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00:03
Welcome, hi, I'm Mikki and this is Mikkipedia, where I sit down and chat to doctors, professors, athletes, practitioners and experts in their fields related to health, nutrition, fitness and wellbeing and I'm delighted that you're here.

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Hey everyone, it's Mikki here, you're listening to Mikkipedia and this week on the podcast I speak to Professor Michael R. Rose. Professor Rose is an evolutionary biologist whose work on aging really transformed the field and earlier when he was uncovering his findings were probably quite controversial. We discuss his entry into evolutionary biology.

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how his mentors encouraged his studies that led to the revolutionary work that he's now really well known for. We discuss how we age as humans and how in some ways we are protected during our younger years from the detrimental impact of modern life so we can as a species survive, you know, Darwinian survival of the fittest. And we also discuss that once past our reproductive years, that this does change. And it

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influences not only the aging process but has implications for dietary choices, activity levels and even how we socialize and how we see ourselves in communities. And we cover this detail in today's podcast which was such a super interesting conversation. So an evolutionary biologist, Professor Michael Rose.

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is really well known in his field and in fact evolution has described the field of aging research as after Rose thanks to his influential book Evolutionary Biology of Aging. In 1997 Professor Rose was awarded the Buss Research Prize by the World Congress of Gerontology. In 2004 he published a technical summary of his work on the postponement of aging, Methuselah Flies

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followed in 2005 by a popular book on the topic of the long tomorrow. He has more than 300 publications and we have linked to his Google Scholar page in the show notes and has given hundreds of scientific talks around the world. He is currently a distinguished professor of ecology and evolutionary biology at the University of California Irvine and as we discussed in today's podcast is looking forward to retirement.

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So I have linked Professor Michael R. Rose, his faculty page at the university with which he teaches, his Google Scholar page, but also a website 55thesis.org which describes in details a lot of his work that is very accessible to the general population. So I really think you're going to enjoy this conversation I have with Professor Rose.

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Before we crack into it though, just a reminder that the best way to support the podcast is to hit the subscribe button on your favourite podcast listening platform. That increases the visibility of the podcast out there and amongst the literally thousands of other podcasts so more people get the opportunity to learn from the guests that I have on the show. Alright team, enjoy the conversation that I have today with Professor Michael R Rose.

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Michael Rose, thank you so much for joining me in your evening. I have listened to you on numerous podcasts over the years and was really excited when you accepted the invitation to come and speak to me on my podcast because of your views on evolutionary biology, aging, and of course, what we were just very briefly.

04:13
just talking about sort of how the modern, how there's that evolutionary mismatch, if you like, between our current sort of diet and what is optimal for health. Can we just kick off by you sort of telling me what initially drew you to studying evolutionary biology all those years ago? So I was already an evolutionary biologist in my interests when in the summer of 1975,

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then at the height of his fame and renown in Britain, suggested that I do a PhD with Brian Charlesworth and to some extent himself on aging. And I described this in my book, The Long Tomorrow. And I was completely dismayed by this suggestion. In 1975, aging was little studied.

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beyond geriatrics outside of cranks. So there was sort of geriatrics, which was respectable and didn't really amount to much. Then there were cranks and they actually weren't that big then. What are cranks? What are cranks? Oh, the term crank in... See, I'm Canadian and I've...

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lived and worked in both England and the United States. So it's hard for me to keep Pracovitium. Cranks in the United States, I believe, means somebody who has some idea in their heads that they are convinced is right with a relative absence of evidence and go out trying to convince the world of their idea. Okay. Right. So the aging world,

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The problem of aging has always attracted cranks. It did in ancient civilization, it does today. So I saw a YouTube on this man who literally spends $2 million a year to stop the aging process and he detailed through, I didn't listen that long, supplement, et cetera, et cetera, and he would be a crank then? No, he would be the dupe of cranks.

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Um, yeah. Um, unfortunately there are lots of cranks in the world with prestigious degrees and some cases prestigious academic positions. So ever since 1975, I've been probably the most skeptical person who works in the aging field, not the most skeptical critic of

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research on aging because there are lots of people who love to throw fire bombs at anything, especially a field like aging, which has had, as I've said, a long, deep and shameful history of crankery and flagrant con artists. So, I mean, it took John Maynard Smith and Brian Charlesworth, both became fellows of the Royal Society.

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Brian Charlesworth became a Royal Society professor, which is probably the most prestigious kind of professor in Britain. It took them more than a year to convince me that I should even try to work on aging. And what convinced me was mathematics. The mathematics done by William Hamilton, another Royal Society professor,

08:00
greatest evolutionary biologists of modern times, and in fact, Brian Charlesworth himself. And their mathematics convinced me there was a very cogent evolutionary theory of aging. They convinced me that there was a very cogent evolutionary theory of aging, and that that theory needed experimental testing. Now, I had already been working as a theoretician

08:30
for three years prior to 1976. And I knew that you could imagine any kind of theory and dress it up so it sounds respectable. Firstly, verbally, and biology has a long and embarrassing history of verbal theories, which don't hold water when you examine them mathematically. And that is to say, they do not make any sense whatsoever. And there are a lot of those in aging research.

