159: How DNA Mutations and Epigenetic Drift Cause Aging with Prof. Jan Vijg

This week, Professor Jan Vijg joins us to discuss the intricate relationship between DNA mutations, epigenetic drift, and aging.

He explains the differences between mutations and epigenetic changes, the role of environmental factors, and the potential for reversing epigenetic changes.

The conversation also touches on the implications of somatic mutations and the future of longevity research, particularly in relation to DNA repair mechanisms.

Learn more about Professor Jan Vijg:

https://einsteinmed.edu/faculty/11318/jan-vijg

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Transcript

Disclaimer: This transcript was generated by AI and may not be 100% accurate. If you notice any errors or corrections, please email us at phil@longevityroadmap.com.

    If you lose, uh, integrity of your apg, so you will get AP mutation. So you will get random alterations in your AP genome. You lose the template. Not

welcome everybody. This is Buck Joffrey with Longevity Roadmap and um, today got a really interesting show for you. But before I start that I just wanted to, you know, I never. I, I should, but I never ask people to, you know, like the show, write a review, um, you know, subscribe to the show. All of these things really help.

Um, the show is growing very quickly. Uh, we actually had, uh, 19,000 views, uh, last month, which is, which is great for a pretty young show. And, and, um, that is, uh, that's something I'd like to continue to grow as you could, as you know. This is a very unique show where we're really just talking to real scientists and physicians and stuff like that, giving you the best possible, you know, real information available out there.

Differing opinions often, but you know, that's what we need to know. Anyway, if you could make sure you like, subscribe, you know, write a review, whatever, and that'd be really helpful. Now, today. Uh, this conversation I have, I think will be very useful for many of you, which with, uh, professor Jan Vijg and he's, uh, chair of Genetics, uh, at Albert Einstein College of Medicine.

Really smart guy who is really one of the pioneers, uh, looking at, uh, mutations. Uh, point mutations. Mutations in. Um, you know, genes and then epigenetic drift, these terms that we hear about all the time when it comes to aging. So there's a real opportunity. To really get a deep dive explanation on exactly what those things are.

Why are they important? Why are mutations in, you know, regular cells, which we call somatic cells. Why are they important? Why and what exactly is epigenetic drift and why is it important? Um, we also talk about, uh, the concept of potentially reversal of epigenetic drift. He has interesting takes on that, that are different from others in the space.

Um. We also, uh, I, I think it's notable that he mentioned a very interesting, um, discovery, a molecule, uh, which is, uh, called the dream, uh, complex, which seems to be showing up in like germlines. In other words, like sperm and egg, where, you know, you don't get mutations in those, right? Because if you did, we, we, we would never survive from one generation to another.

That molecule also seems to be more common in sharks, for example. Where, uh, you know, those sharks never get cancer and live forever, right? So, anyway, really fascinating conversation. If you are into this stuff, you wanna learn more about, you know, what exactly is, is a mutation, why is it happening? What is epigenetic drift?

You're gonna get all that information in this interview, and we will have, uh, that after these messages. Hey, longevity enthusiast. It's time to take it to the next level. I've been fine tuning my longevity regimen for years, and I look better and feel better than I did a decade ago. In fact, my blood work is even better than it was back then, and it's all because of my data-driven regimen.

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Welcome back to the show today. Uh, today my guest is Professor Jan Vijg. He's the chair of genetics at Albert Einstein College of Medicine. He earned his PhD in biology from the University of Leiden in the Netherlands, where he trained as a molecular biologist and went on to become one of the world's leading researchers on aging.

Professor Vijg is a pi, a pioneer in the use of transgenic models to measure DNA mutations and living tissues. And now his lab applies single cell genomics to study both genetic mutations and epigenetic drift. Uh, welcome to the show, Dr. Bitch. Sure. It's a pleasure. Let's start, uh, with some, you know, just getting some of the foundation out of the way just so that people understand, you know, people often, uh, use the word mutation broadly.

Um, perhaps you could clarify, uh, the difference between permanent, uh, changes in DNA sequence, you know, actual gene mutations as opposed to what we call, uh, epigenetic drift. Yeah. Well, uh. Epigenetic drift. That's has actually nothing to do with the basic structure of DNA, it's modification of DNA. For example, a very frequent type of epigenetic uh, modification is, is methylation.

And one, one of the bases, cytosine is actually methylated. There's a small methyl group is hanging on there, and you can take that off and you, you can put it on. And those are functioning as signals for whether a gene, for example. Is active or not active, and it is heavily methylated, as we say. So there are a lot of epigenetic components there on the gene.

