How To Reverse Your Biological Age with Dr. Kara Fitzgerald

Coming up on this episode of the Doctor's Pharmacy. I think that's another cool piece of evidence for our findings. I think, you know, if you have a condition, if you're diabetic or, you know, if you've got heart disease, et cetera, you're aging faster and by extension, if you turn that around, you should have even more powerful age reversal.

Yeah. Hey everyone, it's Dr. Mark. I know a lot of you out there are practitioners like me helping patients heal using real food and functional medicine as your framework for getting to the root cause. What's critical to understanding what each individual person and body needs is testing, which is why I'm excited to tell you about Rupa Health. Looking at hormones, organic acids, nutrient levels, inflammatory factors, gut bacteria, and so many other internal variables can help us find the most effective path to optimize health and reverse disease. But up till now, that meant you are usually ordering tests for one patient from multiple labs. and I'm sure many of you can relate how time consuming this process was, and then it could all feel like a lot of work to keep track of. Now there's Rupa Health, a place for functional medicine practitioners to access more than 2000 specialty labs from over 20 labs like Dutch, Vibrant America, Genova, Great Plains and more. Rupa Health helps provide a significantly better patient experience and it's 90% faster, letting you simplify the entire process of getting the functional medicine lab tests you need and giving you more time to focus on patients. This is really a much needed option in functional medicine space and I'm so excited about it. It means better service for you and your patients. You can check it out and look at a free live demo with a Q&A or create an account at RupaHealth.com that's R-U-P-A-Health.com I'm all about using food first when it comes to nutrition, but there are certain nutrients I recommend everyone supplement with because it's simply impossible to get adequate amounts from your diet alone. One example is magnesium, which our soils, well they're not too healthy and because there's no organic matter, they can't extract the magnesium from the soil, from industrial farming, which is a drag. And that leads to 50% less of these minerals in our food than there was 50 years ago. And then of course we're doing things that cause us to lose magnesium like sugar, caffeine, fluoride, even stress, which none of us have, right? 80% of Americans are actually deficient in magnesium. and that may mean insufficient, not necessarily true deficiency, but just not enough for optimal functioning because magnesium is so important. And it's a huge problem for our health. Considering the pandemic of stress, along with the pandemic of COVID that we're facing, we should all really be conscious about our magnesium intake because it activates the parasympathetic nervous system, which keeps us calmer and more relaxed. Magnesium is crucial for more than 300 other chemical reactions in the body and impacts everything from metabolism to sleep, to neurologic health, energy, pain, muscle function, and lots more. My favorite new magnesium is from a company called Bio-Optimizers. Their magnesium breakthrough formula contains seven different forms, all of which have different functions in the body. There is truly nothing like it on the market. I really noticed the difference when I started taking it, and I've tried a lot of different magnesium products out there. I also love that all their products are soy free, gluten free, lactose free, non-GMO, free of chemicals, fillers, and made with natural ingredients. Plus, they give back to their community. For every 10 bottles sold, they donate one to someone in need. And there's a lot of those. Right now, you can try Bio-Optimizers Magnesium Breakthrough for 10% off. Just go to magbreakthrough.com that's M-A-G-B-R-E-A-K-T-H-R-O-U-G-H.com slash Hyman and use the code Hyman10 and you'll get 10% off this really great formula.

I think you're going to like it.

As much as I do. And now let's get back to this week's episode of the Doctor's Pharmacy.

Welcome to the Doctor's Pharmacy.

I'm Dr. Mark Hyman, that's Pharmacy Without a Place for Conversations that Matter. If you care about figuring out how long you're gonna live, what your biological clock says, and how to reverse biological aging, well this is the podcast for you because I'm so lucky to have my friend, my colleague, my longtime collaborator, Dr. Kara FitzGerald as a guest today on the Doctor's Pharmacy. And Dr. Kara Fitzgerald has been in the field of functional medicine for decades with me. She's on the faculty of the Institute for Functional Medicine. She's a naturopathic doctor, but I don't think that describes really her depth and breadth of knowledge. She's been a leader in putting forth ideas around aging and methylation. And, I actually personally learned so much from her. In fact, we collaborated on a book together, which were really was the first case study book of functional medicine cases that came out of my practice and my patients, and we collaborated to write them up in a way that people could understand how the methodology of functional medicine works. I'm just so glad to have you on the podcast and talk about your new book, which is amazing, and also your research, which was really the core impetus for the book. And, the research really was about how do we reverse biological age. And, you actually, I'm going to give you the punchline, everybody, because it makes, I think, listen to the podcast. In a very short study, she showed she could reverse biological aging by about three years, which is no joke. And her book, Younger your, Reverse youe Bio Age and Live Longer is out now. I encourage you to get it. And we're gonna talk all about why it's important to know your biological age and what to do to reverse it. So welcome, Kara.

It's really great to be with you, Mark. I'm giving you a huge virtual hug. I mean, you know, I first started, like we released an ebook. We were, we were, talking about this to professionals back in 2016 and using it in our practice even before then. And you were really an early adopter. Like you lent me your ear on this content way back in the day. And it's, you know, you and Jeff Blanck, people who just kind of gave me a little nudge along, sort of, you know, by saying yes with your interest, with your, you know, your curiosity. You brought us into Cleveland Clinic. Center for Functional Medicine to train the nutritionists early. You guys were one of the earliest adopters of this material. And it just means so much to me. So I know we've been working together for a long time, like since the beginning of my career really. And I'm just grateful. So thank you. Thanks, Kara. It's great to be working with you.

You just make my life easier because I don't have to do all the work. People are smarter than me, working harder, doing the stuff. It's awesome. So let's get right into it. Your new book is really based on this study that you we did that showed a reversal of biological age. So, you know, we, we cannot change our chronological age. I'm 62. That ain't changing. It's just getting worse every year. Well, maybe not. Maybe getting better. And, but we can change our biological age, which is kind of a new discovery. Yes. And, which means that the, the, the youthfulness of our body is not fixed. We can literally not only stop it, but we can reverse our biological age, which we can measure through objective markers that are now available scientifically.

