[00:02:29] Seb Bunney: I do a ton of research to be able to really dig into the topic, which we’re going to discuss, and how all of this kind of conversation around genetics and enzymes and such, how it all kind of like pieces together. It took me definitely quite a bit of studying to kind of piece this together, but I’m super excited to discuss it.

[00:02:46] Preston Pysh: Amen. And if you’re a doctor or you’re in the medical, you know, industry or you’re a biologist, I apologize upfront. I deeply apologize for all the terminology that we are going to botch or just get wrong, but we’re going to try our best here.

[00:03:03] Preston Pysh: So let’s start off here. I was literally scrolling through X this morning and I see a post and Ray Kurzweil, everybody knows the technologist, Ray Kurzweil, CTO at Google for decades.

[00:03:18] Preston Pysh: And the quote was, he expects to have longevity escape velocity by 2032, meaning by 2032, the science is going to enable people to outpace what our death rate is. And, and that’s not framed correctly, but we’re actually going to have this technology in place to keep extending your life longer than the average death rate is.

[00:03:43] Preston Pysh: So what do you think, Seb, is this nonsense? Are we, you know, and we’re going to get into the book and what the book is proposing is like how some of this is possible, but what’s your, just off the cuff gut feeling about some of these proclamations that we’re hearing from people.

[00:03:59] Seb Bunney: My gut feeling being absolutely transparent is that, and I can dive into a little bit more at the very end. I think it’s good to kind of get the book out of the way, but my gut feeling is that I think we get caught up in the hype of things. And just as we’ve discussed in the monetary system, we tend to point to, well this is the cause of inflation, this is the cause of the banking crisis. And in reality we are dealing with a complex adaptive system that is almost impossible to be able to pinpoint like these black and white stories about what causes something.

[00:04:27] Seb Bunney: And I think the same thing is true for lifespan, health span longevity. I think sometimes we try to simplify a really complex topic and people have been talking about longevity and increasing lifespan for decades. And there’s also some contradictory data, which I’ll dive into at the end that I find really interesting.

[00:04:44] Seb Bunney: That kind of tends to argue that have we actually seen an increase in lifespan even over the last 2000 years, but we’ll leave that for a little bit and I, yeah, I’m excited. And it’s just, it’s fun to dive into these other topics and there’s definitely technology in this world. There’s definitely advancements in understanding that are supporting health, for sure.

[00:05:02] Preston Pysh: Yeah. So David Sinclair out of Harvard, the author of the book, and his core thesis is that aging itself is a disease. And I think from a definition standpoint, he’s trying to get this included as a disease so that the treatment and the way that it’s handled from a health medical perspective is treated differently than it’s currently approached.

[00:05:25] Preston Pysh: Because I think today it’s like, well, they just got old and they died. And he’s like, that’s not good enough. We have to change the definition so that it’s bucketed in as a disease like any other disease. And then you’re going to get a lot more research dollars into it. You’re going to just going to like unlock a whole lot more funding to really kind of dig way deeper into some of these things.

[00:05:46] Preston Pysh: Anything you want to add there, Seb, on why you think he’s classifying it as that? But this was a really important part that kept coming up in the book, is this redefinition of it being a disease itself. Aging as a disease itself.

[00:06:00] Seb Bunney: Absolutely. I think that he highlights it quite a few times throughout the book that essentially there are these hallmarks to aging and he is like genomic instability, telomere attrition, epigenetic alterations, all of these things that basically lead to aging.

[00:06:16] Seb Bunney: But he believes that there’s, we’re focused on the symptom and actually what leads to those things is kind of this information loss, which I’m sure we’ll get into, but he thinks there’s this upstream thing that we’re not talking about. And if we can recognize and fix that upstream issue, then we may be able to increase longevity.

[00:06:34] Preston Pysh: Yeah, so his big theory, his big breakthrough is this idea of the information theory of aging. And we’ve covered Claude Shannon’s information theory on the show numerous times. We had the author of the book come on about Claude Shannon, and just this idea of like, how do you transmit information across, you know, a wire or through the air via signal RF energy.

[00:07:03] Preston Pysh: And David Sinclair takes this idea of transmitting information or information loss and noise factors to biology. And suggests that the reason we age is because it’s a loss of information. Specifically it’s a loss of information for your epigenetics. And so when people hear some of this terminology, they’re saying, well, Preston, I have no idea what you just said when you said a loss of information of your epigenetics.

[00:07:31] Preston Pysh: So what I’m going to try to do here. Is, explain this from the ground up in Preston verbiage and Seb, feel free to step in if you feel like I’m stepping out way over my ski tips here, but, okay, let’s start here. You got your cell and I think everybody’s familiar with DNA. Okay, let me just, let me explain it like this because I think this is fun to frame it this way.

[00:07:55] Preston Pysh: So the typical human has about 3.3 billion base pairs in their DNA. So just think of it like genetic code, like you got all this software, all this code that’s run and it’s 3.3 billion lines. Think of it like that. Interestingly, a tomato also, if you look at the DNA of a tomato, it’s about 3 billion base pairs of DNA as well.

[00:08:22] Preston Pysh: So when a person hears that and they say, well, hold on a second, what do you mean DNA of a tomato is the same, you know, length or lines of code as a human, and it just doesn’t seem to make any sense. Like, how is that possible when you think of the complexity of a human? They got a brain. They got a heart. They got eyes. They can do all these things, they can communicate socially, and you’re telling me that the code inside of the cell is of the same length as a tomato.

[00:08:49] Preston Pysh: Like it just doesn’t make any sense. This is where you step into the epigenetics of the DNA. So what is that? So think of the DNA as this big long line of code, but what’s actually needed inside of the code to read it and create, call it a heart cell or a neuron or the cell in your eye, these differentiations that are happening in your organs and just all the different pieces that make up a human.

[00:09:17] Preston Pysh: How do you get those different pieces and parts out of those 3.3 billion base pairs in the DNA and the way you do it is through what you know is referred to in the book as the epigenetic settings of the DNA. So, just imagine like all of that line, all those lines of code are out on a piece of paper.

[00:09:37] Preston Pysh: Let’s say we had thousands and millions and millions of pieces of paper with all this genetic sequence. Okay? Let’s say you flip to page 50, and in order to create a heart cell, you need the genetic code on page 50, you need it on page 1 million. You need it on page, whatever. There’s just very specific pages that that’s the code for making a heart cell.

[00:10:01] Preston Pysh: And then it’s a whole different set of code. There are pages of that code that need to be read in order to create an eye cell, and the list goes on and on for each organ. Each cell type in the body. There’s only specific pages of the 3.3 billion base pairs that exist. You only need certain pages to read in order to do that.

[00:10:19] Preston Pysh: So when we say the epigenetics, what we’re really saying is which pages of the 3.3 billion lines of code actually need to be turned on in order to be read? And so when you think about going back to this example between, you know, a tomato and a person having the same amount of genetic code, for all intents and purposes, the pages that are being read or the pages that are being flipped open in the book to be read by the transcription proteins are very specific and very different depending on what organism or person or thing is being built and constructed inside of the body.

[00:10:55] Preston Pysh: And so David Sinclair’s book, so hopefully that provides a little bit of a background on like what epigenetic settings are. It’s the pages that are open to be read, and this idea of the information theory of aging is as the cells replicate that go through mitosis as these cells are, you know, as you’re living a life, you’re in year 20 versus year 40 versus year 60 of your life.