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The second step in examining any hypothesis is to develop it mathematically so that you can see exactly how it works. Famous examples, Newton, Einstein, okay? And evolutionary geneticists, which is what I am most specifically, basically took the ideas of Charles Darwin. And starting in early 1900s, he was a very, very, very, very, very, very, very, very,

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developed the mathematics to see if those ideas would work. They do actually work very nicely mathematically. Interestingly, really good experiments on those ideas really didn't start until the 1910s. A high volume of experiments testing Darwin's ideas didn't start to come out until the 1920s and 30s. Here I am, 1976. I'm being told by Chiefly Brian Charlesworth.

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look, there's this then at that time, approximately 50 year tradition of good theory, mathematical theory being done. Charles Wirth had done more than anyone now living to advance that theory. It was my job to go into the lab and test the ideas. How do you test an idea like aging? What did your research entail?

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We're now 47 years later. It entailed a lot. I published around half a dozen books on the subject. I've published more than 200 articles on the subject. I have 341 besides your name, actually. Okay. Whatever the number is. That research has been cited tens of thousands of times. I have had

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Thousands of people work in my laboratory with me over the last 47 years, and we have published millions of words and collected probably more than 100 million individual pieces of data. So it's a very large volume of work. And just this summer, we published a book called Conceptual Breakthroughs in the Evolutionary

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which not only summarizes our work, but the work of everybody in the field starting in the 1880s. Wow. Okay. And we go chapter by chapter through the entire history of the field, most of which is the last century. Michael, so with regards to your theory on aging, how does that or did that at the time sort of challenge other?

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thinking around aging and what happens in the aging process? Okay. So initially, my work did not involve any really creative new theoretical work of my own. I was mostly an experimentalist. A problem with the experiments that I was doing during my doctorate was that they did not support the favorite hypotheses of my doctoral

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which he had in fact convinced me of. I like to do strong inference experimentation, which if you're an objective scientist and you look at the results of one of my papers, I hope you'll be convinced because we bring the largest quantity of data to each of the questions that we examine of any lab in the world. And we did that right out of the gate.

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What was his theory of aging that he was hoping you would prove? Excellent question. His theory is what he and I call mutation accumulation, which is not about somatic mutation. It's the idea that, have you ever seen the film Gone with the Wind? Yeah. Okay. So Gone with the Wind is from a cis male heterosexual standpoint.

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to me, the story of Rhett Butler's progressive exasperation with Scarlett O'Hara. Finally, at the end of the movie, he says to her, frankly, I don't give a damn as to where she will go and what she will do. That's the basic idea of mutation accumulation, that evolution by natural selection, frankly, Scarlett doesn't give a damn about what happens to you when you're...

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past your reproductive years, and it will let you go to hell physiologically. And this theory mathematically is beautiful. It makes an enormous amount of sense. The only problem with it was that none of my experiments, which were designed to support it, in fact did support it. All my experiments constituted evidence against it. And instead, my early experiments supported the alternative idea

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which again was not my hypothesis, though I named it antagonistic pleiotropy. And antagonistic pleiotropy, which is now a generally used concept in genetics and evolution and aging research, is the idea of alleles, genetic differences, having both beneficial effects and deleterious effects. It's not the idea that they always have these mixed effects.

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but that if there is a specific kind of mixed effect, it will foster aging. And the specific kind of mixed effect is when you have a genetic variant that enhances your net reproduction when you're young, but kills you later. The natural selection says, yeah, I don't care about older you, I just want younger you to be hot and reproductive.

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and active and pump out offspring for the next generation because that's the way the mathematics works. Okay, so it's optimizing reproduction at the expense of later years. You could say that. It's a little more complicated than that because it turns out when you have real population genetics, evolution doesn't optimize. That's just a mathematical convenience for

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working on segregating genetic alleles. What it does is, much of the time, it comes close to optimizing, but it can't really get there because genes don't lead to optimization in Mendelian sexual populations like ours, which is why all kinds of weird things happen like sex chromosomes and males, which if evolution were optimal, there would be no males and no Y chromosomes.

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so on because males are a suboptimal aspect of evolution. That's another area I've worked on. This actually provoked me to do my first original theoretical work on the evolution of aging, which was a series of papers on antagonistic platypathy, wherein I showed that antagonistic platypathy is very likely to be a big part of the evolutionary story of aging. I think,

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50 years of research on this point have supported that. There are some special cases, especially in small population sizes, like you get in labs and Pacific Islands, where mutation accumulation is important. But the dominant thing, I think, all the data and theory show is antagonistic pleiotropy, which is evolution sacrificing your health in later life for your health and health.

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reproductive activity when you're young. Okay. And so if I'm, so just as a normal person hearing this, what does it mean actually? Well, there's a very elegant phrase, which is, you know, I've had six children. The phrase is the cost of reproduction. Yeah. Reproduction is debilitating.

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And the more effort you put into reproduction, the more debilitated you are. The most famous example of that is the Pacific salmon, which basically dies at the very onset of its reproductive career. They can live for years out in the ocean. They swim upstream, they're a natal stream. They literally have gigantic Pacific salmon orgies in these streams, squirting gametes out everywhere.

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and within days they're dead. Okay, now while they're dying, bears and eagles and falcons love to feed on them, but they're gonna be dead within days anyway. It's a cost of reproduction. So that's a very tangible experience to anybody who's taken care of newborns. Yeah, yeah, for sure. And human. And I guess just thinking about it

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biology perspective, just what it takes to grow a human and deliver a human and the nutrient depletion and sleep like all of it. All of it. I understand. All of it. Debilitation. Yeah. Debilitation. Yeah. And was it accepted at the time, Michael, like your theory of aging? So the original idea.