So.

You look at how this works through this phenomena of what we call epigenetics. And maybe you've heard about this people out there, epigenetics is a really cool idea. And it sort of, it sort of, you know, it goes back to the ancient debate between Darwin and Lamarck. Darwin believed in the evolution of species and natural selection. And Lamarck was like, hey, you know, traits can be actually inherited in a different way. and there's different regulatory things that are having to do with what's happening in the current life. And so they're both right, it turns out, that genetics is fixed in the sense of evolution and natural selection. But the epigenome, which is this super sort of control mastery system over your genes, the software, which regulates which of your bazillion genes gets read and which gets transcribed and what proteins get made, that's completely modifiable and changeable. And what's even more amazing is these epigenetic things we can call the imprintome get carried over generationally. So, you know, I was sort of just talking to a guy who kind of grew up in the Holocaust and Auschwitz. Yes. That embedded trauma in his parents, in his grandparents, you know, that goes down generationally and can be imprinted on the genes, but they're not fixed, unlike, you know, if you get Down syndrome, well, that's fixed. You can't change that. But you can change the expression even within Down syndrome. By the way, I've had Down syndrome patients. and their biochemistry and metabolism is super screwed up. And you can actually work with it to using kind of heroic functional medicine techniques to actually optimize that and improve their function even with a dominant inherited disorder. So Epigenome is so cool and you're kind of gonna explain all what that is. But tell us about how you use this groundbreaking trial to show that we can reverse biological age and what was the most surprising thing you learned from doing that study?

Well, let me just say that that was a badass introduction, Mark. That's awesome. I'm so glad you actually brought Lamarck in and oh my God, what a great way to position this conversation, a nice sweep through a good background.

Yeah.

The most surprising finding for sure was that we reversed biological age by over three years in our participants as compared to the control group. Extraordinary because, you know, this we were the fourth study. You know, there's maybe six studies out now, but it was the fourth study at that time to show biological age reversal and the only study to do it in a controlled trial and in eight weeks time. And our interventions are so benign. We did diet and lifestyle. The other study that showed a profound age reversal, really the first, and it was written up in Nature and published in Aging Cell and just got an enormous enormous amount of attention was the TRIM trial, Greg Fehmi and his colleagues. That was a year-long intervention. It was growth hormone injections, metformin, DHEA, and zinc. So, growth hormone injections. He was focused on thymus gland regeneration, and they actually did show that. They showed some improvement in T-cell status, etc. has been his sort of area of focus in his work, and biological age reversal in the study participants by, I think, on average, maybe two or three years. But this is over an entire year, and it's using a very aggressive intervention. So by extension, we're looking at medications.

Growth hormone, and all this stuff.

Yeah, it is a lot. And it's a, you know, that's a black box, you know?

Can we just- and what was the length of extension they found? What was the length of extension they found?

I think that they did about two years, maybe a bit over two years.

Okay, so this is really important because you're talking about a very sort of medication and centric approach, and you did a very foundational approach of lifestyle. So take us into the study design, what you looked at, who are the participants, what you measured, what the interventions were, and what the outcomes were. So we really can understand this in detail because I think it's worth people listening up to sort of why with some very foundational basic things that we can really arrest and even reverse biological age. And not only that, when you take that as a foundation, then you can layer on top of that all sorts of additional functional medicine approaches to actually go even further. So that's just foundational and that was really simple and it's quite amazing that we achieved those kinds of results with such a simple intervention.

I know. Well, I want to tell you that why I think we did because, you know, the Mediterranean diet has been looked at with biological age and there is like modest reversal again in a year-long study, very modest in just one subgroup. We designed, so we used functional medicine principles in our diet design. Actually, in the whole program designed, we used solid functional medicine slash orthomolecular, inspired by Bruce Ames, by Linus Pauling, by Jeff, where we loaded the diet with things that would influence methylation. So everything in the program was designed to move methylation in a favorable and balanced direction. It wasn't just, you know, here's a turnkey dietary pattern that, you know, we think is pretty good. It was very much designed to do that. So our study population, this was incidentally, this was run at the Health and Gut Research Institute. My co-PI is Ryan Bradley and the Health and Gut Research Institute is part of my alma mater, National University of Natural Medicine, and I think they do really good clinical research there. And so they, we recruited men middle-aged 50 to 72. The reason that we wanted to look specifically at the, at middle age is because, you know, the scientific term methylation, DNA methylation gets wonky as we age. And we should do a drill down on that as well. And so we wanted to get right in there in the sweet spot when methylation starts to change, starts to look like we're aging starts to look like the chronic diseases that we'll talk about that are associated with aging. And that's where we wanted to investigate. The reason that we only included men, and obviously I'm a woman, I mean we all want to study women and we are doing that now, was because it's a pilot study. We had 20 and 20. We ended up finishing with 18 in our study group and then 20 in our control. If we included women, the age range between 50 and 72, obviously some of them are going to be still menstruating, some of them will be perimenopause, and some will be postmenopause. And so that hormonal influence would be difficult to tease out in this size. So we needed to start with men, which is fine. So eight-week intervention, and the study-- the diet is very plant-forward. All the nutrients that are packed with methyl donors-- so, you know, a lot of greens, a lot of cruciferous, mushrooms, What else? Nuts and seeds. We did include animal protein, so we wanted folks to have about 5 to 10 eggs per week for the choline. Beets are in there for the betaine, a great methyl donor nutrient. Not a ton of beets because obviously they're high in sugar, but a couple of small beets a day. We wanted people to have some liver. Liver is a multivitamin in a food matrix. I mean, it is packed with a daily dose of that.

I love that. I mean, it really is.

It's a multivitamin.

Actually, if you, it's interesting, if you, if you all Google liver and nutrition and like broccoli are the best vegetables, like it makes the vegetables look like cardboard and the liver is like the, the, the, you know, the, the superpower of, of nutrient dense foods.

It's really quite amazing. It's quite, and it's what we were using before we learned how to synthesize, you know, and isolate B vitamins. I mean, we would just emulsified liver and inject it into somebody's butt, you know?

