Geneticist David Sinclair on the Latest Anti-Aging Studies | Joe Rogan

But I had a question for you right off the bat regarding Metformin. There was actually an article, I'm sure you saw it recently, like within the last couple of days that was going around through all the mainstream papers. It was talking about how the use of Metformin, DHEA, and was there something else as well that was taking two years? Human growth hormone. Taking two years, two biological years off of people's lives in terms of their age, which are natural, I'm 52, it would make me 50. Right even 49.5 according to the study. That's what I'm looking for. Getting back to the floors. That was a good study. It's only nine people so we have to repeat this. Were they studs? Did you get like nine super athletes or did you get like schmoes that don't exercise? As far as I know these were just regular. Schmoes. Which is good news for schmoes like me. Yes, good news. Yeah, I mean that's what you want. Some people just respond better. They have super bodies. Great thing about that study is first of all I was with the first, the main author on that paper while it came out. I was over in Israel as part of my journey up the Great Rift of Africa. I ended up in Israel. Anyway the guy there, Steve Horvath is his name. He and I and a couple of other guys are trying to figure out not just why we age, why we don't have to, but is aging truly reversible? That's what this study suggests is that it's not just about slowing down aging, but one day we could be 80 but biologically 30. Now when we're talking about the biological age, how is that measured? Is this measured by the length of the telomeres? Is this measured by physical performance? Is it measured by a combination of these factors? It's none of that. It's something brand new. Most people don't know about it. So it's called the Horvath clock and what Horvath and others have discovered is that if you read the DNA and you don't just look at the letters, A, C, T, G, if you look at what's on the letter C, cytosine is called, there are chemical modifications and those chemicals change as we get older in very linear and predictable ways. Even if you use a computer, AI, you can say, if I took your blood sample right now, I could read your DNA, look at those chemical groups on the Cs and I could say, you are, okay, 52, you might be 46 according to that clock and also I could predict when you're going to die. Whoa. Scary thought, right? Yeah, like a fortune teller. Yeah. But the good news is, well, now that we know what's not just measuring aging, we actually think that clock is part of the aging process. We're learning how to reverse it too. Now, is this just one modality, this combination of growth hormone, is this one way of going about it? Are there other ways of going about it? Growth hormone, DHEA, metformin, is there anything else? Well, that's the first that's ever been shown to really. Just those three things? The first, but I'm sure there's going to be many more discovered. We've only had this Horvath clock over the last few years in humans being used widely. But I think as we use this clock, we're going to figure out that a whole bunch of stuff that we do and things that we can do and combine will not just slow aging but reverse it. Not just by two and a half years, eventually, and some of the technology that I talk about in my book, we think could turn the clock back by a decade or more. Whoa. Now, what things are you talking about that could possibly turn it back a decade or more? And who do I have to blow? Sorry. Yeah, you can blow me, but yeah, you may have to do it a few times. But the amazing thing about where we are now today with aging, and we're right on the cutting edge, so it's great to be able to share this with your listeners, is this clock, it changes on the DNA, right? What I'm saying in my theory of aging is that it's not the DNA that we lose. That's the old theory. That's the old idea that antioxidants hurt the DNA. Just throw that out for a while, maybe forever. What I think is going on is that the DNA is getting modified and the cell can't read the DNA the way it used to. That's really important. And so the clock is not just a clock. It's not a clock on the wall. It's also, if you move the hands of the clock, time changes. That's what I think is going on. Can we pause right here for a moment and explain what you were saying about antioxidants? Well, antioxidants have been the biggest disappointment in the aging field. It doesn't stop 40 million people every day buying drinks with antioxidants in them, but antioxidants have, with very few exceptions, failed to extend the lifespan of any organism. But you are a proponent of resveratrol, at least you used to be. Are you still? I still take it, and we still study it in my lab. But what's ... You brought this up. It's really important. Cell was originally thought to be an antioxidant, and it is a mild antioxidant. But the way it really works, and we know this is a fact from my lab, is that it's stimulating the body's defenses against aging and disease because it's binding to these enzymes that we work on called sirtuins, and these are the defenders of the body. And you were saying, if I remember correctly, you take resveratrol, you take a powdered form ... I actually bought exactly what you take, and you mix it with yogurt in the morning. Is that how you do it? Yep. What's the dose that you take? Well, it probably comes out to about a gram in the morning. A gram? Yeah. Okay, so if someone's taking capsules ... Well, it depends. If it probably capsules at 250 milligrams, that'd be four in the morning. Okay, so it'd take four. Yeah, I'm still alive, so that's a good sign. You look good. Oh, thank you. Is it important to take it with fats? Is that why you take it with yogurt? Yeah. Either high protein, which is a Greek yogurt, suffices, or fat, but water, it's like brick dust. It won't dissolve, and it won't be absorbed. Okay. But a glass of whole milk, maybe, would be okay? Yeah, that's great. But it has to have something to bind to, is