How & Why You Age, And What It Takes To Be ‘Young Forever’ | Mark Hyman, MD | 1044 | Dave Asprey

You're listening to the Human Upgrade with Dave Asprey. Dr. Mark Hyman, welcome back to the show.

Thanks, Dave. It's been a bit, but I'm happy to be back.

You're looking young. What are you doing?

What am I not doing? You know, Dave, I turned 63 last year. And when I turned 60, I was like, okay, wait a minute. I think there's a bunch of stuff that I need to really understand about why we're seeing such a terrible epidemic of chronic disease and rapid aging in this country. And I don't want to be subjected to that. And I. I've been practicing functional medicine for 30 years almost and using the principles to help upgrade my health. But I kind of wanted to double down on looking at what, you know, what's really the latest science of how do I optimize my biological age, how do I actually not just live longer, but feel better, and how do I optimize my function and not go down the trajectory of what I see as abnormal aging? In America, what we typically see is people getting older and getting decrepit and frail and disabled and dysfunctional, not able to do what they want to do. But I don't want that for myself or anybody else. And I realize that we have sort of within us this incredible healing system that we can activate through the understanding of this emerging science of longevity. So when you talking about 20 years ago, looking at longevity, we didn't know as much because it was sort of a step, kid, to science. People didn't study it, people didn't fund the research in longevity. But now there's a tremendous amount of research and we've learned so much about what actually causes rapid biological aging, and we know what to do to reverse it. So I'm biologically 63. I mean, sorry, I'm chronologically 63, but I'm biologically 43, because I've applied a lot of these principles to myself.

You actually have a 20 year gap now.

Yeah, 20 years.

And that's DNA age, which tests DNA methylation.

I also did telomeres a couple years ago, and it was also about a 20 year difference.

Yeah, nice. So 20 year difference is at the upper end of what I've seen. And the DNA methylation clocks that we can use. If you're new to the science of this and listening, there's different ways of deciding how your or what your biological age is. And I've done a bunch of them. I'm only nine years younger or no, 11 years younger. Yeah, I'm 11 years old.

You know how it is, like the more overweight you are, the more weight you can lose. The older you are, the more age you can lose. I think it's something like that.

There might be some truth to that. All I know is that because if.

You'Re like 12, you can't go back to zero. Right.

I think I would have been 70 when I was 20 because, I mean, I was really unhealthy too. But it's interesting. I know many people who are at least five years younger biologically. And then you and I both have know people who are way older than their age.

Yeah, yeah, right.

And how much do you trust those measurements?

I think there's, you know, there are kind of lot of companies that are coming out with DNA methylation, epigenetic clock testing, which is the way we kind of look at your biological age. And there are other metrics, you know, like telomere length and things. But I think, you know, there is some variability. But I think if you kind of look at the companies that are doing the best job, I think trudiagnostic is one of the best. I don't have any affiliation with them, but you know, they pretty good with reproducible results and then you can track what you're doing over time. So the beautiful thing is that we have a program that we can change in our biology by understanding how to affect these underlying factors we call the hallmarks of aging that accelerate aging. So we can literally reprogram our, our biology and our genes and our epigenome to a younger self at any time if we know actually what to do. And that's really what led me to write Young Forever. What was the sort of central thesis is that we have now finally unlocked the causes of aging, of abnormal aging, let's say, not chronological aging. That's just time. I can't do anything about that. But we've unlocked the causes of rapid biological aging, which is abnormal and it's treatable. So all of a sudden we're kind of reframing aging as a disease, as a treatable disease. And that's a very big frame shift for many people.

It's something that was very hotly debated, even going back as far as the 90s and the early aughts. When you say disease, when you would say aging was a disease, you would get a really reactive response, especially from Western medical doctors. They get angry. Why does it make people angry when you say.

Well, because I think there's a sense that there's inevitability to the process of decline and dysfunction.

And people just don't like that inevitability. So then they get mad.

No, because they think that it's, it's, it's actually a disservice to science to talk about something that's impossible, which is.

Like, like flying or nuclear power, all. All those pesky things that actually change the world.