And that was, that's what indigenous cultures, right? I mean, that's what indigenous cultures always have done. That's what, like, Native American tribes have did. They always ate the organs first. It's what wild animals do. When you look at, you know, lions.

Or predators, they don't eat the meat. They eat the organs, and then they, you know, the scavengers get the meat. It's pretty interesting. Yeah, it's so nutrient dense. So we wanted people to do some liver, and, you know, we worked, thank God, we have a brilliant nutrition team, and, you know, we had some palatable recipes that they could do. And the other option is you can take liver caps, but, which I'm honestly doing because I wouldn't say I'm a great liver cook. But, so that was the diet portion.

And, so, wait a minute, wait a minute. Organic, organic chicken livers. Organic chicken livers. Onions, chop up some onions, stir for the onions, little oil, chicken livers in there, fry them up, a little salt.

Pepper, put them on rice.

Oh, it's so good. It's so good. It's so good. Well, I grew up on that because we We were very poor. My mother and my sister and I lived in a one bedroom apartment in Queens in New York. And, and, you know, I thought this was a gourmet meal because it was so yummy and delicious, but it was actually because we were really poor. My mother was a teacher making $7,000 a year in Harlem. And so basically chicken livers and chicken.

Livers and onions a lot.

That is so funny.

That's super cheap too. I remember when we were working on the book, I was like snooping around your cabinet. I was in your kitchen. Sorry to interrupt, but I had to tell that story. Go ahead. Liver capsules.

I got it. Yeah, right. You can make liver. But your liver sounds delicious.

I know one of the guys in our study had, he was making it, he was doing like, he said that they were the new chicken McNuggets for him. He actually fell in love with them. I think he must have like dipped them in like an almond flour or something because there's no, we don't, we don't do grain in this a week. All right. And then we also, we have So it's very methyl donor forward, but the.

Other arm, okay, hold on, hold on before you get in before, wait, wait, before you get in that. Yeah, yeah, I don't think anybody has a clue what you're talking about when you say methyl donor. Can you just unpack that? And why the study was so focused on this idea of improving this phenomenon that happens a bazillion times a second in your body called methylation. And it's very confusing for even doctors, but you, Kara, are an expert on methylation. You've spent your life studying methylation and it really is the regulation of our genes.

So explain what methyl donors is, what methylation is just like the Reader's Digest version and then jump back in. Yeah.

Okay.

All right, perfect. Okay. So, so methylation cycle produce a methyl group is just a carbon and three hydrogens. Carbon is ubiquitous, hydrogens are ubiquitous. I mean, we just evolved using this very simple structure everywhere in the body, as you said, all of the time. And we make it in what's called the methylation cycle. The compound that can deliver methyl groups is called S-adenosylmethionine or SAMe. people know it as, or SAM. And this compound we're producing all of the time in the body and then it zooms around and it engages in one of the 300 plus reactions that use an enzyme called methyltransferase and the SAMe is transferring that methyl group, methyltransferase. So we're using it in detoxification to make neurotransmitters and, you know, to make certain fatty acids, et cetera, just all over the place.

Energy, energy, Yes, yeah. Detoxification compounds, everything.

Right, right, yeah, all over the place. And so, but my area is specifically now, I'm focusing a lot of energy on epigenetic expression. And so, methylation is happening there too. So, there's DNA methylation in all of our cells, in the mitochondria, there's methylation happening. There's other epigenetic methylation processes like histones, the proteins that DNA is wrapped around, they engage in methylation as well. But DNA methylation is unique, and I talk about it in the book. So we're in, we're thinking about gene expression, and this whole field of study is called epigenetics, and we're using methylation there. But I also want to acknowledge that there are many other epigenetic processes. The reason I'm focusing on DNA methylation, and a lot of scientists are, is is there are a handful of reasons. First of all, we can study it. We can map out what they call the whole methylome. So the, you know, the millions of these little methyl groups that are on genetic material, we can actually analyze and study. When there are a lot of methyl groups on a promoter region of a gene, that gene is generally turned off. In science, like if you Google DNA methylation, you'll get and you look at your images, you'll see a strand of DNA and these little red lollipops. The methyl group is denoted by these lollipops. So if there's a lot of lollipops on a piece of on a gene, then that gene is inhibited from being transcribed. So a transcription protein can't land on the DNA and initiate transcription. Conversely, if those methyl groups are not present or if there are less methyl groups present, then that gene can be turned on. And as I said in the beginning, as we age, the methylation on our genes is changed and it's changed, unfortunately, for the worse. So we can see it. The other thing that's extremely important about DNA methylation is that it can be transferred. So there's enzymes, there are DNA methyltransferase enzymes that will continue to pass down those marks through cell division after cell division after cell division. And in this way, they're heritable. So, you know, sperm and egg have very, you know, complex methylation patterns. You know, when the embryo is formed, a lot of those methyl groups are scrubbed off. And there's a family of enzymes that do that, but not all of them are. Some of them are preserved, and that's the imprint home that you mentioned earlier. Methylation is what turns, is what dictates the fate of pluripotent stem cells in embryogenesis. So you're a liver cell, you're going to be a heart cell, you're going to be a skin cell. It turns off, so methylation turns off one of the chromosomes in, you know, those of us with 2X chromosomes. I mean, it's just methylation plays exquisitely important roles. And so for that reason, we're giving a lot of study attention to it. And I think that ability for it to be a preserved across cell generations and, you know, life generations makes it, you know, one of the big players in epigenetics. And that's why we're putting attention there. We can't.

So the idea is basically that, you know, you've got this molecule, carbon three hydrogens. I think of it like the currency of the body. It's constantly changing chemicals all the time. It's being transferred one molecule and regulating everything in the body. It's like the central hub of our biochemistry. And if any working, your system is screwed. You know, heart disease, cancer, diabetes, Alzheimer's, autism, I mean, everything you could think of pretty much that screws up people is involved in some way with this process of methylation. And the DNA part is just fascinating because it's really the regulator of which genes get turned on or off. and like you said, in every cell, in every cell is the entire blueprint for everything in your body, literally. Like in, in your skin cell is a blueprint for your brain or your liver or your kidneys.

