“Age Reversal Is Coming.” Everything You Need To Know - Dr David Sinclair - #1141

28:04But also I'm making sure that I'm not deficient in any minerals or vitamins. And so I'm taking in things like vitamin D, vitamin C as well, and some nutrients that I know I can become deficient in. What do you think is happening inside of your body from day four until day 14? What's going on? Well, we know actually, not from measuring me, but we know from many years of study what happens to the human body. The first 24 hours, you're going to use up a lot of the sugar and then the glycogen in your liver. What I like to think is my liver knows how to steady my glucose and give me the right amount of glucose far more than my mouth does.

28:49My liver is smarter than my eyes and my mouth. And anyone that's fasted knows that your blood sugar, if you're eating like this and you go, oh, energy, oh, brain fog, energy, brain fog, oh, I'm sleepy in the afternoon. That's our normal life. If you're fasting, your liver just puts out just the right amount of ketones for your brain, or you can drink some ketone drinks. or it's making glucose or both. Your brain loves ketones. And if you do it too long, you will start to lose muscle. So I'm working out more than I do normally to make sure I don't lose any weight. And so that scale will tell me if I'm losing lean mass, which I don't want to do, and I make sure that I don't lose it.

29:31Is there not a concern to do with your gut? Does there not need to be transit through the digestive tract? I don't know what happens if nothing passes through your stomach for two weeks. Yeah. Well, I can tell you your stool changes. I imagine it does. It turns fucking invisible. Yeah, right. It's a phantom poo, as it's called. A bunch of gas coming out. So, yeah, that's what I meant. I'm not in the bathroom as often. It's actually much more productive, unless you're productive on the bathroom. I do find that the biggest obstacle to my productivity is the bathroom, actually. Are you sure you're not tweeting away down there?

30:08but yeah your microbiome i think and and this is not proven um by any means but i feel like just like your body it helps to give your microbiome a shake up a bit of hormesis which is a little bit of stress that's good for you and uh i would love to do an experiment on myself as well measure before during and after and see what happens to my microbiome flora and stuff like that. Well, I mean, I know that some of the proposed positive effects for GLPs include slowing motility through the gut, which actually helps with things like SIBO or Candida or H. pylori, because the pace, this is why everybody, every bro lifter that's listening to this, you, you at some point in your life have glanced off the bottom of SIBO or maybe have it right now because just the sheer volume of food that you're putting through yourself all the time, grazing high protein high starch like that's one of the proposed mechanisms i think that helps from glps and i don't know that's what what i was interested maybe creating this very i was going to say sterile environment it's not it's barren this completely vacant environment for two weeks i have no idea what that does it if you had a overgrowth does it kill it all because it's not being fed does it allow it to create castles and cathedrals and you know armor itself yeah Yeah.

31:29Well, I don't know the answer to that. I do know that there's some really interesting things in bile that comes out more when you're fasted. One of the components is a type of colic acid, which is the black stuff that goes into your microbiome. And your microbiome converts that into a molecule that goes back into your bloodstream and turns on a longevity gene that we've been working on. It actually binds to the protein and makes the protein more active. It's called SIRT1. If anyone's read my book, they know what SIRT1 is. SIRT1 regulates the epigenome, slows down the changes to the software. And so long story short, it's at least plausible, and there's a nature paper on this from another group that I reviewed, that when you're fasting, your microbiome is more actively converting bile into healthy molecules, as well as short-chain fatty acids.

32:20There's a lot of literature on that. And these molecules go into your body and they signal adversity. And you know that I like adversity. Adversity is good for your health. There's abundance and adversity mode. They're both good, but you don't want to stay in one or the other. You'll accelerate your aging and you'll die. So you want to cycle between adversity and abundance. And your microbes help you get through that.

32:48What would you say, let's say that someone finds this quite seductive, what would be a good start? a one-day fast, a three-day fast, and what should they do? What would be a rough protocol to follow without having to be a conductor of supplements? Yeah. Well, if you've never fasted and you just wake up and you eat a normal breakfast, lunch, dinner, either you're obese or you exercise a lot because that's going to put on weight. But if you are willing to try, I would suggest skipping one meal and replacing it with a lot of liquids. So for me, I don't mind skipping breakfast. Not everybody wants to do that because they work out and they feel like they need some food.

33:36So instead, you can skip dinner. I would just have a very early dinner. What I was doing for many years, probably 30 years of my life, was trying not to eat anything until late lunch. And you will initially feel hungry. This is the thing. Don't give up. Because it takes a few days for your body to get used to not having the food. It'll be screaming at your brain, I'm so hungry, I'm going to die if I don't eat this bacon and eggs. But get through it. And actually after two weeks, it'll become really weird to eat food in the morning or at night. Your body gets used to it, your brain gets used to it, but it does take a while.

34:13And the cheat code is fill your stomach with lots of liquids, not sugary drinks, not a lot of of calories zero if you can or just a little bit um i do have a little bit of calories in the morning because it's good with my supplements but a lot of water so a low calorie drink like this or water tea um black tea coffee is very good they're both good actually tea and coffee are both very good for you because they contain other molecules like polyphenols that again can activate these enzymes that protect us somewhere along the way low energy just gets accepted as a part of getting older. Turns out there's a reason for that.

34:51As we age, our mitochondria, the parts of our cells that power us, become weaker and make less energy, which is why I'm such a huge fan of Timeline. They've developed this that helps to clear out your damaged mitochondria so your cells can actually renew themselves. Timeline is backed by over a decade of research and has more than 50 patents and is the number one recommended mitochondrial supplement on the planet. This isn't just theory. In clinical trials, people saw mitochondrial renewal increased by more than 40 % in just 16 weeks, along with improvements in their overall energy. I've been using it for over two years since my doctor recommended it to me way before I partnered with Timeline.

35:26And eat your heart out, Martin Shkreli, because they've just dropped the price and it now starts at$99. Best of all, there is a 30-day money-back guarantee, plus free shipping in the US, plus they ship internationally. And right now you can get that$99 price with an additional 20 % off by going to the link in the description below or heading to timeline.com slash modern wisdom using the code modern wisdom at checkout that's timeline.com slash modern wisdom and modern wisdom at checkout have we seen any data that shows calorie restriction increases lifespan in humans i know that this exists in rodents yes um a study that was done was it macaques or something and that didn't actually work because it was a two-decade study and the first version of the study, it turned out that they hadn't fed them the same diet and split it in half.

36:16They'd fed one of them a junk food diet and the other one had been given a healthy one. Then they ran it back and it seemed like the data was mixed there. What's the evidence about calorie restriction for longevity in humans? Is there any? No. There's a lot of anecdotal and historical evidence that fasting is good for you. And there have been some short-term studies over a couple of years. There was the calorie study that showed that you could improve a lot of health biomarkers in humans over that time that had lasting effects, including on the epigenome. But nobody's really done a prospective study with placebo.

36:47It's very hard to do that or even controls. So there's no proof. And I don't think anytime soon there'll be proof, but who wants to wait another hundred years till that happens? You can't. You've got to at least go based on the evidence. And in animals, it's incontrovertible that if you do it with nutrition, not just starving, it's very good for you. um and that's why i do it i would say with the monkey study i know it very well because the two labs that disagreed about this one uh is one of my best friends and the other one is my trainee and they were well you're like switzerland between the two of them yeah i didn't really get involved um but i did bring them together and they they came to the conclusion that yes it did extend lifespan.

37:35It depended on the veterinary care and other environmental things. The University of Wisconsin, where the other lab is, Rosalind Anderson is the professor that I originally trained, what is it, 20 years ago. She runs the study now and her monkeys lived longer. And they also definitely incontrovertible evidence that they had less cancer and I think heart disease, but definitely overall disease burden in these monkeys was lower and they lived slightly longer. But even if they didn't live longer, I would say still look at the data on the diseases. I mean, who wants to get cancer and heart disease in their 60s and 70s?

38:15Why would high calorie turnover increase your likelihood of cancer and heart disease? Well, there's a few different theories. The one that I like the best that's the simplest is that when your body is in a state of perceived adversity and running, building muscle, lifting weights, and hunger are signs of adversity. Also eating plants that are stressed is a sign to your body that your food might run out. This has put your body in adversity mode. And this enzyme that I mentioned earlier called SIRT1, which protects the epigenome, it responds to hunger and exercise. There's a molecule called NAD that a lot of your listeners and viewers would know about.

38:54this enzyme responds to NAD levels. But long story short is when you're in adversity mode, your body switches from growth and reproduction into survival mode. And at least if you do that for some of your day or some of your week, you'll get some protection against the ravages of aging, epigenetic changes, DNA damage, all of these things that we know contribute to aging. Do you think that there would be a marked difference between somebody who restricted their calories by 30 % over a year, let's say, and somebody who restricted their calories by 30 % with big breaks in food, calorie restriction versus calorie restriction through fasting, do you think that those two people would have different kinds of outcomes?