[00:11:20] Preston Pysh: As these cells have replicated, the pages that are flipped open for these different things that need to continually be built and transcribed in order to create the proteins inside of the cells, that information of those epigenetic settings, which pages are flipped open, are changing very slightly, and instead of it being page 50 that was open, now it’s page 50 and page 49, which was never intended to be read is also open. And as those transcription proteins go in there and they read that genetic code that it wasn’t supposed to be reading, it’s now producing and creating extra material inside of the cell. And this, this is creating noise that is not intended and this is what’s causing aging inside of anybody or any living thing.

[00:12:05] Preston Pysh: And so this is a really, like for me, when I was reading this, I was just like, my mind was blown. I was like, this is so fascinating and so interesting. And it’s pretty elegant, right? Like it’s pretty simple when you really kind of pull back and you think about like, well, what would be the ramifications of this, of a heart cell that had certain settings, but now it has additional settings that are not supposed to be being read and being produced and being turned into proteins that were never intended to be turned into proteins inside of that cell. And how do you turn those off so that you can get it reset back to the initial epigenetic settings.

[00:12:41] Preston Pysh: Seb, am I out to lunch in the way that I’m describing this, or do you have anything else that can maybe help the listener piece this together? Especially the ones that have no background in biology.

[00:12:51] Seb Bunney: No, Preston. I think you absolutely crushed it. And I think for me, it had an analogy in the book around this kind of CD player, and I struggled a little bit with the analogy, and so I was, I didn thinking a little more.

[00:13:01] Preston Pysh: Didn’t, yeah, I didn’t like it.

[00:13:02] Seb Bunney: To me it didn’t make a ton of sense and so I was thinking a little bit more and I was like. I was really trying to understand this in terms of an analogy and the way that I interpret things, and again, like correct me if I’m kind of misinterpreting this, but the way I see it is that by getting older isn’t so much a kind of a hardware problem. It’s a software problem.

[00:13:20] Seb Bunney: And so imagine if your body is a computer and your DNA is effectively the hardware, it’s the physical machinery and it’s built upon as you’re talking about these kind of four chemical bases, A, T, C, and G, which I think, what are they? Adenine, thymine, cytosine, and guanine, and I butchered those names.

[00:13:38] Preston Pysh: Better than I would’ve done.

[00:13:40] Seb Bunney: So all of our genetic information is made up of these four bases. Everything is made up of these four bases, and that information is remarkably stable. If you have a 1990s iMac, it’s still the same 1990s iMac, the, the hardware is remarkably stable. They barely change over a lifetime.

[00:13:58] Seb Bunney: But then on top of that, you have the epigenome, which is kind of what you’re talking about, the epigenetics. And this is the software or the operating system that tells the computer what to do. And so it decides which programs to run, how to use the fan, how to basically enable this machinery to run.

[00:14:14] Seb Bunney: And so when it’s saying like, which program is to run from a DNA perspective, to your point, it’s saying, well, this needs to be a skin cell. This needs to be a liver cell. This needs to be a brain cell. The problem is that over time, software starts to glitch and introduces error on the hardware. So you get environmental stress, you get DNA damage, metabolic wear.

[00:14:34] Seb Bunney: And so the hardware itself is still fine, but the computer starts freezing. It starts misfiring, it starts having memory issues as to how it’s meant to run. And that is what this guy David Sinclair kind of talks about is aging. It’s not necessarily the loss of biological information. The computer itself is still totally fine.

[00:14:51] Seb Bunney: It’s more, it’s forgetting how to run and operate efficiently. And his whole thesis is that if we can restore that software to its original kind of uncorrupted state, then we may be able to reboot the system and bring hardware back to its kind of full use. And that’s kind of in my mind, I see genetics as the hardware. And epigenetics is a software telling the hardware how to run, and that is where this understanding of aging comes about.

[00:15:18] Preston Pysh: Yeah. And to that example that you’re providing the software on the computer is what’s telling it how to rejuvenate the hardware itself. So like let’s say that the hard drive was getting old and decrepit, the software that’s loaded onto that computer is providing the information to be able to self reinforce and self fix the hardware itself.

[00:15:43] Preston Pysh: So if the software gets corrupted, it’s never going to be able to perform those tasks of the rejuvenation of the hardware. So really kind of like fascinating insight. He does a really good job kind of explaining all of this stuff that makes it really accessible, which I loved about the book. Anything else that you wanted to cover on the Information Theory of Aging before we kind of go on to like putting it into a little bit more context?

[00:16:09] Seb Bunney: Yeah, so what I found was really fascinating is that like once he kind of breaks down the information theory of aging, he then goes into, well, how did he get to this theory? And he starts talking about yeast. And so at first you’re just like, what has yeast got to do with humans? And what you realize is that yeast ages in one week, humans obviously take decades.

[00:16:31] Seb Bunney: And so you are able to effectively, rapidly test longevity ideas on yeast, which is obviously not possible in humans. And if we can’t, obviously. Create some form of longevity mechanism, a way to extend a yeast life. How are we ever going to be able to do that in a human? And so I think they recognize this.

[00:16:51] Seb Bunney: And this wasn’t even necessarily even just David Sinclair. Like there’s a whole backstory to yeast. And that’s what I found was really, really fascinating. So when it comes to yeast, what he starts talking about is in the 1940s and fifties, yeast becomes like a model organ organism. All of these researchers start diving into how yeast is aging.

[00:17:12] Seb Bunney: And what they realize is this guy, Robert Mortimer and John Johnston, what they realize is the mother yeast cells can only divide a finite number of times before they’re dying. So this is like the first measurable model of cellular aging. And then from there, in the eighties and nineties, they find out that actually there are genes related to aging.

[00:17:31] Seb Bunney: And these are called the SIR, the Silent Information regulator genes. And you can think of, and again, like feel free to step in press, and if I’m butchering this. The silent information regulator. Genes I found so fascinating, and we can dive into more depth on this, but basically the way that they essentially work is these genes have kind of two roles.

[00:17:52] Seb Bunney: Essentially what they’ll do is these silent information regulator genes will sit on the DNA and they will prevent that DNA, that information from being read and turning a cell into, say, a liver cell when it’s in the brain, or if you’re in the liver turning that cell into a kidney cell. And that’s when you start to get mutations, metastases, and all of these other issues.

[00:18:14] Seb Bunney: But at the same time, they also do something else, which is in the event you have a DNA break, you have some form of genetic issue. They will leave where they’re located, they will move to that area and they’ll start to repair that break. And then once they’re done, they’ll go back to the DNA place where they were shutting down this information from kind of a turning into a liver cell, a brain cell.

[00:18:36] Seb Bunney: They will kind of turn that information back off again. And so anyway, it will return back to its original spot and it’ll silence those genes again preventing that gene from exert that DNA from expressing in a certain direction. And so this was in the eighties or nineties. And so this is this silent information regulated genes.

[00:18:53] Seb Bunney: Now we’re going to talk about this more because these SIR genes were essentially the backbone for this whole idea of aging that David Sinclair talks about. So that was in the, going up to the eighties and into the nineties, this is where David Sinclair kind of enters the frame. And so he starts looking at how to kind of age things prematurely and he figures out that there’s these yeast mutants that basically have this mutation and he’s able to age them prematurely, hinting at there’s some universal aging mechanism.

[00:19:27] Seb Bunney: And then in 97 through 99, he recognizes that, you know what? If they’re able to go in and over express these SIR genes, it’s able to reduce and extend, sorry, reduce DNA damage and extend the lifespan by up to 30% in this yeast. And so this was profound, and he kind of gets to this in about probably one third, one quarter of the wind of the book is that there are ways to be able to extend the lifespan of yeast.

