“Age Reversal Is Coming.” Inside The First Human Trials - Dr David Sinclair - #1141

Modern Wisdom

Dr. David Sinclair discusses groundbreaking advancements in aging reversal research, including the first human trials using Yamanaka factors

Key takeaways

• Age reversal is now being tested in humans through gene therapy targeting the epigenome, not just the genome.
• The Yamanaka factors, when used selectively, can safely reset cellular aging without causing harmful side effects like cancer or loss of cell identity.

Main topics

• Human trials of epigenetic reversal therapy
• Yamanaka factors and their safe application in aging reversal

Notable quotes

"Aging is a scratch CD. The music is still there, but the software gets corrupted."

Conclusion

Dr. David Sinclair envisions a future where aging is no longer seen as inevitable but as a treatable

Transcript preview

Speaker 2 (0:00) The first ever podcast episode that I recorded in America was with you in 2019, Harvard Medical School, in your office with what looked like the illustration of a snail on the whiteboard. And it was filmed on two iPhones, one of which I'd had to borrow from a friend, and a single white USB microphone. And that was over seven years ago. Yeah, I remember it Speaker 4 (0:24) well when you were 12, right? Speaker 2 (0:26) I was 12. Yeah, correct. It Speaker 4 (0:28) was very clear from those days that you were going to be a big success. You were smart, driven, came prepared. And look, this is beautiful now. Speaker 2 (0:38) Full circle. Yeah, I didn't realize Starbucks Venti has way more caffeine in than the British equivalent. And it took my fucking face off. I was obviously trying to think about Yamanaka factors and how important NAD and resveratrol in yogurt is. Meanwhile, My whole body was vibrating. But you've done maybe more than almost anyone to make the biology of reversing aging a part of mainstream conversation. So I want to talk about kind of everything that's happened since we first sat down, the Yamanaka factors, what's happening with NAD and resveratrol, news discoveries. Before we get into that, though, what discoveries have excited you most since 2019? Gee. Speaker 4 (1:24) A lot. I'm very lucky to have a lab where there's up to 40 people running around making discoveries. I go back there to recharge. It's like the Willy Wonka. You've been there, so you know what it's like. It's unparalleled. I wish everyone could come visit. The highlights would be, so in 2020, we published on the cover of Nature magazine that we could reverse aging safely in an animal for the first time, a mouse. We cured its blindness. That was pretty big. Cover of nature, it's what most scientists dream of in their lifetime. So that was a pretty big high. Since then, it's been rewarding to see that it's been repeated, not just by other labs, but in different animals, monkeys. It's been working in different tissues, so it's not just the eye anymore where we first tested it. It's pretty much working in every part of the animal's body. And then the big thing is we've now gone into people. So there are people getting their, hopefully their age reversed in their eye to cure their blindness or at least improve their vision at the very least. Speaker 2 (2:31) Why start in the eye? Speaker 4 (2:33) Yeah, good question. This is a gene therapy. So we're introducing genes that are very powerful. They're called Yamanaka factors. You mentioned them. But we use a subset of them that don't cause any trouble. If you just use what Professor Yamanaka used. it's not going to be very healthy. It's actually quite dangerous. So we use a subset of those and we deliver them with a little virus-like particle. And the safest way to deliver a virus-like particle into a human is to go into a space that's enclosed. It's not going to spread. And the eye is where it's most being tested. And so we did it for safety reasons, not because it would work better in the eye. In fact, I told my student at the time, Wen Cheng, that he was crazy to try to cure blindness. Why not do something easier like the liver? But he said, you know, the eye is probably the best place to start for safety reasons. And he was right. Speaker 2 (3:25) I remember that though. That was, we were talking about that in 2019 when I was in your lab. What has, there's been this recent release that came out last month. What's that? Why is that so special? Speaker 4 (3:40) The one about that we've gone into humans? Well, I think most people thought the aging field was a lot further behind. Age reversal, you see online, oh, we've done this in human cells. We've done it in a mouse. But suddenly, there are people now getting what could be the world's first true age reversal drug. So for us, it was old news. We'd been doing this and expecting it for a while. In fact, we made the discovery back in 2000. 