39:40So one is eating more than the other? No, they're both eating the same amount of calories. Let's say that somebody has 100 calories an hour for 18 hours of the day, and another person has one meal that's 1800 calories per day? There's a lot of evidence that eating within the time window is the one that's much healthier. The friend that I mentioned earlier, Rafael DeCabo down at the NIH here in the US, what he did, again in mice, but I think there's a lot of evidence that it would translate to humans. He gave mice roughly the same amount of calories, but he gave it to them all day and they had to gobble it all down quickly.

40:19It didn't matter what they were eating. It was different amounts of protein, carbohydrate, fat. He was hoping to find the optimal diet, but he found that the group that ate within that window lived substantially longer than the ones that ate continuously. I saw you quote tweet something about protein being overhyped, the protein maxing movement. What's your position on that? Yeah. Protein is good. I'm not against protein at all. I eat a lot of protein myself, actually, mostly from plants for reasons that I'll get to. But this die hard, be a carnivore, forget about the green stuff is definitely not consistent with the science of longevity.

41:01It's consistent with the science of bodybuilding. Which, of course, as we know, is a superior science to the science of longevity. Yeah. Well, as much as it doesn't look like it, I really like bodybuilding over other exercise. I'm just busy. I used to work out a lot. I love bodybuilding and protein is essential for building muscle, no question. And you can get a lot of protein from protein supplements and meat. where I think it's been overhyped is we know that plants are essential for providing polyphenols and having a lack of branched chain amino acids specifically is also very good for health.

41:40A lot of data on that, especially in animals, but some in humans. So branched chain amino acids, some people listening will know what they are. Valine, isoleucine, leucine, these are three of the 20 amino acids that are found in more abundance in animals than in plants. And when you give animals a lot of these branched-chain amino acids, they live shorter than if you give them less. And this has been shown in short-term studies in humans. If you restrict protein that has a lot of branched-chain amino acids in humans, they get better metabolically. But I'm not saying you can't eat meat or you can't eat protein.

42:14What I'm saying is just doing one or the other is not really the best way to live. I think the best way is to pulse it. Okay, so if you're working out, you want to build muscle, yeah, you can eat meat. I eat meat occasionally. It's not a problem. But you want to have a period of your life or let's say your day or your week where you're not eating meat or you're just not eating. And that puts your body at least part of the time in this adversity mode. Should you be doing both? Let's say that somebody's doing OMAD or 16-8 or some sort of fasting protocol, would you still be looking to pulse protein intake as well, separately to that?

42:55Yeah, yes. So you'd maybe go one day a week without protein as well? Well, without protein, I don't think you'll live, right? You need some protein, but you mean huge amounts of protein or you mean meat? No, I mean, like you're saying that there's time for you to focus on protein and then there's time not to. You should be fasting. I'm wondering whether you should be fasting from protein from a macronutrient standpoint as well, in your opinion. I don't think so. I don't try to fast from protein. I try to fast from a lot of calories. And I also try to fast from a lot of animal protein, which has these branched-chain amino acids.

43:31And we know the molecular mechanisms. There's mTOR, which anyone who follows longevity will know about this mTOR. And if you're eating a ton of meat every meal or every day, your mTOR is going to be active. And mTOR's role is to help cells divide, grow, build muscle. Great. That's what you want to do when you're young. You want to build muscle. You want to look good. You want to be strong. Even if you're older and you have sarcopenia, mTOR is good. But we know that animals that have active mTOR live shorter than those that have less active mTOR. So how do you get the benefits of both? Well, that's what I'm saying is have mTOR switch down, plant protein mainly, don't eat a lot.

44:12mTOR will help you when it's switched off, but you can rev it up when you want to build muscle or run a marathon or something like that. You don't always have to be in one state or the other. Okay. Talking about exercise, has your exercise philosophy changed? What is the best exercise protocol for longevity in your opinion? No, it hasn't changed a lot. I just keep seeing studies that say the same thing over and over again. And then people argue about the latest one. We know that the best health is a combination of weightlifting. Muscle is good for hormones. It's good for not breaking bones when you get older.

44:49Balance is important. And then the other one is aerobic VO2 max. We know VO2 max is correlated with very long life. And so you do need to lose your breath minimum three times a week, 10 minutes. It's rare that people talk about sex as a way to exercise. I see your eyes bulging. I'm just waiting to see where you're going to go. Well, I was looking at a tweet the other day at an ex, whatever we call him now. And it was saying, oh, I think I won't say who it was, but they said, oh, you can lose your breath 10 times for 10 minutes, three times a week by doing XYZ. And I thought, well, no one ever mentioned sex.

45:32So if you have an active sex life, count that as part of your daily longevity routine or your weekly longevity routine. Okay. But also… Sufficiently vigorous sex can be… If you can go for 10 minutes vigorously, that's a good start for longevity. There's sometimes restrictors for that that aren't simply cardiovascular, but go on. Well, you can supplement it with just running on a treadmill, going outside, rowing, sport, all of this stuff. The way to know if you're exercising enough to build up your VO2 max is you shouldn't be able to carry out a conversation easily like this. You're panting. That's my judge.

46:11I need to do a lot more of it. These days I tend to do a lot of my exercise aerobically running to catch a plane. I admit that I'm not the perfect role model for exercise. But I do know what the science says. And that is the combination of the weights, the balance, and the aerobics. Uh-huh. What about zone two? You haven't mentioned low and slow. Well, if you can't do fast and quick and hit, low and slow is fine. Walk, move, get up. I'm always walking around my office. I have a standing desk. I rarely sit down. So that kind of exercise is very good, certainly for balance, overall metabolism. So yeah, I try not to sit at all.

46:55I'm sitting now, but I rarely sit during the day. It's one of the things people find weird about me. They come to my office and I'm pacing, I'm twitching, I'm often chewing gum. That's not the same as zone two though, right? No, no. You need to do a little bit more than that. What I like to do is a sport. You know, tennis could get you there. I do a lot of gardening, so I'm carrying stuff. Gardening is a sport? Yeah, that's my sport actually. It's my big hobby. Interesting. Lifting a lot of heavy plants and building walls and hammering and drilling and all that stuff. Yeah, a little bit, you know, kayaking is something that I like is good.

47:35I'm not out of breath, but I'm getting a good workout. Sleep and recovery and rest. What is the most up-to-date data saying around that from longevity? It's still the same. You do need to watch your sleep. If you're not getting quality sleep or sleeping for that long, it's going to affect your metabolism. Figure out how much sleep your body needs at a minimum. You can do that using some of these rings. It's very good for that. Some people need eight hours. Some people need seven hours. Typically, if you're younger, you need more. The good thing about getting older is you need less typically. But it's also about quality.

48:12I can get away with five hours sleep and my HRV is still in the 80s, 90s because I'm getting deep sleep. I'm not drinking caffeine late in the afternoon. I practice as best I can relaxation, meditation practices, breathing and that gets me to sleep and into REM and deep sleep pretty quickly I also take a supplement that my partner Serena makes and it's got L-theanine and some other stuff that also I know from my own experiments gets me into deep sleep quickly and so my efficiency is typically according to these rings in the 90s, 90 % sometimes close to 100 and then I can get away with less, which is nice because I travel a lot.

48:55I think that's the big learning that everybody who starts using a wearable takes away from it, which is you're sleeping way less than you think you are. Like, well, you know, I was in bed for eight hours. It's like, no, you thought that you went to bed at 11, but it was actually sort of 1130 and you were reading or watching TV until nearly 12. And then your actual efficiency was maybe 85 % so that seven hours has turned into 545 or six or something. And yeah, it's stark. I've got maybe 1 ,500, maybe 2 ,000 nights on Woot tracked over the years. And you're just always sleeping less than you think you are.

49:33If you don't have money to buy a wearable, just the rule is you're sleeping less than you think you are. That's it. Yeah, I agree. And especially if you're you're eating late drinking coffee or tea late uh or matcha caffeine and alcohol are big ones for bad sleep um not just stress having a hot room or too many blankets is another mistake that a lot of people make um you can get those beds that cool eight sleep eight sleep is anyone that's not using an eight sleep it's medieval i understand they're expensive but there's no one that i've got to do yeah they're a partner on the show or whatever but like this has got nothing to do with it every single person that I've got to try it can't believe that what life was like before they had a cooled.

50:16And there's other cheaper versions out there, I'm sure. Eight sleep's the best, but there's other ones that you can get. Trying to cool your bed from outside of your bed when the job of your bed is to keep the temperature in the bed the same is kind of a little bit like fighting against the tide. Yeah. Oh, exactly. And you should wake up every morning feeling totally rested, excited about the day. If you're waking up and like, oh, I need a coffee. Oh, I need a shower. You're probably not getting the sleep that you need. You mentioned stress as well as kind of the fourth pillar when it comes to lifestyle.