[00:19:53] Seb Bunney: And to me that’s when the book starts to get really interesting because it starts diving into the technicalities of like, well, how is it actually doing this? I’m curious to hear if you have any thoughts on that, Preston.

[00:20:02] Preston Pysh: The thing that I took away when he started there was like, this guy’s a first principled thinker. The approach that they’re taking to try to solve this is very first principle. It’s like, let’s go back to the essence or the start of life itself, which was, you know, the swamp sludge, let’s, let’s see how it all started and how the mechanics of growth or contraction of self-preservation interacts and like what are those triggers or what are those cueings that are causing life to want to expand or contract or just preserve itself.

[00:20:33] Preston Pysh: And so by starting there, I was just kind of like, and he does a really good job of framing this in the book. Way better than probably Seb and I have Donna. We like just kind of sporadically talking about all the different ideas in the book. It’s laid out really well in the book and organized in a really thoughtful way to kind of walk you through how he’s arrived at a lot of these theories.

[00:20:52] Preston Pysh: One of the things that I also thought was really well done in the book was how he was walking through his proof of this information, theory of aging, and one of the things that he talks about is this idea of an epigenetic clock. And so what he’s saying is if aging is truly information loss, okay, and going back to this idea of the book, right?

[00:21:15] Preston Pysh: You got this big giant book of all the code, the genetic code, the DNA and if to make a heart cell. It is page 50 and page 500 and page 5,000. And just name out those very specific pages in the code that have to be read to create that heart cell. His opinion is. If it’s truly an information loss that’s occurring and other pages are accidentally getting opened and getting read, we should be able to peer into a cell and look at the epigenetics and determine how old something is just based off of, and this is called methylation, the methylation of the DNA.

[00:21:53] Preston Pysh: And what he found is that when they did this and they go in and they do it an audit of the entire DNA and they see how much of the DNA is supposed to be opened for a specific cell type versus what is actually opened. They were able to pinpoint the age. Of the rat that they were doing a lot of this testing on, they were able to pinpoint that with a lot of accuracy.

[00:22:16] Preston Pysh: And you can even do an epigenetic clock test on a human. And what they’re finding is that the accuracy of the test is one of the best markers of a person’s actual health because somebody might be 40 years old, but when they go in there and they do this epigenetic clock test, the person might have the age of a 30-year-old because their DNA is so in good working order and hasn’t been, the files haven’t been corrupted.

[00:22:42] Preston Pysh: So if you ever go into like a longevity clinic, I think a lot of them are starting to roll out these epigenetic test clock test to kind of see where you’re at versus where they think they can get you as far as dialing back a lot of the corruption that’s happened in your epigenetics.

[00:22:57] Seb Bunney: No, I think you’re absolutely spot on.

[00:22:59] Seb Bunney: And I think that one of the interesting points that he talks about is like obviously he needed to prove his information theory of aging. And so you could almost prove it in reverse, which is if we believe that it’s this noise which is creating aging, well how do we test that? And so they ended up using, I think they call it the DNA scratch test.

[00:23:18] Seb Bunney: They ended up using CRISPR . And I’m going to butcher if I try and explain CRISPR , but basically for anyone who can explain it better, we would love that go and explain it on Twitter CRISPR , from my understanding, they would go into the DNA and they would make precise edits and they would create these breaks in the DNA of these young mice mimicking decades of accumulated DNA damage, but without actually introducing any mutations.

[00:23:44] Seb Bunney: And the result is that the mice ended up aging rapidly and they showed gray hair fragility organ decline, even though their DNA sequence, the hardware was kind of unchanged. They just added all this noise.

[00:23:57] Preston Pysh: I would say, yeah, basically my take, and I might be wrong too, Seb, but they use CRISPR  to go there and open up additional pages in the cell, in the DNA book, right? To have more noise factors, just like what the theory suggests should make the species look old. And when they did this with a rat, it started getting gray hairs and it was, you know, decrepit. And basically it was just acting like a rat that was on its deathbed by going in and performing this epigenetic methylation of the DNA.

[00:24:28] Seb Bunney: We’re going to take a little bit of a tangent and come back to the mouse here for a second. But what is fascinating is the book starts going into these scenes called Yamanaka Genes. And this doctor Sya Yamanaka in 2006, he basically discovered these four genes. And these four genes were kind of the O CT four gene, the SOX two gene, the KLF four gene in the CMYC gene.

[00:24:49] Seb Bunney: And this is where it just kind of blew my mind because I always believed once a stem cell had grown into some form of specialized cell, a liver cell or brain cell, there’s no way to reverse that aging back into a stem cell and unspecialized cell. And this doctor basically found out, well, actually through these genes tinkering with these genes, you can reset them back to their like embryonic state, their unspecialized state.

[00:25:13] Seb Bunney: And it actually ended up winning the Nobel Prize in the 2012. But what is fascinating is that Sinclair had kind of dug into these Yamanaka genes and wanted to test this on these mice. And so this mouse that they had aged rapidly. They went back and rebooted the epigenetic software using these Yamanaka genes, and they were able to reverse the signs of aging. And so you’re just like, that is, to me, that was mind blowing.

[00:25:38] Preston Pysh: Mind blowing. People hear stem cells all the time, and I would imagine most listeners kind of know what that is, but if not, I’m just going to quickly explain it. Think of a stem cell as the DNA sequence, and it’s open to become any type of specialized cell.

[00:25:54] Preston Pysh: It could become a liver cell, it could become a neuron. It could become whatever. And so, because it doesn’t have any epigenetics set, it’s not saying read page 50, read page 1000. It’s saying you can read any page and become any type of cell you want. That’s what a stem cell is.

[00:26:11] Preston Pysh: And so this is called differentiation of a cell. Once it starts to differentiate itself as a skin cell, or you name it inside the body, that’s when the pages, the book is wide open as a stem cell. But as it starts to differentiate, all those pages start to get closed, and only a select number of pages are open to be read and transcribed.

[00:26:32] Preston Pysh: So to Seb’s point here about the Yamanaka factors, these three genes inside the sequence are almost like a reset button to push the book so that it’s wide open to become anything again and become a stem cell again.

[00:26:47] Seb Bunney: The analogy I think David Sinclair gives is like, imagine a marble sitting in a mountain range, like all marbles start out at the top of the mountain range unspecialized. But as they kind of like roll down the mountain down into a valley, they become specialized. And the problem is, up until this point of these Yamanaka genes being discovered, we just assumed that it was kind of a one way trajectory.

[00:27:09] Seb Bunney: Once the marbles are down in the valley, how are you getting them back up the hill and then crossing over into another valley? We thought that was impossible. And so this to me, I had no idea this was possible. And it really opened my eyes and they, and it, it shows a whole bunch throughout the book. It kind of gives a whole bunch of studies in which they’ve done.

[00:27:25] Seb Bunney: Most of them are mice, but some of them they’ve mentioned even with. Some humans, but most of them have been on mice. They did an eye regeneration study. They even had ones where they had old female mice that were infertile and they were able to restore eggs after like chemotherapy and everything through a similar approach. So to me, I’m just like this, I had no idea this was possible.

[00:27:46] Preston Pysh: Not only are the Yamanaka factors really important in the grand scheme of things as far as being able to reset the cell back to this stem cell state, which would enable it to differentiate in any way that it wants. There’s also a thing called sirtuin proteins or enzymes, and what the sirtuin proteins in enzymes do is they’re able to go in and update or fix the existing settings.

