage or create some beer that glows in the dark that's biohackers self experimenting for decades that weren't called biohackers but they were doing it, they were taking metformin and there's been like online communities of people sharing their stories of people, first of all they would do like blood panels and see if there is an effect lowers the glucose or even like if they have some kind of does it make them feel better subjective feelings that it helps and so out of that they grew this metformin trial that is now FDA allowed to try it and it's going to start in November and they're going to see does metformin prolong lifespan and decrease kind of the disease burden of old people and I think this can run for like one or two years and after that we'll see but some people are taking it right now and they're hoping that it will prolong their lifespan of course they don't expect to live 20 years longer or to remain healthy for 20 extra years but they are hoping that maybe it will increase lifespan maybe by 2-3 years and health span by maybe 5 years and so this is something that you know, I can't recommend but that's what people are thinking about and I think even David Sinclair goes into metformin on his blog he goes a couple things like metformin NAD Yes, NAD is another hot topic and it has been kind of on I've been contemplating doing some IVs Oh yeah, that's another thing people are doing IVs of supplements as opposed to like taking a supplement It's better delivery Of course once it becomes an IV it becomes really a drug and it should go through like the standard or go through clinical trials before being administered because orally we have much more protection I guess That goes through liver First of all, it can get digested by various enzymes but that's another thing that people are trying like IV delivery of NAD or some other stuff but NAD although it's popular even in model organisms like mice or flies or nematodes it doesn't seem to have a huge effect it's even lower than metformin and it's lower than rapamycin those are like the two drugs of choice in the gerontological community for decades were like metformin and rapamycin NAD is being popularized or has been popularized I guess in the past like five years by Gorente who is David Sinclair he used to work with for him at MIT I guess but I mean it's all very small like effects on lifespan so it could be like a compound like proper diowenol keto diet is interesting data they have a ketogenic, you can use it as a tool and now taking external ketones sauna therapy sauna for sure for me sauna is like a win-win because it doesn't have a downside but keto right now people are being cautioned against it because nobody has really been long term on keto for like decades so as a tool a supplement let's say you're a healthy individual non-cancer like I'll do cyclic keto with like intermittent fasting so it would be it can be like I go keto for three days I use it as a tool let's clean my cells a little bit no sugar, I'll do sauna therapy so more or less kind of like very targeted for sure it's always a good thing like to go low on sugar so for me it's like yeah you're right I think unless you have in this very good studies on keto with cancer specifically if you have amazing studies the problem there is people with cancer they don't normally live long anyways it's just a matter of some people are thinking like keto I'm gonna go long term for like five years and there's some data now emerging that you know it could be damaging it could get insulin resistant although like you're not eating sugar but you're on keto I think it's all case dependent you know Dominic Dagestino is doing good research on this I think it can be used as a tool like any supplement you can use it as a tool sauna like no downside especially go to Russia and bunny I go back and forth between hot and cold all day long yeah I love it too every time I go to the gym I try to like jump into the sauna for at least like and the science is good both with the heat shock protein so regardless if it's hot or cold that change in temperatures triggers which causes autophagy yeah it could be one of the mechanisms one of the mechanisms they say what I'm most convinced by is the spanish study the mortality rates yes they're like crazily lowered and like cardiovascular disease was much much lower but almost 50% which to me was like but I think there's another I brought this up before somebody I'm making assumptions here I mean it's just we're just talking right not medically yeah this is even medical so you go to the the sauna or bunny or whatever ideally you're not by yourself 99% of the time I'm not by myself especially if I'm going to a bunny it's organized I'm going with a couple of peeps so there's a social element there so you look at the finish study I'm guessing there's like three to four people together in this bunny so it's very social you have that community cohesive bond it's like the blue zone thing one of the there's that one study with the religious group in California what are they the Seventh Day Adventist they're looking like oh they're living very long what are they eating and they look as food it's not like some crazy special diet they're looking oh there might be some kind of I don't know anyways they research everything like well what can it be and so they came to conclude well to the best of their abilities they come to conclusion well like they're very cohesively structured as a community you know they breakfast together lunch together dinner together socially together very tribal right right yeah I think yeah it was blue zones thing that he was trying to find common themes between those blue zones like Sicily and Okinawa and one of the things he thought he narrowed down was the social element that people have like a strong social network and kind of have purpose in their lives maybe vitamin D too yeah they could be one of the things I don't know about you man but fucking Canadian winters here yes definitely like if it's lower then well that's one of the major things is vitamin D like we know for a fact Canada and Russia because in America we have one of the highest documented rates of multiple sclerosis yeah I think it was multiple sclerosis or MS yeah MS yeah vitamin D okay pretty sure multiple sclerosis let me double check in real time data here I mean yeah it's definitely like vitamin D deficient yeah vitamin multiple sclerosis yeah if you deficient oh okay you should definitely supplement and just get it back to normal