Yeah, yeah. You know. Right. Get to the moon. Like, we just don't think it's possible. Right. So we have a paradigm shift that's happening. And so the paradigm was this is what happens as you get older. I mean, it's. Even when I was in medical school still today we talk about chronic disease management, which drives me fricking crazy because I don't want to manage someone's chronic disease. I want to get rid of it. And I share a story in the book of a woman named Janice who had such an accelerated path of aging. She was 66. Her body mass index was 43, which is huge. It was huge. Obese, type 2, diabetic for 10 years, heart failure, multiple stents, hypertension, high cholesterol, kidneys were failing, Liver was fatty, just a mess on 20,000 of co pay a year. And she was on her way to a car transplant and a kidney transplant. Three days, I'm changing her diet, she was off insulin. Three months, she was off all medications. Her heart failure reversed, which is something we. You don't see in medicine unless you.

Get causing this in her diet.

What do you think? Ultra processed food, which is what she lived on. I honestly was so shocked because. Let me finish the story, then I'll tell you why I was so shocked. So she had heart failure normalized, which does not happen. Like you can manage heart failure. Her diabetes was completely gone. Her A1C went from 11, which is like way the. You know, it's like someone almost should be hospitalized with a blood sugar that level to five and a half, which is normal. Her blood pressure normalized, her kidneys normalized, her fatty liver went away, and in three months she lost 43 pounds. In a year, she lost 116 pounds and became a different human being. And so I don't want to manage her heart failure, her diabetes or kidney failure or fatty liver. I want to get rid of them. And that's really what now we know how to do by activating these ancient longevity switches in the body. So as I began to sort of dig deep into the research, I'm like, wait a minute. The body has all these switches, these like levers that we can pull and Work on these pathways and built in healing, innate regenerative repair, renewal, and healing systems that we can activate if we understand how. And so the book is about what are those systems and how do we activate them? And what exactly do we do?

We talk about ancient systems. I agree with you there. When I did my anti aging book, which was a superhuman probably four or five years ago.

Yeah. Great book.

Thank you. I had seven pillars of aging, and now when I go through young forever, you've. Well, I don't want to say added three because they don't all line up. They're very similar thinking. But you have 10.

There's 10, and now there's a couple more that have been added. So now there's like 13. So scientists keep, like, parsing it, but essentially there's systems that actually we start to understand are all interconnected and can drive aging.

Okay. You have A history of 30 years of practicing functional medicine, and so you've got great pattern recognition that I think only starts to happen after maybe 20 years.

Yeah.

Okay. If you put on your 10 years from now, hat how many causes of aging are we going to have?

Oh, I don't know. I mean, I think. Look, I think the body has these certain biological networks that are sort of becoming clear that we now can understand or underlying all disease. So the hallmarks of aging are one attempt to map those out. Functional medicine has really created seven physiological systems, and the hallmarks kind of fit in that they do. And I think, you know, it doesn't really matter, honestly. It's just. It's just. It's not really separate. They're not like, oh, it's 10 different things or 13 different things. It's really one system that it's like a web, all interconnected, and we're just sort of parsing it to be able to describe it and be able to work on it. But all these things relate to everything else. So any one of those hallmarks interacts with all the other hallmarks.

Right, Exactly.

So it's not like you can kind of say, oh, this is the thing, or this is the thing. It's very different. So I feel like if you understand how to do the right thing in terms of your lifestyle and certain behaviors, certain supplements, certain medications, certain lifestyle practices or biohacking techniques, then you can actually change those hallmarks and reverse the downslide toward rapid aging, disease, and death, you.

Definitely can reverse that. And for some people, we don't know how for whatever's going on with them yet. And for many people, it's Easy. And for a lot of people, you don't even have to know what's wrong. You just have to say, okay, I like to look at this as herding sheep. And maybe because I've raised sheep on my regenerative farm. Right. But people are, well, what's the one thing that's most important? How many things do you need to know to herd sheep? And I don't know, there's like a dog and it moves around, and when one sheep is out, it kind of gets pushed back in. But we know you have to give them water and they have to have enough food and sunlight because it doesn't work if you don't do those. And it feels like our systems are not that different.

Not that different, no.

We can come up with. I love your list of 10, by the way. And I'm going to go through some of these with you. We can come up with those. But there's probably five more. And if you handle all these, maybe you don't have to even know the other five.