[00:28:13] Preston Pysh: So if there was damage to the DNA, if there was damage to it can go in and unmethylated certain histone tails so that the epigenetics reset in the right way. But these sarin, I put it into two different camps here. You got the sarin proteins, which are going and kind of fixing what’s already there.

[00:28:30] Preston Pysh: And then you have the Yamanaka factors, and these are four specific genes that enable the DNA to go reset completely back to the stem cell. So he talks about a lot of these, and he talks about a lot of the research that’s happening because the sirtuin proteins, there’s seven different types and goes on and on. It gets very technical, but I would just put those two camps or those two factors as where a lot of his research, or at least the research that he talks about in the book comes from.

[00:28:59] Seb Bunney: And yeah, I think you made a really good point, and that is being able to break those two things into two different areas. And I think that you’ve got, obviously these Yamanaka factors are four genes, and then you’ve got these pathways. Then I would even add two more to that because he talks about the, the sirtuins and the sirtuins are named after, as I mentioned, when it came to yeast, there were these SIR, SIR, silent information regulator.

[00:29:22] Seb Bunney: These are enzymes which sit on the DNA and preventing it from expressing, or it goes and repairs DNA. And so you’ve got sirtuins, which are basically these enzymes, and it’s the body’s longevity managers or maintenance crew. So they’re basically, there’s these seven various enzymes which are being found in humans, and their job is essentially just to stabilize the DNA, repair, the DNA, and then make sure it’s certain genes are properly switched on and off.

[00:29:50] Seb Bunney: And how they work. And this is where again, it just opened my mind. They rely on a molecule called NAD IDE Adenine. And I’m not even going to pro dine nucleotide. I cannot pronounce any of these.

[00:30:03] Preston Pysh: This episode is part comedy too. We’re just trying to make sure y’all are entertained.

[00:30:07] Preston Pysh: Go ahead, Seb.

[00:30:08] Seb Bunney: And so you’ve basically, they rely on NAD, NAD is what fuels these sirtuins. And when levels of NAD in the body are high, as they are in youth or during like fasting and exercise, sirtuins basically become active and they repair damaged DNA and they silence genes. But when they falter, as we age and as we age, we also see our NAD levels decline sharply by about like half by midlife.

[00:30:34] Seb Bunney: These sartuin just can’t keep up. And without this NAD genes start to lose coordination. DNA repair, chalos and cells begin to basically just forget their identity. And so you’ve basically got these sirtuins, and then you’ve got two more, which he talks about. One of them is called mTOR, MTOR, which is basically the mechanistic target of rapamycin.

[00:30:54] Seb Bunney: Side tangent. I’ve found that the hardest part about reading these books is once you actually understand how they work, it’s not actually that complex, but the words themselves become, amen. Just never come across these words. Amen. My mind is just lost half the time, so I’m like, wait, wait, what are they talking about again?

[00:31:09] Seb Bunney: Yeah, so I’ve have got to go back and actually figure out, like just trying to understand how they work, and so mTOR. Is basically the body’s growth switch. And so mTOR tells cells when to grow and when to divide, and so when nutrients are plentiful, so if you’re eating a lot, mTOR is active and it signals the body is a store energy, make proteins go and build tissue.

[00:31:29] Seb Bunney: However, when it’s overactive, you can get like constant activation from this is like overeating, frequent meals. I think this is what we’re happening, what’s happening globally. We’ve just got an abundance of food and then it keeps cells in this growth mode, which then can accelerate aging, lead to like cancer and all of those other things.

[00:31:46] Seb Bunney: We are able to turn on and turn off through things like fasting, low protein intake or the drug rapamycin. And so when we’re turning it off, that’s when it’s able to help with like maintenance or repair. And so the final one, and I’ll summarize these after just so kind of to bring it back full circle, is we have this other one called A MPK.

[00:32:04] Seb Bunney: And this is kind of the body’s energy sensor. And so this activates when cellular energy is low again during like fasting exercise, cold exposure. And essentially what it does is it switches the body into energy saving mode, which increases fat burning and insulin sensitivity, and boosts mitochondrial health.

[00:32:22] Seb Bunney: And so going back to kind of  what we were just discussing, you’ve effectively got these kind of two areas. You’ve got these genes. The genes themselves are absolutely necessary for kind of like governing aging in the cells and you’re able to reset cells back to their unspecialized state as pressing you were discussing.

[00:32:39] Seb Bunney: But then at the same time, you’ve got these pathways, which then help do this, and that is through the sartuins, which is their kind of longevity managers, the maintenance crew, mTOR, which is kind of  the body’s growth switch. And then you’ve also got the AMPK, which is like the body’s energy sensor. And so this is kind of, I think the foundation of the book is diving into these kind of different areas and how to test for these things and what to do in humans to be able to activate or deactivate certain areas.

[00:33:05] Preston Pysh: I’m going to use an example that I read from, not this book, but a different book that really kind of helped me understand this idea of growth versus the cell kind of hunkering down and optimizing itself. The author of the book was Bruce Lipton. He has a book called Biology of Belief. I think there’s another one called The Wisdom of Your Cells.

[00:33:25] Preston Pysh: And in the book he provided, you know, an example that I think everybody can kind of wrap their head around. He was, and I might mess up the example because I read this book a long time ago, but it went something like this where he was saying, imagine a farmer that’s there, you know, working in his fields because the sun’s out. There’s no storms, there’s nothing to be worried of.

[00:33:44] Preston Pysh: He’s out there, he’s harvesting, he’s doing all this work. He’s in growth mode. Now imagine that there is a loud speaker in the town that alerts him when there might be bombers that are coming overhead. So he hears the alert, get inside, hunkered down, get safe, and so the farmer goes into a bunker, he closes the hatch, he goes in there, he has no idea how long it’s going to take, but while he’s in there, he’s trying to do things that allow himself to self-optimize.

[00:34:15] Preston Pysh: He’s coming up the plans of like when he’s going to harvest, he’s going to come up with the plans on where he is going to store all of his crops. He’s going to do all of these like self-reflective type things as he’s hunkered down because there’s fear and there’s concern in the environment, in the outside world that he is trying to always operate in and trying to grow within.

[00:34:37] Preston Pysh: And Lipton used this example as a way for you to kind of understand how the cell. Operates and how the cell, every cell in your body is functioning. If you are experiencing hardship, let’s say you don’t have any food, let’s say you’re lacking water. Let’s say you’re, you’ve just run a marathon, right? You name it, stress, the cells in your body are kicking into efficiency mode.

[00:35:05] Preston Pysh: How can I operate most efficiently? How can I fix the damage inside of the cell? How can I do these types of activities that it can’t do when it’s expanding or, you know, transcribing the DNA in order to build new proteins and expand its growth? Right? And what he says is this back and forth where the cell is basically cleaning up.

[00:35:29] Preston Pysh: Itself and having this time to reset is actually extremely healthy. And you know, David Sinclair in his book is talking about the sarin proteins that then go, and the enzymes, the seven enzymes that go there and kind of clean up the cell and, and fix the damage that’s been done in the cell. The queuing for this, for these sartuin proteins comes from stress.

[00:35:53] Preston Pysh: It comes from hormesis. The stress inside the cell. And so this could be through fasting. This is why he’s promoting the idea of fasting. Eat in an eight hour window, go out there, experience cold exposure, experience heat stress, go into a sauna, go exercise. All of these types of things are actually very healthy if you do it in somewhat moderation.