Then it's usually silent and when you can take it off in by whatever mechanism, then uh, the gene is active. Now we call changes in, in those molecules, in those modifications, we call them actually AP mutations. So that came later. Then the concept of mutations. Mutations are known. Since around 1900 when we didn't even know the structure of DNA, so we couldn't know, of course, that mutations were alterations in the DNA sequence because we didn't know DNA, but people did know that those were heritable changes, for example.

They could find out that in in flies or also in mice, that the coat color, uh, was determined by a particular gene. And if you inactivate that gene, and they didn't know of course how that worked, but they could see when they radiate these flies or these. Mice that who, they saw a change in code color and, uh, they called that mutations.

So heritable changes. And it was only later that we realized that those mutations were actually changes in the sequence of DNA in, in particular cells, skin cells or cells, wherever in your body. Yeah. So, I mean, just for the audience, just to sum that up, essentially mutations are in the DNA and the, the drift that we're talking about are changes in, uh.

Chemicals, chemical changes to the DNA, that will change fundamentally sometimes how that DNA is read. And so it can be, it can basically turn genes on and off because of those kinds of changes. Yeah. Is that a fair? Yeah, is fair. And uh, you can also say that epigenetic changes, what they call AP mutations are actually quite frequent.

They're much more frequent, maybe. Uh, three orders of magnitude more frequent than actually changes in the sequence of DNA. And that reflects the relative importance of that because when you really have a mutation and. Permanent change in your DNA sequence that's much more serious than, than when you change one particular base cytokine.

You take the methylation group off that can, it depends a little bit of, of where it is, of course. But in general, the effect of that is much, much smaller than a, an actual DNA sequence mutation. Right. So let's talk a little bit about the DNA sequence mutations in aging. Um. What kinds of mutations, uh, do we see in particular that seem to relate with aging or accumulate with aging?

Yeah. Well, I mean, you raise important point because there are many different types of mutations. The most frequent type of mutations is simply when you replace one base, pair two bases that are complimentary to each other, so like a GG two C, and you replace that for another one. For example, an at. That's a very small change, and most of these changes have, as far as we know, no effect.

Some can have an effect. Now, a more important type of mutation is the loss of a, of an entire base pair. You really lose it that the base pair, the frequency of such changes has to do with the seriousness of it. When you look at these one base per loss, that is tenfold or less frequent than a replacement of a base for another base.

That has to do obviously with the fact that this occasional base replacement, we call it base substitutions, quite often there's no effect at all. So the genome can allow many of these mutations to occur because their effect is not that dramatic. But when you lose a base, that's more important. So it cannot afford to have too many of those, and especially when you lose large chunks of DNA, like whole chromo, whole chromosomes or chromosomal chunks, large.

Species of DNA. Those are very rare because again, if they happen, the effect of that is almost always very large. By the way, what I, I didn't say you didn't ask it, but how do mutations arise? Because interestingly enough that that whole, the whole idea of how they happened came later. Then the concept of mutations, because Wilson and Creek published the first paper where they described the structure of DNA in 1957 or so, I believe, or 1954.

I can't exactly remember. Right. Early 1950s, let's say. And then, uh, physicists Leo Cellar and, uh, geo Chino faia, they actually published papers in science and, and in the New York Academy of Sciences, uh, hypothesizing that aging must be due to the accumulation of mutations because they said those are probably causing cancer as well.

And we now know of course, that that is exactly right. Crypto is an age-related disease, if ever there was one that's cancer, cancer is only really occurring. Well, there are cancers of children, but they're very rare. It's really older people who almost always get cancer, so their argument was mutations accumulate and therefore your chances of getting cancer increased with H.

Right. That fills the whole argument here, and, and, and it's pretty much, for the most part, can we say that the, the mutations that we get as we age are largely. Um, environmental or would you say that that's also a very good point. Uh, some of them of course can be environmental because people have heard of, uh, people exposed to radioactivity.

Think of the, of the nuclear bomb in Hiroshima and Nagasaki and people of course, who were not killed immediately, but lived a little bit further away cause cancer. They've got cancer because there's a radiation and radiation can induce mutations. It's very, very well known mutagen. There're also chemical pathogens.

However, in, in the normal conditions, people are not exposing themselves to this kind of radiation or chemicals. And then we have endogenous, we call them endogenous factors. And for example, think of free radicals. Free radicals are byproducts of breathing or using oxygen. Yeah, living, yeah. Pretty useful.