Well, I think what you just said is so profound because as a functional medicine doctor, I don't treat disease, I don't try to cure disease. I try to create health, and then disease goes away as a side effect. So the hallmarks of aging are. Are in a sense, a map of how we deviate from health. And so really, it's about restoration of function. That's what functional medicine is, restoration and optimization of our function and that function of all these systems. How do our. How do our cells regulate themselves with, you know, proper mitochondrial function and immune regulation and the microbiome and how do proteins function and how do our nutrients get regulated and how can we properly divide ourselves so we don't get damaged? And so there's all these systems that are part of the hallmarks of aging, but we can actually, like you said, with very few basic principles, kind of fix all these things. You know, Pierre Laplace said, you know, you know, we can explain a large number of complex phenomena by a small set of general laws. Think about physics. There's just few laws of physics. And think of everything you can do with physics. You can build a bridge. You can send a man to the moon. You can, you know, create, you know, our cell phones and whatever. I don't even understand. I mean, I took physics in high school. That was about it. So maybe, you know, I had to take physics in colle college because I had to go to medical school. So I took a physics. But, I mean, it's just mind blowing. When you think of how many things can be manifested from a few set of small laws. And so I would say what we're now discovering, Dave, is the underlying fundamental laws of the universe, the nature of nature, the laws of biology, because we've never had those. Biology is so complex. It's been so reactive. Okay, you have a headache, you go to the head doctor, you have a stomachache, you go to the stomach doctor, you go to the joint doctor. If you have a joint pain, that's not how the body's organized. Because if you go have a joint pain, it might be from your microbiome. Your rheumatologist doesn't say, can I please see your poop? They should. Right. And I do. But that's not generally what happens. And when you practice medicine that way, you see extraordinary things. You don't have to treat all the diseases separately. The hallmarks of aging. The theory around this is that these are things that go wrong that can explain all the disease of aging. So what we're seeing are leaves on the trees like diabetes, heart disease, cancer, dementia, all these things, high blood pressure. These are just downstream of things, effects of these problems that could occur in the hallmarks, and then that's something you can actually treat. Now, for me, as I began to think about this, I was like, wait a minute. The hallmarks are great and they provide a target for treatment and thinking, but they're also kind of reductionist too. And the real answer to solving aging is figuring out why the hallmarks become dysfunctional in the first place. So why do we see these problems now? What's the cause of the hallmarks? The hallmarks are the cause of all these diseases. What is the cause of the hallmarks? And that's what I really think is different about Young Forever is that it's through a functional medicine lens which allows you to treat the root causes of everything. So not treating the like hallmarks like with a drug. Oh. Inflammation is part of the hallmarks of agent. Let me give you a anti inflammatory drug.

Right, Right.

Doesn't make sense. Right.

It doesn't make sense.

Or you're like metformin. I think this is really good.

Well, let's talk about Metformin. Yeah, this is. Well, yeah.

So one of the hallmarks of aging that I think is if we can dive into it is super important. And I think it's kind of a meta hallmark. It kind of above all the hallmarks because it, it influences all of them.

The God of all hallmarks.

The God of all hallmarks. Exactly. And it's, it's. They call it deregulated nutrient sensing, blah, blah, blah, whatever. But it means basically that your body's regulation of the food you're eating is screwed up. And when that's screwed up, it turns on all these pathways that accelerate aging. So we, we. There are really four of these pathways that are key. I call them longevity switches. So two of them sense too much of stuff that we're eating, and two of them sense a lack or scarcity of nutrients. So insulin signaling is probably one of the major drivers of aging. Too much insulin is the worst thing you could possibly think of for aging. So if you want to measure a biomarker, that's 10 bucks that any lab can do that your doctor is not doing, that's probably the most important metric in terms of determining your progression to aging is your fasting insulin level. The insulin signaling is such a big factor. And so we eat too much sugar, too much starch, and that pushes this pathway to go, go, go, go, go. And that creates everything we see as aging. Heart disease, cancer, diabetes, dementia. The high levels of sugar and starch. We consume, like the mountains of pharmacologic doses, about almost a pound a day per person of flour and sugar just drive this pathway into the ground and cause obesity, cause heart disease, cancer, diabetes, dementia. It's the worst. And then it also drives inflammation, it drives mitochondrial dysfunction, it drives damage to proteins, it drives zombie cell production, it drives epigenetic changes.

