Dr. Steve Horvath on epigenetic aging to predict healthspan: the DNA PhenoAge and GrimAge clocks

Blood

epigenetic

s sped up slightly, that makes sense, yes, I spoke to a sleep expert not long ago. Dr. Matthew Walker, he runs the Human Sleep Center at the University of California at Berkeley and he just talked about all the diseases, basically, various diseases and all the causes of mortality and how everything increases when the quality of sleep decreases and certainly I feel like always, always. I hate these studies because I don't sleep well. I like studies where they study so-called super sleepers, you know, who only sleep five hours a night and are still perfectly healthy, so I like the optimistic spin on things better, but also, um.

To tell you, the effect of sleep quality, you know, versus

epigenetic

aging

in the blood, these associations were statistically very significant, but again they were weak, you know, and that gives me hope, yeah, compared to the semi -supercentenarians who had an epigenetic age of 8.6 years younger. younger than your chronological, that's pretty solid, right, that would be robust or stronger, I guess so, I mean maybe it wasn't eight years, I mean it was five years, so it depends on what you're not into. absolute the um, not the offspring, but the actual offspring, yes, that's right, so you're right, so if you test the blood of a centenarian or supercentenarian, it's because our age estimates are way below their chronological ages, they could be 15. years younger, you know, so there's a real leveling effect in the office, you know, yeah, what about studying how other professors like that there are other biological processes that, at least in animals, When you disturb them, they are known to regulate

aging

, for example, you can mutate certain mitochondrial factors and have accelerated aging or you know, cellular senescence, you can also have a certain mouse where you are, you can accelerate aging or the opposite, where you lower the growth hormone levels and you will know that they live longer.

If you or anyone has observed epigenetic aging? How does that relate to this? Yeah, what you mentioned, these growth hormone knockout mice that are known to live longer, according to the epigenetic

clocks

in the mice, they actually age more slowly, so it was a beautiful validation of the fact that the Epigenetic

clocks

measure biological factors. age because growth hormone receptor knockout mice, um, that's really a gold standard anti-aging intervention and you want the clock to speed up, and um, when it comes to other strategies and senescence right now, it's a hot topic, the so-called zenolitics that eliminate senescence. cells that you know and we're about to look at the data collected by James Clement who looked at who did the clinical trials of these analytic strategies and hopefully we'll have an answer in a couple of weeks, but I don't know whether to remove them. senescent cells have an effect on epigenetic age in general the relationship between senescence and epigenetic age is complicated because when it comes to inducing senescence there are several ways to induce senescence, one is simply what is known as replicative senescence, you pass the cells and divide them. and let them grow and grow and grow and that form of senescence is somewhat related to epigenetic clocks.

You know, then there are other forms called radiation-induced senescence. You irradiate the cell and that form of senescence does not seem to accelerate epigenetics. watches, you know, it's complicated and, conversely, there are ways to immortalize cells by overexpressing the telomerase component. Now that immortalizing a cell doesn't actually stop epigenetic aging, you know that you can have immortalized cells that you can pass on. for decades, but epigenetic age continues to increase, really yes, so do you see that epigenetic clocks are not simply markers of cellular senescence, but they actually capture a different aspect of biology? Radiation and DNA damage is kind of surprising because I think in one of the papers he looked at it and this was another question I wanted to ask: where do these methylation patterns occur in the genome?

Are there genes that are particularly known to be involved in the aging process? in general, yeah, these are like you know metabolism genes or DNA repair and things like that. Yeah, I wouldn't make that claim, so let me start by saying that my original watch used 353 loci when we looked at Akilu's grim age. scientist in my lab uses over 1000 locations in the genome and now one question is: what would happen if we removed these locations from our data and simply built a new clock? We build alternative clocks that use other locations in the genome, you know, at that level, these locations are not unique, you know, and when you look at the genome, we have in principle 28 million locations in the genome, they are cytosines, you know, and I want to say a quarter of them change with age, some gain methylation, some lose methylation, so these methylation changes are almost global, you know, and in that sense, epigenetic clocks, um, look at the perfect representatives of everything that is known as methylone, they represent everything that is happening, but you can see that maybe looking at just 300 locations this is not ideal, you know, having said that, we certainly look at it and say if these locations are enriched , you know, with certain pathways and there are certainly, you know, sites that gain methylation with aging.

It is known that ums are located in the so-called target sites of proteins of the polycom group, so certain proteins that play a very important role in the maintenance of stem cells or, conversely, sites that play a role in differentiation and cell development, so these sites tend to gain methylation with aging, you know, sites that lose methylation are also enriched with certain subjects, for example, they are often in so-called enhancer regions, you know, the field of Epigenetics has greatly characterized the genome, which parts change with aging, it is wonderful. check out articles about it, yeah, um, and then I just found out about stem cells, which is so interesting that a lot of them are regulated, going back to the clock mechanism, that's really a profound idea, you know, um, when you look at the data that you keep seeing you see themes related to development, tissue differentiation, organ development and it's a profound idea because if you had asked an aging researcher five years ago if developmental processes matter in aging , they would have said no, you know, a lot of people think that aging is just noise or wear and tear, you know, but these epigenetic clocks have actually linked development to tissue dysfunction directly.

An epigenetic clock is a continuous readout that links prenatal tissues directly to very old samples. It's really driving me crazy, that's actually it. I never would have thought so because when a lot of people obviously studied the development, but these are not old researchers, you know, but these watches really point to commonalities, you know, yeah, it's surprising, it's very interesting, um, I just think I want to. thank. Thank you very much for doing all the work you are doing and we can continue to follow you. You know your job. Thanks for your interest. Yes, people who want to learn more about your research.

Probably the best Wikipedia places we talked about. Yes, I wrote a review article and reviews on nature, genetics, people have written Wikipedia pages and then you mentioned Josh Mitteldorf's blog, you know, there are several ways to learn about them, you know that well, thank you very much, Steve. I really enjoyed this conversation, great, thanks, oh you're still here, I'm just sitting here mixing up next week's premium fitness membership benefits and they're spicy, that's right, almost every week we send out something interesting like our bi-weekly newsletter . scientific compendium where we summarize the main news and science of the week or our Q&As that happen monthly or the aliquot which is an exclusive podcast for our members, we take clips from interesting interviews like this one and add a little extra information if you want .

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