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is not mine. That idea has been around since 1946, presented in words. I was the person who converted the words most thoroughly into mathematics. Yeah. Okay. And then I was the person who provided the bulk of the experimental evidence for this theory. But now there are dozens, hundreds of papers which invoke antagonistic pleiotropy in the context of aging, of cancer, of many other.

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It's such a prevalent concept. Nobody even knows that I invented it as the phraseology and that I did the math, partly because biologists don't like math. Yeah. No, I don't know. And other than mathematicians, I guess. So, on the basis of sort of what happens at that sort of genetic basis, if you like, I'm not even sure if that's the right way to describe it.

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does the environment then layer on top of that? Like, I've heard you speak on that evolutionary mismatch. What are some significant differences in particular diets that might lead to more deleterious sort of outcomes? Okay, so there are three different ideas to think about when we're

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only well adapted to diets that their ancestors have been exposed to for many generations. You might think in the abstract that a fruitarian diet supplemented with tofu would be the perfect mammalian diet based on some set of stories you want to tell yourself. There's some reasonable stories there like

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saturated fat is hard to transport through our circulatory system. But if you give a cat a diet primarily based on plant products, you will get a very sick cat because cats have been living off of small prey for thousands and thousands of generations. That is what they are adapted to. So you can only be healthy on a diet which has been part of

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the normal diet of your ancestors for hundreds to thousands to tens of thousands of generations. First basic principle. Second basic principle, and this relates to antagonistic pleiotropy and the cost of reproduction. In animals that have a great deal of flexibility in their reproduction, and one of the best examples of this is actually rodents.

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So rodents have a tremendous capacity to take in a lot of nutrients and convert them into offspring by enormously expanding their investment, literally as females, in their uterus and then in their lactation to produce a large number of pups. So rodents can go from hardly reproducing at all with a low caloric and nutrient intake.

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to reproducing explosively, like more than 10 pups per litter, possibly. When they've got the nutrients there. When they have an abundance of food. That's also something that we have worked on in the lab. Basically if you're given you, especially being a female, but to some extent even males, if you're a flexible reproducer and you can reproduce.

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from the dozens to hundreds of offspring within your breeding period.

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you will pay an enormous physiological cost for doing that, in terms of your survival. So the greater amount of food gives you much greater offspring, but that's going to tend to kill you faster. And natural selection loves this trade. Okay? I'll give you a still more concrete example of this, which I call the Jimi Hendrix effect.

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which is, you know, in the late 1960s, Jimi Hendrix was the ultimate guitar god of rock music. And he was notorious for his prolific sex life. And he died at 27. And he died because he led a very self-destructive lifestyle. And in our lab, we can emulate this by giving males

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unlimited supply of females that enthusiastically want to copulate with that male. Normally, when we handle males in monogamous or one male, one female, or normal social conditions where there are lots of females who will say no to this male, they might copulate once or twice a week maximum.

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This is an interesting scaling variable for human males. If you give them unlimited access to enthusiastic female partners, they will have sex to the point of fertilizing those females, starting off between like four to nine females a day, day after day, until they're dead.

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and death follows very swiftly. They usually die within about a week. Goodness. Well, it seems like quite a lot of work. Well, ironically, copulation tends to last longer on average in Drosophila, the fruit flies I'm talking about, than it does in mammals. Oh, wow. So ejaculation, basically, continuous male orgasm, in a female fruit fly,

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lasts on the order of 20 minutes. Right. Wow. And during that time, they are pumping a large volume of sperm relative to their body size. Yeah. Whereas in mammals, sex generically lasts like half a minute to six minutes, as many disappointed females discover.

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Whereas it's a relatively trivial fraction of time, energy, and literally bodily materials for a mammalian male. But in a fruit fly male, it's a massive commitment. How long do the fruit flies actually live? Just thinking the relative lifespan compared to the amount of time they spend ejaculating, what's that, half their life?

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So fruit flies are not mayflies. Mayflies may only live hours as adults. Fruit flies can live for weeks depending on how much nutrition you give them, the reasons we're discussing now. If you give them very little nutrition, it's not a big problem for the total and you deny them sex. It's not a big problem for a fruit fly to live 60 to 70 days.

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Okay. Yeah, yeah. No longer than I thought, actually. Yeah, most people don't know that. So you can just crudely think in terms of a day for a year as a way to think of it. Of course, for the last 46 years, I have been coming up with evolutionary genetic and nutritional tricks to control how long fruit flies live, both males and females.

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And if you want a female to live longer, you will reduce her nutrition so that she then has much lower egg laying and she'll live actually in her case only 10 to 20% longer. In the male, as I've just said, you give them unlimited access to females. The male will copulate himself to death within a week, roughly. If you keep them as virgins, then they can live 10 times that.

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Michael, what you just described with regards to reducing caloric intake in the females is that the basis for a lot of the longevity theories out there now that if we, the calorie restriction theory of longevity, you know, we just like eat 30% less from now until the day we die and we'll be miserable but also live 30% longer. Is that about right? Oh, nicely, nicely posed. So if you're a rodent,

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especially female rodent, and you restrict your food intake by about 50%, enough to survive, but too little to have much reproduction at all, you can roughly double the rodent lifespan. Depends on the strain, depends on the species, but huge impact. To me as an evolutionary biologist, that makes perfect sense because rodents put enormous amounts of energy into reproduction, and they have tremendous reproductive flexibility.