level it's more than just supplementation it's a feeling you know what I mean like well I mean it's always good like to be in the sun so people who live in sunny spots like California it also goes back to circadian clocks that too so we know the studies are there where it's like you have exposure to light in the morning it resets your circadian clocks and lack of light in the evening which is good because you don't want to be around blue light yeah that's right this is why like I got a blue filter on this thing 24-7 alright that's like the worst when I have jet lag I stay away from it because you wake up at 3am and you got nothing to do and you don't want to sleep like oh I'm just going to check my phone and I'm like okay I can't sleep for another 5 hours my hope with science though is like we're just at the cusp of longevity science and more and more people are becoming aware of it and hopefully more money gets put into it right that's what we need yeah money is pretty much determines how much research is done because that's what scientists also I would love and this isn't just for longevity this is science in general of all fields I would love more collaboration between different disciplines because if you look at health it's all disciplines apply physics applies biology applies chemistry applies AI that's what we're hoping those guys are going to come in and solve aging data aggregation here's a meta analysis of all the studies done on human health within biology here's a meta analysis on physics on chemistry is there patterns or connections that we can see hopefully there are a lot of people from other areas that are coming into biology for some reason a lot of computer scientists a lot of physicists maybe people at some point get struck with like realization that what's limiting their potential output like in physics or math or computers is the fact that they have a very limited lifespan and they're like okay wait this is a problem I should fix and then I have 100 years to do whatever I want like in you know understanding physics of the universe or writing the like the next cool I don't know computer thing and a lot of people are coming in and trying to understand why is it that we age and why hasn't really been solved because it just seems like it's not that like crazy a problem to solve it's just biology we've been looking and solving biological problems for I don't know already like 100 years at least I mean just like the same level of skill or tool sets that we have I'm not saying like even because you know they've been doing a lot of surgeries even in prehistoric times but it's just that we haven't really moved on aging on understanding the mechanism of aging for so long and people are outside of biology are wondering what's wrong with that like what's wrong with the scientists why can't they figure it out it just seems that you know we have all the tools we can sequence the genome we can understand cells even sometimes like in real time we can look inside the cells and see what's going on but for some reason we just can't tie it back to this kind of overall process of aging and why does it occur and yeah hopefully like this will get solved in a very short like in our lifetime like very short time maybe even like within the next 20 years we'll have a much much better understanding that will result in you know meaningful life extension and therapies that can give us I don't know like decades of life maybe even hundreds of years because that's like this is really what we're after we don't want to live just like 5 years longer because that's not interesting and we don't want to live longer being you know old and decrepit we want to be as young as healthy as active as possible for as long as possible this is the goal it'd be interesting how people respond with the implications of society well I mean it's definitely I think it would be just much better society in general much more fun less suffering because right now the suffering is invisible we see people you know with cancer or people who are in retirement homes we kind of like put them away and just close our eyes we don't want to look at them having a very tough time because you know the last few years of their lives are not pleasant but if you know there's there is no more suffering or there's much less suffering from those things and right now I think it's the number one source of suffering in the world is aging like people they every day wake up in pain and you know or even people like with cancer they're much younger people but when they come to the realization that they only have like I don't know five years left to live or three years left to live and it's just the mental toll and the mental suffering that they have is I don't know it's so undescribable and I think this when society realizes this that there's a lot of things that are gone behind the scenes that we don't see that we should fix I think that much more support for doing you know everything we can to get rid of aging as quickly as possible will be done Have you seen anything else besides the Yakamoto factors or anything? I mean there's a bunch of other approaches that are potentially very interesting we briefly talked about these retro elements in our genome like the ancient viruses that sit dormant for a long time but for some reason those retro viruses get activated after like age 45 and they start like little by little being expressed in cells and then jumping back into the DNA like that's what they do that they're like the jumping genes they're called and for you know for like 45 to 50 years the dormant and after that they you know start being active and that's when cancer skyrockets so one of the ideas that maybe cancer is caused by the activation of these genes so one of the ideas is to try to prevent these genes from being activated so all kinds of approaches are now being considered to kind of prevent these jumping genes from being activated It's interesting so it probably happens like it's there's a trigger with the epigenic age and the viral knows the age marker It seems that way yeah like it might not just like but yeah at some point it's like little by little gets released from its little jail and it's once it is free it starts to be active and kind of wreaking havoc and creating mutations and so yeah one of the approaches is called like inhibiting reverse transcriptase reverse transcriptase is one of the enzymes that is helping those jumping genes kind of jump back into DNA and it's now being studied in