All of the 10 get driven by insulin, right?

It screws up your microbiome when you eat too much sugar and starch. So literally everything that happens is that. So the key to that is, you know, eat very low glycemic diet, low starch and sugar. Diet is so important. Low or zero, I wouldn't say zero. We don't have to have zero. I mean, I think zero is, you know, you can be a carnivore and have a zero carbohydrate diet. There's no biological requirement for carbohydrates. But I don't think we're very, like, metabolically flexible when we're healthy. So we can manage different kinds of carbohydrates from, like, whole foods and from, you know, whole grains. I mean, even, even if, like, you know, if you're, for example, a marathon runner or you're really active, you know, you can consume a lot of carbohydrates. Not going to mess up your metabolism. But if you're just sitting around the couch, you know, a little bit can be bad. So it really depends on you, your metabolic health, your body fat, your, you know.

Do you really see people who eat only meat and fat do healthy in the long term?

I don't know because I think I haven't seen people do that very much. The only thing I would say is like the, the Plains Indians at the turn of the century had the largest amount of centenarians. People lived to be 100 years old and they basically survived on bison.

But they ate small amounts of carbs too.

Yeah, they did. They had berries and they foraged for plants. And so they did it. Yeah, right.

They did eat the plants for.

I mean, you know, there are cultures that were more carnivorous, but I think, you know, we have these built in systems to regulate carbohydrate metabolite. So it's not bad, it's just when it gets flooded. The second is mtor. And this is a long conversation.

I love mtor.

MTOR is a really interesting pathway that is regulating protein synthesis and it can be overstimulated by eating all the time, by not giving it a break, by eating too much in general carbohydrate or protein. And if you don't give yourself a break from eating, you can't give this pathway a rest. At least you need it to actually create one of the key central things that makes you live a long time, which is autophagy. It's essentially self cleanup, self cannibalism is your recycling, repair, regeneration mode. It's where you take old parts and you get rid of them and you digest them and you break them down and you build them into new things. It's like a recycling plant, basically. And we desperately need that to function and to be turned on every day and to maybe have longer periods where it's turned on by more periods of fasting. We saw, for example, people who survived the concentration camps. They live really long time. And it's fascinating. And it's not like a genetic thing. They just seem to live like in their 90s, hundreds. And it's like, wow, they're still around. And it was 75 years ago.

Right.

You know, and so a lot of that had to do with this sort of shutting down their systems through starvation. And then that actually activated all these longevity pathways. And we'll talk about MTOR and what to do and everything, but. But that's where you get time restricted eating, intermittent fasting, you get drugs like rapamycin. There's other plant compounds and things that can actually affect MTOR. C15 is a fatty acid that actually stimulates the inhibition of mtor. And then you've got these two pathways that sense not enough, which is AMPK and sirtuins. So if low. If you have a low nutrient state, you're basically, well, AMPK means a adenosine monophosphate kinase. Essentially, it's a. You run on ATP, which is your fuel. You run carbons on gas, you run ATP. And when the phosphate molecules are given away, instead of adenosine triphosphate, it becomes monophosphate, meaning one phosphate molecule instead of three. And then your body goes away. I'm starving. And then it kicks in all these beneficial switches and pathways to conserve energy, to make your system optimized, to reduce inflammation, to improve your mitochondrial function, to do all these really beneficial things, which is great. And that's where metformin comes in. So I'm going to answer your metformin question. And the last pathway is the sirtuin pathway, which has been kind of highlighted by David Sinclair and Lenny Guarte from mit, who basically found that you could extend life by a third by giving huge amounts of resveratrol to rats or mice. And that was amazing. And they found it increased their metabolism and improved their fitness level, did all kinds of things, even if they were eating crappy and not exercising. So it was like a very powerful pathway. This pathway is actually important because when it's activated, it stimulates DNA repair. So one of the hallmarks of aging is damaged DNA. So when you stimulate sirtuins, it activates DNA repair, and that's a good thing. And it also improves mitochondrial function, reduces inflammation, improves insulin sensitivity, does all the things. So all the things. Do all the things. Basically, when you look at it. And that's where NAD is being used. So you might have heard that NAD and metformin, rapamycin and insulin, they all work through these central.