Right. That's right.

Well, how does the skin cell know to be a skin cell versus a liver cell or a brain cell? Well, it's these, it's these regulatory controls on our genes and which ones gets expressed or not. This is all the methylation stuff. And that really is regulated by B6, B12, folate, beta, you mentioned methionine, all these important molecules. that are in our diet and in our food that, by the way, Americans are mostly often deficient in or insufficient in. And so we've got this sort of pandemic of methylation problems. And, and, you know, I, for those who kind of want a little bit deeper dive on this, I've wrote a couple of blogs years ago, and you've got probably a ton of information on this, but you can Google hymen and methylation, and you can learn more about.

It and all the things of ways.

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No, but he should. Their very first paper is the most cited paper in the history of science. So there's a little bit of that.

It's pretty amazing. Yeah, incredible. So what he did was he took a genetically identical mice that are designed to be fat and diabetic and really unhealthy.

Blond and blond.

They're very visual and yellow. Yeah. Like they're blond, yellow. They're like these big fat yellow mice that look like a big piece of fat. Okay. And genetically identical. And in, and in one litter of these mice, they, they just did their normal thing, you know, bread, the mice and all that. And this other litter, they gave them methylation factors, you know, B6, folate, B12, and it completely changed their gene expression in such a way that the mice that had the B vitamins and methylation were little, skinny, brown, not diabetic or fat or anything. And so that was just amazing. It's like you've got identical genes and you've got a completely different expression. That's what Kara is talking about. And understanding how to regulate that process is a key to unlocking health and biological aging. So now carry on with your explanation of the study because I want to take that little detour.

It's an extraordinarily important and big, big deal what they showed. And it's very visual and I'm, he should get the Nobel. And it's impressive that it's the most cited paper in the history of science. That's nuts. But yes. And it really put what the power of nutritional interventions on the map. So, but you know what? One of the interesting things that they cautioned, I don't even, you probably don't remember this, but at the very end of that abstract, the final sentence is basically a word of caution around appreciating how potent nutrient interventions are. And I think, you know, that ushered us into the era of epigenetics, that particular study, and nutritional epigenetics in particular, because A, we were starting to be able to actually see at that level, you know, epigenetic expression. They had they what they did was they methylated and turned off the Agouti gene. But they said, look, we introduced B vitamins and we turned a gene off and look at this phenotypic change. It's favorable, but we need to be mindful in general about the power of our interventions. And for me, as I dove into epigenetics, That was my huge aha. It was around 2013 and I was tussling with all of the epigenetic literature coming out around cancer. The thing that just really stopped me and prompted the development of everything was the fact that in the tumor microenvironment, cancer takes over our gene expression for its own survival. shuts down genes we want on, it turns on genes we don't. It is aggressively abnormal methylation in cancer. And my question mark was, if we're slathering everybody, if we're going very B vitamin forward, is this what we want to do all of the time? That was my first step.

I know you really brought that up because it was like, oh, we should never be taking all these high doses of B vitamins and methylation factors. and maybe that's not always a good idea.

That's right. And now that we can see at this level, I think we want to be a little bit more nuanced in how we approach. And there are, without question, times we need to go and go hard with B vitamins. Actually, there was a study in glioma using very high-dose folate we can talk about later that had some interesting good outcome. So the point is that our interventions, we're not just going to pee those B vitamins out and not have to worry about it. We need to just think a little bit more nuanced. But we know we need methyl donors. We know as we age, basically our genome becomes, generally speaking, less methylated. So we need to just consume as many methyl donors in our diet as possible. So that was our first piece. There's no evidence in the literature that there's anything negative with a high methyl donor diet. So in that food matrix, go for it. Binge on kale all day long. Have a couple of the chicken fried livers that Mark is talking about, and you're good. amazing things. So that's item number one. Food forward always works. But the other piece, the other huge aha for me in this journey was looking at the literature on polyphenols. It turns out that these beautiful compounds that have time and memorial use histories like the catechins in green tea or curcumin or luteolin or resveratrol or quercetin, all of these compounds that we know and love and use and eat prescribe, etc., etc. They appear to direct methylation traffic. I mean, at least that's what our findings suggest. So when I first started to read about it, again, we're looking at this oncology literature. And so in cancer, actually in aging as well, tumor suppressor genes, which are important genes we want on, get hypermethylated and shut off. Okay, not a good thing. The in vitro studies were showing routinely that these polyphenols will allow for the re-expression of these inhibited genes. So that's cool. So polyphenols seem important in vitro. Yes. And there's a whole table in my book that walks through various tumor suppressor genes and the polyphenols that have been studied. This has also been demonstrated in animal studies as well. And, you know, diindolylmethane, sulforaphane, we know these things to help us detox, etc. But you know what? There are actually I think they're doing the heavy lifting mark at the level of the epigenome. I think they're changing genetic expression, and then we're studying the downstream effects and saying, oh, they're anti-inflammatory, they're anticancer, they're antioxidant, they're detoxification. But I think as we tease it out more and more, we're going to see its gene expression. As packed into this methylation donor-based diet is all of these polyphenols. very dense polyphenol diet. So again, lots of cruciferous, lots of colorful veggies. You know, we wanted people to consume green tea. We had a curcumin requirement. And actually in my book- Wait, are.

You saying food is medicine? What are you saying? No, no, no, I wouldn't go there. I mean, listen folks, this is just, you've got to kind of tune into what's actually saying. What she's saying, she designed a way of eating, picking certain foods that have very particular compounds in them, both methyl donors like choline and betaine, things like B vitamins, but also these phytochemicals that also regulate our genes and regulate enzymes and regulate our biology and inflammation and detoxification. And so, when you're eating, it's so far more than calories. Food, as Jeffrey Bland taught us all, is information. It's code. and it's going to upgrade or downgrade your biological software literally with every bite. And that's really quite amazing. And you showed it. I mean, yeah, that's what you showed. You didn't take these fancy, expensive drugs with side effects and this and that. It's like, what's the side effect of eating, like, sardines? Nothing except good side effects, right? You get, you get choline, you get.