50:48What does that look like? How do you come to think about stress as a longevity doctor? Yeah, well, you can measure cortisol, for example, or DHEA cortisol levels. we're all stressed you know the the old days of sitting around a campfire not really there anymore we're driving to work we're worried about income and so what we want to do is uh learn to to deal with the daily stress you know the world is changing faster than ever so what what i've learned personally is really not to let worries of life get me down i try not to focus on them. I have a happy place, which is an orchard on Cape Cod. And my mind, when it's stressing out and I feel my body tense up, I take myself there.

51:38I breathe. I'm amongst the trees. If it gets really bad, I go there physically and do some work. But yeah, it's all about learning not to ruminate. And a lot of us A-types, I'm sure you in your success are like that. What did I do wrong? I could do that better. I'm worried about tomorrow. I'm worried about next week. I'm worried about 10 years. Don't do that. It took me 50 years of my life to figure out don't do that and how not to do that. How do you stop worrying? You have to train yourself. It's like, don't be an idiot. Stop thinking about it. It's not going to kill you if you distract yourself with something else.

52:17Overthinking something is a real issue for modern life. So I don't do that anymore. If I find myself overthinking, I'll just say, I'll think about it later, put it off to the side. And I used to be the kind of guy that I had to text back immediately and email back immediately, put it aside, I'll get to it. I think a lot of people are riven by the overthinking intrusions, that they just can't get their brain to focus on what's in front of them. There's always this concern, there's always this situation that could be a little bit worse, this thing that could make life a little bit harder that's coming down next.

52:55And yeah, you're kind of being puppeted by these ghosts of the future that haven't yet come about. Yeah, that's the thing. What you realize when you get to my age, I'm now 57, is that it's never as bad as you think. And what I do now is I depend on myself. I know that these big problems in my life, and I've had big ones, deaths and issues, is you get through it, you trust yourself, you know. Maybe when you're a teenager in your 20s, you don't know that you can get through these things. I'm at an age where I know I'm not gonna die. I'm gonna get through it. It's gonna be okay. If I have a problem, I'll solve it.

53:36The sooner you can realize that, that you are capable of anything, if you put your mind to it, then you shouldn't stress about problems that come up. Tell me if this sounds familiar. You train regularly, you eat reasonably well, you feel fine, but you're just kind of going off vibes. Most people have absolutely no idea what's going on inside their body, and that is why I partnered with Function. Function gives you access to more than 160 advanced lab tests spanning hormones, heart health, kidney function, and even detects early signals linked to more than 50 types of cancer. To put that in perspective, your typical annual physical might test 20 markers.

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54:42Okay, let's talk about your current drugs stack. What are you taking? How's your daily stack changed versus what you were doing when you wrote the book? It hasn't changed. That's the amazing thing. I thought I'd have to change things depending on the science, but the science has held up. So in the morning, and if you go to page, what is it, 304 of Lifespan, it's still there. And I still do that. Risvertrol. It's been back and forth, controversial. It's not controversial in scientific circles. There's a few naysayers, but they make a living out of it. resveratrol is from plants that are stressed and they activate SIRT1, this resetter of and slower of the epigenome noise.

55:23So I've been taking about a teaspoon, call it a gram of resveratrol every morning, almost every morning for the last, gee, probably 20 years. Doing all right. It seems to help in clinical trials. It's been tested in a number of clinical trials. I mix it with either a little bit of olive oil, that's my calories, or Greek yogurt or vegan yogurt. And it's been good to me. I also take that with NMN, which is an NAD supplement. It's a precursor. We studied both in my lab. And we just resubmitted a paper. This is something I can reveal. We just resubmitted a paper to be published that showed that NMN is very good for the health of old mice and can extend the lifespan of mice, particularly females.

56:13And so that'll come out probably. Resubmitted. Yeah. We had reviewers' comments, criticisms, spent another year working on it to please them and send it back. We'll see what they say. What was the controversy? Because I know since the last time we spoke, there's been some furor around resveratrol, some morpho around NAD, maybe NMN as well. Can you explain what happened? Yeah, sure. These are all typhoons in a teacup or whatever it is. I can't stop drinking your drink. It's very good. Good. That's all I needed. So let's start with resveratrol. I try not to bore everybody. SIRT1 is an enzyme. I'll use my hands.

56:54It's an enzyme that carries out reactions that stabilizes the epigenome so it doesn't decay. So think of it as stopping the corruption of the software, more SIRT1 is better. So there are two ways to activate SIRT1 with a pill rather than exercise and dieting. And if you do all of them, I think it's the best. So you can either take resveratrol and that we showed in 2003, long time ago, I'm old, activate SIRT1 directly. So the enzyme is removing chemicals from the epigenome and making it stable. And it can do it slowly you know what a pac-man is you're old enough uh so it's chewing away uh chemicals stabilizing things faster the better whereas virtual we know binds physically to the enzyme and now makes it chomp faster okay the controversy that came up was that pfizer a team at pfizer not the whole company just a group in the company put out a paper in 2010 that said resveratrol doesn't do this.

57:56It must be an artifact that's doing something else that makes it look like this. So we then spent three years testing that and found exactly how it works to the atomic level. We could even block it by changing an amino acid in this protein. And we actually have a study now that we've made a mouse that has this block and resveratrol doesn't make the mouse healthier anymore. It doesn't live longer. So that's as good as evidence that you could get that we were right in the first place and Pfizer was wrong. And we've put out papers since and others have shown that we were right. So no controversy.

58:32Going head to head with Pfizer is no small task. It was brutal. That was one of the hardest things in my life because I remember trying to defend myself in public. It was on NBC. And I said, I'm not sure what Pfizer is doing, but our chemicals don't kill mice and they activate the enzyme. And the comments were brutal. Sinclair thinks he's better than Pfizer if Pfizer knows what they're doing. I will say that I don't have ill will towards those scientists because it's the job of scientists to challenge theories. What I do have a problem with is the people who still say it's wrong and are trying just to get at me.

59:14What's the remnant? If you've put something out which pushes back against Pfizer, what is the remnant argument? There isn't one. The problem is that what I've gotten to see in my career over 30 years is the media loves the negative story, but the redemption story isn't as popular. So it's never come out in these journals like Nature. They put out the negative story, but they never did the, oh, that was wrong. So it's just a matter of reporting. But in scientific circles, everyone's read our science paper from 2013, and it's not debated. That's put into rest, that the evidence is put to rest, in your opinion.

59:55Yeah, it's at the atomic level. Unless you want to complain about atomic theory, you know, we're done here. Okay, and what happened with NAD, NMN? So yeah, let's bring everyone up to speed on what NAD is. So SIRT1 also can be activated by giving it fuel, which is NAD. SIRT1 chomps with NAD. And in fact, this is not often known. The chemical that it takes off the epigenome structures is donated to NAD. So without NAD, you can't take the chemicals off. And more levels of NAD make it work faster and better. And if you give it to cells, you see more stable and healthier cells. there was dogma that nad levels went down with aging and that boosting it back up was healthy so the second part is true we have shown in cells in animals and even in humans for the last and by we i mean the field not just my lab that raising nad levels above normal baseline is very good for humans.

1:01:00Okay. I can give you examples. Shelley Basin, you could look up in PubMed. He's got a couple of really good papers giving NMN, which is the precursor to NAD to people that are either obese or have pre-diabetes or even super fit ones. Maybe the super fit isn't published yet, but he's done the work and reported about it. You see improvements from lipids, whole bunch of lipids, cholesterol, blood pressure, body weight. So raising NAD, I think most people would say that it's good for humans and animals. And again, we're going to publish that it's good for longevity too. Where the debate that came up, I think you're talking about the one that was maybe a few months ago.

1:01:44Somebody showed that human blood levels in white blood cells, the white blood cells don't have less NAD as you get older. So some people who love to make a living of being naysayers, especially towards my career, jumped on that and said, the whole theory is wrong. If white blood cell NAD levels don't go down with aging, then the whole theory must be incorrect, which is, as you can tell, is complete BS. In fact, we've known for probably a decade that that was true. And it doesn't affect the theory. We know that raising NAD levels in humans, either by exercise or by supplementation is good for you.

1:02:21So it was crazy to say the whole theory fell apart. It was just a way to get clicks, I think. What's the status? I'd looked at something to do with it was a pharmaceutical, then it was a supplement, and now I don't know what the level of access is with NAD and stuff at the moment. How's that classified? Yeah. Just a final thought. There is a really good study that showed that people who have lower levels of NAD in their muscle um i think it was not as metabolically active as those that have higher levels and or they had metabolic syndrome anyway we could check it out but but there is some good correlations between nad levels and age-related conditions want to be accurate all right so the FDA thing.