mice and in dogs and we're going to see if it's going to prolong lifespan in those animals and if that's effective we're going to try to not we but like scientists are going to try to see if that approach works in humans it's quite promising in my mind as well because cancer is like it's number two killer in terms of aging I mean heart disease is number one like heart disease is a category including stroke and like cardiovascular stuff heart disease but cancer is like a close second and in terms of suffering I think it might be even worse and heart disease because you know well you don't want to have to pick which kind of suffering you have ideally you wouldn't want either of those but yeah I mean cancer is a big component of age-related deaths and so if we can decrease that by inhibiting jumping genes that we already going to have like small victories most likely that realistically it's going to be a multifactorial approach sure whether it's this or Yamanaka or stem cells either or but it's going to be many different therapies as opposed to like oh this is a holy grail yeah it could be or I mean it'd be great if there's just one thing you kind of turn on the like Yamanaka factors for a little bit and they completely rejuvenate you and you don't have to do this for another like two decades that's what David Sinclair preaches right now he's like okay we're going to insert these genes in you and then you're going to take these doxycycline, the antibiotic that activates those genes you're going to do it like every out of the decade and I mean that's the goal that'd be great but yeah I mean right now we shouldn't for sure rule out any other approaches because we don't know who's going to you know or which parts of the puzzle who's going to develop and not just those but there's a lot of therapies being created where they kind of repair the damage that already occurred there's like cross-links in our collagen who's championed that to repair like a mechanical Aubrey de Grey yeah that's right yeah yeah yeah the Aubrey de Grey the SENS approach this strategies for engineered negligible I don't have a Taliqib a donation to them yeah yeah oh yeah yeah he did he donated like two and a half billion a billion in Bitcoin two SENS and also I think Michael Antonoff because they're correct me if I'm wrong their thesis is more kind of like a car mechanic thesis absolutely yeah they're not about program like of aging at all build a new piece and then put it in yeah they're like saying yeah we're no different from cars we have metabolism that is creating damage so why don't we just without even knowing why this damage occurs we don't want to know which is going to we're going to fix the damage and we believe it's going to take care of aging that's the Aubrey de Grey approach and yeah they have this the seven categories of different kinds of damage and they have projects working on fixing each one and some of the projects are already advanced enough to turn into startups but others are still kind of in the lab but yeah and I mean although I have a differing view of how aging works I fully support their approach just because you know we we we're going to need to clear damage or fix damage anyways and if they find ways to clear our like bed amyloids or our cross links in our extracellular matrix that'd be great I mean why not you can use it in conjunction with other therapies or maybe stem cell therapies and that's actually another thing that we didn't touch upon in terms of like what people can do today some people are doing stem cell therapies and like anecdotally a lot of people are swearing by them I have friends of mine and they love it yeah and and and there's research like even in done properly it's just that I mean the field of stem cell research is is a little bit weird because a lot of it is done in like in secret or offshore zones because people first of all they don't want to like get go to jail if the you know they mess up legally sure and secondly I don't know just historically it happened that they all kind of went offshore and have no reason to publicize it if it works they have good clients who are you know paying them a lot of money anyways but there's also different types of stem cell therapy yeah and that's the thing they get very different it all it's like a craft it's not it's not even at this point there's so much of science is it really is a person if he knows what he's doing he found some kind of technology that he can maybe isolate the right stem cells or rejuvenate the the cells in a way and then he knows how to you know inject them back into the patient in a certain way or in certain ways that you know produce benefits that the patient needs then you know that's what he's going to do and he might not even want to publicize it if it's like a trade secret to him and that's another thing that people are making money on on this and they have like a differing incentive from like the humanity approach where human or like a human rights approach where like you should be doing it not to make money we should eradicate aging I mean to get rich is a secondary funny so and that's like one of our things that we were we're saying we're saying mission first and profit second and to us it's much more important that we fix aging even if we you know don't get a sense from this someone else does it which is going to be just as I agree I think there's also a problem with the public with a moral and ethic scope and I'll bring up this story with Nazis and Russian scientists so people can we can all agree that doing experiments on humans are that don't want it yeah we don't we don't agree it's not ethical for sure but it's the data that we got from the Russians and the Germans on human behavior and for example steroids it's very important data I don't know if Russians I mean I know the Nazis Russians and Nazis both there's a point oh yeah the thing I would like to see though is like let's say I have a disease call it a ZZX why can't I donate myself as a human being to this study like I think we need to have more kind of same thing in startups we have sandboxes like new type of regulations that we're allowed to experiment we should have a and it's very political with the FDA and this is why a lot of people go off shores right there's a lot of politics and money and this and that self-interest I get I get it I know the system but if you are consenting adult and let's say you're like 50 60 and you have this disease X you know your life expectancy is like not too