[00:36:17] Preston Pysh: Do you want to go out there and not eat for a week? That’s probably not healthy. Do you want to go out there and not eat for, you know, maybe a day? That might actually be a really healthy thing to do from time to time. because it’s forcing your cells, all the cells in your body to go in there and. But yeah.

[00:36:35] Preston Pysh: Anything to add on that?

[00:36:37] Seb Bunney: No, I think you nail it. I think you’re so good at being able to articulate these complex ideas, and I think that’s a perfect analogy. He essentially just talks about kind of these four different areas which make a big difference, and that is eat less. To your point, it is plant heavy foods, and this is something that.

[00:36:55] Seb Bunney: We can talk about at the end. I tend to disagree with somewhat and I think there’s a lot of evidence. Support it. He is more vegetarian, plant based, and then you’ve got the fasting time restricted eating, and then the cold and heat exposure. And the idea behind a lot of this stuff is essentially that hormesis idea.

[00:37:11] Seb Bunney: It’s that you want to stress the body. Stress is good because it puts the cells into kind of cellular repair. Again, like I can’t stress people that are kind of listening to this. To me, I would say like what was so fascinating about this book is just understanding these sirtuins, like I had no idea that we essentially have, like we’ve got obviously our DNA and these sirtuins sit on top of the DNA, preventing it from expressing in certain ways.

[00:37:36] Seb Bunney: As I mentioned at this part, and I’m repeating this because I, I think it’s really important to understand because I would say it was the biggest takeaway from the book for me, is just how these sartuins work. That they’ll sit on the DNA preventing it from expressing in certain ways. And so you don’t want a liver cell in the brain that’s going to create massive issues.

[00:37:51] Seb Bunney: And so the sartuins will sit on the DNA preventing that cell from expressing as a liver cell, however. At the same time when there starts to be genetic damage, those sartuins leave their little outpost. They go and repair that genetic damage. However, while they’re gone, many times that cell can start to have issues.

[00:38:09] Seb Bunney: It can start to express as things that it doesn’t want to be in that area of the body, which is what leads to a lot of this decline in health and aging and such. And then the moment it’s repaired that DNA, it goes back to its little outpost and then silences that gene. The problem is as we get older and we get more and more DNA issues throughout the body and our sartuins leave their little outposts, they’re no longer preventing the DNA from expressing in certain ways.

[00:38:33] Seb Bunney: And so we start to get mutations, we start to get tumors, we start to get all of these other health issues. And sometimes Tuin, from my understanding, can also get lost on their way home and they can’t find their way back to where they initially were. And so this is where essentially what he’s been doing is how do we stimulate more tuin or to increase their activity?

[00:38:53] Seb Bunney: And that is all through, as I mentioned previously, NAD. And if we can get more NAD that fuels the sartuin, which helps with repairing DNA and it helps with preventing genes from expressing in ways that we don’t want them to be expressing. And that is just what I found really, really fascinating. And so ultimately, yeah, going back to kind of what you were talking about, Preston, I think it’s, he very much recommends focusing, eating less plant heavy fasting time restricted eating and cold and heat exposure, and that helps support these body’s natural repair mechanisms.

[00:39:23] Preston Pysh: Yes. Let’s talk about what I found to be a really interesting part of the book, which was this, where they took the optical nerve on the rat. So going back to this idea that they were making the rats older, the mice older, by adjusting their epigenetics through CRISPR  to prove that they could create age or someone aging faster.

[00:39:47] Preston Pysh: Sinclair had this comment in the book, if I can give you age, if I can increase your age, then I should also be able to take the age away. And for him, the way to prove this, I guess there’s a test in this community where they can go and they can perform surgery on a mouse of its optical nerve. The optical nerve connects the eye to the brain, it sends the signal back to the brain so that the mouse can see.

[00:40:13] Preston Pysh: And what they do is they perform a surgery where they go in, they pinch this optical nerve to cause damage, and the optical nerve is one of the parts of the body that cannot rejuvenate itself. So once this damage is done, it’s irreversible, or at least it always has been irreversible. So what they did is they did this surgery caused the optical nerve to have damage through pinching it. And they crushed it. And then they went to these Yamanaka factors, these four genes. And my understanding is they, they used three of the genes and they pulsed the genes so that they were only being transcribed occasionally. It wasn’t like it was full on because there’s issues with it becoming cancerous if they can just constantly have these turned on. Because basically the cells in that region basically reset to a stem cell.

[00:41:01] Preston Pysh: There’s no differentiation and the cell has no idea what to be or what to do. So what they did is they pulsed it. They did it through forcing the mice to drink some water occasionally with I forget what they had in the water that caused these four genes, or I’m sorry, three of the four Yakamoto genes to basically reset the epigenetics of the cells in the optical nerve.

[00:41:23] Preston Pysh: And so when they did this, it was provable that they were actually able to restore the eyesight of the mice. And so this was kind of, a really big point in the book where they’re proving that depending on how they’re able to access these Yamanaka factors, they’re actually able to reverse aging and bring something, basically a full reset back to the cells.

[00:41:47] Preston Pysh: Now, does this mean that they can turn back the clock and let’s say you’re 60 years old and now all of a sudden that they can make you 40? I think the answer is that’s what they’re trying to do, that they’re not there yet, but they’re experimenting with really crazy ideas like this that almost seem like it’s out of a fiction novel and it seems to be moving their very quickly.

[00:42:10] Preston Pysh: Going back to the original comment that we had at the start of the show when we, you know, said about the MIT Ray Kurzweil comment that we’re going to be at the longevity escape velocity by 2032. You know, a lot of this research and a lot of the things we’re talking about, I think some of these things are five years old to seven years old.

[00:42:29] Preston Pysh: Some of these studies that have been done, so there’s been a lot of progress. I’m kind of curious your thoughts on AI. Just accelerating so much of this because when it comes to the terminology, right, like to your point, Seb, I’m with you a hundred percent. I think everybody in the audience is with you a hundred percent, especially if they’re not in, you know, the medical or biology space.

[00:42:51] Preston Pysh: Piecing this all together for something that is so complex and so terminology heavy. AI, I think is going to just eat through so much of that chaos and confusion with ease and it’s going to lead the insights that I don’t even think that we can possibly, maybe that’s why, you know, you have Ray Kurzweil, he’s really good at seeing a systems of systems kind of culmination of like how everything kind of vectors into, you know, an accelerated timeline because of these additional factors like AI.

[00:43:24] Preston Pysh: What are your thoughts, do you think that that’s going to play a huge part in a lot of this moving forward?

[00:43:30] Seb Bunney: I believe so. because I think the way I look at it, and similar to what you just mentioned is part of the learning curve is not actually the complexity of what’s happening, it’s the language to be able to actually piece everything together.

[00:43:42] Seb Bunney: So half the time I’m going back and being like, wait, wait. What is NAD again? What is NAD doing in the cell? And so, although you understand this stuff, it’s just, it’s essentially like learning a whole new language. But once you’ve learned that language, it’s not that much different communicating in English as it is to communicating Spanish.

[00:43:58] Seb Bunney: You just have got to understand the terminology. Yeah, and I think going back as well too, some of these studies, but it really, it opened my eyes as to what was possible. I mentioned it very briefly previously, they were also looking at like fertility and mice. And one of the things, there’s this kind of common held belief in society today.