that the deal? For sure. Yeah, in our studies, in humans and in mice, if we didn't give them high-fat food, it barely got in. It was five-fold less. Now, this study of metformin, DHEA, and human growth hormone does not include NMN. Right. So, but NMN is also effective. Well, let's delve in a little bit. Please. If you read the paper, and I have, it turns out one of the effects of this treatment was the reduction in the levels of a protein called CD38. CD38 resides on immune cells, and it goes up as we get older. And what they found, one of the biggest effects of the treatment was the levels of this CD38 protein went down. So what is the CD38? This is the main enzyme in our bodies that degrades NAD. NAD is required for the sirtuin defenders to work. So one possibility is that, and I'm sure it's complicated, but one way this could be working is by allowing your body to make NAD and store it rather than degrading it as we get older. Interesting. So, would supplementing with NMN, which is a form of NAD, correct? A precursor, yeah. Precursor. Would that enhance the effects, do you believe? Like if they tried to do a new study? It could. It could. I mean, each of these patients cost $10,000 for the treatment. So it's not easy to do these studies. $10,000 for the entire T of the treatment and the treatment lasted how long? I don't remember how long they treated the patients for. But I do know that it wasn't cheap. That's why they only did nine because at first I said to my friend Steve Horvath, nine patients, are you kidding me? Why didn't you do 50? And I went, well, we didn't have the money. That's the problem. Anyway, my point really is that we need to test a lot of different combinations, include NMN, include, there's one called rapamycin, which is a little bit more risky and toxic, but there are better molecules in development. The question is, what is the best combination? And do you use it with exercise and fasting? Or is it bad to combine them all together? We don't know yet. That's a good question, too, that I wanted to ask you because one of the things that came out of the podcast was input from some other people that I know that are nutrition experts and performance experts that were skeptical about metformin. And they were saying that metformin, although it may have an anti-aging effect, it actually decreases physical performance in athletes. Well, there is a study that shows that, and Resveratrol, too, actually, can prevent the great gains from hard exercise. So here's the solution that I think is worth trying, a solution. And that is a theme that I have in my book and in my research. And that is we don't want to be doing everything every day necessarily. We want to pulse it. We want to shock the body and let it recover. We know that you can't just exercise. Some people who have been on this show run 100 miles every weekend. But generally, you want to hit it hard and let it recover, hit it hard to let it recover. So what I am planning to do and actually started doing is, on days that I'm exercising and recovering, I don't take metformin. And then when I'm just sitting around or on a plane, I do. And that way, I think that my body can have the best of both worlds. So when you are not exercising and you take it, you feel like it doesn't have a hit when you are exercising and not taking it. So somehow or another, whatever performance hit it has, it's temporary? Yeah, right. So while this is all just theoretical. It is. We're right on the cutting edge of human knowledge. We don't actually know what the best thing is. But my best guess is that we want to allow the body to recover. So I don't take metformin on those days, rather than taking metformin every day like a diabetic would. Now what is the hit? What is happening? What's the mechanism behind the performance hit from taking metformin? Oh, we don't know. But I can tell you the best explanation that I can give you. So metformin is a derivative of a plant molecule, the French lilac. So it's not a crazy molecule. It's pretty natural. But what it does is many things in the body. This will quite annoyingly argue about it for the past 40 years. So there's no correct answer. But what I think is going on is that metformin is interfering with the mitochondria in the cell. Mitochondria, we call them battery packs. They're basically making chemical energy. Without that chemical energy, we'd be dead in about 20 seconds. So we need that for life. So metformin interrupts that energy production in the mitochondria. But you need the mitochondria to amplify after you've exercised. So they're antagonizing each other. So why does metformin work? By inhibiting the mitochondria, the body gets a signal that it doesn't have enough chemical energy. It's not making enough. So it expands the number of mitochondria. These are ancient remnants of bacteria that entered our cells. And we have less if we sit around, like we are now. And we have more if we exercise. And metformin, by telling the body, shit, we're running out of energy, the body responds and makes more mitochondria, just like exercise does. But I think if you're taking metformin and exercising, that inhibition is preventing the benefit somehow of what you get with exercise. Preventing it how so. Like what did the study, what studies have been done and what did they reveal? I don't remember the precise details of the study. It was giving metformin every day to people who were in a controlled exercise. I think it was treadmill a few times a week. But then what they measured was the mitochondrial benefit. And I think they measured a bit of strength. It's so confusing that there's a mitochondrial benefit, but a performance hit. Well, no, actually, metformin prevented the mitochondria from amplifying up. Oh. So it must be interfering with the signal that you get from exercise, whatever that is. We don't know exactly what that is. So you'd really have to be some sort of a guinea pig to try to fuck with this stuff, to go back and forth from taking it and exercising, not taking it and exercising. I'm one of those guinea pigs.