#046 Dr. Elissa Epel on Telomeres and the Role of Stress Biology in Cellular Aging

Forget weight - metabolic health (glucose, insulin) predicts telomere length better than BMI

Lean people can be metabolically unhealthy; obese people can be healthy. Telomere length tracks insulin sensitivity, not BMI.

"Yeah, it's a good question. It's paradoxical, but it turns out the longer... Sperm are unlike the other types of cells where the longer they are around and replicate, the shorter the telomeres, sperm opposite. So older fathers have sperm with longer telomeres, and there is an effect in the offspring. So when we do studies, when we have the data to know how old was your father when you I'm going to go to the next episode. older fathers have sperm with longer telomeres and there is an effect in the offspring. So when we do studies, when we have the data to know how old was your father when you were born, that's a covariate. That's something that shapes telomere length. And what's the effect in the offspring? Is it shorter or longer? So longer. So sperm is telomere length is longer and that can affect the offspring telomere length to be longer. Are there studies that have looked at whether or not having a longer telomere length to start predicts, you know, healthy aging? Okay. So that is, I believe, and I think many of us in this field believe that that is probably one of the biggest stories out there, which is telomere length at birth, that initial setting, which we know is partly genetic, but partly prenatal environment and, you know, health of mom and dad and their germline, you know, epigenetics. So that is one of the biggest determinants of their tilmer length in late life. We all, you know, we can change it a little bit, but you know, what you start with is a big factor. So no one has followed people to say like, is it true that what you're born with then predicts, you know, how soon you get sick and when you die? We don't know, but we think it probably is pretty big. So you guys want to look at that? Yeah. Yeah. Someone should. Yes. And not just lifespan, but like you said, you know, look, does it predict cardiovascular disease? Does it predict dementia? Well, let me tell you how important it is. National Institute of Aging, which mostly studies old people, they have started to fund, they started to say, okay, midlife determines older health. So now they fund studies of midlife. And they've even funded us and our colleagues to look at pregnancy now to see telomere length, how it's transmitted and affected at birth from social and economic disparities, race, sex, stress, how all of those shape telomere length at birth because they believe it is going to create a healthy trajectory of aging or not. And so that's where they're investing now. It's kind of like having runway, right? You want to have something to start with. But you also just, I just thought of an important factor with a lot of nutrition studies that are looking at telomere length and how various types of nutrition or even I would say other lifestyle factors like sleep affect telomere length. It sounds like because there's such a really big effect of the psychological stress on telomere biology, that socioeconomic status and educational background, all that stuff seems to be a huge confounding factor for those other studies, right? I mean, that's something that really needs to be accounted for because you can have people that have poor nutrition, but that's because they're, you know, they're, maybe they have a lower socioeconomic background. And it is a factor. Education in particular. And so they're also stressed, you know, so it seems like, yeah, education. So it seems like certainly something that really should be considered big time. Yes. So it is, it is, it has to be a covariate and age, chronological age has to be a covariate. You can't quite make sense of the data. Yeah. The education, the SES effect is interesting. It's there inconsistently small effect. What shows up the most is education. And I think that we even found... So the more educated, the longer the telomeres? Yes, exactly. Positive correlation. My colleague Janet Wojcicki found that in a low-income sample of Hispanic women, they're all pregnant. Those who graduated high school had babies with longer telomeres in their cord blood. Those who did not graduate high school had babies with shorter telomere length. So we couldn't figure out anything that could explain it. We co-varied, you know, everything we could, and they're all low income. So the education is probably filtering in so many different ways of promoting better health. You're making me feel good about my PhD. But so to just sort of transitioning to the next sort of topic is what you can do in your life to not only delay telomere shortening, but maybe even reverse it. For example, things that can activate that enzyme we talked about earlier, telomerase, which is important for, as you said, putting nucleotides back on telomeres. So things...I mean, people ultimately that are concerned about the aging process and about living healthier and increasing their health span and wanting to, you know, basically hold on to their telomeres, you know, what sort of factors in the lifestyle not only can delay but even possibly reverse, so activating telomerase, for example. Yeah. So there are supplements out there. They haven't been studied much. TA65? That's one of them. You know, I think there's always, I mean, telomerase is also pro-cancer. So there's always that kind of... Right. I've been concerned about that. Yeah. You want to see the long-term studies. Cancer doesn't just take one year. They follow people on one of those telomerase activating supplements. And one year later, telomeres look good, better. So that's exciting, except for that's only one year. You don't know what's brewing, right? Cancer takes a long time to develop. So there's that worry. There's the, there's the omega supplements, which of course seem healthy for so many reasons, depression, inflammation. They appear to affect telomeres in a dose response way, depending on how much we absorb them. So a colleague, Jan Kiekel-Glazer, did a study on high dose and low dose omegas. And it wasn't the dose. It was how much omegas people actually had in their blood cells that predicted telomere lengthening over four months. So it can't hurt. It's one of the few supplements that we think is good for telomeres and safe. Oh, that's interesting. Yeah. I take omega-3 for a variety of reasons. Yeah, me too. Brain health. So basically, I think I remember this study. The blood levels omega-3 did seem to positively correlate with longer telomeres. That's right. I can remember that. I think vitamin D, there was another one also with vitamin D, correct? Where there was a sweet spot of vitamin D levels. I think it was something like 40 to 60 nanograms per mil, which was associated with better telomeres as as well. What about exercise and meditation? So telomerase activation. So yeah, so these lifestyle things, and Liz and I wrote a book summarizing all of the different things we know about telomeres from their biology and genetics to the lifestyle factors. And it's interesting. I would say that there's a pretty big literature on nutrition, exercise, sleep, showing healthier levels, longer telomeres. But of course, these are correlational. So what we really want are these intervention studies in humans. How much can we really move these things around? Is it just that they're all correlated at birth? You're born with disadvantage, you have shorter telomeres, you're less likely to do all these health behaviors. So we really need to experiment and move these things. So one study that I believe you just read, maybe just came out, was a study by Eli Petterman who took sedentary high-stress caregivers, so men and women caring for a partner with dementia, and he had them exercise for six months. At the end of six months, their stress was lower, their telomeres were longer compared to the control group. And so that's a hint. It's, you know, it's just one study, but it's a hint that we can improve our circulating immune cell telomere length. Exactly how that happened, we don't know. Is it per cell? Is it a refreshing of naive cells in the immune system? It's very crude when we do this in humans and we look at blood. We don't know exact mechanisms, but we see telomere lengthening, and that's probably a good thing. So another study, Ashley Mason just published this. We did a weight loss trial. And we found that, first of all, no one really keeps off a lot of weight a year or two later, right? The people, the handful of people who kept off 10% of their weight a year later had telomere lengthening. So that was pretty exciting."