16, 17. So for us, it wasn't so amazing. But for the world, I think it was a shock to hear that people are actually getting this potentially age reversal drug for the first time. Speaker 2 (4:19) What would be the issue that somebody has in their eye which would be reversed? What's the sort of patient that this would fix? Speaker 4 (4:25) So this is the thing that makes me super excited is that every piece of or type of damage and disease that's been tested in animals, not just... mice but larger animals, it's work to improve the vision of either a disease or damage. So for instance, if you pinch the nerve, you laser it, or you give a mouse glaucoma, pressure in the eye, we can treat that effectively. And nothing reverses blindness currently except for this treatment in animals even. And so that's what's exciting. Even macular degeneration, glaucoma. the two leading causes of blindness in the world, both of them are really easily treated by this new mechanism. We call the drug ER100, which is epigenetic reversal 100. But yeah, pretty much any disease or injury could theoretically be fixed, treated by this technology. Speaker 2 (5:24) theoretically, any disease or injury could be treated by this? Speaker 4 (5:28) Well, in the eye, but even beyond that, the liver, motor neurons, so ALS, the brain has been reversed in aging, memory comes back, even joints. There was a Chinese study that came out recently, looked very good. They used our technology to rebuild bone and cartilage in osteoarthritis. I don't know anything else that just rebuilds body parts like this. Can Speaker 2 (5:53) you explain how it works to a simpleton? Speaker 4 (5:57) Not you, but I don't think anybody listening is a simpleton. But it's actually quite simple, the good news. We take three genes that are normally turned on early in life, and these three genes make factors that turn on a cascade of events that the cell uses to reboot itself. The simple way to think of it is that I hypothesize that the body has software that gets corrupted as we get older. So an old person still has information there. It's just that it's been corrupted, the software. We call that the epigenome. It's separate from the genome, which is the DNA. The epigenome sits on top of that and controls the DNA. So in my book Lifespan, it's a little dated now, but you might remember. I chose a CD as the analogy. The epigenome is the reader of the music and the DNA is the music itself. And aging is a scratch CD. So for those listeners and viewers who don't really know what a CD is, there are really cool things we could put 20 songs on. But a better analogy now would be your phone has software. A really old phone is slow. It can be corrupted, can get overused. And so we can reboot that. And we found that these three genes that we put in, which we call O, S, and K for short, these Yamanaka genes, trigger a program that embryos normally use to reset their age or something very similar to that program. Something you might not know, most people don't know this, is that when we're fertilized, and we've all been fertilized, we wouldn't exist, and then we need to reset this epigenome. The software needs a reset to go back to being young again. And that happens Speaker 2 (7:38) - Speaker 4 (7:38) No way. It's a fact. It's shocking but true. Very young embryos are old and then they get reset. So the software is really, it's not software, it's the way the DNA is folded in the cell and every cell has to compact the DNA because it's six feet long, has to fit into a microscopic little ball. And how that's compacted depends on what kind of cell you're going to get. So if you want to make a nerve cell, you compact different genes. And when you compact them, they switch off. But you need to read nerves that make nerve cells, so you open those up. And this bundling and opening of DNA is what the epigenome does. And my theory, called the information theory of aging, said that this pattern of bundle, loop, bundle, loop, which is different for every cell type, gets corrupted, gets eroded during aging. And that literally is aging. And we tested this and published it in 2023. Speaker 4 (8:36) And we created a mouse where we could disrupt those loops and bundles. And the mouse's cells lost their function. They lost their identity. The nerve cells forgot how to be nerve cells. And the mouse literally got old. We could speed up that process by corrupting that software, the epigenetic software. And then when we did that, which took us 13 years, we started working on reversing that process, which is how we get to here. Speaker 2 (8:57) People see aging as a certainty, but you call it a disease. Is it truly a disease or is that just a useful metaphor? Speaker 4 (9:05) Well, it's just a word, really. So we can call aging whatever we want, but I prefer to think of aging as a disease because otherwise we're not really treating it. Most doctors don't think of old age as something that is preventable or treatable, even though now we believe we understand that it is very treatable or at least slowable. So I think it's a useful way to look at aging as something that we should address. even starting early in life to try to slow it down at least. We all need to stick around for longer because the technology that's coming is incredible. And I proposed this in my book and even