GLP-1 drugs like semaglutide slow aging faster than calorie restriction alone, but losing muscle mass can erase the gains. The DO-HEALTH trial found omega-3, vitamin D, and exercise all help. Social connection, sleep, and stress matter too, and no single intervention works for everyone.
caloric restriction, is there a— I know there's a difference between, say, alternate-day fasting, intermittent fasting, fasting-mimicking diet in terms of certain diets having greater potential to, say, preserve lean muscle mass through calorie restriction. But what I'm curious about is have you seen or come across anything that would show the impact of calorie restriction if it's done via, let's say, just steely willpower versus calorie restriction accomplished through the use of a GLP agonist?
Yeah, great, great question. No, that's not been studied directly. And we have actually done studies with both Novo Nordisk and Eli Lilly on semaglutide and, and tirzepatide.
Okay.
And interestingly, both of those compounds, those GLP-1s, have other kind of longevity effects too. Some have been published now, and they get a lot of press, and that those, those were our studies we did analyzing that data. Others haven't been published yet, but what I'll tell you is those are two very different— like, we see it in caloric restriction. We also see it in the GLP-1s. They seem to be two different things and additive. It's not just from the caloric restriction. Now, having said all that, one of the things about— like, no tool gives you the entire picture. So just because you're done eating PACE and your pace of aging goes down with caloric restriction, it doesn't mean more of it is better. You and I know how important muscle mass is. So you could have an incredibly low Dunedin pace, pace of aging, great biologic age, and then you fall and get a hip fracture.
Yeah, exactly. You fall off your bicycle and you die.
Exactly.
Yeah.
It's so just, you got to be smart about this stuff and know that everything is a piece of the puzzle. It's not the entire puzzle.
Okay.
And the other thing, calorie restriction, Calorie restriction, a couple things that have been studied, and then I'll get into what we've just seen. I mentioned the pitavastatin and HIV. That was great, but I mean, I don't know how many of your, your listeners have HIV, so I don't know how applicable it is to them. There's been some supplement studies. There was the DO Health study, and what they showed is omega-3, vitamin D, and exercise all had good effects. Those were kind of basic things. Now, what they didn't do is separate out people who had good levels of baseline versus not. But when you looked at the population, those vitamin D, omega-3, like those are ones that people take, and they had, they had effects. There also was a really cool study of preschool children where these kids had some, some psychosocial issues, and they gave the parents training in how to approach them. And the parents that got training versus not, the controls versus they actually— reductions in, in rate of aging for these kids. So there's social factors we know make a difference. And the other things you would expect, like sleep, optimizing your stress, which has to do with the social things. An interesting one that there's not, not published out on this yet, but we've just seen it anecdotally, that— I mean, just today I had a fair amount of exogenous ketones. Like, when we've seen— I don't have, like, good big studies on this, but it's pretty reliable when I've seen people do studies on themselves of, I am going to increase my ketone levels, even if it's not fasting, it's through exogenous ketones. We'll see interesting effects on pace of aging. And I wish someone would do a bigger study on that because the magnitude has been interesting.
Yeah. So that would be interesting. It's kind of similar to the calorie restriction with the GLP agonist versus without. It sounds like there's different effects of both and they could be combinatorial. It'd be interesting to see, okay, so maintaining high blood levels of ketones not via carbohydrate and calorie restriction, just via exogenous ketones, if there's a clear winner or if those also are, are combinatorial.
Yeah, yeah, it would be. Now, the fact that caloric restriction, a big study showed it worked, um, I— and obviously in that caloric restriction, they may have had raised ketone levels. Who knows what their diet was? Um, but just exogenous ketones without really changing caloric intake seems to make a difference as, as well, but there's not a big study on that yet.
The Solution to Aging Might Be Closer Than Anyone Realizes - With Ben Goertzel