Uh, process, not, yes, but there's a very tiny amount of side products and those we call free radicals, activated oxygen, and they can damage DNA. That's very well known now. But there are also other. Molecules, normal metabolites that can cause DNA damage. In fact, DNA damage is very frequent. There are probably a hundred thousand lesions in the DNA per cell per day.

And when I say DNA damages, I'm not talking about mutations. DNA damage is a break in the DNA or it is a particular chemical molecule. Itself to the DNA or it's a cross-link between two pieces of DNA or a protein and DNA. Now there's, that is very frequent, but you have fantastic DNA repair systems.

They're continuously monitoring the DNA for this kind of damages, of which there are many, and then they repair it. They usually do it very well. Everything is reconstructed perfectly. But there are errors and the errors are mutations. Then they have to re-synthesize a piece of DNA, for example. They cut it out because there's a damage.

Then they re-synthesize it, they make a mistake, they put the wrong basing. There you are. That is a mutation. Yeah. So I guess one of the questions, um, you know, 'cause we, we wanna. Kind of get to the root cause of aging in some way. And so we know, we'll talk about epigenetic drift in a, in a moment, but do do these somatic mutations.

Do you think it's fair to say they're the cau one of the causes of aging or in, or are they the result, uh, of aging? Yeah. It's in other actual comments. Uh, I, I said I use a sentence in my own papers occasionally. It's, uh, are mutations, uh, causal of aging or are there some consequence? Obviously we do not know that there are, uh.

Reasons to assume that it is a causal factor. I just mentioned cancer, which is an age-related disease, and that the, the risk of cancer increases dramatically with age and, and we also accumulate mutations with age. We know that we found that others found it by now. So, so it's really not, not known on the other hand.

Mutations are, are actually frequent, although are actually not so frequent. I'm sorry. Uh, I say that because initially we thought that mutations were a hundred fault, less frequent than they actually proved to be. This is why I had problems in getting my first papers published because people said, well, everybody knows.

That mutations are not as frequent as you find found them to be. And I said, well, but this is what we found. And what can you argue? Now? It turned out we did know a little bit about the frequency of mutations. How could we know it well from germline mutations, we could know whether there were changes in the germline 'cause you can see those from parents to children.

But it turns out, as we uh, showed, not even that long ago. In a paper that mutations in the germline are much less frequent than somatic mutations. So we have great systems to keep our germline clean. And you can imagine, of course why that is not. I mean, if you have a high mutation frequency in your, in your germline as a species, you will not survive.

It's basically the species becomes extinct immediately. With somatic cells, you only need them for one lifetime, not so basically. Why would you need to keep the mutation frequency low in somatic cells that we know? But that's actually another argument to say that mutations are probably functional and they could cause aging because again, nature in its wisdom, uh, didn't even try to give somatic cells a perfect repair.

And that's why mutation should say, but, but still, we don't know the, I cannot also, you, uh, that. That mutations are the cause of aging. Can we, um, I'm sure scientists look at germlines and the repair mechanisms there that seem to be, you know, nearly perfect. Otherwise we'd be, you know, we, we wouldn't survive as a species.

Right. Exactly. Yeah. And, and try to figure out or understand, you know, how we can apply some of the things that we know about the germline to try to. Combat somatic cell mutations. Yeah, yeah, yeah. Together is a very good friend of mine in Germany, Schumacher. He discovered in worms, uh, a complex that, that we know is the dream complex.

It's an abbreviation, D-R-E-A-M, whatever. It doesn't matter. It's called dream complex. The dream complex was discovered because it, uh, it basically was responsible for the fact that cells quiescence. So they couldn't divide any anymore, but in the germline, in germ cells is not expressed. That's what he found out.

But he noticed that in symmetric cells it is becoming expressed. It's active, and then it suppresses DNA repair. Now you wonder why is dead? Well, when it's not active in the germline, germline has a very good DNA repair. As it just said, somatic cells do not need a very good DNA repair. So the evolution in its wisdom decided to temper down, uh, DNA repair because it it's costly.

Energetically costly. So why would you spend all that energy on cells that are basically don't live, uh. Are not immortal, but basically lost only a lifetime. But that gives us a handle on it, you know, because we could try to deactivate dream instrument tissues. And this is exactly the experiment that we are currently doing.

We are working on that experiment. Now we, we have done some first results only days ago, and they seem to suggest that indeed. Then we, uh, lower dream activity in somatic cells. There's, uh, less of a mutation. Uh, rate mutations are going down a little bit because the repair is better. Apparently we activate D repair.