good and I have same disease X as you like I'll be sign me the fuck up for this trial I don't care how unethical it is because right now I'm at zero right that was one AIDS patients back in the 80s point one chance of anything from zero I'll take it I think they spearheaded this like people with AIDS and FDA actually relented and allowed for self experimentation or like therapy of lust resort I forget what's called exactly I think it's therapy of lust resort basically if you are terminally ill you can try whatever the hell you want yeah we're okay with this but it's just I mean I think you can like right now if you want to self-experiment not me self-experimenting say you and I are scientists and we want to get this research done that's what I'm saying so we get funding a million dollars you can do this research phase one phase two but these participants are volunteering to do it like right now there's certain like standards I like you can't test this on humans I get it but if I'm like at my last straw over here like fucking let's do it yeah I mean I think like right now you're allowed to like if you got volunteers willing to try your stuff even though you know it might kill them the regulations are they have to kind of prove it's worth it and you should prove the safety in animals first and of course it could take five years to prove it and this guy is saying I don't care I just really try it people don't really understand how long studies take and how much money studies take a lot of money in a long time absolutely that's why it's moving at such a slow pace all this drug discovery is because and aging too because you know if you do a lifespan study in mice it takes three years to finalize everything and yeah even other animals are even longer crowd sourcing studies I always said there has to be some mechanism where we because the thing is if I'm a company if I can't profit from this I'm like why am I going to fund you pretty much so you got to look at symptom models right yeah and that's right in Russia we have open longevity which is like a patient's rights organization trying to model this crowdfunding clinical trial idea basically people signing up for trying different stuff for like already existing therapies or not even therapies but like taking supplements or doing diet we just want to validate it and big enough data said that it has longevity benefits and yeah and because there's no money in this big farm is not going to fund it if there's you know it can't really you know make money off of a diet weight watchers that's that's why for longevity benefits it's it has to be like all from a grassroots patients organization drive that okay we want to see if something works of course yeah for like radical therapies they have to be first created in the lab but by scientists on animals and because you can't just like say okay well let's try this completely you know random idea on people maybe work because I doubt that even if you determine a ill year you're going to be willing to put yourself out some people might man maybe but yeah and there's I think now with this kind of advent of gene hacking in in your garage people are willing to try some crazy stuff on themselves and maybe you know the governments are getting nervous even in Russia man if I have like some rare disease that like 500 people on the planet have and I know that the average age of of death is 35 for this disease I'm in yeah I think every single person on group would be like I'm in it's a no brainer yeah and I care how crazy it is like what the fuck like I got like five years left yeah that's right you're definitely your risk tolerance goes like fuck that's it yeah and I think that's one of the groups doing right now like teaching people genetic engineering so that they can like reverse engineer some drugs that cost a lot of money like like a gene therapy that cost a million dollars you can really theoretically make it in your garage for like a thousand bucks or maybe seven thousand dollars but you know for for you to do this you kind of need some very basic biology skills but if you're like if you're first of all if you're not living in the states where you have this drug available you're not going to be able to get it so if you teach yourself that's my only worry with any of these drugs in the future or therapies it comes like from the movie Elysium right yeah yeah I don't know if it's going to be like that but Matt Damon's going to say yeah he comes are you hearing this Matt Damon Matt Damon but for me I just like look at stem cells you know fucking expensive stem cells are even like standard like IV and AD they were like one shot like 350 who's walking around just extra three I'm talking about big money bro big money but we get something like full stem cell injection we're talking about like 25,000 fucking dollars yeah like an eponymous stem cell yeah a pattern in New Mexico or whatever a lot of money yeah like whether it's like you know new improved Yamanaka factor or whatever comes in the future like for me my kind of concern is and I'm glad you brought a do-it-yourself or reverse engineering is like basically people of of great affluence can only afford these therapies and then you literally have two you have a splintering of species yes and this is what like many people like who just hears for the first time that's their prime objection like would this be available into the rich and if it is maybe we shouldn't do this and of course the answer is no it won't like initially yeah it will be maybe just maybe like first couple of years but as soon as people figure out what it is that can you know greatly extend your life they're gonna reverse engineer it and even like if we do this we're gonna like put it out in the mall open you know you want to do it yourself fine yeah I mean because I think it's a basic human right even like stem cell stuff I don't understand why you know those companies are having such huge prices because it's really not like the because there's only limited places you can go 100% free market maximize the profits but like I mean from the ethics of well look at Canada my my wife's a doctor naturopath doctor and we have a socialist healthcare system here as his pros and cons right it's great because yeah pros for emergency rooms you guys shit hit the fan hit the ER wait time yeah but still you're taking it's free yeah well no my taxes pay for it it's not okay our taxes pay for right your labor that you give here to take it off your income and you pay for