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It was pointed out to me by a former postdoc of mine, Jay Phelan, that primates generically don't have that great reproductive flexibility and one of the least reproductively flexible species is humans. Fruit flies are actually in the middle. Jay Phelan and I did this quantitative study of the impact of nutrition on longevity.

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He came up with the best data, which are Japanese. I did some sort of extreme all mathematical analysis. And the estimate that we came up with was that the maximum plausible benefit to lifespan, and in our case, we were mostly analyzing males from very substantial caloric restriction was two to four years. That's if you get all the nutrients exactly right.

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And you don't die of infection, which is a very big risk at low body weights. You don't die of suicide, a very big risk at low body weights. You'd be relatively infertile. You'd probably be somewhat cognitively impaired. Or the majority of people who have a diet like that, they go off it immediately. As soon as they're given access to food. But there are

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are some, Roy Wohlford is my favorite example, who are happier on that diet, although Roy Wohlford died, in my opinion, relatively young, I think in his 70s. And he died of ALS, amyotrophic lateral sclerosis. Very, very sad, I liked the guy enormously. He was like the ultimate cool dude. Nobody was cooler than Roy.

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Actually, there was kind of an experiment done on human caloric restriction with and without isolation. One example is Okinawa, which because of its unusual placement and its lack of – relative lack of rice cultivation, and things like the Second World War and its prequel, which was war.

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between the Japanese and the Chinese and places like Manchuria. And then the devastation following the Second World War, they had a protracted period of restricted availability of nutrients on top of an economic situation which generally didn't give them that much access to nutrition. And they are quite famous for being long-lived. In fact, we use their data in our analysis of fluoric restriction.

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The other contrast is Cambodia between 1975 and 1980, where they did a multi-million person experiment in caloric restriction. But in Cambodia, in addition to the people deliberately killed by the Khmer Rouge, many, many people died of things like colds, influenza, tuberculosis, and so on. The difference is that in Okinawa, the indigenous populations were largely protected.

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from pandemics or just routine diseases passing through. In Cambodia, they were completely exposed. So if you're on the brink of starving to death, literally one round of influenza can kill you. I don't recommend severe caloric restriction to anyone as an anti-aging method. Having said that, I have to say that most people on the standard American diet, which is now becoming the global crap diet,

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people on that diet overeat titanically for at least two reasons. The first one is those foods are designed to be addictive. Good luck eating just one potato chip. Once you pop, you can't stop. Yeah, one kernel of popcorn, half an ounce of high fructose corn syrup, sweetened soda. It's addictive stuff.

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So there's that aspect to the whole thing. So in addition, we live in a culture, I mean, I live in the United States, where food is such a big part of our culture and it's all over advertising. So we're encouraged to become food addicts. Agribusiness profits off of food addiction.

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We're vulnerable. I mean, you know, we all need to eat food. So resisting the insanely sweet, salty, mouth-feel foods that have been literally engineered to get us addicted to them. Good luck. And I've heard you talk, if we relate it back to your, the sort of theory on aging and, obviously you'll correct me if I've

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got this wrong, but that sort of during the reproductive years, it appears less important because the priority is reproduction, that in fact, under these suboptimal conditions for diet or whatnot, we're still able to reproduce. But it's in our later years post-reproduction where it can be even where the effects of the diet are far worse. Have I got that correct?

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I mean, in general, young people can survive abusing their physiologies better than older people like myself. But there's an additional factor. This is the third factor. And that is natural selection acts tilted toward the young in general. That's the basic antagonistic pleiotropy principle.

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Even a healthy organic agricultural diet, which is fantastic for people with agricultural ancestry, like Europeans, Asians, people with those ancestries, in our early years reflects very rapid adaptation to agriculture over the last 6,000 to 12,000 years, depending on which particular ancestry you have.

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But remember, the basic idea is Rhett Butler getting fed up with Scarlett O'Hara. Natural selection is getting weaker and weaker as you get older, or more precisely, the action of natural selection acts most powerfully on the young, making the young best attuned not only to longstanding diets, but new diets, new diets in our evolutionary history. So if you're from Iran, Iraq, Iran,

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Shanghai, you're under 30, you're really well adapted to the historical agricultural diet of your area. When you are 60 or 70 years of age, I don't care where you're from, you're not adapted to an agricultural diet anymore because the adaptation process is accelerated for the young.

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And that was a theory, was an idea I first had around 2010. And I published with others a verbal proposal of that in 2011. We then did some math, the math worked. We then did a whole bunch of experiments and we published those experiments in 2020 and 2021. The first author was the doctoral student, Grant Rutledge, R-U-T-L-E-D-G-E.

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who is the primary experimenter on those projects. And the experiments dramatically illustrate that if you've been through a recent change of diet, even for hundreds of generations, and most people who do the reproducing are young, which is the human historical case, at least since the advent of agriculture, then it's your...