put it on the back cover. And it was, a lot of people were telling me that that's crazy. Don't say that, David. It's going to be scandalous. People are going to not take you seriously as a scientist. But I'm glad Matt, my co-author, Matt LaPlante, convinced me we should go for it. Actually, that was his. main role besides writing was to say, David, just do it. Because don't worry what your colleagues will say, because some of them can be pretty brutal. So we put it in there and it's seemingly been embraced by a lot of people. And now you hear it quite often. Speaker 2 (10:14) What's the technology that's coming? If that's what we've done so far, what did the next few years have in store for us? Speaker 4 (10:21) Well, there's a fork in the road. I don't know when it's coming, but... It's similar to the singularity with AI or AGI. Speaker 4 (10:32) When we show, and it's a matter of when, not if, that aging is reversible in humans, because it works in all these other animals. It'll work in us. We're basically just slightly more intelligent monkeys, and it works fine in the monkeys. That's going to be a turning point, I believe, for humanity. There'll be a lot of people who say, all right, now let's get on board. Let's invest. Let's blow this out of the water. There's already a lot of billions of dollars put into this, but it's going to be big like AI. when that happens. But these technologies, let's say it works in the eye and now we can treat, perhaps cure, most types of blindness. Then we're going to, we're already doing this. I should, you know, I can't talk about too much, but we're already looking at other tissues, the liver, for example, and maybe there's joints and hearing that we can also repair. Ultimately, where this is going, obviously, is whole body reset. And we can do this in mice easily in my lab now, and others have done this. Every cell Speaker 2 (11:31) in a single organism? Speaker 4 (11:33) Well, we don't have the technology with the viruses and the genes to reset every cell. And that's a limitation of getting the genes into every cell. You can't do that. We can basically at best get it into half of the cells, but still a lot of them. We've taken a path that's a little different now. You know, I was saying we've been doing this for a while. and the world doesn't really know what we're up to in my lab. I can reveal that over the last five years we've made breakthroughs in turning it into a pill. That's the next big thing that'll come out of my lab is revealing that we can give a mouse, an old mouse, something orally. So they don't chew on the pill. We give it down their throat for three days a week for a month, and we see that they are rejuvenated in many ways, including... Not just their memory, but things like even their skin quality. Speaker 2 (12:25) What's happening? What's the pill doing to them? Speaker 4 (12:28) Well, that's a lot of work. We're still trying to figure that out. So you know it works, but you don't Speaker 2 (12:33) necessarily know why or how it works. Speaker 4 (12:35) Well, we actually literally don't know how the genes that are in the eye of humans now work, really. That's a big question in my lab. I was trying to answer, where is this backup copy of software? But we do know it works. That's the hard part. And then figuring out how it works will be important to make these drugs even better and more powerful and more potent and longer lasting. But what we do know is that the epigenome is involved in the pill, not just in the gene therapy, because we can disrupt that polishing of the CD or the reset of the software. There are genes called TETs, which make proteins that strip away chemicals off DNA. These are key to the epigenome reset in embryos as well as in our bodies. And we can get rid of them or inhibit them with a chemical. And we can feed those to the mice or give it to the cells. And we have some good evidence. I hope my students don't kill me for saying this publicly. But we do have good evidence that the pill, let's call it, the cocktail, does work through this epigenetic thing. It's not just, oh, the cells. are getting stressed out by the chemicals and they fight back and they live longer. It's not that. It's truly through this reset mechanism and we can show that Speaker 3 (13:50) by Speaker 4 (13:51) getting rid of these tet enzymes that strip chemicals off the DNA. Without that mechanism, the cells don't get younger, even with the chemicals. Speaker 2 (14:00) Do you think there's going to be a realistic upper bound to human life? Speaker 4 (14:04) Well, the question is when. I think that ultimately there is no upper limit to human life. I just visited a bonsai garden in Japan where The trees are a thousand years old and they're not even halfway through their life. So biology doesn't have limits. It's just a question of what our genome encodes and our epigenome. But we have control this century over our own biology. We don't have to just be at the whim of what evolution and the Serengeti gave us. And I see no upper limit. It doesn't mean I think you and I will be immortals. That's