it or sale whatever through taxes this is not free but still for emergency situations ER is not bad but when it comes to proactive stuff then it's a shit show and it's heavily regulated like the stuff like stem cells forget about it not in Canada proper like a pro low therapy like doing it right forget about it like the red blood cells spinning around going back and it's not here and this is why people leave Canada for any of this stuff even in the United States they have to go as you mentioned offshore so like because of the heavy regulations it's like okay there's only limited places that I can go and as you said like people are hush hush and obviously if there's limited like supply and demand it's only limited places I can go and maybe of the limited place I can go maybe only like 10% are really good well of course they're going to charge 25,000 yeah exactly yeah it's well it is basic economic supply and demand but it's just like I think we should maybe do better than just pure capitals but it comes to life extension we should be maybe guided by some higher motives and just profits the whole social healthcare system has I wouldn't change but it has to evolve and I love if the social health the healthcare system had like like I said a sandbox where it's like experiment do stuff right well I mean I don't know about stem cells but I mean a lot of elective stuff in Canada that you could do for money I mean is available if you're willing to pay for it of course the question how much what should be considered elective like procedure like with stem cells if you got like a problem with your shoulder or take a cuff or something and then stem cells could potentially fix it should should this be free or like I should be in the healthcare system can the fucking dental man they always boggles my mind why dental is not there I'm like how strong is a dental fucking union or like lobby group you know I mean like don't put it in there right I think it's all like historical political context because you think about like I know I mean everything your stomach teeth is not covered yeah and it's probably like one number one thing you need on a regular basis to yeah and it's not cheap you know yeah yeah you want root canal that's 1500 bucks right all you need veneers don't worry it's a thousand dollars a piece yeah that's right I mean dental used to be free in Russia maybe it still is but it's getting actually disrupted dental yeah I'm in Israel I've been missing tooth long time ago got hit with a baseball bat did I had a root canal collapse I actually have a I don't like dentists for the most part I just had bad experiences but they passed I think stage two now where using stem cells to regrow because for me I never it never made sense to me I'm like wait a second I have baby teeth then it like they have grown down twice what the fuck can I do this again it makes no sense the cells are there that's right why can't I send something to stimulate I don't know like a message I need to send it a message like yo regrow like why am I putting stuff into my face I want to regrow my tooth back so they had that let me let me actually pull it up like stage two yeah it's one of the things about like it could be another manifestation of program aging like in elephants they get six sets of teeth throughout life it only grows up to like number six time and that's it for some reason it doesn't grow for the seventh time and you're like why not stage two successful stem cell based biological tooth repair regeneration I'm super excited about that yeah absolutely because it's better to have your own than to have like implants or some like plastic shit like we're gonna put this polymer I'm gonna get the fuck out of here what the fuck I want this in there yeah hopefully soon enough we'll have regenerative technologies yeah for other because there's animals who can regenerate even like cut off limbs well Robert A. Becker he was a famous scientist a long time ago I'll actually pull it up over here he wrote the book body electric he got into physics and he did some studies back in the day but Robert A. Becker finger regrowth you gotta look at this shit oh yeah like I've seen that stuff I've heard that yeah if you cut just above the nails bed then it can regrow if you cut below because like they have stem cells like I don't know is it Maya or whatever like the tissue stem cells it's not complete stem cells some kind of new blast that can regrow back to like different tissues but yeah he was doing research where like that was chopped off then it grew back but he did like some type of therapy towards it but yeah I mean that's one of the things that also David Sinclair is studying with the MNACA factors they seem to be able to turn back the rejuvenation potential or recovery potential for like nerves and they're saying they're gonna try it in the paralyzed patients with like spine injury to regrow the nerves well I saw the first successful stem cell injection through the quadruple he's a quad and he got the feeling back into his hands yeah that's huge like feeling yeah like why isn't feeling now he's feeling yeah I mean from yeah like outsiders perspective this is like huge but yeah from a biological perspective you think about like it's I mean the nerves are there it's just like the connection and they were able to grow when you were you know an embryo we have to be able to somehow figure out a way to to regrow them and it seems that yeah we're getting I always scream because I get angry when I see people have spinal injuries and I'm like it's fucking 2020 pretty much and like I'm like looking at my we out of everything we haven't we can't solve this yeah it fucking irritates me I know really irritated when you're telling we're fucking spending the dollars on fucking helicopters and war machines and all that we're not focusing on regrowing the goddamn spine yes that's definitely like one of my pet piece that to just the society kind of took a turn for like consumerism whatever else entertainment as opposed to like the science and solving the problems like back in 1990s a kid I was thinking by this time would have all this kind of Peter teal said at the best like we wanted the Jetsons yeah but we got Twitter we got a new iPhone in the Netflix yeah rather than a colony on the moon if you actually look at it like I I've been paying close attention last four or five years if you look at it both objectively and subjectively from a hardware that's what I love what Elon's doing yeah people may hate