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really only going to be adapted to it when you're a child or a young adult. And then when we get older, we are less adapted to the agricultural diet, as you said, we're not adapted. So what is the implications there if we continue to consume the diet that we did when we were younger? Okay, so you live in New Zealand and people with strictly Maori ancestry are made sick by the organic,

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agricultural diet. It's the wrong diet for them. But the truth is that if you're over 60, the way I am, you're not much more adapted to it than the Maori are. After the age of 60, we're all Maori in that sense. What kind of foods then are the—I mean, obviously, I'm just going to say obviously,

38:19
the three primary ingredients of the ultra-processed food in the diet. But what about things like bread and pasta and rice and dairy? What's this story there? Those are great foods when you're 12 and 22. But if you're 62, forget it. Yeah, just ruining yourself. Yeah. And is this going to be an obvious, is it going to be obvious to the individual? And

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is that I work with a ton of people who are around my age and older and that perimenopause many menopause stage, obviously I'm talking about women in this stage, and they start experiencing symptoms of food intolerances like they're no longer able to tolerate dairy, they get bloating or inflamed, gluten gives them brain fog, whereas this didn't happen sort of 20 or 30 years ago.

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Is this what you're describing? Yes. Are there people who might not have a noticeable change in in how they feel, yet you would still say, you know what, you're over 50, that is not an ideal food choice for you? Okay, the generic, more than generic, the general effect of eating the wrong diet for your evolutionary history is inflammation. Okay. Inflammation as an initial

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pathological response to diet, then fosters high blood pressure, cancer, brain fog leading to dementias. So do you really want to die for pizza? I mean, it's your choice. I literally have colleagues who know the science, agree with the science, sometimes are even involved in the science. They're willing to die for pizza.

40:18
I am not willing to die for pizza. So I had my last conventional pizza more than how many years ago now? More than 15 years ago? So your research then, and what you describe with your colleagues, I mean, I see that quite a bit as well. And I imagine people in their sort of fields of expertise may see it in Illustrated or things like that Illustrated quite a bit.

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How long, so Michael, you did the research and got the results. At that point, did you go, huh, I've really got to think about what I'm doing? Or like, what was the trajectory like for you personally? Okay, all right. Are you willing to hear a five minute story? Yeah. Okay. So I have a lot of Scottish and Irish ancestry.

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So very peripheral to Eurasia. And I first was diagnosed with grass allergies when I was a teenager. Then in my 20s, I realized I had problems with milk. Then in my 30s, I discovered I had favism, which is an intolerance of legumes. Okay. So I started restricting my diet in my 20s.

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And in my 40s, I was developing significant, life-threatening GI tract problems, mostly with myosophagus. And I noticed that the more stringent I was about avoiding the foods that I had diagnosed problems with, the better off myosophagus was. But I was still having problems, and I couldn't figure out why.

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Then, this was October of 2008, a friend of mine I was meeting with complained of some of the same problems I had with my esophagus. And I said, well, you know, you should really see a doctor about that. And he did, and he had esophageal cancer. And he died about three months later, two days before I finally got an appointment with a diagnostic gastroenterologist about my problems.

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And they took my blood pressure shortly before that appointment, which was like within two days of my friend dying and my systolic blood pressure was temporarily like 200. Unsurprisingly. I mean, I calmed down and it went way down. But it took me five minutes. And so I see the gastroenterologist, who's still my gastroenterologist, all these years later.

43:15
And I explained to him all my struggles with my diet and all my diagnosed food allergies and intolerances and all my esophageal symptoms and so on. And he disappeared, he came back and he said, he handed me a printout because by then he knew I was a biology PhD. And he said, you have eosinophilic esophagitis. I said, what's that? I've never heard of it. And he said, basically it's an acute inflammatory condition.

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which causes esophageal problems. Then I asked him, so what can I do about this? He said, well, we have two main alternatives. One is I can give you glucocortico steroids to reduce your inflammatory response in general. I said, no, thank you. I've seen what decades of glucocortico steroids can do, like chronic edema, brain fog, and so on. No, thank you. What's the other option? He said, well, you can go farther with being restrictive with your diet.

44:16
And I thought, wow, I'm being pretty restrictive already. So what's going to be left for me to eat? Furthermore, I was then at a seminar within a few months where it was pointed out to me that, though I was thinking of the cereal species like wheat, rye, barley as very different from rice and corn, they were in fact all grass species. And I knew I had a severe grass allergy. So I thought, huh.

44:45
maybe the key is to eliminate all grass species from my diet. And then, you know, I had been eating like cooked cheese to that point, like pizza. And I realized, well, if I go farther, I have to eliminate everything from a mammalian udder. Goat cheese, cow cheese, doesn't matter. And then finally, I was still exposing myself to stuff like soy oil and stuff, which is one of the hardest things to avoid in a modern.

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modern world. So I started to become way more stringent about legumes. And once I'd done all those things, within six months, my health was transformed. Wow. And in all kinds of ways, large and small. Number one, my esophagus was a lot better. Number two, the typical, you know, I was in my mid-50s, middle-aged backache, that was gone. Brain fog, that was gone. Stamina, that was improved.

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just went on and on. And I thought, what the hell? Yeah. You have incredible skin, by the way. You look a whole lot younger than your actual age. 68. Thank you. So I thought this is like the weirdest thing that's ever happened to me medically. So I thought and I thought and then I thought

46:11
Hey, everything that I've completely eliminated from my diet is a novel agricultural food, which we never would have consumed in large amounts before the advent of agriculture. And then I thought, well, that doesn't make sense to me. As an experimental evolutionist, I know you can get very rapid adaptation over the course of hundreds of generations. And then the penny dropped. And I realized, but no, it's the Rhett Butler problem.

46:39
the health of me and my ancestors late in life. When I was younger, I could eat the pizza and not pay a big price for it, although I paid some price. And as I've gotten older, I've become less and less tolerant of those things. And then I realized, oh my God, this is a completely general evolutionary genetic idea. This is one of my aha moments in my career.