right now beyond our imagination. Well, it's definitely imagination, but... It's beyond technology that I can think of. But I do think that some of us will have a chance to live decades longer and probably the first person to live to 150 is already alive. Speaker 2 (14:54) First person to live to 150 is already alive. Speaker 4 (14:56) Yeah, I'm not the only one in my field saying that. It's now realistic. I mean, think about it this way. It's hard to imagine the future, right? But a kid born today is going to live into the 22nd century. And we can't even imagine what the world's going to be like 10 years from now. So the longer you live, actually, the longer you get to live. Speaker 2 (15:17) Surely if someone took age reversal pills for long enough, they'd just become a baby. Is that not the way it works? Speaker 4 (15:22) Well, we made sure that wouldn't happen. That was one of the things that Wang Cheng might question. Benjamin got Speaker 2 (15:27) everybody into it. Speaker 4 (15:28) Yeah. Well, that was the trick. Embryonic Speaker 2 (15:30) death. Speaker 4 (15:31) Professor Yamanaka won the Nobel Prize for making cells go back to age zero and making them into stem cells. But that's not going to help us. We don't want to strip away the identity of all our cells. We die within a couple of days. And in fact, if you do that to an animal, it tragically does die or gets cancer. So what took us the longest time from 2014 to 2017 was figuring out how to reverse aging, but not so much that it loses the identity of the cell, but erases it. And my student, Wan Cheng, famously almost quit the project. He was doing his PhD. He was in his last year and nothing was working. He was either having no effect on the human cells in the dish or they were becoming cancerous. And he said, David, I don't know how to stop it halfway. And we came up with one last experiment that thank goodness it works because we wouldn't be talking about it now. We tried a subset, just three of the Yamanaka genes, and leaving one of these Yamanaka genes out was key. Without that final gene, it's called CMIC, we call it M. Without M, the M gene, cells don't go back 100%. They go back about 75 % and stop. Speaker 2 (16:45) And Speaker 4 (16:45) that was the breakthrough. The stop was really hard to find, but it's there. Or else you just turn Speaker 2 (16:51) everything into stem cells. Speaker 4 (16:52) Yeah, yeah. Or cancer. It's even worse. Well, maybe not worse, but it's definitely bad. You're not going to live longer or cure blindness. But that was a breakthrough. And Wan Cheng sent me the pictures of the cells that were younger and said, Eureka, I think we've done it. And it was a remarkable thing to witness. Speaker 2 (17:10) What do you think most longevity experts secretly believe? but can't prove or won't say publicly at the moment? Speaker 4 (17:17) Gosh, that's a good question. I was going to say most of them secretly think that I hype this stuff way more than I should, which is, again, not a fair thing because my lab is eight years ahead of what we've published. But I think most aging researchers, I can say for a fact behind the scenes, say this is going to be much bigger and more powerful than we expected. I've been told by some of my colleagues, don't say that number 150. It makes us look bad. And I'll say, well, do you believe in it? Yeah, but we can't say that because we're scientists and we'll lose credibility. So yeah, I think a lot of the scientists are very cautious by nature, by the profession. I'm considered an outlier speaking my mind and what I believe in, but most scientists don't because it's not something scientists typically do. Speaker 2 (18:07) Why is it that you're seen as an outsider? Are you throwing more caution to the wind than other people? Is it that their criteria for evidence is different to yours? Is it that your lab has got access to information that other people don't? Speaker 4 (18:26) Well, there's a few reasons. It's definitely that my lab has information that nobody else knows. And that's been difficult my whole career, knowing that something's true, but it's not published yet. So in the minds of my colleagues, it doesn't exist yet. And in fact, my book came out in some cases years before we published the work. So the public knew my lab's work before other colleagues had seen it. That's also rare. Another reason why... I'm a bit of an outsider is I'm not doing this to be a scientist. I'm doing this because I'm on a mission and my life is irrelevant. I would literally die to achieve this mission. And so, you know, if I get criticized or if I speak my mind, I really don't care. What's the mission? To impact in a positive way as many lives as possible. This was since I was four years old. My grandmother gave that mission to me because she lived through World War II and the aftermath in Europe. And she told me the horrific things that humans did and can do. And she was always saying, we can do better as a species. And I feel like I want to die knowing that I've done the most for humanity that I could possibly do. And if