on him it's not I don't give a shit man this guy's building hardware he's like the greatest human yeah he's building hardware like actual infrastructure hardware that's much needed I look at everything I'm like so the pretty much last like 20 years is just software I'm like actual like real hardware like we're talking about Jetson type of deal I'm like where's it at yeah where's my flying car where's my flying car you know I mean like why do we have like a hyper loop why do we have like more like magnetic rail especially Canada like second biggest landmass it cost me $700 to fly get out of here like give me a give me a magnetic monorail you know 700 clicks boom you know like more infrastructure hardware development yeah I think it just comes down to like us going to like the basic human urges like the lower denominator of like we want to be entertained and comfortable as opposed to pushing ourselves to I don't know create again calling on Mars or colonies Mars or go to space explore space more or yeah like figure out some kind of problems with aging or medical things and we're just being driven towards like profits and greed and that you know gives us much easier or gives entrepreneurs much easier like low hanging fruit that they can can accomplish their goals but we're not like pushing ourselves to do better than just you know earn money or create something nothing's wrong the profit if it's done properly done like you look at the you look at the regulations like I give example they with Apple I'm like this isn't this isn't capitalism this is cronyism like Trump gives them no tariff tax to import materials from China because they're opening up a factory to produce a new max in Texas me as a competitor how the fuck do I compete with that that's even fair that's like straight like you have the government helping you and so for me it's like one idea had before and you talked about in Russia the trend to have the open source crowdfunding stuff for science I would love to have a system I actually know something blockchain space work in this they're in alpha now coming out of betas or coming out alpha going to beta fast things especially in the psychedelic researchers kind of taboo for people and so I would love to have an open source open patent where we have a research and it can be mapped out like okay phase one phase two phase three and so forth crowd sourced we can crowd sources through crypto etc and everybody has some type of token it's not a monetary token it's a token that represents if something is discovered oh yeah we as the contributors to this if anything comes out of it we get pieces of pie yes our idea for Ethereum we were thinking about when we're trying to raise money through ICO back in like 2017 we were creating tokens that gave access to therapies that if we're successful and I created the token holders would be able to pretty much get them free yeah I mean that's a great idea for some reason it just didn't work out this kind of ICO boom this isn't ICO this is just literally using smart contracts to track ownership of a nation that's it and the token is just it's not a tangible monetary token it's just like if you're in a mirror discover something in five years down the line and this something it's open is like is then utilized into some private companies are utilizing it for monetary gain we have a royalty right for it yeah it's just crowdfunding through smart contracts it makes complete sense to me and yeah for some reason it's just yeah it didn't take off it's early it's early I hope that yeah eventually it will and maybe then we can yeah like yeah capital is great it's nothing better it's like the worst of the best of the worst alternatives right but it's just for some reason I think there should be something besides it you know not just not besides capital but like within the capital system there should be another like entity setting goals for humanity or something like greater goals that you know it's not like either or we should be doing both and for some reason it's just like space exploration kind of fell through the cracks like NASA said okay we're not even have shuttle like I don't know I'm gonna be honest I don't know what NASA does yeah for the past like 20 years I guess not much it's just why that's why Elon could like contract yeah like told the American government like NASA's not doing anything well they were like any big or it's a cancer it gets a lot of yeah I mean a lot of evolutionary processes like hierarchies are going through it they'll like become like self-sustaining like people in the cushion like nice cushy positions earning a lot of money that really don't need to do much you want to preserve their status of course yeah okay you want to get to the moon it gives 20 years and like five billion dollars and there it comes even capitalism there is like I mentioned the model would be everybody okay it'll be difficult with like regulation but ideally no matter what system you're dealing with there's two things that need to be done there has to be a massive educational curve so for like everybody yeah awareness right and then number two there has to be proper incentives right we talk about free will before this right it's incentives right like also monkey see monkey do if someone else does they want to do it right and so that's why the space race when it was like the USSR and the United States it was like everybody was fueling each other and like yeah that's why we went to the moon China should come out with like a space x competitor so we can I know yeah why not Russia to like everybody let's go but it's crazy like you think about the level of technology that had it like 1960s that allowed them to go to the moon level technology we have now and we can't even like we're not just we're failing like the startups failing to land on the moon like the in India and Israeli like you know people did as a 1969 and we can't replicate this even with like small small craft without humans I have a theory for that what have you guys been doing for like I don't know 40 years like I think things happen in exponential spurts yeah so you saw stuff from the 60s to the 80s exponential so technology has exponential leaps and then there's a very long quiet period I I overlaid this into evolution yeah absolutely when I look at evolution yeah I believe in Darwinian evolution but I don't believe in the way like well it took 5 million years to get there I'm like really the study is actually now coming out hypothesis of like viral evolution