[00:44:16] Seb Bunney: Women are born with a finite amount of eggs, and as you age, the amount of eggs you have slowly die off. They become unusable. That’s, as we see in fertility. What he was able to do is he put female mice through chemotherapy and they’d lost all of their X support. They were given something called NMN, and NMN is the precursor to NAD.

[00:44:41] Seb Bunney: I dug into this a little more because I didn’t quite understand it, but NAD, which is necessary, well, NAD, which is necessary for these sirtuins that feeds the sirtuins to be able to remember silence genes and go and repair DNA breaks or NMN. If you actually take NMN, it is the precursor to NAD production in the body so that it actually feeds the turns.

[00:45:04] Seb Bunney: If we just go and take NAD, from my understanding, when enters the gut, most of it just gets destroyed. We can’t actually absorb most of the NAD when we go and take it through supplement levels. So they were feeding these mice, NMN, and which is boosting these NAD levels. And then what was happening is these infertile mice were regaining fertility and some even produced offspring.

[00:45:24] Seb Bunney: Again, you’re just like, that is mind blowing. And if I remember correctly in the story, one of his friends or family member, so don’t quote me on this, he ended up recommending, I think she was going through menopause or something like that, and he recommended NMN to her and she actually went back and started having a period again.

[00:45:41] Seb Bunney: And so you’re just like, this is fricking fascinating. And so I think the world around longevity is definitely an interesting space. And I think there’s some belief such as the fact that we have a finite amount of eggs that I think we’re increasingly going to see studies that allow us to reverse that.

[00:45:57] Seb Bunney: Yeah, I don’t think that we have any idea how crazy some of this is about to get. I think in the coming decade it’s going to get pretty wild.

[00:46:04] Seb Bunney: So for those that are listening to the podcast, you just showed a container of, was that NAD?

[00:46:10] Preston Pysh: That’s  why we laughed if, if you were just listening to the audio, you just heard us burst out laughing and we just kept talking. I’ve been taking, since I read this book. You know, I read this book years ago, but since I read the book, I’ve been actually taking NMN ever since I read it probably two years ago or whenever. Do you think you notice a difference? No,

[00:46:31] Preston Pysh: I don’t notice a difference at all. But you know, in the book, my big thing was is if I was feeling any different, like in a bad way or upset stomach or whatever, like I was going to stop immediately. But I think the thing that surprised me most was how I don’t feel anything at all. Just for reference in the book, David Sinclair says that he has his father taking NMN and you know, whether it has a longer lifespan, you know, enhancement.

[00:47:00] Preston Pysh: I don’t know. I don’t know. But I’ve been taking it and this boost, going to Sebs point, this boost your sirtuin protein, supposedly it’s boosting your sirtuin proteins to repair, you know, your cell. It’s a precursor to, you get a very similar effect if you do these hard things that we were talking about earlier, which was eat less.

[00:47:19] Preston Pysh: Go out there, sit in a, in a sauna, go do a cold plunge. You do these types of things and you’re kind of creating the same n MNav d plus levels and signaling to your cells to repair themselves. So you can just do the free version of that by, by stressing yourself a bit. And then you don’t even have to the bills.

[00:47:40] Seb Bunney: But I’ve been trying, it brings me, I’ve been trying it. This brings me to the pushback on a lot of this longevity stuff is that we’re always looking for a pill for something. Yeah. Right. People don’t like doing the work. Yeah. People want to skip the work in order to be able to just take some form of pill that gets the benefit.

[00:47:57] Seb Bunney: People want to be able to have the benefits of the gym without going to the gym. Mm-hmm. And so it’s just like, I think there’s countless studies which are showing the amazing benefits of sauna, cold plunge, restrictive eating, those kind of things. But people don’t like discomfort. That’s the problem.

[00:48:12] Preston Pysh: Yeah. Amen. Yeah. That is the issue. What are your thoughts on. Let’s say you can dial back the clock. Let’s say that people want to tap into these Yamanaka factors and they can knock 10 years off their life and reset. And they start, you know, the wrinkles start going away and whatever. So what are your thoughts?

[00:48:30] Preston Pysh: Like, you know, Sinclair talks about this in the book. He goes and he does all these different speaking tours. He asked the audience, you know, what are your thoughts if you could live to 120? And he frames the question this way. Like, if you could live to 120, 130, and everybody in the audience, for all intents and purposes are just like, oh God, no, I wouldn’t want to do that.

[00:48:51] Preston Pysh: And he says that a lot of the stigmatism around like not wanting to live longer is people equate once I’m a hundred, I’m literally in a wheelchair, or I am, you know, going around with a walker and I’m not living a life that I want to live where I have full mobility to do. And act the way I was when I was 30.

[00:49:12] Preston Pysh: And Sinclair’s kind of making the argument, well, what if you could, what if you could have full mobility, full cognitive control and all these types of things at a hundred or 110? Would you still want to live longer? And it just kind of throws people into this. Cognitive, like confused state of like not even really fully knowing if that’s what they want.

[00:49:33] Preston Pysh: And I think this goes to a bigger point, but I’m going to pause right there and just kind of get your thoughts, Seb.

[00:49:40] Seb Bunney: So there’s so many different ways you can take this. And the first thing I’ll say is that I think you can look at it purely from a selfish perspective. And it’s like, for sure, let’s just go extend life.

[00:49:51] Seb Bunney: As long as I’m expanding my, as he calls it, his health span, the difference between lifespan and health span. And I think as long as my health span is matching somewhat of my lifespan, then I’m actually living a quality life and I’m able to go and do things. I do not want to be a vegetable laying in a bed unable to do anything.

[00:50:06] Seb Bunney: Poor memory. That just does not interest me. And so you could say at the base of it, if you’re kind of thinking about it from a purely selfish perspective, it sounds great. However, there’s a couple things that kind of come to mind. First off, I think that it’s actually the finality of life that gives value to life.

[00:50:24] Seb Bunney: It’s because we only have a finite amount of time on this earth that actually allows us to enjoy these amazing moments. Whereas if I live to 500, if I live to a thousand, you can pretty much go experience most careers. You can go dive down most rabbit holes and I think you’d lose a lot of interest in life.

[00:50:40] Seb Bunney: And I think that the other thing that’s interesting is I went and dug into a handful of studies. And one in particular, there’s a guy called Samuel Ellis, and in 2018 he followed 52 different species and found post reproductive stages are rare in mammals. And there’s essentially, it’s only humans. And there’s a couple of tooth to whales that have post reproductive life.

[00:51:01] Seb Bunney: And you could argue that this is an accidental, it’s a evolution tends to favor lifespans just long enough to ensure successful reproduction and survival of the offspring. But once that job is done, continued existence offers very diminishing evolutionary returns because you’re obviously now consuming resources that could be for the next generation and are necessary for that generation to survive.

[00:51:25] Seb Bunney: And so I think there’s an adaptability issue that arises with longevity around as older generations kind of pass on, newer ones emerge that are better suited to the current environment. And the longer species live, the more ossified I think they become both like biologically and behaviorally. And we even see this in like the financial world, the S&P 500, the average age of a company in the S&P 500. Today, if you look a hundred years ago, it was like 50 years. Yeah. Today it’s like nine years or something like that. Like it’s dropping so rapidly because it’s so easy to become ossified. And I think that as a species, if we want humanity to thrive, I would argue that longevity is probably not going to be the way for humanity to thrive.