it upsets a few people, I don't care. Speaker 2 (19:44) I've learned from over a thousand podcast episodes, the easier that you make your health routine, the more consistent you'll be. It's like golf, right? You want to keep it simple and not makes a bunch of pills. You want the eye of the tiger, not the DUI of the tiger. That's why I'm such a huge fan of AG1. One scoop contains 75 vitamins, minerals, probiotics, and whole food sourced ingredients in a single daily drink. And that's why I've been taking it every single morning for nearly five years now. And they've taken it a step further with AG1 NextGen backed by four clinical trials. In those trials, it was shown to fill common nutrient gaps, improve key nutrient levels in just three months, and increase healthy gut bacteria by 10 times, even in people who already eat well. Plus, if you're still unsure, they've got a 90-day money-back guarantee, so you can buy it and try it every single day for three months if you don't like it. they will give you all of your money back. Right now, you can get 20 % off a welcome kit and that 90-day money back guarantee by going to the link in the description below or heading to drinkag1.com slash modern wisdom. That's drinkag1.com slash modern wisdom. Longevity is a huge field, right? It includes everything. When you think about all of the different types of interventions that people can do, how do you chunk them into groups? Sort of what are the buckets that people should be thinking about as contributing to their lifespan? Speaker 4 (20:55) Yeah. So I talk about this on my YouTube as well. So there's a lot of detail on there now and I've relaunched it. Congratulations. Welcome back into the fray. Speaker 2 (21:02) I'm glad that you've stopped doing the wasteful work in your lab and gone into the serious work of YouTube videos. Yeah. Speaker 4 (21:07) I was working on solving aging and now that the clinical trials have started, I'm back to more important things. But yeah, so what we talk about on the podcast is what are the major things that people can do to slow down aging? and even reverse aspects of it. Speaker 2 (21:22) But if we've got this technology coming soon, you're eight years ahead, everybody is doing the longevity escape velocity bet, right? For every day that I live, there's more days that I can hopefully live. So in the interim, those are the buckets, right? That's the stuff that people need to focus on now. For Speaker 4 (21:37) sure. I think anyone that doesn't focus on their longevity might miss the boat. It'd be tragic if you died a few days before, you know, some of these technologies came out. And this is... I'm not worried about you killing over anytime soon. You're very fit. But your parents, your grandparents, think about them. So try to encourage them to live the healthy lifestyle that we're going to discuss now. The buckets are lifestyle. So within that, there's the obvious things that we can talk about, which is what you eat, how you move, how you rest, your stress, these kind of things. That's what you can do and you should do on a daily basis. It's what I do. Then there's drugs. which some of which may work. So that's metformin, rapamycin, some senolytics, and probably GLP-1 receptor agonists would fall into that bucket. And then there's supplements, which is the wild west. There's a lot of things said about them. I believe in a few of them based on a lot of animal research and some human data. Those are the three main things that you should do in your daily life to maximize your chance of getting these medicines. Speaker 2 (22:45) Okay. Lifestyle stuff. Yeah. Last time that we were talking, it was all about calorie restriction and primarily fasting as a route toward calorie restriction. Speaker 2 (22:56) How should people eat if they want to live as long as possible now with the 2026 data? Speaker 4 (23:00) Well, actually, what I've been saying, actually, on my podcast for now, what, four years, it hasn't changed. And my book, Lifespan, which came out, we were talking about when we first met in 2019, nothing in that book I've had to revise. It's all consistent. So there's no Speaker 2 (23:16) retractions from the book in 2019? No, Speaker 4 (23:18) no. And my lab's never retracted anything and at this point never been proven wrong, which is a blessing. Knock on, touch on wood. But that's good news, which means that the things that I've said before, people can go back and learn still. If this is the first time you're seeing me, let's start. So the main things about fasting are we know from animals and some human data, but mostly from animals, that if you restrict how often you eat and to some extent how much you eat, you get longevity benefits. And we can talk about... protein ratio to carbs to fats. That's also a whole big debate, as you know. But generally, I like to eat one meal a day, maybe two if I'm being social, but not three. I think three meals a day plus snacks is marketing. Breakfast being the most important meal of the day was General Mills, I believe, one of those companies, Kellogg's perhaps. But this