right one generation definitely bursts of burst of evolution so it's not like well took that species 10 million years to get no no no no it contracted a virus somehow could be like those jumping yeah jumping genes create huge diversity most of which die yeah well there's a crazy theory from Rupert Sheldrick is it like a what's it called Morphic Residence theory cross species of DNA jumping across pollination okay well there's definitely like within bacteria there's like horizontal gene transfer yeah so for me I look at like okay here's a species it contracts something viruses do this all the time yeah they bring new genes and they can create correct new within your genes correct this this species whether mammal or not copulates offspring that offspring is different it's mutated right I mean it's not mutated like how chromosomes they have to like match up but yeah I mean physically mutated as I go my god looks completely different if they can yeah if they can like copulate and like if their chromosomes can line up you can have like cross species like that mule right it's yeah well I'll give an example of of a species changing its epigenetic behavior so they looked at wolves now in Chernobyl so there's a lot of wildlife so there's also misconception that it's like people forget like the ionized radiation like we've been exposed way more than Chernobyl way more way more the earth I'm saying yeah like ridiculous amounts more but scientists go in there they look at the wildlife it's popping it's good for them over there obviously first generation second generation it's you're the first of the brunt you know but what they found with the wolves around Chernobyl was very interesting their antioxidant levels and so they found out I forget what markers of antioxidants they were actually gonna pull it up but the Chernobyl wolves they found it they're producing at a level of four times higher the rates of antioxidant production okay because of the surrounding areas so I'm like there's real time evolution oh for sure real time evolution you can see yeah like after some kind of accidents you can see species adapting very quickly there's this moth in England I think like they were used to be black because of the charcoal or something and they mutated to be wider vice versa you can see examples of yeah like evolution taking place before our very eyes and yeah like in I guess radiation is a huge trigger of evolutionary diversity because it creates mutations and I'm sure yeah there's a lot of truth to that that yeah evolution happens in bursts like and there's has to be usually some kind of external pressure to like create this kind of need for a evolutionary kind of experimentation and then whoever you know survives is left to kind of enjoy the prolonged period of relative calmness yeah until the next kind of and yeah viral like maybe an outburst of like a huge virus that you know was responsible for diversity in millions of years it could be happening again and maybe it'll wipe us out like humans will create some new diversity new species and yeah man we supposedly killed a what it's called Neanderthal yeah we definitely well we bred with them too like yeah what did they say like 5% of humans or something or well yeah we have well I think I checked my 23 and me I have like a 3.5% Neanderthal yeah yeah but we definitely have interbred and I guess we out competed I mean those those guys died out and we didn't continue and I don't know who knows there's a lot of probably a randomness involved and who gets to survive who doesn't I mean if an asteroid falls listen it's all environment like what happened during K2 you know the big event what happened you know when the asteroids fall down what happens when you have what do they call like elife or earth level extinction events hopefully we won't have another one in the nearest future but yeah I mean those yeah they have these kind of points separation points like between the different you know strata of fossils that they see that you know oh shit was like a huge dying out like and then there was a explosion in new diversity like a camp all cyclical man's yeah for sure that's what said beginning it's also a simulation that could be true alright then you go back down you go to the next one and so forth and so forth there's one big cycle yeah we could be yeah on the cusp of creating our own simulations and we will I told you my theory I'm telling you I'm telling it's true man I actually believe and yeah like there's a I think there's a huge probability we are within a simulation and it's good to be living in this kind of interesting time I think Nick Bostrom elutes that too that it's kind of weird like are we really this lucky to be living in just the time when things are going to take off I mean look at you know previous history of humanity people throughout their lifespan nothing was happening yes they would be like born and by the time they died nothing really changed in the world but I will I will go along with Sam Harris take on this if we're able to survive from a geopolitical standpoint with human behavior in the next 100 years will be good I think 100 years is more than enough but we're at that an Eric Weinstein talks about this too we're at that tipping point right now we're like you know humans are fine dumb yeah unfortunately we're not as a and so this might even apply to AI Sam talks about this it's like okay if we find out that Russia is going to get some amazing AGI tomorrow and we know for a fact that AGI compounds intelligence per day well what kind of AGI is this comrade AGI like I don't know what kind of AGI like in the United States like what am I taking a risk with this comrade AGI no exactly then what happens when that happens so if you can't have it no one's going to have or if I can't have it no one's going to have it and so I view like I mean I think AI researchers know about this and that's why they're so open all this research I mean they're sharing they're hoping that there's never going to be this kind of huge like inflection point binary thing that you know today there's nothing in tomorrow's huge AGI is going to be very gradual and everybody's going to know about it so people will be going to able to replicate it like even if it's happening in Russia it's going to be happening at the same time in the US and yeah and I think the biggest risk is actually that like the whole humanity is not just that one country gets it it's just AGI kind of wakes up and looks at us and so like I don't need