1:03:08And basically, it was that there's a rule in the US that if any molecule, whether it's natural or synthetic, goes into a human clinical trial, before it's on the market, people can't put it on the market because then it negates the reason to do a clinical trial. And we need clinical trials to know if things work. makes sense the law makes sense where things got crazy was a company that i started called metro biotech started a clinical trial with nmn and a little later people started putting nmn on the market and i've always said publicly you can read it fine let's do both let's do the clinical trials make a drug it's going to be pure it's going to be tested and there'll be supplements that are less rigorously produced for people that are not sick but for the sick ones who have diabetes or need a drug, we'll have that.

1:03:58Happy world. The legal team at Metro Biotech made a decision without my approval, actually with my disapproval, to write a letter to the FDA pointing out that there was this law that they shouldn't have simultaneously sales and clinical trials. i objected um the fda uh initially said you shouldn't be selling uh nmn on the market in the u.s according to that law though they didn't enforce it and then it was recently reversed so now it is enforced it no i mean the opposite the fda i believe says it's okay to have nmn on sale now interesting okay there was a court case uh that i think resolved that are you still taking the baby aspirin?

1:04:51Yeah, I am. That's controversial too. One baby aspirin a day? Yeah, the 81 milligrams, though 81 is only because a trial did 81. It's not magical. Brilliant. But yeah, you could take 100 probably. But talk to your doctor. Do you want to talk about aspirin in detail? Sure. The reason for the controversy is if you dig into it, and I do this because it's my a living, most people don't have time. The American Medical Association weighed the risk of having stomach bleeding and other complications versus lowering the amount of risk of cardiovascular events and came to the conclusion that looking across everybody, it doesn't make sense.

1:05:36But I'm totally against the word everybody when it comes to health. Everybody's different. so I believe in precision medicine and there's a group of people for example that where it does make sense to take baby aspirin it's been shown that there can be benefits and it's those people just as an example who have high levels of lipoprotein A or LP little a I'm one of them so I continue to take baby aspirin but these are decisions to make with your physician What else? I can't work out whether we call resveratrol a supplement or a drug or a pharmaceutical. I'm sure you can get it in pharma grade, but what else from the not foods consumption stack are you taking?

1:06:23Aspirin would definitely be in the sort of meds category, I suppose. What have we missed off? Well, there's whole websites devoted to what people think I take every morning. Okay. Set the record straight. What is it you're taking? Well, that I'll have to come back for another show or people can listen to my podcast. Because it's a whole box of things and I'm not taking them all the same day. But I still like alpha lipoic acid for mitochondrial health. So I've been taking that for over a decade now. I did a PhD on it, so I know a little bit about its benefits. But that was a long time ago. Let's see, CoQ10, of course, because I'm actually on a statin.

1:07:03I might switch to a PCSK9 inhibitor because it's more effective, but my family is very high cholesterol. I'm on Repatha. Great. You like it? uh i've actually stopped taking rapatha because i want to see if it's causing some brain fog oh that is sometimes associated anecdotal uh but i noticed apob went through the floor fucking brilliant brought everything back in line isn't that lovely yeah brain stopped working quite in the way that i wanted it to okay well let's see what happens if i take a little bit of a break and let's see if brain comes back in line with where I want. But I found Repatha largely.

1:07:42I've got the every two weeks one rather than the monthly. And that's been good. But I've also been taking Talmasatin as well because I've got, I didn't realize this until, I guess I've done a lot of health discovery since the last time that we sat down. I have every polymorphism under the sun for somebody that's going to have high cholesterol and high blood pressure. They're just a really perfect suite of hyperabsorber, hyperretainer, all of the dispositions that you want. Are you on Zetia? No. What's that? That's the common name. I thought I'd use it. It is the drug that blocks uptake of cholesterol.

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1:09:27And modern wisdom at checkout. I did carnivore toward the back end of 2024, meat and fruit, technically, for six, nine months or so when I was recovering from living in a house with toxic mold. It was really brutal, but I actually felt phenomenal. Looked great, shredded, jacked in the gym. Energy was good. Little on edge, like a little adrenaline-y all the time, but that's maybe to be expected, without any starch or carbs to sort of really bring you into land. And I managed to get my cholesterol up into the 400s. 400s? Yep. Yeah, it was really impressive. It was kind of like a personal, only briefly.

1:10:04You had creamy blood. And then brought it back down. But it's kind of what I've come to, you're right to say that everybody is different. Everybody body has a different system. And the fascinating thing when you do these sorts of playing around with self-experimentation and intervention is you find out there's something that can make you feel amazing, make you look amazing. It's like in all of the subjective metrics that I care about, shit's going great, except for the one that might kill me pretty quick. And then I went and did a clearly scan, which is fucking unbelievable technology, by the way, basically this special type of contrast scan is able to look inside of the arteries of your heart and look at plaque buildup without having to do anything invasive.

1:10:55It's magic. And I'd had a small, very small, but mild amount of plaque progression. Okay, I need to put the kibosh on this, regardless of how jacked and alert I feel, I need to eat a much more sort of Mediterranean, low-fat, low-protein diet. Yeah. And I know it's not proven, but I do like the idea of plaque reversal. So there's two ways that we know of that might do it. One is reducing your LDL so low that it reverses. So Repatha, that kind of drug. There's an oral PCSK9 inhibitor that has come on the market, which I've got a prescription for. I'll try it out. That's one way. And then the second one was based on a study that had a thousand people in China.

1:11:43I know it's not the perfect study, but to me, it looks like it might be true. And given that this substance is so safe, the downside is, cost me a few bucks, natto kinase. Do you know about natto kinase? No, what's that? So do you know what natto is? It's natural? No, you're lucky. Anyone who's been to Japan probably has seen at breakfast in the hotels, They serve this goopy bean sticky substance that if you lift it up, it looks like cobwebs. Okay. And it smells like vomit. Okay. So Serena eats this stuff. I don't know how she does it. I have to hold my nose. That stuff, it's bacillus subtilis and smother bacteria eating soybeans.

1:12:27They found that there's an enzyme in that stuff that if you swallow it, it can remove, well, at least it looks like it can remove plaque. Hence natokinase. Kinase is the enzyme. Nanto is the food. And so I swallow, depending on the day, about 10 ,000 units of this stuff every morning. And I'm going to - Some sort of capsule? Yes, just a capsule. You swallow it in the morning. And I'm going to measure it. I typically do an ultrasound on my carotid every year. Similar, it's like the clearly, it's just on your neck. And you can actually do your intermediate thickness, which is important. Tell your doctor if they do that.

1:13:10Tell me my IMT. And that is a number that will tell you very similarly how you're doing cardiovascularly for your whole body. And I'm going to see if netokinase makes a difference. Fascinating. What's all this hype around erectile dysfunction medication?

1:13:26That's a lead in question. Well, yes, it's recently come into social media because it was found that these ED drugs are also good for some types of cancer and can change the immune system so that it goes from protecting the cancer to killing it. And I tweeted out what's not to love and millions of people saw that. But I'm serious. I take, what is it? Cialis is the common name to Dallafil every morning, a low dose. it's just a little bit and I do that because in 2012 we published a paper that showed that one of the most pernicious causes of aging is low blood flow and we could reverse that with NMN through SIRT1 more blood flow and it's really underappreciated how much a lack of blood flow leads to diseases, especially your muscles and your brain.

1:14:30And so I take this low dose in the hopes and expectation that if I get dementia, it will be a decade later. And now add on that cancer killing, it's an amazing drug. And it was actually not even developed initially for these. It was an angina medication. Exactly. Do you know the story of why they realized it had that side effect um was it was it pulmonary they when when they were doing the the trial typically you do a meds trial and patients come back into the lab and you ask them to give the drugs back and nobody has an issue but none of the guys wanted to give the drugs back anymore and the nurses noticed that the uh patients when they were doing their interviews were sitting cross-legged and they had this strange contorting of the posture to try and hide the fact that they all had hard-ons.

1:15:23And they said, hey, the angina thing we're not so sure about, but we've done some wonderful stuff to the penis. Well, I can say taking a low dose, the good news is it doesn't make your penis get erect without warning. That isn't a problem. But the low dose really, let's put it this way, I haven't had any downsides yet. Fantastic. There's one other thing, Chris, I want to say, which before I forget in my old age and my lack of blood flow is, so there's a study in mice at least that hints that lack of blood flow to hair follicles is a reason that you lose hair. And so my hope scientifically is that continuing to get blood flow in my hair follicles will keep my hair.