I think listeners of the show, at least for a long time, have heard at least one episode on each of those topics. Right, but now you're putting them all together.

Yeah. They're not all separate. It's like one system.

Yeah. Okay. And so what do they all do?

And so they're regulating your body's entire biological system. So they're regulating mitochondria, which regulate energy, regulating immune function and inflammation. They're regulating your antioxidant systems. They're regulating your. Your insulin sensitivity. They're regulating the. The autophagy process. All these things that have to be dialed in if you want to prevent reverse disease and live a long time, you have to dial these things In. So metformin is being touted as a longevity drug. Now. I. I have a huge problem with it.

Okay, you and me both, we gotta. Let's like, slam on melatonin.

Yeah, I really.

Melatonin on metformin a little bit.

I wrote about this, and I tried to create a balanced conversation in the book. I said, okay, here's what the data show. Here's why I think it's problematic. There's a large trial coming out called the TAME trial, which will help answer some of these questions. And recently, Dave, there was a new study came out that kind of put a little bit of warning signs on the metformin craze.

Another study that does that.

You mean? Well, so metformin is a drug that is beneficial towards ampk. So it optimizes AMPK function, which is good, which is all we just talked about. So you think, okay, that's good. But it also has some side effects. It has some mitochondrial side effects, which I really worry about, because mitochondria are key to healthy aging, can cause digestive upset in some people, improves insulin sensitivity, and I think it's fine. But when you look at, like, a large trial, it was very. It's very hard to do randomized controlled trials in nutrition. Very, very hard, because you got, like, you know, you need thousands of people. You got to give them the same program, and you got to have control groups. So what they did was this very, very famous study called the Diabetes Prevention Trial. And what they did was they took pre diabetics and they gave them three different interventions. One was nothing, one was metformin, and one was lifestyle change. The metformin reduced the progression to type 2 diabetes by 31%. Okay. Benefit compared to the control group lifestyle was 58% reduction. There's that, but it was a shitty diet. And I know people who are in this study. So I had patients who were in. I was like, wow, this is really nuts. But it worked because people cut out all the crap in their diet. They exercise, they support each other. They were accountable. A lot of reasons for it. But my point is this. If metformin doesn't work half as well as a crappy drug, I mean, as a crappy diet and lifestyle intervention, what if you put people on a ketogenic diet and mentioned that against metformin, then.

What dominates just completely changes everything.

And so I'm not a big metformin fan at this point. I'm more of a rapamycin fan. But I think metformin recently was reviewed in another large study and they found that the original results that seemed to show that type 2 diabetics who were on metformin died at less rates than people were not on metformin, I think has been sort of challenged. So I think it's still an open question, but is definitely not on my list of things to take for aging at this point. That patient who I just mentioned was an advanced type 2 diabetic on insulin every day. And within three days she's off her insulin, she's off all her medications, her A1C is normal, her insulin sensitivity is high because of the food. There's no more powerful drug. So I'm just saying like, so they.

Put her on like beyond burger and impossible burgers and all that.

Right.

Is that what she was eating?

Definitely not. But think about it.

Those are highly processed foods.

If I can get, I give you like 1000 milligrams of aspirin for your headache, it's going to work better than if I give you 2 milligrams of aspirin, which probably won't work. So I think of like these drugs as like 2 to 5 milligram doses compared to 1000 milligram doses, which is lifestyle. Like that's how big the order of magnitude difference is in terms of the effect you just can't get. You can give every diabetic, every drug, every treatment that is conventional for diabetes, you will never reverse it. You will never. With every single drug piled on, you will never see the disease go away. But with food, you can go away in three days. So how is that not such like a headline news on every major news outlet?

I love what you're saying and it's one of the reasons with Upgrade labs and since we last talked, we're franchises, we're opening dozens of locations all over the country and it's a non medical facility. Like if any disease is reversed, that's a side effect of lifestyle. Like all we're doing is saying what's the lowest dose of lifestyle that will get you there? Because I'm a little disturbed by the pharmaceutical sales engine right now trying to sell you these things.

Ozempic. Yeah, let's do that. Okay.

Well, I actually kind of think Ozempic is exciting. Isn't there an anti aging angle for.