Omega-3 fats, you get protein, you get all this wonderful stuff.

Right.

So I think that that's why You know, that has to be why we were able to move things as rapidly as we were, because we looked at it through a sort of orthomolecular functional medicine.

Functional medicine.

This is true functional/orthomolecular medicine where we're doing the right amount of a nutrient, you know, for the right effect.

And, and I, orthomolecular means to correct, to straighten or correct molecules. Like orthopedics is a straightener, correct bones. Orthomolecular is to correct and straighten your molecules. Right.

That's where functional medicine is essentially derived from. And I think that that's, that's why we were able to make a difference. And when you look at other studies where they're doing sort of there, you know, there's some caloric restriction data out now, which is beneficial, you know, for sure, or the Mediterranean diet, or, you know, there's a study that showed, you know, some modest age reduction with just sort of general healthy eating patterns. That's all great. You're going to get no argument.

It's all an upgrade, right? It's an upgrade from fast food and junk food, right?

Yeah, that's right. But using this technology that we're steeped in and our training just really showed something special that I feel is important for we get it. But I want the world to get it because I think it validates the science that we practice from.

So were you also using supplements and exercise and stuff in the study?

Yeah, so let's talk about that. The only supplements that we used, because I didn't want to use isolated nutrients, we did a greens powder to kind of, you know, extra hit home those all-important polyphenols. So a couple of hits green powder a couple times a day, and we used a probiotic. We used a Lactobacillus plantarum. The reason that we did that is multifold, but our, you know, a healthy gut microbiome makes a B complex. You know, you want a natural B complex, take care of your gut, you know? I mean, seriously. And so, Lactobacillus plantarum has been shown to increase endogenous, you know, microbial production of natural folates. And so, we introduced that, but a healthy microbiome.

Okay, in English, that means, in English, that means your gut bacteria make B vitamins like folic acid. She likes to use big words, but you know, my mother's always like, use the kiss method. Keep it simple, stupid.

Yeah, for sure.

Okay, I can be your translator. You know, like Obama had his anger translator. I'll be your translator.

Oh my God, that's so funny, Mark. Yeah, for sure. Yes. So we want, and the other piece is that our gut bugs regulate us, you know, and when they, you know, they're playing an intimate role in healthy genetic expression. So we need to love on our gut bugs. So in this study, we did. We kept it simple and we just used lactobacillus plantarum. And we significantly increased circulating methylfolate. There were no B vitamins to be found, but we did increase that in our participants, actually, by quite a bit. So that's the diet. And then, oh, actually, the diet is low glycemic, it's anti-inflammatory, No grains, no legumes, no dairy. And listen, I am a big fan of Blue Zone data, and I know they're loading up on certain grain and they certainly eat beans and stuff. And I want to say that this is a finite period of time. This is not a lifetime diet. It could be if you wanted it. It's a healthy eating pattern. But I'm all about transitioning back in and bringing the legumes in. But we wanted to really control glycemic cycling. It's just the other thing you did, by the way.

I mean, the other thing you did by doing that diet, and just to clarify for people, getting rid of dairy, gluten, sugar, processed food, grains and beans, no alcohol. That's exactly my 10-day detox diet, which I use all the time to help people quickly recover from all sorts of problems. And, the reason it works is not only because it contains all these nutrient-dense phytochemicals, and all the B vitamins and all this stuff that you're talking about, but it also eliminates the inflammatory foods. And inflammation is a cornerstone hallmark of aging. In fact, it's often called inflammaging. So, you kind of were doing a double whammy. You were powerhousing all these food is medicine compounds at the same time you were taking away, because I believe if you gave all that stuff and people were eating still in addition to that, a lot of processed foods, or even gluten, dairy, or sugar, it might not have worked. Right. Yep.

Yep. I think that's a reasonable supposition. And hopefully as we continue to investigate it, we'll see. We'll see. And we'll be able to layer in individualization and all sorts of exciting stuff. But yeah, I think that's possible. It's like Sid Baker, right? Get rid. Add this, get rid of this.

So basically, diet, you did the greens powder and what else?

Yes. Oh, and so yeah, a little bit keto leaning, a little modest, very modest time-restricted eating, just 12 hours on, 12 hours off. We didn't want to make it onerous, and we also didn't want to just study time-restricted eating, but we wanted it to be doable for our participants. We had nutritionists meet with our participants weekly. They didn't sure lead them. They had to read from a very stale script that was IRB approved, but just basically, do you have questions? Do you need recipes? Yeah, we couldn't. It was very structured what they were able to do. But I will say, so when we first designed this study, Ryan over at Health Coach Institute was dubious that we would be able to have such a sophisticated, multi-variable study really be successful and have it participant adherence. And I think that it was our nutritionists being there, being present, that was the difference in our success. And we do have adherence data that are very good. And it's something that we'll need to write up on. But Mark, I was like, this is my big chance to engage in clinical research. I'm like, this is going to be successful. These guys are sticking to it. And then the nutritionist made that difference. And incidentally, for folks who want that kind of support, we've got a digital platform that has the nutritionists we used in our study available and all sorts of other stuff to really have pull the branch down for folks who want that. and that's also where we're going to continue to study it if anybody wants to participate in contributing their data to research. So that's diet. And then we had other interventions. And this is where we need to think about, you know, in our world we're focused on the methylation cycle. Anybody who studies functional medicine knows biochemistry in an extraordinary way, and they know a lot about the methylation cycle. But when you get into the science, you will see that methylation is regulated by far more than whether we've got, you know, that little cycle is humming along. So exercise, the data on exercise and methylation and more broadly and specifically DNA methylation is extraordinary. And exercise and biological age is extraordinary. And there's a handful of things. So exercise is as a rule, potently anti-aging. But if we overdo exercising, then that can be pro-aging. And I talk about that inside a handful of studies in the book there. So we want a realistic amount of exercise. In our program, it was a modest and easy. We wanted it to be doable. We wanted people to adhere to it, and it was just 30 minutes, five days a week, at a perceived exertion of 60 to 80%, doing whatever they want to do. So it's your perceived exertion of 60 to 80%, which is going to be different than mine. 60% is going to be like, you know, maybe a little bit of a light sweat. You're just, you know, your breathing is increasing a little bit, and then 80% you know, 20% more than that, 60%. So, you know, a little bit more sweating, a little bit more heavy breathing, but you're still able to have some level of a conversation and do whatever you want. Our participants, let me say, and I think this is another cool piece about our findings, our participants were extremely healthy. They couldn't be on medications or come in with diagnosed conditions, you know, even high blood pressure. We wanted to look at healthy men. We wanted to really study DNA methylation in healthy men, so in aging healthy men. So we were really isolating the influence of the aging journey. And I think that's another cool piece of evidence for our findings. I think if you have a condition, if you're diabetic or if you've got heart disease, et cetera, you're aging faster and by extension, if you turn that around, you should have even more powerful age reversal.