1:16:06More hard-ons, less balding. That's the equation. Yeah. I don't know which one I'd choose if I had one. That's true. I guess a lot of guys don't have that choice. Huberman had said something to do with the perfusion of the prostate as well, that opening up blood flow, especially given how close you are to ground zero, might be a useful side effect. I don't know, man. I said my favorite conspiracy theory about this. I hope that it's working. I hope that it's pretty much all gains intervention. that everybody can use. But my favorite conspiracy theory about why erectile dysfunction medication is being pushed so hard is that it reduces any of the stigma of any one guy having to take it.

1:16:50So darling, I've got to take it. It's important for my hair. Dr. David Sinclair told me that it would stop me from going bald. And also, you know, a great grandma, she had Alzheimer's. It's very important for my neurodegeneration. You don't want the prostate. You know, granddad, he had the prostate thing. So the ED, you don't need to worry about that. It's normalizing ED medication. A lot. I think you're 100 % right. And I'm sure there have been some wives like, honey, why are you eating 10 of them? Yeah. What about omega-3s? Omega-3 is commonly touted as something that's very important for people's longevity.

1:17:24Where do you come into land on omega-3 levels and supplementation? I take an omega-3. The data looks really pretty good that if you have some of that, it's anti-inflammatory whether or not it totally prevents heart disease it's controversial now but have you got a brand that you prefer

1:17:45yeah but i won't say it okay i'll tell you what i use nordic naturals 2x are the best um i do like i do like them yep um their products are really pure and distilled so you want to avoid the cadmium and lead products the what what the ones that have heavy metals okay so i i mean i remember this. My mom would tell me this 25 years ago when I was a kid and she would be taking, and there would always be this line of low quality cod liver oil back in the day, low quality omega-3 supplements aren't really that good for you. So this is like, you know, mythological fucking ancient wisdom. It really is.

1:18:25And actually, while we're on the topic of contamination. I and other labs have measured supplements and they're often contaminated with things. And I even got sucked into a lawsuit because I said, I tested this product or this type of product and it had contamination. But I do want to say at the risk of some litigious activity against me that nmn and these nad precursors can have contaminants in them now i don't sell i don't market anything i don't get any money despite people using my name and even video across the internet so i have nothing to gain or really lose by this well i've got a lot to lose but nothing to gain nmn can have things like well first of all i think the study that was published it's worth looking at by Andrea Meyer.

1:19:18She's out of Singapore. She found that a lot of the NMN supplements didn't have NMN in it. And if they did, it was a low amount. And we found in my lab, which I don't think is in Andrea's paper, is that there is endotoxin in NMN bulk and supplements. Endotoxin comes from bacteria, causes inflammation. It's part of the purification process, but they don't get rid of it. And we found out the hard way we were feeding it to mice to make them a little longer, which is not going to work if it's contaminated. Hang on, so even the NMN that you were using in your lab that you thought was pure was so contaminated that it was infecting the study participants?

1:19:54100%. Wow. So we've had to really work hard with manufacturers to get it really pure. How hard do people need to work? If somebody's taking an NMN supplement now, is there anywhere that a normal person can go that's not going to risk being contaminated? Well, if I ever mention a brand, it'll blow up the internet, might bring it down. But I will say that to help the viewers and the listeners of this show, I would go for a company that has a strong reputation, that provides the analytics. So sometimes they give the spec sheet and you can see the purity. And some companies, they've got such a big reputation, they're not going to risk adulterating it or putting something else in it or giving you less.

1:20:44GMP is important always. Any supplement should be good manufacturing practices, USB label. Look for those badges of purity. And if your company that you like doesn't share the analytics online, you can write to them and say, can you please share that batch? And they often do that. They're not cheap interventions for people. And if you're spending a lot of money on something, you want to make sure that it's actually... The worst thing is, I'm taking this thing that I think is going to make me more healthy, and it's actually making me sick. That's the real problem. And I'm going to do a shameless plug, if that's okay.

1:21:18I'm launching a community, a website community, for us to figure this stuff out together. I'll be testing products. We'll learn what works together. and I hope that it becomes the world's largest longevity community. What's the community built around? What is it? Yeah, it's called lifespan.com. So my show is Lifespan. This is the website version. My goal ultimately is to fix healthcare across the planet. We've done a top-down government, big industry, HMO. We know that doesn't work. The US especially is spending close to 20 % of GDP on their healthcare and got some of the worst healthcare. So you've got to do something.

1:22:00So grassroots movement, lifespan.com will be a community that comes together to learn what works, what doesn't. And eventually where I want to take this is that we change how healthcare is done and with AI, with knowledge, we're also funding medical research and testing of brands. So we know what's pure and we'll find new medicines together. I want to share in the profits of that with all of the members. So that's being launched soon. That's cool. It's probably launched by now. There's for members, so there's an unpaid version. You can do show notes and you can see some stuff. But if you pay the$8 a month, we've pulled together something really interesting.

1:22:47We've got this community that we've built, but also there's information that will basically complement what we've been talking about today. There's a magazine, world's first magazine, well-written by people who are doing the research. So you don't have to rely on some newspaper or reporter who doesn't know anything who also wants clickbait. I actually brought a copy of this magazine. I had it printed in hard copy just for you. Oh, let's get it. I want to see. You haven't seen it. This has been hidden here. This is Lifespan magazine, first one I've given out to anyone. And this is a gorgeous magazine that every member gets online.

1:23:27What if aging isn't damage but lost information, a radical idea now entering human trials? That's the paper from Nature that I thought I'd give you as well in 2020 that changed everything. This is so cool. Thank you. Have a look inside. I'm so proud of how it looks now. this is going to be coming out every month and it's got about 100 pages of the real science the real stories of what it's like and what we're learning before it even comes out in journals and in the media oh this is cool inside it's very beautifully put together beyond your birthday steve horvath on the science of epigenetic aging i know steve horvath yeah yeah steve discovered the epigenetic clock the simple multivitamin mineral supplement slow down aging.

1:24:12This is awesome. Congratulations. Thank you. I'm very proud of the team. It's a small but mighty team that we're really driven by mission. We want to change the world and we want everyone to join us in it. Unreal. Okay. Other interventions, other stuff that's happened. Because since we first sat down, the world of longevity, biohacking has really sort of, it's not exploded. I think it's become more sophisticated. You may say otherwise, the evidence may say otherwise but at least from the like self-experimentation uh you know 2017 18 19 it was a lot of the biohackers handbook it was you know ben greenfield's friend of the show sticking ultrasound things on his penis to see if he can improve his his erection quality and his orgasm length and stuff and then it seems like it's really come on data backed a lot more um evidence-based crowd stepping into this well thank you to you for example uh guys like you are bringing scientists like me and people who know what they're talking about so that people can hear it from the horse's mouth whereas before it was just somebody hyping and selling stuff which you couldn't trust it's true i mean what's been interesting has been to see at least in in Greenfield's case, like how right he was about tons of stuff super early on.

1:25:36Yeah, though I didn't mean to imply Ben was one of those people. But there's so many people. Even Timu Arena, was it, that wrote the Biohackers Handbook? It's his coffee table book. I've still got my house in Newcastle. Now look at some of that, and it's the same as the bodybuilder thing. So many bodybuilders stumbled onto a particular way to look at health or dieting or whatever, that a decade later, science then comes back around and says, hey, that's the way. But then also there are a lot of people that throw shit at the wall and much of it doesn't stick. One of the most popular interventions that people are talking about, contrast therapy, sauna and ice baths.

1:26:14What does the evidence say around cold and heat exposure for longevity? Increasingly, we're learning. In 2019, when you and I first met, there was very little evidence, actually. And you're right, biohacking was something that was looked down upon, especially by doctors, and the public didn't know what was going on. Then came the pandemic, and most people saw their mortality, and it's like, what are we going to do? And it's amazing to see what's happened since, that it's become mainstream, and even doctors have had to learn about this because their patients are coming to them with more knowledge than they have, especially with AI now.

1:26:53But we are in a world now where the individual can know more about a certain topic than their own physician, which is incredible. That does include sauna and cold bouts. When we met in 2019, there was a little bit of data in saunas and nothing on cold bouts except a mouse dunked in the cold. Now there's much better evidence. I put it in my book, Lifespan, because I was told by the editor that that would be interesting. but I was hesitant because there was such little data on saunas and nothing on ice baths really. That's different now. I can now say as a scientist, scout sauner, I was a scout, I forget how we do it, that definitely sauna, there's a lot of evidence, mostly Nordic men have been studied, less women.

1:27:41But if you do regular, what they call sauna bathing in Finland a few times a week, your rate of heart disease can be much less, and that is reproducible. So that, I think saunas are great. I try to do some of that myself, as hot as I can bear. Ice baths contrast, it makes sense scientifically, hasn't really been studied. But cold therapy, we do know it can activate brown fat, which is very good. What does that mean? Well, so we actually, going back in history 30 years ago, we didn't know that we adults, humans, had brown fat. Babies have brown fat. It's a highly metabolically active type of fat in babies that keeps them warm because they can't shiver initially.