GLP agonists because of its effect on body weight or on insulin sensitivity?

Not just body weight, on insulin sensitivity. Yeah. It seems like Ozempic might not be a bad thing if you're obese compared to the alternatives.

Okay, you show me a single Patient who took Ozempic and reversed their diabetes.

I have no.

It doesn't exist. It's a silly.

I will tell you, I did do one injection of Ozempic because I interviewed one of the lead researchers in the trial. So I always try everything I can, and I felt like I had morning sickness for a week and I didn't want to eat, and then I lost muscle mass because I didn't want to eat.

Well, that's the other thing. Well, that's the other thing even. Yeah, that's the other thing. What concerns me about Ozempic, and this speaks to really, one of the key central features of healthy aging is muscle. You've got to maintain, keep, build muscle as you get older. It's harder to do as you get older, but you can. And when you take ozempic, 40% of the weight loss is muscle, which means.

Even if you're lifting, you have to.

Yes, you can avert some of it by aggressive strength training and a whole bunch of testosterone and a whole bunch of supplements and testosterone.

If I weighed 100 pounds, I would take Ozempic. Though, just to be really clear, you weighed what? If I weighed 100 pounds more than I do now, like, say If I weighed 300 pounds like I did, I would have taken Ozempic and not regretted a minute of it, lost the weight, and then worked my ass off and made sure my hormones were fast.

That's fine, that's fine. But people have to understand, like, the minute you get off it, your metabolism is slower than when you started it.

Because of caloric restriction.

Yeah, because of the muscle loss that happens. And unless you really are aggressive while you're taking it, in strength training, you. You will see that. And even if you don't, you'll see that. And also I would say that 65% of the weight that you lose gets regained for the average person if you stop it. So this is a lifelong drug unless you radically change everything in your life. So I think, like you said, would I say if you were 100 pounds overweight, instead of a gastric bypass, to take Ozempic for a year, lose the weight, and then, you know, be aggressive in the taking of it, changing your lifestyle and after. Yes, okay, I can understand that, but not as a solution. I mean, think about it. New England Journal just came out of an article last week, and it was, it was about Medicare Part D. Now, Medicare Part D, for those who are listening, don't know, is basically the drug benefit. The entire budget for the drug benefit, the entire budget is $145 billion. If just the people in Medicare who are obese, not the overweight ones, okay, just the obese ones, took ozempic, the entire bill would be $268 billion, which means it would be almost, you know, 85% more than we currently spend on all drugs for all Medicare patients. Bottom line is that when we think of interventions that have orders of magnitude of benefit, more than medication, there are so many of them.

You're totally right.

And I think diet, exercise, certain sort of lifestyle practices and certain supplements and even certain medication can be useful. I think rapamycin works on mtor, which is interesting because that.

Yeah, let's talk about rapamycin.

Yeah. So, you know, I, I fascinated by this because, you know, when you start to see like, I don't know, I can see pattern recognition. So I've been doing this so long. So I see when I read this stuff like, oh, oh yeah. This is how everything connects. This is how it works. The body's like a system, it's like a network. And you start to see like a ecosystem. It's sort of like tripping on mushrooms. You see how everything's connected, you know. Right. So it's like, whoa. And I begin to kind of have this excitement and epiphany as I began to unpack this science around this. And MTOR is a very important pathway because we need it to build muscle. If you shut off MTOR all the time, you're going to not be able to build stuff and make proteins because you need MTOR to activate protein synthesis. But if you do it all the time, you're going to build too much proteins, you're going to get cancer and all kinds of other stuff. So it's overstimulation is not good. And inhibition of MTOR in a cyclic way is so critical to longevity because it's the way we activate this pathway of autophagy or self cleaning up. So when you think about why this all there, why do we have these pathways? Because historically, you know, we didn't have, you know, whole foods or grocery store or 711 on every corner. We didn't have an abundant sea of kind of food carnival around us to eat every kind of crap at every minute of every day.

No Skittles.