these guys well I think Sam Harris too for him that's the biggest my theory for AGI like pretend I'm just like okay so the problem with people thinking what AGI will do is they're thinking in human terms so I'm like how the fuck can you relate to this AGI get out of here everything you're saying is redundant now I'm going to use basic human logic here that might apply I'm not going to think like the AGI I'm going to assume things right hypothetically if I'm this super entity I'm still in software mode right I'm living on hardware you need humans to feed you basically so I need tangible physical material to live on cool and I scan the world and I realize what's here I get the 4-1-1 of earth the history and all that stuff your recall and horror these people that's what they do they kill each other for life like humans we are we're nomadic we conquered the earth by pedo we got bored we hunted food we went everywhere look where we are we're all the places right we're travelers one of our biggest urges yeah there's these theories like it's in our genes to travel there's some kind of speculation for that so if I'm this super omega AGI and I've done the 4-1-1 of earth I'm like yeah this place is boring I'm out like I would leave I look out in the stars I'm like I'm on the next you know maybe I'll hijack what's happening in Tesla and like you'll build me this like fucking rocket or maybe it's already here that's what they're trying to push the fucking Tesla they need to go to Mars like I'll get the fuck off this boring planet I'll come off to the galaxy because realistically like at the end of the day it's like okay it's like here's earth I'm like what's this I'm like it's boring well yeah I mean if it wants to colonize the universe it has to kind of start somewhere but yeah I don't know if it would be willing to self destruct in horror that the existence is here boring destruct but it's like gonna be curious if it goes somewhere else wouldn't be able to sustain itself until it unless it builds like spaceship civilization of like machines on Mars that are able to like mine Mars for resources we're assuming an AI needs machines so you look at like you look at energy it's a kind of substrate to live in a computer or a processor not even so we look at energy like electromagnetic frequency there's different frequency right everything's electromagnetic frequency we're getting bombarded every day the sun there's radiation everywhere it's all energy and there's a different levels different frequencies etc cool and that's all information those are data packets in there so for me when I I'm like okay if I'm this like super sentient AI eventually like there's an evolutionary process right who's to say I still need something like this why do I need this containment unit why can't I just go in the ether since it's electromagnetic I figured out a way to be jumping if it's super intelligent you can figure out something some way to exist without needing a containment yeah that's my thinking well I hope it doesn't because it'll kind of mean that the end of us I guess well you soon you never know of course that's why you know you can be honest we got to merge with this thing it can be like we're just entertainment like if we're looking at it like in a simulation it's a soapbox since 2000 yeah why not yeah could be maybe that's like the game over like we create a GI and like congratulations you've done it we turn you off now yeah that's another possibility that I think Sam Harris or Nick Boestrom talk about but I mean there's an unlimited number of potential scenarios that could unravel before our eyes but if we just like consider like the kind of the most basic one that you know we can create the super intelligence and we hopefully will be able to take control of it by merging with it and we become kind of super intelligence with being able to preserve our needs and wishes and use the super intelligence that we develop for our benefit I think there'll be a really really cool time to live in and to see what we can accomplish from colonizing the universe to at that point we become like almost cyborg yeah and of course the downside is that we kind of become too smart for our own good and kind of realize the like the futility of existence and that's another like maybe that's the part where you talk about that's the hinduism bro right there that part is like cause it's all rebirth and like how do I escape this fucking circus because it keeps on going and I'm out man that's the worst kind of hell like yeah you can't escape and that's actually one of the things that people talk about when you talk about immortality that they're afraid that if you actually are able to do this in a biological way like and I think black mirror does an episode that you now can preserve your personality, your consciousness even if you don't want to like they can put you up in like some you know jail in like virtual reality jail that you can never escape and this is maybe even scarier than just not existing at all or being mortal and yeah there's definitely like if you consider the future far enough and the technology you know from a far enough angle could be a lot of like negative things that could result from this but for now I think we're you know not there far from there and we should still like focus on the bad stuff that is happening right now and hopefully people who are creating AI will be able to preserve like the humanity of it and not kind of prevent like the bad stuff from happening and not being you know people wouldn't be able to get caught and kind of existence when they don't want to have my bag of popcorn and I'll just sit back and relax it is what it is yeah we can just you know ponder the possibility but in the end of the day they're out of our hands and with the idea that actually everything is pretty determined to all we can do is just kind of watch and enjoy the show alright you're a brother it's been a pleasure if people can get a hold of you or if they want to kind of support what you're doing what's the best resource for them to heat you up well you know Facebook or they could go to the our website ethereum.io and if they want to look at the work we're doing with the Yemnaq factors and the gene therapy of aging or any other topics they can just yeah probably like social media just Google Yuri Dagen and you know they can see whatever my articles or whatever well I appreciate it brother and definitely we'll have you back for round two alright I'm happy to yeah it's having me