[00:52:07] Seb Bunney: It’s actually probably just maintaining whatever lifespan we’re meant to be born with because it allows us to adapt to our environment. And the final point that I’ll kind of mention along those lines is that I think that a lot of this longevity space evolved out of fear. Like if we look at the difference between western medicine and eastern medicine, well pre like current modern medicine, when the eastern side of things, like if you got ill, you got a terminal illness, you’re going to die within a few months.

[00:52:35] Seb Bunney: And so a lot of people experienced and sore. Their elders kind of pass on very rapidly. And so they spend a lot of time with their elders. They passed on wisdom. Death was a part of life. But I think that as we’ve got better at being able to extend life, but not necessarily health, we see people that live for another 15, 20 years with Alzheimer’s and tumors and their suffering and the quality of life is just not there.

[00:53:00] Seb Bunney: And so we’ve now got this fear of death. People in the western world are so scared of death because they just don’t see it. And we end up putting a lot of these elderly people in homes. Yeah, we essentially just kind of lock them up. We don’t see them. We don’t experience death. So I think that a lot of life to today, we are fearful of death, so we want to constantly extend life.

[00:53:18] Seb Bunney: But I don’t necessarily think that’s the reason why we should be extending life. And I’m curious to hear your thoughts.

[00:53:22] Preston Pysh: I just think at the core, if a person doesn’t feel like they’re providing value to society. Like, what’s the point? What’s the point of extending your life? Because deep down inside, I don’t think people are going to be happy if they don’t feel like they’re contributing in some way, some fashion, or feel like they’re providing some type of service or productivity to society.

[00:53:44] Preston Pysh: You get bored, you get stagnant. You just get unsatisfied. You know, you hear this all the time with people that make a bunch of money all the time. People say, oh yeah, I made $50 million, or whatever the number is. And then they’re like, and I sold my business. And like I just didn’t really know what to do after that.

[00:54:03] Preston Pysh: And I was just deeply dissatisfied for quite a period in my life. And I think that when you think of a person that’s really older and of age, a lot of that comes from just not physically being able to do anything. They’re just kind of, they’ve become a victim of their own environment because they just can’t even really get around and be mobile and do things.

[00:54:25] Preston Pysh: So how can they create value to society at that point? They’re cognitively declined. It’s really hard to compete. You know, they’ve got their friends and whatnot, but at the same time, they’re just kind of ready to go. It’s not that they want to go, but it’s not like they’re upset about it at the same time.

[00:54:42] Preston Pysh: And I think a lot of it comes down to just your happiness of feeling like you’re contributing something new to the world or something novel to the world

[00:54:50] Seb Bunney: A few years back. I remember looking into, and don’t quote me on this, I remember looking into the oldest working individual in the UK, and if I remember correctly, this guy has basically smoked since he was like 15 years old.

[00:55:02] Seb Bunney: He finishes work, he goes down to the pub and has a pint and drinks sorry, eats like fish and chips, which basically just cooked in seed oils. And this guy was like 106 or something like that. And he’s still working full time. And you’re just like, this guy’s just defied everything that we’ve been discussing in the whole idea of longevity.

[00:55:18] Seb Bunney: And so then you ask, you’re like, well, what is at the root of this? And I think sometimes we are trying to alter ourselves on a cellular level. Yet what if it’s, and to your point, what if it’s actually got, if you want to extend life, it’s not about the cellular level, it’s about finding purpose.

[00:55:32] Seb Bunney: And if you ever read the book, man’s Search for Meaning by Viktor Frankl, who was kind of in World War II. He talks about how like the tension between what a man has achieved and what they want to achieve is what basically allows us to survive. And there’s people, there was, I think one of the analogies, or one of the examples he gives in the book is there was this guy that was, had been in one of these camps for during World War ii, had been in one of these heinous camps for multiple years.

[00:55:57] Seb Bunney: And what had kept him alive is knowing that if he’s able to get out of this camp, he’s going to go find his wife. Mm. And he ends up finding out that his wife had been killed and he dies the next day. And you wonder, you’re like, that was just hope keeping him alive. It was his mental perseverance, keeping him alive.

[00:56:16] Seb Bunney: And so I think that we can change ourselves on a cellular level. As much as we want. But in the end, the most important factor, and this goes back to your point, Preston, is purpose. It’s like actually feeling like we’re creating value in society because even if we may be healthy, even if we may be able to extend longevity and stuff, if we don’t have purpose in life, what is the point?

[00:56:37] Preston Pysh: Yeah. I think a lot of people just don’t want to reinvent themselves too. because that’s a lot of work, right? It goes back to like the difficulty of sitting in a cold plunge or getting into a sauna. Some people can’t stand it, other people like it. But I think when you think about adding value, the world is a super competitive place.

[00:56:57] Preston Pysh: And a lot of the times people want to be in control of whatever they’re creating. And a lot of jobs, you’re not in control. You’re just answering to somebody else that’s telling you. And so if you’ve worked that job for somebody else and you’ve never really even had the opportunity to create something yourself, because it’s super hard and super competitive, as you get older and you’ve gone through this and you’re 80, 90, a hundred years old, I think a lot of people may not want to keep battling the competition to add value.

[00:57:27] Preston Pysh: They’re just kind of done. They’re tapped out. I don’t know, maybe that’s a pessimistic way to look at it, but I think there are going to be some people that enjoy the hell out of that competition and they’re going to want to keep going. Right.

[00:57:39] Seb Bunney: One thing that I found really interesting is. A little while back I read a book called Deep Nutrition and this lady Catherine Shanahan, this book I highly recommend for anyone who’s kind of is diving into the health side of things, the food side of things.

[00:57:52] Seb Bunney: And she mentioned a study and I had to go back through her notes to try and find this study. One of the things she mentioned is they did this study in 1994 called Lengthen Life in the Ancient World, a controlled study. And they basically looked at Rome between the years of 650 BC and 602 ad. So this is like a a thousand year, no, 1200 year period.

[00:58:15] Seb Bunney: And they looked just at males. They removed infant mortality, they removed people that were assassinated through the death penalty, and they removed death in battle. And what they found is that the average person in Rome during that time was living between 75 to 80 years old. And you’re just like wild.

[00:58:33] Seb Bunney: Yeah. So when you remove these other issues, infant mortality, death penalty, death in battle. Well, now let’s compare that to the US today. Well, in 2023, and I had a look up this yesterday, the CDC, the Center for Disease Control, says that the average male in the US in 2023 lived to 75.8 years old. Now, if you remove infant mortality from that.

[00:58:55] Seb Bunney: Which in the US is very, it’s like six deaths per, I think it was like a thousand or 10,000 or something. And so if you remove them from mortality from that, it increases it to 76.2. Well, 76.2 is no longer than what the Romans were living. Once you remove out those factors, and so this is where I think you start to look at the incentives and there is an incentive for pharma and the medical industry to push that.

[00:59:18] Seb Bunney: We have been aging, that we have been able to increase the average age of the individual in the face of all of these things that are going on in the world. But in reality, I think there are some studies that would say that’s not necessarily true. And I think that what you can also say is that the health of the general population today, like from over the last say 50 years.

[00:59:39] Seb Bunney: We have seen rising rates of diabetes, we have seen rising rates of allergies, chronic illness, all of these things. I would not say that the average person is healthy. And so that’s where I tend to think that if you’re looking at the journal data, the scientific journals, a lot of this stuff, when you start going down these rabbit holes is curated.

[00:59:58] Seb Bunney: A lot of it is manipulated. And I would argue that when you start looking at the data from a different perspective, we may not have increased lifespan to the extent that we might believe we have increased lifespan. I don’t know what your thoughts are on that.