1:28:29And then using PET scanning, people at Harvard, some friends of mine discovered that adults can have brown fat on their own bodies as adults. Often they're in the back. you can get it, more brown fat, by doing cold plunges and being cold. Do you want more brown fat? Yes. I was going to say the brown fat's full of mitochondria, which are healthy. Brown fat seems to secrete factors that are good for health. But yes, people that have more brown fat tend to have better metabolism in general, and they also burn more energy, which is good in today's world where there's too much food around. So yeah, in general, yes, brown fat is considered very healthy.

1:29:15But the older you get, the harder it is to make and convert from white to brown or beige. And so my view on that is, and that's true for mice, I'm not sure it's true for people, but let's say it is. I still believe that the earlier you start to build up your brown fat reserves, the better. Because by the time you're in your 80s, it's hard. Cold exposure is a good way to do that. Exactly, right. I don't know if it's true, but I like to experiment with sleeping a little cooler. And as I wrote and have said a few times, turn down the temperature, don't sleep with a lot of blankets. We've already talked about eight sleep beds.

1:29:54That is a way probably to burn more heat, more energy. But it might help if you're feeling cold during the night, build up brown fat. That is a might. You will get more brown fat if you cold plunge. and do those kind of things, roll around in the snow. It is controversial, though. I did see a little bit of pushback against Wim Hof and what he was saying. It may not be as spectacular as what he's claiming. The evidence for heat seems to definitely be stronger than the evidence for cold. Like 10 to 1, 20 to 1, something like that. Yeah, and it's strange because the immediacy of the reward, if anyone's had a cold shower or used a cold plunge, you feel really good.

1:30:35As long as you stay in for a little bit, you feel so good afterward but i'm i like to do it it's fun or whatever but i would probably take a sauna 20 times over taking a cold plunge if i'm gonna try and do something for my health i'm the same i do a hot every every day including a steam shower but i cold plunge probably once every two weeks at best by by turning on the cold tap what you make of brian johnson's approach to longevity? Well, it's totally different. Putting the two of us side by sides, some people do. It's not the same animal. I'm doing science. I'm doing the research. I'm figuring out the molecular mechanisms.

1:31:18He's a compliment to that. He is self-experimenting. It's not a clinical trial, obviously. He will admit that. But where I think Brian shines is in a couple of areas. He's very courageous. I like that he stuck his neck out. I have a lot of admiration for those people who are brave that way. He's also been helpful bringing a spotlight to the field of longevity. And I remember a lot of my colleagues, my highbrow colleagues in longevity, really said he's the worst thing that's happened to us, to this field. He brings a bad name to longevity. but I disagree. I think that we as a field of scientists had a marketing problem.

1:32:04As much as we talked about longevity, it wasn't getting through. Up until 2020, almost nobody had used this word even. Brian came along. I came along, but definitely Brian got a lot of attention. And I think it's been helpful to wake people up from their stupor. Not everybody, but a lot of people just live their lives and eat whatever they want, do a little bit of exercise. Brian said, we can be much better about this. We can science the heck out of this. And I love that approach. And so I think it's complimentary. I'm saying, let's do real science, clinical trials, molecular, but also with an N of one, doing pre-treatment, post-treatment, see what happens under doctor supervision, we can learn some things too.

1:32:55Yeah, I think Brian deserves a lot of credit for that, for bringing attention to what's possible. You've got a highly unsexy field. I'm not saying Brian Johnson's sexiest guy on the planet, but he's definitely made an existingly unsexy field at least a little bit more sexy. Knowing what you know about his approach to the fundamentals for longevity, have you got any smell test or sort of lick your finger to work out where the wind is coming from where you think oh he might really be on to something there is there something that he might be out ahead of where the the data or the research or the science is at the moment

1:33:36um not really i i i don't pay as much attention to him as i probably uh should or could um i do look at some of the blood work that he posts. And there's a particular test that's called the Dunedin pace of aging, which is a measurement of your epigenome changing. So Steve in the magazine, Steve Horvath discovered the epigenetic clock. For those of you who don't know what that is, it's chemicals on the DNA that change with time. These are like the scratches on the CD or the software corruption. You can measure that. You can do it before and after, or you take it every three months or every year.

1:34:19And Brian has published publicly his results. And you can determine what is representative of your pace of aging. And his was, I recall, something like 0.4 something. And one would be you're aging one year for every year. And if you're two, you're doubling your rate of aging. So you're going to die early. According to that, that's one of the lowest paces of aging I've ever seen for a human. So that's pretty impressive. if that's maintained he could live decades longer than the average he's supposed to then he would if he didn't take care of himself is that taking into account telomeres or no with that dunedin pace of age no it's not no i don't believe so it's just uh looking at the what's called dna methylation pattern on the dna what do you think are the biggest wastes of money that people spend on longevity?

1:35:14Oh, well, the overdosing of vitamins, particularly B vitamins. I think that if you're on a vegan diet, yeah, you should make sure you're not deficient in any B vitamins. Generally, if you're taking a lot of multi, what do you call it? Multivitamins. It's excessive and it can actually be toxic if you have too much. So vitamin C, can be pro-oxidation, not antioxidant, if you take a lot continuously. So overall, I'm not for multivitamins. I do believe you should measure your vitamin in your blood. And if you're deficient, you should make sure you're not deficient. But overdosing on vitamins, especially B, you could do IV.

1:36:02Some people do that. I think, yeah you'll get a short-term hit but i i nibble on my b vitamins i don't take the whole thing i tried again the self-experimentation over the last couple of years recovering from this this mold complex illness stuff has been interesting to say the least and the start of last year one of the potential culprits for why i was feeling so shitty was methylation so did a bunch of genetic testing came back i've got four different polymorphisms that make me suck at b vitamins, like one in the blood, one in the brain, one in the methylation, and one in the something else. One of the potential put forward explanations was, well, your mean collicular volume, your MCV is high.

1:36:43It's like just like 101 or whatever, which is just above the upper range. Oh, well, maybe this is something to do with Bs. I was like, okay, well, I'll try some intramuscular methylated B12, like 500 micrograms, a tiny, tiny, tiny, tiny little, it's almost like got to put a huge needle in your leg to put this teeny tiny amount of B vitamins in. I didn't realize that you can get something if you push it too far called B12 induced confusion. So you can actually just make yourself confused and your brain gets very slippery, given that this was the thing that I was trying to push back against. What I'm saying is I know what happens when you push B vitamins too far.

1:37:19And I actually did that the week. It was the biggest week of the show last year where I had Rogan. I was on Rogan on the Thursday and then recorded with the Naval Ravikant on the Saturday. And I went into it going, I've like poisoned myself with fucking B vitamins and now I can't think straight. It was fine. It all ended up being great in any case. But yeah, okay. So spending too much money on vitamins, multivitamins is one of the biggest wastes. What else? Well, at the risk of being sued, I would say - There's a big queue. I'm not sure about, again, I'm not saying it's wrong. I'm just not sure about certain laser therapy um serena my partner loves shooting lasers at her body but i for skincare uh internal as well how do you shoot a laser internally well which which hole does it go in yeah well it it shines on your skin back and forth so i don't know if that is doing anything i'd like to see some data on that is that like red light stuff it's red light but it's different colors and wavelengths Oh, yes.

1:38:23Yeah, I've seen those things, those huge big panels that people can stand in front of. Well, the red light is not crazy, so certain infrared. I've got near-infrared panels. I have that actually, I shine that in the shower sometimes. And the science is coming around to confirming some benefits there, so I think that's fine. And the red light saunas, I'm going to get one and see how that goes. But the yellow lights and the others? Yeah, these other things, it looks like. It's 4th of July in the house, but I'm not sure about that one.

1:38:57But, you know, you've got to be careful what you say is BS now turns out to be true. This is where the biohackers get it right, dude. This is where the biohackers get it right. Yeah, even peptides, you know, now we're seeing a lot of them are actually really helpful. Talk to me about GLPs, because, you know, this has been, this wouldn't have even been a discussion. Right? Three letters that I'd never have even heard put together the last time that we sat down 2021, and certainly not in 2019. What's your opinion on GLPs? In general, I'm very favorable. The number of studies that come out are showing that they're actually quite useful, especially microdosing for healthy people.

1:39:38If you're obese, it's almost a must. Go talk to your doctor. I think if you can't lose weight alone, please consider using these. I think obesity is the fastest way to an early grave. It certainly ages you faster. But if you're like you and you're already close to optimal, are they useful? I think so. There are off-target things besides obesity and metabolism that seem to be important, brain health, immune system. New things are cropping up all the time. It's as close to a longevity drug as we probably have right now, given what we're seeing. yeah it's still early days because we need to do long term and there are some downsides there is increased risk of but low uh risk of kidney issues and even blindness um don't panic it's it doesn't happen very often so it's still really rare but there it's not perfectly safe so i just want to make sure people know that it's not like going out injecting uh candy into you or anything um but i do think that and i have taken chilpy ones um small doses to see how i would feel what would happen i definitely didn't have hunger that was obviously what would happen and i lost weight more easily um i didn't take it long enough to be able to tell if other things were benefited it looks like uh there's protection against uh dementia from those who are on the weight loss drugs.