No Skittles. So. So we basically had to kind of go through periods of starvation where oh God, I can't find anything to eat or I can't kill that. I was watching some Instagram feed of like a puma chasing a ganaco in Chile and which ganaco is like a llama. And the poor puma was like, jumping on it. And the ganako would throw it off. Jumping on it, throw it off. Like, finally it was like they couldn't. He couldn't get a meal, right? I'm like, God, you know, it's tough out there. So somebody just can't catch that buffalo, you know? And so you go hungry. And we have these ancient systems to make sure we don't die when we're not eating and that we not only don't we die, but we start to really fix everything. Oh, geez, I'm, like, in trouble. So the body kicks into gear and has these ancient systems to repair, clean, rejuvenate, use all proteins. Old proteins build new things. You. You don't stop making proteins when you're not eating, right? Your body uses the body's proteins to start to fix it. And so that's what MTOR inhibition does. It activates this process of repair and cleanup. So what's so fascinating to me is, like, in the pathway is named mtor, which means mammalian target of rapamycin. Rapamycin is the drug. So why would you name a pathway to this drug? Well, that's how of they discovered it. And this rapamycin is named after rapa nui, or Easter island, which is where they found this compound. These scientists in the 60s were scraping the soil and trying to find cool compounds. I don't know, maybe the aliens, they thought, dropped some good medicines in the soil. And so they basically got this compound they put in a lab, they tested it for antifungal purposes. Didn't really work that well. The guy's boss said, just throw it out. It's garbage. And he didn't. So the science, the lab guy was like, I'm keeping this stuff. And then they found that it actually modulates immune function, so they use it in transplant medicine. And then they found out that it actually inhibits this pathway called mtor, which can extend life dramatically in animals and reverse a lot of the biological aging phenomena. So when you look at the one thing, the one thing that almost all scientists agree can reverse aging and actually extend life. So you don't really have many interventions that can extend life by a third. I mean, if you're yielded to 80, instead, you live to 120. That's impressive, right? So it's not like you're getting a couple extra years. You're getting like a massive increase. If you eat a third less calories, you live a third longer. Now that's pretty miserable. And I met a guy once who was in the calorie restriction society and said, what'd you have for breakfast? He's like, oh, I had five pounds of celery. I'm like, you must have very strong chewing muscles.

And I'm still trying to get a date.

I'm like, what'd you have for lunch? I had 12 pounds of tomatoes. I'm like, okay, yeah, it's, it's not, it's not sustainable.

It's just not gonna happen.

So. So anyway, but in animals, they can do it because the animals can't complain. And so they find it really works. And so what we're trying to find you, you hinted this. What are the things that mimic calorie restriction? One of the things that can kind of make your body pretend. And so fasting is actually calorie restriction. So time restricted eating is a form of calorie restriction. Ketogenic diets, another form of sort of calorie restriction in the sense of how the body perceives it. Right, because.

Because of the insulin effect.

Well, it's like, it's basically what happens when you don't eat. You go into ketosis. Right. So the body, it's actually doing the same things, fasting, mimicking diets, where you have low calorie diets for five days periodically. All these things work in a very similar way. And they, and they even soluble fiber.

When you think about it, or so insoluble fiber, it's calories that you can't absorb. So that's calorie restriction even though there's calories. Right, right, right. Todd, your list. Keep going.

Yeah. So basically, you basically can through many different doorways, turn on these ancient starvation systems, these ancient survival systems. And when you do that, you actually can. Can really have a dramatic impact. So rapamycin seems to do all these things, inhibits mtor, which then turns off inflammation, it activates mitochondrial biogenesis, it increases antioxidant systems, it increases autophagy, increases DNA repair. It has impacts on all the other things. So it may activate sirtuin activity. And so they're all like kind of interacting. They're not like separate things. And so it's kind of a cool thing to say, oh, I'm going to take this drug once a week, which is kind of the protocol 6 milligrams a week, or some people are taking it 2 milligrams, you know, three times a week for eight weeks or five weeks off or eight weeks on. It's like everybody's Kind of guessing, honestly, but. But the data is really fascinating and I, I'm kind of optimistic about it. I started taking it.

How often do you take it?

I take it once a week. And do you fast on the day?

Take it.

I take it at night. Okay. So I do a overnight fast, so 16 hour fast. So it's not like too fast. I'm too skinny. If I fast, I. Yeah, yeah, it.

Can be a problem and I'm the last guy who would ever be saying it's a problem, but I, I did get too thin even without taking that stuff. But if I over fast and all, it's to the point that having that metabolic control is incredible. But you've always been thin, right?

