Rhonda: Awesome. I'd like to ask this last question to a lot of podcast guests, and that is, you know, what lifestyle changes, like, do you incorporate the most, you know, into your life based on science?

Dr. Levine: Yeah. I mean, for me, there's kind of two things, diet and exercise I try to pay a lot of attention to. So, exercise I think is such a simple thing that so few people...you know, everyone's waiting for the magic pill. I mean, if they could bottle the effects of exercise, it would be the biggest thing in aging research that, you know, exists. It's probably the most powerful tool we have to actually intervene in our aging process, or at least to slow it. Or they've even shown, you know, you can reverse diabetes through exercise or any of these things.

Rhonda: Better than Metformin.

Dr. Levine: Yeah, I know. So, again, exercise is amazing, it makes you feel good. So, for me, trying to maintain an active lifestyle as much as possible, you know, I sit at a desk a lot, so...

Rhonda: What's your favorite kind of exercise that you do?

Dr. Levine: I mean I like to do things that just are fun. So, hiking or anything like that or, you know, any of these classes. But probably, if I were thinking the most beneficial, probably things like HIIT, just try to do that as much as I can. And then the other thing is just diet. I eat, I would say, 90% to 95% plant-based, I do eat some fish, try to keep kind of like a Japanese type diet. And then I do intermittent fasting where I don't eat until usually like 1:00. Again, that I think, we don't know for sure whether that's beneficial, but for now, just sticking to it, seeing kind of what happens.

Rhonda: Yeah. We had Mark Mattson on the podcast, not long ago, and he definitely convinced me that there are some benefits for sure in intermittent fasting with respect to, you know, keeping in ketosis and the metabolic switch. But so, did you see that paper that came out of Yale from Vishva Dixit's lab?

Dr. Levine: Oh, yeah, yeah. Yeah.

Rhonda: Like, I didn't in-depth read it, I just sort of glanced at it, but like there was a two-year caloric-restriction study.

Dr. Levine: Yeah, that's from the calorie study. Yeah.

Rhonda: Okay. So, and thymic aging was like slowed, which was kind of...

Dr. Levine: Yeah. Yeah, I think, you know, calorie restriction has been going around for quite a while. I think the issue is most people can't actually sustain...

Rhonda: Right. No, I mean I think there's, you bring up a really good point, like there's been a lot, it's like the classical intervention that's been done in rodents, it's been done in non-human primates, and it's been shown to...you know, it does improve health span of those animals that are not humans. And in some cases, they really restrict it, like 30%, like they eat 30% less calories or fewer calories. Whereas I think this study the calorie restriction was like 15% or 14%.

Dr. Levine: Yeah, so, I think it's like 12% or...yeah.

Rhonda: I don't know what that translates. Like we don't know if caloric restriction actually is how beneficial it is for humans. And it always comes back to, again, that like...well, overeating is not good, you know, overeating is not good, we know that, and, you know, there's many ways that you can affect calories in, calories out, and one of them is exercise too. You know, so, there's a lot of ways that you can sort of get to a similar, you know, end point where you're not just eating as many calories. Right?

Dr. Levine: Yeah.

Rhonda: It doesn't have to be like you're...and you certainly don't want to starve yourself. Like, calorie restriction, like, you know, there's a problem with muscle wasting and frailty with age. Right? So...

Dr. Levine: Yeah, especially if you're getting older.

Rhonda: Right, exactly. And getting enough protein. So again, yeah, all these little nuances, especially when you start to translate the research. But epigenetic age was, if I remember correctly, shown to be slowed in the rodent, in...

Dr. Levine: Oh yeah, so, in mice, epigenetic age is affected by calorie restriction and substantially slowed. And the longer the animals are on it, the kind of slower the increase in epigenetic age over time becomes. But again, I think, you know, how much of this is the absence of excess food? And there are studies in rodents showing that different genetic backgrounds have different responses. Some actually do worse with caloric restriction. So, that amount of restriction I think is probably going to, you know, depend on you personally, not just preference but, you know, some of your genetics.

And the other thing, the reason I don't do caloric restriction personally is because there's studies, even in mice, that, if you stop it, you lose the benefit. And I can't imagine spending my entire life on caloric restriction to continue to get this benefit. So, I always say to people, "Do whatever you can stick to." Right? You don't have to be perfect in your diet or exercise but, as long as I think you have the knowledge of how things are affecting, you can make just an informed decision on, "This part's worth like, potentially, an extra four years of healthy life. Or maybe something else isn't worth it to you, and just having that kind of information and feedback I think it's going to be critical.

Rhonda: Right, yeah. And there's also the aspect of confounding it with time-restricted feeding in mice. I know [inaudible 01:18:57] has talked about this many times on our podcast about how the people, like postdocs and graduate students that are feeding these mice, they come, they're there for like eight hours, you know, so, there's a component of these calorie-restriction diets that actually...

Dr. Levine: That is a time-restricted diet.

Rhonda: Yeah, how much is it that they're just not eating for 16 hours? Because that's when they did all at once and then that's it. Right, yeah.