47:07
So I turned to my very good colleague Larry Muller and we do the math and do numerical calculations and the idea works. Your adaptation to an evolutionarily novel but not completely novel diet is weighted in favor of the young against the old. So yeah, young people can do really well on organic agricultural diet if they have agricultural ancestry, not malories.

47:36
not Australasian Aboriginals, right? But most people with Eurasian ancestry have lots of history of selection that adapts them when they're young to an organic agricultural diet. And it's very important to say no one at any age is adapted to high fructose corn syrup, seed oils, processed seed oils.

48:04
and so on and the long list of gums and emulsifiers and everything else is added to our diets. The modern, I call it standard American diet, but now really standard global diet, is completely toxic for absolutely everyone and it sets you up for a lifetime of health problems, of food addictions. I think those food addictions can lead to more general forms of substance abuse.

48:33
and sets you up for obesity and all those things. But even if you're a conscientious, like nutritionist, concerned about your health, what you need to do for the first 30 years of your life, what you can do, is completely different from what you should do for your last 30 years of life. Okay? And in between there's a transition. So between the ages of 30 and 50, you're in transition.

49:02
is sort of the age that I was asking about or talking about with the people that I see in and around at 30 to 50. Michael you're, so obviously in sort of mainstream the idea of a paleo diet is much more mainstream now than what it might have been as when you were experiencing your health difficulties. At that time did you come across the work of Lauren Cordain and others who...

49:29
sort of researched in that ancestral diet space? I actually met, it was either Boyd or Eaton, a Boyd and Eaton fame who published on this, I think in the 1980s. I really wasn't convinced because I was an experimental evolutionist and part of what I've done in my career is make something evolve from one thing to another. I have used evolution, that's one of the methods I've used, to produce animals that live

49:59
twice as long. Okay? And then conversely, I can take animals that live twice as long and make them live half as long as that. You know, it could back and forth. Complete, complete power. So my intuition, like many evolutionary biologists, was that the paleo idea was based on the misconception we get from Darwin that evolution only proceeds very slowly. Now that was frankly a prejudice Charles Darwin.

50:29
came by from being a uniformitarian geologist, a student of Charles Lyell, literally. It's not actually correct. Evolution by natural selection can work with incredible speed, so long as it is working with maximum intensity, which it does on the young, but it doesn't for the old. So originally you weren't convinced, did you?

50:58
Not at all. Yeah. And did that change or did you think, oh, yeah, yeah, yeah. So where are you at? So yeah, because that's interesting, isn't it? You basically proved yourself wrong. Well, I've done that repeatedly, but I've also had the pleasure of proving many other people wrong. So I have no respect for biological intuition. If there's anything that in my experience is consistently wrong, it's human intuition

51:28
biology. And number one about aging, if I hear somebody talking about, you know, TNF metabolism or FOXO or rapamycin, and they're using words, okay, I never believe them. Yeah. They may, and there are two levels to my disbelief. Firstly, I don't think any biologist whatsoever.

51:55
is very good at figuring out all the different things a particular enzyme will do or a particular gene will do because of the word pleiotropy and antagonistic pleiotropy. Pleiotropy means one gene, many effects. As soon as you get – and that's the generic condition is pleiotropy. We're now learning enough genomics, transcriptomics, metabolomics to understand that our physiology is a vastly complex network.

52:25
The way to think of the physiology of your body is like all the stuff that's going on on the entire worldwide web. All right, that's how complicated human physiology. And if you think you can talk your way to an insight about that, well, you're either very close to a deity or self-deluded. Yeah. Okay. I haven't personally met any deities walking around.

52:54
telling me about which pathway will do what, using verbal reasoning. However, we can now figure out what genetically underlies a complicated character. The character for which we know most about the genetic determinants of that character is human height. And that's not only in humans, that's in everything.

53:21
there's been more genome-wide research on human height. And what that research shows overwhelmingly is hundreds, if not thousands of different sites in the genome contribute to the genetic determination of height. I have done, using somewhat different methods with a whole bunch of colleagues, analogous work on the genetic determinants of aging.

53:50
In fruit flies, which is a lot simpler than human aging, a minimum estimate for the number of sites in a fly genome that controls its aging is greater than 500. 500. And it's not like there are two or three master genes. And interestingly, almost none of those 500 correspond to the usual Drosophila geneticists

54:19
genes that control aging in fruit flies. So humans suck when it comes to analyzing aging. They even suck if they have a lab because if they have a regular lab and they're not doing genome-wide research on large numbers of animals, which means actually tens of thousands to millions, they just don't have enough data.

54:49
I'm not saying that my standard molecular genetic reductionist colleagues with their stories about aging are always wrong. So we found one gene in our genomic studies which turns up, which is also talked about by cell molecular geneticists who study aging, and that's superoxide dismutase. That appears to be important.

55:18
And there's a way to do this statistically. And you take random guesses about what's going to work in the genome. And you line up the random guesses against all the cell molecular genetic stories against hardcore genomic results. The random guesses do better than the stories that molecular geneticists will tell you about one gene or another. Is it just a lack of data at this point? Or?

55:49
It's so unknown, isn't it? We're at a certain point in research with everything, but there's still so much we don't know. Circa 2000, Craig Venter created modern-day genomics. Not only could modern-day genomics answer these questions, we, my colleagues and I, have been doing this since 2008 and publishing our results. There are well-established methods now for answering these questions.

