Rhonda: I interviewed Dr. Elissa Epel on the podcast. She works closely with Dr. Elizabeth Blackburn. She's at UCSF, and she has published some studies showing that, like, stress plays a big role...it plays a pretty good role in tumor biology. So, you can find that, like, different types of stress can actually affect telomere length. So, lifestyle factors that affect the epigenetic clocks, so for example, diet, exercise, smoking, or even, you know...

Steve: Education.

Rhonda: Education, exactly. So, how do those lifestyle factors, in general, affect epigenetic aging?

Steve: Yeah. Everything your grandmother ever told you about living a healthy lifestyle is kind of corroborated by our epigenetic clocks, you know. So, for example, people who eat vegetables, people who exercise, also actually educational level, you know, to some extent even alcohol consumption show a beneficial effect. Now, the problem is these effects are weak, you know. Again, you need a couple of thousand people, then you pick it up. In terms of statistical significance, there's no debate. Clearly, these associations are there. But for the individual, the question is what if I follow the perfect lifestyle, do I make a big dent on epigenetic aging? And the answer is, unfortunately, not really, you know. I mean, I'm as much of a health nut as many other people in Southern California, you know, so I am trying to have a healthy lifestyle. So, yes, you want to avoid diabetes and all of that, you know, and certainly, you don't want to smoke, but the truth is a lifestyle intervention will never have a profound impact on aging at the population level. Because what I would like to do is I would like to increase healthspan by 10, 15 years, you know, and in my opinion, lifestyle interventions won't get us there, in healthy people, okay? So, let's say you have a friend who smokes and is obese, and yes, tell your friend to adopt a healthier lifestyle because, for this person, it will have a huge effect. But let's say you take somebody like me who is reasonably slender, doesn't smoke, and now you're telling me, what about if you become a vegetarian? Or what if you double the amount of exercise you do? Will you have a strong effect on my lifespan? And the answer is no, not really.

Rhonda: According to the epigenetic clock?

Steve: According to the epigenetic clock.

Rhonda: So, the physical activity was only, like, a weak...?

Steve: Yeah. Physical activity, exactly, unfortunately weak. So, I want to say correlation 0.08 for people who know what that means. That's a very weak correlation in blood, though. Because the question is maybe if we studied heart tissue or muscle, maybe we would find a much more pronounced effect. At least in blood, we didn't see it.

Rhonda: Well, that sort of brings the question about tissue types too as well. I mean, you know...

Steve: Yeah. Example is the effect of obesity on epigenetic aging. Turns out obese people age faster in blood. However, the strongest effect can be found in liver tissue. So, obesity greatly accelerates the epigenetic age of liver tissue, you know. And so, I think a lot of stress factors really have an organ-specific effect. Conversely, anti-aging interventions also have an organ-specific effect. So, for example, when we evaluated the effect of postmenopausal hormone therapy in women, we found no beneficial effect in blood. However, interestingly, the buccal epithelial cells or the cells inside of your mouth, they actually revealed that women who took hormone therapy were aging more slowly in these cells.

Rhonda: Oh, interesting.

Steve: Yes.

Rhonda: Many cell types are also epithelial cells. I mean, many of your organs have epithelial cells.

Steve: Yes.

Rhonda: Blood cells are a little different, I mean. So...

Steve: And now the finding made sense because blood cells don't have as many estrogen receptors as buccal epithelial cells, so yes. Obviously, if you have a hormone intervention, you want to study cells that are susceptible to it, you know,