1:41:08And this is from a mechanism other than just calorie restriction? There's something else going on? It's hard to tell, right? Because most of the people on them are already overweight. But yeah, I saw a study recently. I don't remember the journal, but I'll look it up and post it online on my social. But I did see one that had really good evidence that it was not due to weight loss. It's just, I would say in general, whenever I go to a longevity conference and there's a company uh like novo nordisk or lily like you should see this latest study we've shown that it does this thing that we didn't expect at all as a side effect um and it's funny these companies are now calling themselves also longevity companies it's become that fashionable as well i suppose anything that anything that reduces morbidity technically in one form i mean people that make helmet bike helmets are longevity companies you know you're right and it's it's a word that's unfortunately getting overused like anti-aging was 30 years ago and we'll have to come up with something else to assume something sexy huberman says he thinks retitrutide will be a trillion dollar drug do you reckon about that um i think it's possible uh if the oral ones really look good, they may actually be even more interesting.

1:42:33But yeah, what is it? Something like 10 % of Americans have either tried it or been on these drugs? I think 45 % of Americans say that they would. Jerry, can you chat GPT, whatever the numbers are of GLP users and desired users in the usa to find that out uh but yeah i mean what is it obesity is twice as big of an issue as malnutrition as a starvation now globally it's a billion people that are obese and half a billion people that are starving it's like the number one leading cause of malnutrition globally is obesity currently around about 11 of us adults 29 million americans ever used to glp 15 so that means that only what's that about two-thirds of people who have used one are currently using one and 91 % of Americans are aware of them uh 20 % of U.S.

1:43:33households you say uh how many people want to uh I'm sure that this is from uh the most recent book that Johan Hari brought out saying that it's like 45 % of Americans would either have tried or want to try them.

1:43:56About 40 % of US adults have obesity. Yeah, I will say that my number is correct. Yeah, that sounds great. Yeah, I mean, the off target effects of this, oh, it seems like people don't want to drink alcohol so much, though it seems their cravings for video games and porn get curtailed sometimes. I mean, we're getting into not just neurobiology, but the framing of your own sense of self. What is your mission? I am the sort of person that is disciplined. I'm the sort of person that can do hard things. I don't need to eat that food. I'm not going to have that junk. What is the snowball effect that turns everyone into kind of a micro David Goggins because they're working hard in one area of their life and diet is usually the first frontier that people get stuck into when it comes to discipline, right?

1:44:52On both sides of it, whether it's good or bad. And okay, well, maybe I'm going to get up on time. You know, I didn't eat the junk food last night. I'm on a bit of a roll. Yeah, maybe it was pharmacologically assisted with what i did with my discipline around food but i'm getting up or maybe there is some you know super magic wizardry that's going on inside of the brain i don't know but it's definitely interesting and fuck like it does feel the one the one problem is it feels like an artificial solution to an artificial issue which is we shouldn't have a food environment which is so hyper palatable and calorie dense and attractive that we now need to medicate our way out of this yeah it is dystopian for sure.

1:45:32But it's a blessing that obesity has declared a disease and then companies worked on it and now we have these meds. I want aging to be the same. Aging should be declared a disease. We work on drugs and then we treat it. And in the same way that GLP-1s now are saving the world, the same will be true, I believe, 20, 30 years that people will say, why didn't we treat aging earlier? What common health advice today do you think people will laugh at in 50 years time? uh yeah i think the uh eating three meals and snacking that this you go to the you go to the supermarket and there's health bars down the whole aisle aisle that you're supposed to never be hungry that's going to be seen as extremely toxic you your body needs to feel hungry sometimes uh have a break from food so this this trend of you're a bad parent if your child feels hunger is going to be looked at like, oh, what are we doing to our kids?

1:46:33Do you think AI is going to make bigger inroads into longevity research? I don't know why. I mean, again, seven years ago when we sat down, AI, with your snail, your drawing of a fucking snail on the whiteboard, there was no AI to be found. I don't remember what the snail was. I asked you about it at the time, and it was something to do, it was explaining, it was some nerd stuff. This is how the molecular something, something. Oh, I remember we said, Chris is coming. Let's draw a snail. Draw a fucking snail. The idiot British guy will get him in and he'll be convinced that it's actually something really important.

1:47:07What's AI doing to longevity research? Yeah. Well, you asked me, do I think? I know it's having a big impact already on research. My lab is thriving on it. It's going way faster. We just did something in a few months that would have taken us 160 years. And that's using old technology. These days we can do... I'll tell you a story that's funny. On Friday, I had a meeting with a student that just came to my lab over the summer. And he's been here maybe three weeks. And he's 19 years old. And I gave him a task. I said, according to the information theory of aging, if you look at all this data that's out there that nobody's looked at in a certain way it should have this signature and uh if it has that signature we might be right we might have found the backup copy to the software and i said okay that that's your task go go do that thinking you know how that'll take him the next five years yeah exactly because i've had about three people in my lab try to do that and they were not really successful and he came in on friday uh and he's with his team and his mentors and we sat in my office and they've all got this big grin on their face and they threw up on the LCD screen in my office the results.

1:48:21And this wasn't just the usual, I wrote some code in R and ran it and we got some graphs. This was truly using AI. He was using one of the leading AI models and he presented it like it was already published work with beautiful graphs and looking at terabytes of data that's out there in a new way. and he found something that professors and the experts in the field have missed for the last 10 years. And it's right there. There's this signature. He goes, I've given it a new name because I didn't know what to call it. This signature, I'm calling it the reverse tail. I said, what the heck is a reverse tail?

1:49:01And he said, well, I called it this because of that. And I said, dumb name. We'll think of a new name for it. But it's amazing. Love the idea of shit branding. Yeah. We'll work on branding later. But the fact that you found it is incredible. And that's a 19 year old uh he just finished high school and with ai he's going to revolutionize biology i believe and that's just one kid imagine when whole teams are doing this that's wild that's wild so have you has there been anything as far as you're aware in the field of longevity that's been generated or inspired by ai that has gotten itself to trials testing and and fully published as a world change or are we still at the frontier of that not meeting the real world yet?

1:49:49We're undergoing this revolution, so tomorrow's going to be better than yesterday. But we're now at a point where almost somebody on their phone can discover a drug candidate, whereas it would have taken a pharmaceutical company years and hundreds of millions of dollars. It's that world. We can go from, now that Demis Hassavis and his team, not just him, has cracked the code for protein folding. We now know all the chess pieces. We were guessing and it took years to find out what one chess piece looked like. And there's over 15 ,000 of these pieces now. These are all now modeled in 3D. Now we know not just how they look in 3D, because they used to be one-dimensional based on the DNA.

1:50:39Now we've got three-dimensional amino acid structures. Now we're seeing how they fit together. Computer is actually smart enough to figure out which ones dock with each other, and eventually we'll figure out how they're all working together, an artificial AI version of a cell. We can do in silico experiments at the molecular level now and dock trillions. Last year it was billions. Now, this year, it's trillions of chemicals, real drugs, and imaginary drugs. It's kind of like a virtual environment. Yeah. It's like a virtual lab. Yeah. Are these accurate? So if I run the synthetic lab, is it one-to-one with the real world?

1:51:19It's not one-to-one, but it increases your odds exponentially. Because you don't need to do test, test, test, okay, maybe this. You can discount a lot, and then the interesting ones get moved into the real world? Yeah. Yeah. Yeah, and the old way of doing it, which felt really modern, was you have libraries of little plates, hundreds of these little plates with 96 or sometimes 384 little wells. And each one has a different chemical that's physically in a freezer somewhere. You have to pull it out, give it to the robot. The robot then does its work overnight, tests it on cells, take a picture of the cells.

1:51:54this kind of work is is slow compared to today which is we don't even need to have the fridge we can make up trillions of potential drugs test them run it for a few weeks it'll tell us here's the top 200 and probably at least half of them are pretty good it feels fucking primitive and now we can do that experiment with hundreds instead of trillions and trillions is impossible by the way The most a pharmaceutical company would screen would be in the millions. Now we do trillions. And then you can even order them online. That's the thing that blows me away. We got a set of 200 that we think can reverse aging using AI.