Yeah, right. So basically what you're saying is you took healthy guys that are healthy study participants that didn't have a chronic illness and you saw this massive change. But actually, what I would say is if you don't have a headache, an aspirin doesn't do anything. So if you actually, like I remember this patient, Janice often talked about she came into Cleveland Clinic in one of our group programs, Functioning for Life. She was like, you know, BMI of 43, I think, which is a massive, like she was just massive woman, type 2 diabetic, on insulin, heart failure, kidneys failing, liver failing, high blood pressure, and, you know, tons of meds, stents, and like a cardiac disease, the whole thing. In three days, three days she was off her insulin. In three weeks, she was off all her medications, heart failure, reverse, kidney failure, reverse, diabetes was gone. A1C went from 11 to 5, which is like our five and a half, which is like ridiculous. No, that never happens. I mean, you know, if you get a drug that has a 1% drop in A1C, that's like a hallelujah. This is a blockbuster drug. We're talking about, and we're talking about not only a 1% but a 6% reduction, which is a logarithmic scale. So, it's a huge thing. And then a year, she lost 116 pounds and reversed everything. Her biological age, I'm sure went back 20 years. Not three, right? So anyway, go ahead. Yes. So you did exercise, you did the greens. What else was it? We did.

So we wanted our participants to sleep. So the data on sleep, it's strong and specifically relating to DNA methylation. If you're not sleeping, you're aging. I mean, that's really the bottom line. And you're, you know, you're walking out DNA methylation. And, you know, this is strongest we can see in animals where you can actually, you know, dissect and take a look at what's happening in the central nervous nervous system and the damage to the neurons with just like one sleepless event. I mean, it's extraordinary how nourishing sleep is on genetic expression, on DNA methylation specifically, but more broadly we know sleep is poor sleep is the risk factor for all of the chronic diseases of aging. So we wanted our participants to get at least seven hours and they would We gave them sleep tips and they would check in with the nutritionists as part of that structured IRB document that they would, the checklist. So at least seven hours exercise, we prescribed meditation. A massive aha for me is specifically relating to the clock that we used. We used the sort of the flagship Horovath clock, the first biological age clock on the map by Steve Horvath at UCLA, another Nobel Prize to be winner, because he's changed the longevity field with his extraordinary work out of his laboratory. So we used that original clock. There are second and third generation clocks now that have come out subsequent to our study. The field is galloping forward, and if we have, you know, if you want to, we can talk about that. this original clock is still badass and it's got the most science on it and just loads of publications. It is 353 of these methylation sites are measured in it. A full 25% of those are associated with glucocorticoid response elements, meaning they are driven by stress, driven by cortisol. So think about it. The biological age clock 25% of it is driven by stress. Isn't that nuts? Like 25%. Yeah.

Okay. So this is quite amazing what you're saying. Let me slow down for a minute because you're saying basically using these very expensive high-tech interventions like eating better, sleeping, meditating, and walking and taking a green powder.

Right?

Yeah. And everybody is looking at these expensive drug trials and all these mechanisms and you know, you know, very intense interventions. And you're saying, eat better, exercise a little, sleep better, relax, and basically you can reverse your biological age. This is profound because it doesn't even layer in to me all the things that we do in functional medicine that are about upgrading everything in a different way. I mean, yes, this is just a foundational lifestyle factors, but we got a whole other toolkit to optimize the immune. and detoxification, the microbiome and your mitochondria and on and on and on. So, I mean, it's just, it's just stunning. So tell us what, what, what, when you start looking at what were the outcome measures? So we know what the intervention, what were the outcome measures? What did you find? And, and, and, and what are the, what are the things people looked at that actually saw that you saw this biological age change? So what were the primary and secondary outcome measures?

So, so we looked that quality of life changes the subjective questionnaires, which didn't in this healthy population change appreciably. There was some trend towards more energy, et cetera, but really nothing much. But we wouldn't expect a lot in this population, like you would say in looking at some in a population with IBS or whatever. Their cholesterol dropped, their LDL dropped, but again, you know, they weren't particularly hypertriglyceridemic. But they were just eating healthier, more fiber, triglycerides dropped, which suggests to me that they, you know, work in fact keto leaning. And so we did achieve that, which was nice because we didn't measure ketones. We didn't change. So we looked at a host of methylation biomarkers, classic methylation biomarkers, homocysteine, s-adenosylmethionine, methionine, et cetera. We didn't change those appreciably. So that's an interesting piece in our study. We changed where methylation was happening on the genome. We didn't push methylation forward. We changed where it's happening on the genome, which I think is really cool. We moved it around. And so in this first publication, and there'll be subsequent publications to this, we showed that as compared to the control group, the biological age clock the biological age clock reflected a biological age that was 3.24 years younger in our study group at the end of eight weeks as compared to our control group. And the within group comparison, so comparing the study group to themselves at baseline, it was about two years younger.

That's amazing. So help us understand the idea of.

Of.