[01:00:09] Preston Pysh: Yeah. I think to date, I think you’re exactly right. I don’t think that there’s anything that, especially comparing the metric back to Rome, right. Like that’s crazy. It doesn’t surprise me though. It doesn’t surprise me.

[01:00:22] Preston Pysh: I think that when you look at a Western diet right now, I think that’s one of the reasons why it’s as bad as it is. But I think I kind of suspect in the coming decade or two that we’re going to really start to see the glass ceiling get shattered with respect to the ages that we see people start living.

[01:00:42] Preston Pysh: Especially if people are, you know, eating appropriately and you kind of lean into some of this technology that I think we’re really starting to deeply understand of how the body actually functions and how it regulates itself.

[01:00:53] Seb Bunney: And I think it’ll be interesting over the next say 50 years.

[01:00:57] Preston Pysh: Yeah.

[01:00:57] Seb Bunney: So Preston, when you hit a hundred and when I hit 80, we’ll have a look back and listen to this episode and see what’s happening.

[01:01:04] Preston Pysh: What are you implying here, sir? What are you implying? I’m turning red. Okay. That’s all I had. Is there anything else you want to cover on this particular one, Seb?

[01:01:13] Seb Bunney: I did a little bit of research again because I like to try to understand like what is the accuracy of this information? And I think to be able to be fair to the science, what’s interesting is there is actually quite a lot of studies that go against what Lifespan has also been saying.

[01:01:28] Seb Bunney: And so there was a guy specifically Charles Brenner, and he did a whole bunch of studies on this stuff, and one of the things he found is like in yeast, SIR, two and genes help. Only one in 5 million cells live longer. And across the whole batch of 5 million cells, they actually shorten lifespan.

[01:01:45] Seb Bunney: Lifespan extension effect and yeast is statistically negligible. There was another study that looked at, in 2011, researchers from seven institutions published that Tuan genes do not extend lifespan in worms or flies. And then there was basically just a whole other bunch of results that there was a lot of media bias.

[01:02:03] Seb Bunney: Like while the positive results make global headlines, a lot of the negative results were not published. And so there’s a bit of selective storytelling. And so overall, and I’m curious to hear your thoughts, I thought the book was really fascinating and I think that from deepening my understanding about how our body thinks about the pair, how our body thinks about aging, it opened my eyes.

[01:02:25] Seb Bunney: Massively. However, I would say that the author, it sounds like he’s very much like bought into the medical industry, the pharmaceutical industry. And as a result of that, like he’s citing things like, well he wants to be like vegan, vegetarian is best. Yeah. But now we’re starting to see a lot of the literature coming out, which is disproving a lot of the historical literature because you realize that historical literature has been bought and paid for by certain corporations and entities that benefit from that narrative.

[01:02:53] Seb Bunney: So I think that there’s definitely fascinating points that you can dig into throughout the book, but I think there’s some interesting points as well, which I think aren’t necessarily backed up by current understanding of food and health and such.

[01:03:06] Seb Bunney: But overall, I thought it was a really super interesting book.

[01:03:08] Preston Pysh: Yeah. I would say on the contrarian point, to kind of add some to what you’re saying, number one, he has a lot of investments in a lot of these companies that are, you know, working in some of these areas. The other thing that I had heard this was years ago was that the book was somewhat of a fundraising tour to raise money for his lab and the research that he was doing to get more money there.

[01:03:32] Preston Pysh: The point on the sarin, the enzymes was, was really interesting because I never even thought about that life or the time of the algae and whether, you know, statistically being able to prove whether that’s actually extending it or not, because it’s such a short span of time. I never even thought about that, but that’s a really interesting point of view.

[01:03:53] Preston Pysh: The one thing that I think is. For whatever reason, I just really buy into it. This idea that it’s based, the aging is based on information loss. I just totally buy into it. Like the way he lays it out in the book, it just intuitively makes sense. It seems to be simple enough to actually represent what’s probably taking place.

[01:04:14] Preston Pysh: And I think that the loss of information with respect to the epigenetics, I think they’re onto something really, really big with that simple idea. But you know, as we know, the body is so freaking complex, and I guess that’s why I’m kind of excited for them to kind of stick AI on it and to assist in some of the further research and where it might be all going in the future.

[01:04:37] Seb Bunney: But this is where I think it’ll be interesting to see, like this is all very multifactorial, so we may be able to go in and reverse aging in some of these cells, but if a person doesn’t have a desire to live. Is their life still going to come to an end? And so I think that that’s where it’s really interesting is like weighing up all of these different ideas and purpose and spirituality and all of this stuff, I think is really, really fascinating.

[01:05:00] Seb Bunney: But again, like it’s definitely an interesting book to read and I definitely recommend people giving it a read and some of the stories, some of the examples of what they’re doing in mice is mind blowing.

[01:05:08] Preston Pysh: One other thing that I’ll say, having gone to a lot of Bitcoin conferences and meetups and talking to a lot of Bitcoiners, Bitcoiners, love talking about longevity.

[01:05:18] Preston Pysh: Like you can throw around a lot of these terms that we were talking about on this show, and most people in the Bitcoin space are like, oh yeah, yeah, yeah, I know all about that. And then they go off on their tangent. And I don’t know if that’s been your experience, Seb, but that’s been my experience talking to Bitcoiners as they’re totally into this stuff.

[01:05:35] Preston Pysh: Absolutely. Yeah. Anyway, just a side note, that’s all we have for you guys. I apologize if our terminology is off. Our, our examples we provided weren’t helpful. We were trying, we had fun recording it personally. I had fun recording this and we really appreciate you guys tuning in and if you have any good longevity books or any new insights into this space, we would love to cover it more.

[01:06:00] Preston Pysh: I love learning about this kind of stuff, and Seb give people a handoff to anything that you want to promote or talk about. Cool.

[01:06:07] Seb Bunney: Thanks Preston. Yeah, and again, like I really appreciate everyone just giving this a listen and just as Preston mentioned, I apologize, we butchered some of the explanations. A lot of this stuff, I feel like you guys are going to be learning alongside Preston and I. And I highly recommend like giving the book a read and really just trying to dig in and think about what it is that they’re saying, because I’ve found that actually having to speak about this. Together on this podcast has hugely improved my understanding of these topics.

[01:06:34] Seb Bunney: It may not seem like that, but it has hugely improved my understanding of these topics. And so highly recommend taking notes, going and digging into this stuff. And if you don’t quite understand something, type it into YouTube, type into AI these days.

[01:06:46] Seb Bunney: AI has blown me away. You just ask a question, I don’t quite understand this. Can you explain it to me and give me an analogy? And , it just lays out phenomenal examples. But if anyone wants to find me, you can find me at just said Bunney, B-U-N-N-E-Y on Twitter, and then you’ve got my website sebbunney.com, which you can find my books, The Hidden Cost of Money and such. But again, as always, I appreciate you guys giving it a listen, and thanks a lot, Preston, for having me on.

[01:07:08] Preston Pysh: Okay, until next week, thanks for listening.

[01:07:11] Outro: Thank you for listening to TIP. Make sure to follow Infinite Tech on your favorite podcast app and never miss out on our episodes. To access our show notes and courses, go to theinvestorspodcast.com.

[01:07:25] Outro: This show is for entertainment purposes only. Before making any decisions, consult professional. This show is copyrighted by The Investor’s Podcast Network. Written permissions must be granted before syndication or rebroadcasting.