Turned out there's another research group, uh, Trey Iker in, uh, university, uh, California San Diego works on the same thing, and he, he found exactly the same, uh, results. We hope, of course, that that's true. And then we have a handle on improving DNA repair. There is also another example where there's probably, you know, there, there's virtually no cancer, for example, and that's in sharks or in other species.

Do, do we find similar, the dream complex potentially involved there as well? Well, yes. Uh, I just mentioned Trey, I in this pre-publication of his, this is not peer reviewed, so it, you can find it in biogas. He found evidence that that's indeed the case. Yeah. It's less active in long-lived species. Now we just published a paper together with Vera, go Nova.

It'll come out in nature very soon because it was just accepted and we will, we just got the proof of it where C had cells of naked more rats. Uh, I'm sorry. Uh uh She had cells of behe, well also, she also had of neck more and she has lots of species. But we're talking about behe. Well, that paper is about behe.

Well, Bo as well is an enormous animal as you know, and it lives very long. It lives probably like 230 years and we looked at those cells at mutation rates and they are indeed. Lower than humans, much lower than the mouse. Avera looked at the repair processes as she found that the repair processes in cells from boad will are really much higher than in human cells, other cells.

So again, it, it looks like we slowly begin to understand the role of DNA repair, DNA damaged mutations in longevity. You, you may ask me about, uh, epigenetic drift that of course we don't know yet, but that's. Probably also a consequence of, uh, DNA damage. So, yeah. Let's switch to epigenetic drift a little bit.

Um, when you track epigenetic drift across tissues, what patterns stand out, um, in, in the sense that do some organs lose regulatory control faster than others? Well, um, this is not something that people have, uh, studied, uh, extensively. We are. Trying to do that now, but it's, uh, I mean, we can detect mutations, but to detect ap, AP mutations is really not that simple.

Uh, the first tools to detect mutations were was our, actually our, well, our mouse model is a selective system, but our single cell analysis system, single cell sequencing, was sort of the first tool to do that. Now we have better systems. Cheaper systems, you can do much more. But for AP mutations, we also, we and others published papers also on single cells.

And so that's how we found out that, uh, the frequency of AP mutations or changes in the epigenome is far higher than mutations, but it's still, these are very difficult techniques and it's very difficult for us to find out. Which epigenetic trigger is loose in which tissue. If there are tissue specificities there, it's really not very well known.

You know, uh, um, especially in the longevity space with biological clocks and all these things, who you, they're, they're looking at epigenetic drift and trying to give a, a biological age and, uh, that kind of thing. Um. I'm just curious in terms of, again, sort of framing the question back to when I asked, you know, what is causal versus, you know, uh, which cause the witch aging, cause epigenetic drift or epigenetic drift caused its aging.

A lot of people seem to think that epigenetic drift is one of the big hes to the aging process. I'm curious what your thoughts are there. Well, um. Ultimately it could be important. Uh, but I think it's part of a more general phenomenon. I mean, our cells, they are functioning because there is a network of genes that interact with each other and that also interact with what we call gene regulatory sequences like promoters, but also enhancers.

So the part of, uh, the part of the genome in a typical difference in cell that is important for this kind of control of gene expression is probably 10%. So it's not small at all. Uh, we have the idea that very gradually during aging, the cells lose control, they lose regulatory control. Uh, we sort of made the discovery at some point.

That, uh, cells in young, for example, we use mouse, a mouse model to study that. And we looked at the heart, different cardiomyocytes in the heart, and we looked at the expression level of multiple genes, and they were exactly the same from cell to cell. So we look at gene X and it's expressed to the exact same level in one cell, in the other cell, in the next cell within a young mouse.

But if you looked at an old mouse. You can see that that was no longer the case. The same gene was now expressed to different levels in different cells. We call that transcriptional noise, but that's essentially also what you are just saying in, in a way, you talk about epigenetic drift, but the agen, of course, is controlling the expression level of genes, not when there is something like epigenetic drift.

You will probably get this kind of transcriptional noise so that cells. Begin to deviate from a, a fixed level at which they are supposed to express a particular gene, and now instead they are, begin to fluctuate. So they lose control. Now, that ultimately could be due to a epigenetic drift, but epigene drift could ultimately be due to mutations.