56:19
They involve genome-wide sequencing, transcriptome-wide sequencing, that's all the RNAs that your DNA makes. They involve looking at all the metabolites, and we're doing this and publishing it. And by we, I don't just mean my lab now, there are other, more and more labs are doing this. So the way ahead, very simply, is the world of omics, multilayer omics, genomics, transcriptomics, proteomics, metabolomics.

56:47
We can answer all these questions, and we already have initial answers at genomic, transcriptomic, and metabolomic levels in fruit flies. Now that before your listeners think, well, fruit flies, who cares about them? Well, fruit flies, Drosophila, have been the pioneer organism for a large fraction of all of the biological and biomedical breakthroughs of the last hundred years.

57:17
We only figured out genetics and how chromosomes worked thanks to fruit flies. We figured out developmental biology with fruit flies. We figured out neurobiology with fruit flies. And in fact, since the 19 teens, so for more than a century, fruit flies have been the most powerful organism for us to understand aging in animal species, where animal means more than mammals, includes insects and so on.

57:47
So once again, the fruit fly is our omic pioneer for unraveling, for penetrating into the mysteries of aging. Okay, so if I'm on Twitter and I'm reading someone's claim that their lab found something affected this pathway, the Foxo pathway, and now I should...

58:15
now I'm like, oh, maybe I should take something to boost my NAD that's a little bit too reductionist. It's radically too reductionist. I listened to a podcast summarizing 10 or 12 human studies on NAD and related forms of supplementation. No robust positive results at all. And that doesn't mean that people's favorite supplement might not be a good idea.

58:44
And there are ways to combine bioinformatics with omics, with large amounts of data, with machine learning, you can call it AI, to test whether or not NAD and related forms of supplementation have any prospect of working. What about sauna or cold plunge or cold water immersion? Do you have any?

59:12
opinions about those as they might impact aging or longevity. Okay. So you know the term hormesis? Yes. So we've basically been studying hormetic effects for more than three decades. If you mess with an animal in a way that reduces their reproductive effort,

59:42
but doesn't threaten their survival, they will tend to live longer and be more robust. Stress resilience. Well, stress tunes down reproduction in all its forms. Now, in males, a big aspect of reproductive effort is hanging around and attempting to court females. Okay. So that's...

01:00:11
Physiologically, it seems like males don't invest much in reproduction. In terms of tissue-level male physiology in humans, that's true. But if you think in terms of all those males hanging out on online dating or going to clubs or trying to become rich and famous, e.g. Elon Musk, that's a huge amount of effort. Okay? If all you want to do is survive.

01:00:39
as a male, you really don't need to do that. Okay? So anything you do, so caloric restriction, a lot of exercise, extremes of temperature, and so on, so long as you're not impairing your survival capacity, but you are saying to your body, wow, physiologically, you're

01:01:08
This is a bad time to do something as expensive as reproduction. Um, that will enhance your survival and functioning a little bit because we're not a very good candidate for hormesis. Okay. Rodents are excellent candidates for hormesis because they, if you give them lots of food and great conditions, they'll reproduce explosively. Same thing as turn fruit flies.

01:01:38
They're good candidates for hormetic effects. Okay? Hormetic effects do in fact work in humans, but I think a much more profound benefit can be obtained by adjusting your diet to your age and your evolutionary history. So that's the big dial mover, diet. What about exercise? I mean, you mentioned exercising a lot, but that must play a role as well.

01:02:06
Yeah, so extremes of exercise kill humans sooner. Extremes of exercise can kill you, especially if you're over 40, like in an afternoon. But even when you're very young, so people dropping dead from heart valve problems who are athletes, unfortunately, is too common. But moderate levels of exercise is what hunter-gatherers do all the time, every day.

01:02:37
They do not sit on their butts for hour after hour, whether doing podcasts or attending lectures or driving cars. That's not their lifestyle. But nor are they Olympic athletes, it should be said. There's this myth that all hunter-gatherers are running 30 miles a day. Absolutely false. In fact, if you look at the total metabolic expenditures of hunter-gatherer populations compared to

01:03:06
everyday Americans, it's about the same. Yeah, that's interesting, isn't it? Well, I think a key to understanding that is realizing that your brain can use up to 50% of your serum glucose in a day. Now, if you're doing any type of activity, that proportion falls. But we have a very metabolically expensive brain. But, you know, we spent more than a million years with hunter-gatherer lifestyles.

01:03:36
That's the permanent residue of adaptation that is there for us once we're over 50. It's not just the diet. Once you realize the evolutionary pattern, which is that as you go forward in chronological age, you go backward in your evolutionary history, you realize you shouldn't just walk the way agriculturalists walk. But the more activity

01:04:05
that is not life-threatening that you can go through in a day, the better off you're going to be. Yeah. And is that what you do as well, Michael? I wish. If I didn't have my two youngest children to take care of, yeah. But on the other hand, having two young children to take care of, and by young I mean under 20, means I'm constantly having to get up and do things for them, from cooking to addressing their issues to...

01:04:35
breaking up their squabbles. So it literally keeps me on my toes. And I'm retiring this year, but I used to walk to my office building and then stand up and give anywhere from one to six hours of lectures a day. So I was very active. Now that I'm retiring, I have to find...