1:52:33And then I thought, oh, it's going to take us a long time to synthesize these 200. No, we just order them up. The company can make them for us in a matter of weeks. Now we've got them in the lab. We're testing them on human cells. we've developed an ai system that can tell us whether the 90 year old cells skin cells from a human are going back to being 20 or anything in between just by looking at them we paint them with dyes different colors and then where we're at is hopefully in the next uh month or so give it two months we will have a set of chemicals that can replace the current cocktail that reverses aging in the mouse.

1:53:13That if you're paying attention earlier, not you, but listeners, if you've just joined us, I was talking about we've got things that we can give a pill or a swallowing thing, a drink to a mouse. Swallowing thing. A drink to a mouse and it reverses its age. We've got that, but it's a cocktail. A very secret cocktail, but it's got at least three things in it. We want to bring it down to one and turn it into either a supplement or a drug or a patch or a thermal thing and some kind of cream or all of the above but we're getting really close to being able to have the single molecule that can truly safely reverse aging in human cells we'll test it on the mice and we'll run from there how big of a role is expectation in how someone lives if somebody thinks about aging as being associated with frailty and degeneration, can that actually make them live less long?

1:54:12Oh, you mean mentally? That's well studied. If you're optimistic and you're enjoying life and you don't just retire and be bored, yeah, mental attitude is huge. Robert Voldinger, a Harvard scientist, has found that the mental attitude and your social life is as important as your blood pressure and cholesterol, if not more important. And the one thing that was the best was have a reliable partner. I went through a divorce. It was horrific during COVID. And I believe that it took years of my life. So it felt like it anyway. But it was a shock. I didn't know it was coming. But it's brutal. Anyone that is young getting married, just beware.

1:54:56We all change over decades. So that's something to keep in mind. But the point there is the amount of stress and cortisol that runs through your body when you have a really big life event, moving house, breakups, death in the family, your own illness. These are age accelerators. And on the other hand, we've talked about today the kind of things that keep you healthy. The exercise, the diet, the social life, the sleep, the relaxation, these are all we know are likely to not just slow aging, but eventually keep you disease free. And I do want to mention that. Often people think, oh, I don't want to live longer because I don't want to be old for longer.

1:55:36That's not what we're talking about. We're talking about still being young and vigorous in your 90s. My father is almost 90s, 87 now. He'll be here on Friday from Australia. It'll be, I think, second or third time he's come to the US. He was just in Japan. This is not a typical 87-year-old. He is living life probably better than he did in his 40s. He's out every night with different people, mostly women that he's excited about. They're good friends. I don't want to disparage my father. He's not a dirty man, but he is a very sociable guy. And in his 40s, he was raising me and I wasn't easy to raise.

1:56:17I was a pain in the gut. He will say he's never had a better time in his life than now at 87. If you were 35 or 40 again, and you could only do two or three things for longevity, what would they be? Definitely don't overeat. Be lean. Watch your weight. Have a BMI of around, let's say, 22, 24. Make sure you don't get overweight. Obviously, don't overdrink and don't smoke. These are clearly really the worst things you can do, having lost a mother to smoking. um so don't eat too much right try to skip meals uh work out maintain a very good body mass and exercise those are the fundamentals everyone will tell you that what i didn't realize till i was in my 50s was how important food is i thought vegetables were a garnish for meat i love meat um they taste meat tastes great but i've i've switched over to being more plant focused and i've seen a great improvement in my overall health and biomarkers so those are good learn not to stress we've talked about um that took me a long time to to learn that as well but i've never been healthier because i've it's been slow but i've learned how to do all these things really well i'm going to do a lightning round so in a sentence or two give me your review on these interventions for longevity okay okay creatine we doing how are we scoring just however you want give me a review yes no like it don't like it useless buy it do whatever you think whatever you don't all right so creatine um in favor of it and take it stem cells interesting and if you have a certain condition like a joint that needs repair can be helpful but it's not long-term solution cpap machine really important um for folks that have anoxia, lack oxygen at night for the brain.

1:58:15Though you could try other methods, which is lose weight, don't drink, get a thin pillow, try to sleep on your stomach. Hyperbaric oxygen therapy? In favor. There's good evidence that certainly cycling up and down in pressure is good for the brain and blood flow. And I've done it myself and have seen improvements in wound healing in others. So yeah, in general, it's a plus. blue light glasses yeah you mean yellow uh blue light blocking glasses um i prefer to turn down the brightness of the lights at night and have a tv that's not so bright but yes i think they were much more fashionable five years ago but i still use them so yes but definitely in general watch out for bright light at night but try to get violet and blue light in the morning.

1:59:10It's very important. A friend of mine in Japan found that if you don't see violet light and you're a mouse, you get short-sightedness. So early morning light can be protective, like for your eyes? Yeah, yeah. And we live indoors and we don't get enough of it from LEDs. Okay, glucose monitors. Love them. They're really good. Yeah, I think that we should all be empowered by our own data. Anyone who says, I don't want to know about my biology, I think. I don't agree with that. The CGMs have been very useful personally. I can see how I react to foods and I was surprised. Grapes send me through the roof, white rice through the roof.

1:59:51I remember the grape thing. You told me about that last time. Yeah. And it's still true. I'm wearing one right now. I wear them fairly regularly. The other thing that surprised me about CGMs was I gave one to my son who at the time was, I think 17. And we had a competition who can have the best blood glucose levels. And he would eat a lot of bad stuff. It changed his life. He is eating much healthier. He's now aware of what food does to his body. Now, I'm not saying go give it to children, but I do think there's an education and a behavioral change that can come with CGMs that, as I think you mentioned earlier today, can really, really make a difference.

2:00:29therapy you mean just general uh psychology psychotherapy well i think it depends on the person and the therapist um i think that talking about your problems can really help um i think it can be overused um as a friend um i've i've tried everything um i didn't find a lot of the therapists to be that useful i found it better to read books and listen to experts. But I do think therapy is very important. I've had kids that benefited from therapy. It's very hard being a teenager these days with the pressures. So yeah, a thumbs up for therapy, though. Make sure you have a therapist that is well qualified and provides benefits rather than just listens to your complaints.

2:01:19Grounding. What do you mean? Grounding. Walking on grass, negative electric discharge stuff. I don't think that's scientifically based, but I do think getting out in nature and touching nature, smelling nature, listening to nature is very valuable. And our body will turn out to respond in ways that we don't even understand yet. Marriage. Be careful who you marry. And know that it's not always forever. Know that people change over decades.

2:02:01Know that it's a long-term investment. Be loyal. Never lie. And if kids are involved, try to work it out. mouth taping and mouth taping uh so i i do snore if i uh have a thick pillow or eat certain supplements at night i've found so i have tried mouth taping and serena says i make even more noises gasping so i don't use mouth tape i i do use those nose strips because she thinks they help But no, I haven't had success myself with mouth taping. Testosterone therapy. I prefer natural versions. If you can't raise it naturally, yeah, for older people, there's been a lot of benefits. I mentioned Shelley Basin as a scientist that's worked on NMN.

2:02:55He's also done a lot of testosterone work, which shows benefits. But it doesn't extend lifespan. There was no evidence that it does that for longevity. How do you talk a lot today about supplements, lifestyle, interventions, rest, recovery, what the future is going to look like, AI, GLPs. Something that we never got to talk about when me and you first sat down were the perils of over-optimization. I think that it was so frontier-y in 2019. Everything was new and exciting and you couldn't really be drowning in data in the same way as you can now. And I wonder what you've come to believe about the negative health implications of caring too much about your health, of over-optimizing, the neuroticism taking away not only your enjoyment from life, but the effects of supposedly all of the interventions that you're actually trying to do.

2:03:50How do you come to think about over-optimization? well obsession about anything is possible and also deleterious to health uh so if you have those tendencies be careful you know it's true for anything social media use as well um and i i can be obsessed what what i've done myself which i recommend is treat it like a hobby it's fun it's not too serious you're not going to die if you didn't sleep well last night um and you Everything's a challenge. My meals are an experiment. Not always. Sometimes it's a failed experiment. But I live my life like it's a journey and it's fun and I'm testing things.

2:04:36And so don't get too obsessed if you are not perfect when none of us are ever perfect. And none of us are going to live forever, in my opinion. So enjoy the journey. Do as best you can. Don't stress. heck yeah david sinclair ladies and gentlemen david you're awesome i appreciate you seven years later where should people go to check out everything that you've got going on uh well the big one is lifespan.com become a member get the magazine learn how to live longer and we'll learn together we'll do some big things together um and i'm on social media you can see what i do season podcast is big uh so that's on youtube and all all podcast uh that's called lifespan And with Dr.

2:05:15David Sinclair, we're building. We're about half a million followers, not like you, but we'll get there. You're doing good. We did take some time off to do the trials, but we're back and even better now. So join us there too. Thank you, Chris. Appreciate you, mate. Likewise. Until next time. All right. Goodbye, my beauties. Dude. Yes. So good.