#427 Longevity Scientist Shares What Affects Biological Age and How to Slow Aging - Raghav Sehgal

Raghav Sehgal (0:00)

Your body is telling you, if this state remains as it is, if I have this constant state of inflammation, your lifespan would be shortened. You can't decrease the number of candles on your birthday cake, but you can modify your biological age.

Siim Land (0:16)

Welcome to the Siim Land Podcast. Our guest today is Raghav Sehgal. Raghav is a PhD candidate at Yale University, who uses AI to tackle the question, can we slow, stop or reverse human aging? He's also the creator of Symphony Age, which is a biological age clock based on 11 organ systems.

Raghav, welcome to the show.

Raghav Sehgal (0:37)

Thank you for having me here, Siim. Really excited to be here.

Siim Land (0:41)

Yeah, I found or stumbled upon this paper that you recently published and co-authored, and it was about this epigenetic age interventions, which is a pretty popular topic over the last few years, these different epigenetic age clocks, and biological age itself as a concept, and how it relates to longevity. So yeah, I'm super excited to have you on the show. So I guess we can maybe start with, maybe you can give like a short overview of what did you look at in the study, what were like the kind of overview of, okay, what was our main findings?

Raghav Sehgal (1:22)

Yeah, for sure. So I'll give you some context of how we actually came about to think about this study, because I think the context here matters a lot. So I come from sort of the field of epigenetic biomarkers and I was trained with Dr. Morgan Levine, who sort of built one of the first mortality predictors in epigenetic clocks. It's called PhenoAge. And under her mentorship, I built this clock called SystemsAge, which can measure aging in sort of 11 different organs of your body from a single DNA methylation blood draw, which is very exciting. And when we were doing sort of the validation of or this new biomarker called SystemsAge, one of the things that I observed was a lot of the validation of these biomarkers was mostly in context of prognosis, which is how does a biomarker behave in terms of future disease outcomes? So I was really curious about, what about responsiveness to interventions? How do these biomarkers respond to interventions? And that was kind of my key question here when I was thinking about this study.

So what I did was, the question was, how do these biomarkers respond to interventions? So for that, what we really needed to do was look at clinical trials. So what I did was, I went to the literature and started looking at clinical trials. And the sad story about that is that unfortunately, when we go into literature, there are clinical trials looking at these epigenetic clocks or DNA methylation aging biomarkers, but they're typically looking at maybe a handful of them, one or two of these biomarkers. And that poses a problem because then you can't do a systematic analysis of saying which of these biomarkers are being responsive or not responsive, so on and so forth. So we were like, okay, I guess that's where we need to solve a problem. And that problem was, why don't we systematically collect a lot of clinical trial and interventional analysis data for a lot of different types of interventions, whether it's lifestyle, pharmacological, supplements, medical procedures, all related to longevity. And then try to see which DNAM or epigenetic biomarkers are responding to these interventions. And that kind of about this study. And as you can see, the results are really astonishing and surprising as we are seeing.

Siim Land (4:13)

Right. Yeah. We will go into the results of the top performers shortly, but yeah, like that's kind of interesting that, or at least like maybe we can talk about like some of the concept behind like this epigenetic age or biological age as well, because, you know, many people aren't aware of what it means, and also some people use it differently. So like, how do you define epigenetic age? And is it different from like chronological age as well as your biological age?

Raghav Sehgal (4:48)

For sure. So in some ways, so chronological age, as you know, is I would say the number of candles on your last birthday, right? As simple as that, right? And that's how I define it. Biological age is a little more complicated. There is no frontifiable way of saying what biological age is. People use different proxies of saying what biological age could be, right? It could be how much time you have left to dying, for example, right? Which we call time to mortality. It could be how much time you have left to getting your first chronic disease such as diabetes or cardiovascular disease, right? Which is often described as health span.