is all marketing. Humans are not built to eat that consistently. I don't think... cavemen were sitting around eating their big breakfast saying, what are we going to eat for lunch? I think, you know, maybe if they just killed a mammoth, but generally they were pretty hungry a lot of the time. And our bodies have adapted to that. We're not meant to always be satisfied. And so I try to be hungry. And if I gain a little bit of weight, sometimes I travel and I eat well. And Serena and I, we do sometimes love to eat. I'll come home from travel and just, I won't eat for three days. Sometimes. Two weeks I can go without food. It's not a big deal for me. Two weeks Speaker 2 (24:51) without food? Speaker 4 (24:53) Yeah. Okay. I might munch on a piece of celery or something, but that's not really nutrition. I will drink a lot. I'll drink a lot of low calorie, zero calorie drinks, a lot of tea, that kind of stuff. But I can go without food for two weeks. It feels great. After the first three days, I'm over the hunger feeling. I can see on my monitor, which I've got one on here. Speaker 2 (25:15) CGM. Speaker 4 (25:16) The CGM. Yep. I can see the great impact it's had having on my body. I can monitor it on my rings. I do blood tests, which is important. You don't want to just guess what's working, what isn't. But yeah, I know two weeks sounds like a lot. It is a lot. It doesn't sound like a lot. It is a lot. It is a lot. And I'm a regular guy. I'm not like some people that spend millions of dollars on their body and measure everything. I'm kind of lazy. I don't like being hungry. I like food. I like to snack. I like to stay up late. I'm a typical hedonist if you let me go. And actually up until a year ago, I actually hadn't fasted more than 24 hours. I just couldn't do it. This is painful. And I'm stressed. So if I'm stressed, I'm going to eat. But what I've learned over this past year is I can go beyond 24 hours. And once I'm over three days, something kicks in. Actually, we know molecularly there's something called chaperone-mediated autophagy or CMA, which is the deep cleanse of these misfolded and modified proteins that you want to get rid of for aging or slowing aging. And after those three days, you know, I start to feel amazing. My mind clears. I don't feel bloated at all. I don't even have to go to the toilet that often except for all the tea. But you know what I mean? And yeah, I feel energized. And I'm measuring myself. So I'm making sure I'm not overdoing it. This is not for everybody. If you're skinny and you've got barely any fat or you're elderly, it's not for you. But for me, I gain weight and muscle pretty easily. I can fluctuate. And so I watch my weight come down. I've got a scale that measures my weight. I don't know if I can say the name or if it's forbidden, but I do like the Withings scale. Smart Speaker 2 (27:00) scale links to the phone. Yeah. It would get you composition as well if you hold the handle. Speaker 4 (27:04) Yeah. And I've had one since 2013. So I've got all this data on my body weight and composition, which is awesome. And I'm trying to maintain that at the optimal level over these last... This Speaker 2 (27:14) two weeks thing is blowing my mind. What are you running on after 10 days? Why is malnutrition? Are you supplementing with vitamins Speaker 4 (27:22) and stuff Speaker 2 (27:22) so that you don't get scurvy? Like why are you not dropping dead? Speaker 4 (27:25) I am. I'm glad you said that, Chris, because it's important to say I'm a scientist about this. I'm not just willy-nilly giving up everything. So Speaker 2 (27:32) you're Speaker 4 (27:32) celery Speaker 2 (27:32) and green Speaker 1 (27:32) tea Speaker 2 (27:33) surviving for two weeks, just bro-sciencing it. Speaker 1 (27:35) Well, Speaker 4 (27:36) no, I'm not doing that. The reason I'm using my hands is I travel and at home I have a little carry pack. with vitamins, supplements, and medicines that I've been using and know very well what I need. Every morning, it's Speaker 2 (27:50) a Speaker 4 (27:50) symphony of supplements and medicines, actually. I know what my body needs. I know what works. So I do that. So not anybody can do that. So it's really important if you do fast for long periods, make sure you have enough hydration. Very important. We know that. But 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. Speaker 2 (28:17) What do you think is happening inside of your body from day four until day 14? What's going on? Speaker 4 (28:25) 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. My liver is smarter than my eyes and my mouth. And anyone that's fasted knows that. Your blood sugar if you're eating is 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. Speaker 2 (29:31) Is there not a concern to do Speaker 1 (29:32) with your gut? Speaker 2 (29:34) Is there not, is that, 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. Speaker 4 (29:42) Yeah. Well, I can tell you your stool changes. I imagine it does. It turns fucking invisible. Speaker 2 (29:47) Yeah, right. It's a phantom poo, as it's called. A Speaker 4 (29:50)