This biological age clock and how it's measured, why we should care, why is it relevant, why is it now this new idea that we can look at? I mean, this new thing, we all knew that DNA methylation was a thing, but it's not something you could go to the lab and get a test for. Now, there's a lot of companies offering diagnostic tests where you can actually measure biologically. So, I'm actually doing this myself. I'm working on another book on longevity as well. on them. I wore all the methylation kits. I'm going to do them, and I'm going to implement all kinds of strategies, and I'm going to retest, and I'm sort of going to use myself as a guinea pig. But I think that it's important people understand, like, what, what is the, what are these biological clocks? What is, what is the, the biological age? How is it defined? And how do people understand it better? Because what you showed to these interventions.

Was this reversal and Improvement in all these biomarkers. Right. But, but what is it exactly?

Yeah.

Good question. Well, I'm going to just Jump in and you'll clarify and interrupt as needed.

Sorry, I don't mean interrupt. I'm listening and going, I don't think everybody's listening is going to get that, so I gotta just slow this down a little bit.

I know. Listen, I don't say that facetiously at all. I'm completely cool with that. And you and I have been talking for many, many years now, so I'm completely cool with it. And I know it's complex. And so it really helps to have almost another set of eyes on what you're saying, so I appreciate that. And I had somebody actually help me who did a lot of this heavy lifting around the translation, because that's the hardest piece, getting, you know, expressing this content in a clear way. So Steve Horvath, you know, back in about 2013 or so, was asked to take, you know, methylome data, all of these, the DNA methylation sites, and figure out patterns that correlate with chronological age. So the first clocks were trained against against chronological age. So from embryogenesis, so from pregnancy all the way up to centenarians, he had these massive data sets, and he looked at methylation patterns and crunched huge numbers with big computers. He's a biostatistician and was able to pull out 353 methylation sites from these massive data sets. that correlate with a 0.96 degree of accuracy with chronological age. I mean, so the first clocks are just like in lockstep. By comparison, telomeres are, you know, correlate with about 0.4. And so prior to the advent of DNA methylation, biological age clocks, telomeres were gold standard. And there's still a place for telomeres. Like nobody's getting rid of telomeres, but we're thinking about them in a different lens.

Like I did mine a few years ago, and my At the time, I think I was 58 or something, and my biological age was 39 on the telomeres. Does that, does that like, I'm not.

Gonna argue with that.

I'll take it, I'll take it, I'll take it. I wish my gray hair would know that, actually. But anyway, yeah, for sure. So, what you're saying is that this is actually a better marker and is more accurate.

Oh, yeah. It's changed. It's changed the face the case of, you know, the field of biogerontology. Yeah. Having these markers of biological age are, they're just going to transform science. I mean, I think we already see that, you know, my study, like, people going forward and doing nutritional research are probably, you know, going to try to get epigenetic data in there now, but hopefully going forward. But I think in general, with the, with these clocks and the, you know, the Next Generation Yes, they're extraordinary.

So what does that actually mean?

So that's what he was able-- yeah, so you can-- so there are-- so the pattern of methylation on certain genes changes predictably over time. So in utero, there's a pattern that's consistent with a negative age. I guess you're not born yet. And then obviously it goes orders of magnitude and change structure and, you know, when you're a centenarian plus. So there's these just these predictable, reliable changes that correlate with chronological age. What's interesting though is that in this very first clock, it's a better predictor of health and mortality than chronological age itself. So very early on in the biological clock journey, the DNA methylation biological clock journey, we could see that they were better predictors of health outcome very early on. And that's only improved and grown and become more robust and more insightful. You know, it's interesting, there's a DNA methylation telomere clock. So it's looking at the DNA methylation expression on telomeres. It's actually more reliable than directly measuring telomeres. So we can see DNA methylation patterns are more reliable around biological age. and your health and your longevity potential than your chronological age. So it's really a new era of science. And I want to say another thing. So after that, your thinking could logically be, well, these are surrogate markers of biological aging. These are surrogate markers of another process happening of the inflammation, of the inflammation or the hallmarks of aging, the loss of DNA patency or the loss of antioxidants or the increase in inflammation, et cetera, the whole hallmarks of aging. So you might think they're surrogate, but research, I think, is starting to suggest, especially out of Sinclair's lab at Harvard, that they're not just suggestive of aging, that DNA methylation patterns are probably fundamental to actually driving aging. Okay, so and that is another cool thing for us because we put our eggs in the DNA methylation basket. We were like, we really want to change that. So two studies out of Sinclair's lab that are extraordinary. The first one is looking at an age-associated optic neuropathy in a mouse model. and so they created this optic, this age-associated optic neuropathy by damaging DNA methylation. I think that's how they initiated it. It sort of doesn't matter, but the way that they were able to restore vision and reverse aging in the optic neurons was by changing DNA methylation and demethylation.

Dr. It just sounds biblical. You know, you make the blind to see, right? You take a mouse, you blind find them. And then you, like, give them a bunch of stuff that is pretty, pretty simple and cheap. And then you, like, bring back their vision. It's like, yes.

Well, so they used something called Yamanaka factors. They used three of the four. Yamanaka. Yamanaka factors are famous because, well, Yamanaka. And actually, one of the Japanese doctors, scientists. Yep. He discovered, he discovered them, and they did get the Nobel, but. He and the co-discover, the co-scientist in that. Anyway, Yamanaka factors change methylation. And in so doing, you can take a somatic cell and just turn it back into a defined cell and turn it back into a pluripotent stem cell. So you can take cell X, a brain cell or whatever, and douse it with some Yamanaka factors. and bring it all the way back to an undefined stem cell. And they do that.

Which then can become anything. So, it's sort of like a super power superhero trick. You take a, imagine like taking a person and then completely reversing them to their embryo and then restarting again to become another person. It's pretty freaking cool.

Crazy.

Yeah, it's crazy.

I mean, if you think about it too much, yeah, it's nuts. I sort of see like a person and then they're like a little puddle a little of booze on a chair or something.

I don't know.

It's sort of weird. Yeah, you're back to a pluripotent state. Yeah, you're an undefined entity.

And pluripotent means you get to be anything you want. Like if you're a pluripotent cell, you can be a skin cell, an eye cell, a brain cell, heart cell.