That's also, I just mentioned. I, he publish a paper in Nature Aging, I believe. A year ago or so where it showed that one mutation can change an entire bulk of AP mutation or epigenetics, or of methylation actually. So in other words, there's relationship between all these different levels. So you can have random changes in DDNA sequence, there are linked to random changes in the epigenome, which are again linked to random changes in what we call the transcriptome.

So all the transcriptionally active genes. Together that could, that res havoc on your whole, uh, regulatory system in your cells. So it's not that your cells all die and stop functioning. Not at all. That's also not what aging is not. Aging is not that you don't drop that instantaneously. You gradually degenerate.

Well, that could perfectly explained, but this kind of, uh, loss of gene regulatory control. Think for example, of a heat wave. There's a very old person in, I remember the story in France. This is already a couple of years ago. Go out of his car, walked, he had beautiful house, so he had to walk for a couple of minutes to the door.

He died because of the, of the heat he had hit. We all have very fancy systems that can, uh, absorb this kind of heat. No, they are beautiful thermostat. They're all combinations of gene activities, but of course it still worked in this person. Also not as good. It was degenerated and that could. Perfectly well be explained by all these gene regulatory patterns that sort of gradually lose control.

And that's probably what, what happens during aging as well. Think of the universe for example. One of the things that people often talk about, again, related to biological clocks, is that, um, some epigenetic changes are potentially reversible. Um. Your comments on that? I'm, I'm curious about this sort of efforts by some with, you know, various, um, you know, types of, um, things like, uh, uh, fasting or various other methodology to sort of try to reset their epigenome.

Is the epigenetic drift or these changes, are they reversible to a certain extent? It's a difficult question. Uh, I think most of them are not. And the reason is actually fairly simple because if you lose, uh, integrity of your apg, no, so you will get AP mutation. So you'll get random. Alterations in your epigenome, you lose the template node.

So how will you be able to revert that and bring back the correct pattern based on what there, there's no like, uh, tape somewhere stored in your body that can tell you where all these, uh, methylations need to go, or these histon groups need to go. They either you don't know that, so I, I don't think that's possible.

It is very similar to mutations. If there's a mutation, you lose a piece of DNA or there's a base substitution, there's no template left. When there's a template left, yes, then you can do that. That's why DNA is double stranded. So when you have, uh, a DNA damage from one strand, your enzymatic systems use the other strand to put the correct base in again.

But you cannot do that when you begin to randomly lose, uh, epigenome, uh. Chunks stent is possible of course, because think of, uh, DNA replication. When cell, when cells divide, they also have to break down the whole epigenome and they have to build it up again. Now, we still don't know the details of that process, but we do know that methylation, for example, can be restored by particular enzymes that use the.

The other strength of DNA, their sister strength, of course, and they can use the other strength and as templates, it's a very complicated process, but they do very student but not perfect. They make errors there. So it's only like, uh, say, let's say 95% of the. The epigenome, which is correctly restored. Uh, so it is also true for DNA repair of DNA damage if you have breaks in DNA or other chemical damage enzymes are coming in and they take away the epigenome.

They have to repair the chemical damage to the DNA, and then when they do that, they have to put back in the correct epigenome. Now they can do that. They also have ways to do that. But again, not perfect. So that's why I do not think that, uh, you can really. Perfectly. To some extent you might be able to do that because you can imagine AP genome can also be the same from cell to cell.

It can be a program. You can, you can imagine that there, there are epigenetic changes that are part of a program that's doing something to yourself. Like, for example, memory formation in the brain has been argued to be part of a program where you change the epigenome. But that kind of changes because they are, they are really consistent.

They are the same in every cell, not random. You can do that. You can probably, uh, fix that problem as soon as you. There's a sort of a pattern that, that you can store somewhere. You are able to do that, but then you have stochastic changes, as you call it. Random changes. You cannot. So I think to reverse aging in that way will probably prove to be impossible.

But again, uh, what, whatever I say, I mean, I can only answer questions based on what I now know, but, uh, there are all these things that, that I don't know, uh, as you can imagine. So it could be that. 10 years from now or 20 years from now, or images from now, I will be proved wrong, but for the moment I think it's not possible.

Some groups, uh, out there are, you know, have been reporting, uh, experimenting with Yamanaka factors, uh, to reprogram cells and potentially reverse epigenetic drift and that kind of thing. Tell, tell me about what your thoughts are on that. Yeah, I think that's, uh, absolutely fascinating because first of all, we now know that using the factors, you can bring a cell back from its differences state into a stem cell state.