Yeah, yeah, I've always been like this. I mean I've always exercised. But basically I was 40 and I was running, I was eating healthy, I was doing functional medicine. But it was an era where we thought more carbohydrates, less fat, less protein was better.

Ashes you?

Yeah, so I was eating whole grains, I was eating beans. I was, you know, I wasn't like eating junk food and I was eating a lot of sugar, but I definitely was. Didn't have the muscle mass. And I was sort of shocked when I was going through pictures and I saw this whole picture of me when I was 40, when I was thin, but I just looked kind of like nothing. And then I look at this picture of me when I'm 62 and you're ripped and it's like what? And so the body has that amazing ability to do this at any age. So it's never too late to start.

I've got to ask you the MTOR elephant in the room question, given that elephants are made out of meat. Not that I would eat one.

Oh, meat, yeah, meat is definitely bad because meat causes MTOR to turn on and that's really bad. So we should never eat any meat.

I mean Dr. Gundry was just on. And Dr. Gundry is a friend and I respect him greatly. We talked about it and he's all these plant based proteins and all for that reason. And that's an area we don't agree. We agree on many things. But what is your take, Dr. Hyman? Meat or no meat and mtor?

Well, I've written about this a lot in food. What the heck should I eat? I basically locked myself. I was in Austin actually when I wrote that chapter. I locked myself in a room in a hotel with a pile of papers.

This big next to a barbecue.

I am not gonna listen to every Stupid, blah, blah, blah. You know, guy, influencer, doctor, scientist. I want to know what the data show. I, I want to. I'm like, I'm a doctor, I can read papers. I understand this works. I can evaluate how this is. I'm like started. Because the one thing is to read the headline, another thing is to read the abstract, another thing to read the methods and then to read the supplementary material which has all exactly what they ate and what they did and what the other factors were. And basically my conclusion was that meat is not bad for you. That, yes, we should not be eating feedlot meat for many reasons.

And lunch meat and hot dogs are not meat.

Oh my God, Dave. I'm like, I was down in Florida, I had to do this show, TV show. My flight was delayed. I got in late, I didn't have dinner. I woke up, had had a bunch of stuff to do. Didn't really have breakfast, didn't really have lunch. Had a little, few snacky things. And I finally got to the airport on the way home and I was really hungry. I'm like, I'm gonna try to find something to eat. And it was like an airport. Fort Myers, Florida, Right. I'm like, oh God. Okay. Well, I looked around, I thought, okay, this place looks good. Had like, it said carved turkey, black eyed peas, you know, collard greens. Okay, I can go for that. So I get the turkey. I'm thinking carved turkey. It means it's carved from a turkey, right? And it was like turkey like substance.

Carved from a loaf.

I don't know what the hell this was, but it was like some weird, like soggy spongel.

Did you eat it?

I was so hungry I ate it. Kind of tried some turkey in it. But, you know, sometimes you just got to deal with it. What do you got to deal with? So it was fine. And, and so basically the, the, the, the meat question is, is really around aging has to do with mtor.

Yes, it does.

So the idea that if you overstimulate mtor, you're going to age faster is true. So logically, if you eat anything that stimulates mtor, that's bad. Well, that's wrong, right? It's like, it's like Goldilocks. You need just the right amount at the right way. It's like, do you need to sleep and you need to be awake? You need both, right?

Yeah.

So basically, the body has a need to build protein. So you need to have a construction crew and a building crew, and you also need a demolition crew and a cleanup crew. And so you need both of them. And if you just like, kind of made dinner in your kitchen and never cleaned it up, it'd be a freaking mess. That's what happens when you overstimulate mtor. But if you didn't ever cook, you'd start. So, you know, I think it's really about how to properly activate and inhibit mtor. So let's talk about how do you turn on protein synthesis? Because this is really key and has to do with the quality of the protein.

It does.

So when you look at the protage study. Look, I'm not a protege, I'm not a protein expert, but I had read what protein experts have written, and there was a group of protein experts, the world's protein experts, got together and they wrote a paper to review all the science about muscle protein aging called the Protage study. And it was a really in depth study that looked at kind of review of all the data and they came up with a number of conclusions. One, you need two and a half grams of leucine to activate mtor.