01:05:04
think of ways I can be as active. Because inactivity kills you. That doesn't mean you have to be an Olympic athlete. Like literally just walking a lot and carrying stuff and avoiding sitting for long periods, which unfortunately I've been doing. The more sedentary you are, that's the second terrible thing you do. The third thing might not occur to most people, but occurs to me.

01:05:33
which is humans live in tribes. These days we live in metaphorical tribes, but before the advent of agriculture, we lived in tribes of 40 to 120 people all our lives. We might switch tribes from time to time, depending on fights, usually over some mating situation. That hasn't changed. But the modern

01:06:01
atomistic social life where, you know, we see the people in our nuclear family and a small number of people at work, for most of us, that's really unnatural. We thrive in tribes. If you don't have a tribe, get one and spend as much time as possible being with them face to face, talking to them. Yeah, yeah, for sure. And

01:06:29
you got that sorted for when you retire? Again, that's a project. My academic lifestyle was very good in terms of points two and three. Yeah, for sure. Absolutely. When I added the diet component, it really was a health revolution. My friends basically perceived me as having reverse aging on a scale of five to 10 years.

01:06:58
I will also say anecdotally, the people I've persuaded to fully take my advice, which is mostly people very nerdy like myself, they have also experienced health revolutions where they go back. And there's one last thing I would really like to leave your readers, or listeners I should say, with. And that is the most important fact about aging that has been established over the last 30 years is that it stops.

01:07:28
it stops later in life. And when it stops, it depends on your diet. On the standard American diet, there's more than enough data to show you continue to age until you're 105 and trashed physiologically. On an organic agricultural diet, which came to an end in the 1920s, people who live their whole lives that way, they stop aging at about 90.

01:07:58
There is the possibility, not yet shown in any data, but it's in our math, it's in our experiments, that if we adopt a hunter-gatherer diet after the age of 50 and lifestyle and have a tribe, we might stop aging in our 70s under vastly better health circumstances than the other two diets.

01:08:27
or the organic agricultural or standard American diet. Now, you're not talking about living forever, though, are you? Well, technically, when you stop aging, you have biological immortality. Age means not that you have one or another level of. Likelihood of dying in a year, it means that likelihood of dying in any year is getting steadily worse.

01:08:54
So the most important thing anybody could do with their aging is to stop it. And my thumb level, thumb on the scales level guess is that on fully hunter gatherer lifestyle or as close as you can get to it, that aging stops somewhere in your 70s as opposed to your 90s or your 100s, the way it does on the other two diets. Because you're taking full advantage of the residuum

01:09:24
of a million years of selection for adaptation to a hunter-gatherer lifestyle. We've only had on the order of 10,000 years of adapting to an agricultural lifestyle and most of those benefits go to the young, not to the older. And nobody's adapted to the standard American diet. That's why it steadily kills us all the way to 105. Yeah. Things are worse and worse. And Michael, just one last thing. Do your kids listen to you?

01:09:54
Well, they don't really have to listen to me except when I argue with them about high fructose corn syrup and seed oils. Because they're young, they don't really need to worry. My oldest is 38 and he's noticing that if he avoids gluten and dairy, he does better. Yeah.

01:10:19
I have to say that you are certainly a very good example of the principles that you've just outlined for the listeners in terms of aging and how to stop aging essentially, and also like quality of life as you age as you get older. That's what I meant. I do actually have one final question. So the hunter gatherer diet is appropriate.

01:10:48
your ancestry. So actually, like understanding where you're from would play a big role in terms of figuring out the appropriate diet. Yeah, if you're Maori, you could never eat pizza. Yeah, basically. If you're Italian, you can eat pizza into your 30s. Yeah. Yeah. Okay. Yeah. You know, I once did actually buy an ancestry DNA kit, which I've never done. I should probably try and hunt that out just to... I mean, it's actually...

01:11:17
You know, it matters when you're under 30, but over 50, the only thing I think our bodies are good at is leading a hunter gatherer lifestyle. Yeah, okay. So it doesn't matter. No, okay. And actually, I am closer to 50 than I am 30. So yeah, good call. Michael, thank you so much for your time. And I will pop.

01:11:46
links to your ResearchGate page, to your books as well on my... May I make some suggestions about that? Yeah, please. Much better than ResearchGate and unencumbered by attempts to get you to pay money is Google Scholar. Okay. And I have a Google Scholar page with my middle initial, Michael R. Rose.

01:12:15
And everything is free there. Secondly, I have a free website called 55, numerals five five, theses, t-h-e-s-e-s dot org, where everything I've been saying to you today is presented in about 55, a little over 55, little mini podcasts. Brilliant.

01:12:44
And with each pod cast is a sentence that summarizes the podcast. OK, well, that is awesome. And I will put links to 55 thesis and the Google Scholar page for Michael R. Rose into the show notes. Thank you so much for your time, your evening. And today, I really appreciate it. It's been fun. Thank you.

01:13:22
Alrighty so hopefully you enjoyed that conversation and as I said earlier definitely check out his Google Scholar page but also his website 55thesis.org which goes into a ton of detail. And next week on the podcast I'm excited to bring to you the conversation that I had with Dr Christabel Yeoh on mitochondrial dysfunction and fatigue.

01:13:51
Until then though, you can catch me over on Instagram, threads, and Twitter @mikkiwilliden, Facebook @mikkiwilliden, or head to my website mikkiwilliden.com and sign up to my recipe access. All right, team, you have a great week. Talk soon.