Now, there's also something they call that partial reprogramming. What you do then is you do not go through the whole process. Nobody really knows how far you need to go or why this has beneficial effect. It has beneficial effects. On, on they, did it show that a mouse model not completely convincing to my, in my opinion, that we really need to do a lot more research.

But maybe when you have a little bit of an imagination, you can argue, well, there is actually evidence for a clear. Beneficial effect in particular mouse models that actually are not during normal aging. As far as an, there is only one paper, but not even peer reviewed. It seems to suggest that you can live longer in that way, but we do not really know what happens there.

It's partially reprogramming. It doesn't mean that some cells went are go to the whole process, but not all the cells. Then you have a few, uh, new cells, stem cells, that is, or is there something else happening now? We are doing experiments right now where we do reprogramming of, uh, somatic cells. So we get, uh, induced pluripotent stem cells and we measure the mutation rate.

It seems pretty clear that the mutation rate in these stem cells is significantly lower than in the mother population of differences cells. So it looks, it's possible that what you do during reprogramming is you reprogram DNA repair, you make DNA repair from how it is in differences cells. You turn it more like a germ cell.

Stem cell, a stem cell is closer to a germ cell than a difference in itself. So we are now studying of course, and I, I'm sure we not the only one. If this reprogramming is doing exactly that, if it is improving DNA repair, uh, if that is true, then you can also consider partial reprogramming without actually creating stem cells, but just the reprogramming process.

Will have a beneficial effect on DNA repair. And if you can understand that better, then that would explain why partial reprogramming could be beneficial. Namely because it improves your DNA repair, not so that's the hypothetical, obviously, but it would, I, you see it's always irritating when they seem to be beneficial effect of something.

You don't know why. It's not satisfactory to me. I need to know what it is. This seems like a logical explanation. So from your perspective, big picture, and I always like to kind of ask people in your position this, is that if you had to, you know, if you had to make a bet, uh, on something that materially could, uh, extend healthy lifespan.

Uh, you know, tackling mutations, the genome correcting, uh, drift. Where are you most excited about? Where do you see the most potential for those kind of large breakthroughs? Yeah, well. In a sense what you, I'm not completely sure if what you mean with this question. I mean, there are two possible ways to interpret this question.

One you can say, and you sort of said that we want to improve health span. I think there are lots of ways to improve health span and we do it all the time. We've done it since the 19th century and we seem to, well on our way to continue there. There are lots of interesting molecules. For metformin and rapamycin to you know that do that, but there's no evidence that these kind of interventions are actually improving your maximum lifespan.

Right? So are they changing the lifespan of homo sapiens? Do they bring in a previous paper in nature? We sort of calculated that our maximum lifespan. Approximately 115. The question now is, can we improve that maximum lifespan to let's say one 50 or 60? Now, to do that is a completely different question.

You see, because now you're no longer asking for a health span, you are really asking for maximum lifespan. Can we basically move that barrier? As we argue in that paper at one 15 plus or minus, uh, whatever couple of years is actually a barrier. It's a barrier, a biological barrier. And we this far, we have not been able to, to, to go over it.

We, we couldn't. So your question could also be, what do you expect to find in the future that, uh, take that, take that barrier away. Now that question, um, is more difficult to answer, obviously. That's sort of the research that we are doing, not, we feel that the topic of this, this whole meeting, like somatic mutations, epigenetic changes, are ultimately a consequence of damage to DNA.

That we feel is a universal cause of aging in one way or the other. Either because it results in mutations, maybe because it interferes with healthy transcription. Maybe it causes epigenetic drift. Maybe it directly causes transcriptomic changes. We don't know all these things yet, but we are close. We getting close now.

So if, you know, find a way to intervene there at a very basic level to bring back that whole. Ingenious system of preserving your genetic material longer by improving DNA repair. I think that would be the breakthrough if we are able to do that. I think now, now we can. Slowly begin to think of really letting people live to one 50, which of course, open super, a can of worms.

Not there are many, many other questions you can now ask. Well, maybe you'll uh, the dream. The dream complex. The dream complex. Exactly. Maybe that, maybe that'll be the answer and well, well, look, we always spoke this part of male. Yeah. Yeah. Thank you so much. I, I do appreciate your time, professor, uh, for being on the show today.

It was a great pleasure. Alright, thanks for listening. A quick reminder that while I am in fact a surgeon, nothing I say should be construed as medical adVijge. Now, make sure to include your physician in any medical decisions you make, and also, if you're enjoying the show, please make sure to show your support with the like, share, or subscribe ride.