That's what that means. Yeah, that's right. Oh my God. Anyway, so they used three of the four in this study and they restored the neurons to a younger state. And they also restored vision in the study. It's amazing. And they did it by specifically changing epigenetic expression and DNA methylation in particular. Then in 2021, they published another study looking at aging in general, exploring the genesis of aging in general in a mouse model and reversing that. And it was the same thing. So aging is, as they outline in epigenetic dysregulation. And they reversed aging again using Yamanaka factors. So they went from an optic neuropathy model to just aging in general and analyzed it and reversed it again, you know, using three of the four Yamanaka factors. And what they said in their paper is that we all retain a youthful epigenetic pattern on our epigenome and we can uncover that yeah. Okay, wait a minute.

Wait a minute. What you're saying is there's a younger you locked inside of you and you have to unlock it. And this is where the science of aging and longevity is going. We're learning how to actually create a younger you that's already there, locked inside of you, ready to come out if you take away the crap and put in the good stuff.

Yeah. Isn't that amazing?

It is pretty cool.

I mean, it's like tingly. right? It's extraordinary.

I'm so excited about it because I'm 62, so I'm, like, way more interested than I was 10 years ago.

I know. I know. I am, too. Well, I mean, I. I became a mom. I'm 54, and I became a mom.

No, you're not. Come on.

Yes, I am. You're not.

I am. I am. No way. Oh, my God. I thought you were, like, 35, maybe 40. Okay. You are ageless. You look no different than when I met you, like, 20 years. go. Really?

Well, I need glasses now, though.

Well, I needed glasses then, but not as long.

Maybe I do, too. That's why it looks like.

Yeah, that's right. That's right. Anyway, let's keep going. So, so I'm still, I'm still not quite, I'm still not quite sure about this biological clock thing. Like, what, what is the test actually measuring? It's measuring where the methyl groups are on the genes.

And it, how does it know how old you are based on those methylation tags? Because, you know what? You need to just get Horvath on.

Your, on your podcast, or you need.

To just get a biostatistician on your podcast because, okay, introduce Yeah. Okay. Okay. Okay. There are predictable changes that happened with biological age. So, you know, I've got my methylation sites, you know, at 54 on, you know, 12, 21, and 72, and yours are on 16, 13. You know, I mean, there are predictable changes that happen over time. I love it. You know, we were talking at the beginning how you were pelting me with these same questions in my very first lecture, I think, as a newly minted physician, I did a lunch and learn at a conference, at an IFM conference, and you were pelting me with these same questions. It's great. It's a great question. And I think the answer is a biostatistical one about just the predictable pattern changes. Let me tell you this. When we did our study, we had extra kids left over. The kids, by the way, back then, were, this was just a few years ago, were over $1,000 per on discount. But we had a couple kits left over and so we gathered them here and I got my daughter Isabella's, who was two at the time, and her epigenome was wildly different. And it's, you know, it's just a bunch of numbers on this massive, massive insane spreadsheet. But when you crunch those numbers and you can look at it, it was, you know, she had the epigenome, she's got the epigenome of a two-year-old at that time. time. You know, it's really cool. Everybody else is an adult, and it's just like, it's glaringly different.

Yeah. So taking all this sort of conclusions from your study, how, how can you advise people to optimize their epigenome? What are the things we can do practically? This is really awesome science. Yeah. And encourage people. We're gonna, we're gonna have in the, in the show notes, we're gonna have a link to the study to Kara's new book, younger you. We're gonna, we're gonna provide all that and. so various ways to access her subjective biological aging questionnaire, how to get the methylation tests, all that's going to be there. But tell us in a nutshell, what are the take-homes for people around how do we live to optimize our epigenome and hence reverse our biological age?

So, for those of us who are adults and are wanting to remain optimal or a team an optimal biological age. We want to be, you know, dousing our DNA methylation with the nutrients it needs to perform, you know, optimally. And that is our, I would argue that it's our diet or some variation of our diet, which layers well with anything, actually. You can make it keto if you want to. You can make it, you know, FODMAP friendly and whatever you need to do. Take the, so take the fundamental principles of what we figured out and layer them in to whatever that it what it is you're doing. And if you're an Uber biohacker who's doing growth hormone injections and on Greg Fahey's next study, awesome. Layer these principles into what you're eating because you still need to consume calories. Just layer these principles in. Take stress seriously in the pro-aging effect of stress, which is stress is gasoline on the aging fire. And take that seriously and take some time out. There are a lot of amazing apps out there. I love the Healthy Minds app out of University of Wisconsin. I just use it all the time. They have these micro-meditations. You can just pop on your phone and take a couple of breaths and bring yourself down a notch. That's an anti-aging intervention right there. Have some green tea. Have some curcumin. All of those polyphenols you know and love, they are important and they're probably epigenetically active. In the back of the book, I have this massive nutrient index of epi-nutrients. It lists the polyphenol and then it lists the foods that they're found in. All of us can go in there and eat a ton of those every day. It's doable.

Amazing.

I would take it seriously. The other piece in our book, Mark, that I think is important is that we talk about epigenetic changes through the lifespan. I tweak the diet a little bit around some of those thoughts. There's, Sue, for instance, because pregnancy is so important, actually in pre-pregnancy and conception, and we talked about the heritability potential, we want to be thinking about these. So, not just as an anti-aging intervention, but if you're going to be conceiving, men are on this hot seat as well. This is not in a women's domain. This is where we see the impact of of a man's epigenome on offspring right here in this DNA methylation patterns. You want to be adopting these principles. We tweaked, I created sort of a younger-you hybrid is what I'm calling it in the book because it just, I felt, I would have felt remiss if I didn't give preconception and pregnancy and postpartum. Here's what you can do. You bump up this nutrient, continue with this. It's more protein, there's more carbs, there's actually more calories in general. But all of that is in there. And when we're in, so in infancy, so the data in infancy and early infancy, there's quite a bit on needing cuddling. There's no time, obviously, we don't need cuddling, but in terms of epigenetic expression, in terms of epigenetic expression, early infancy is a big deal. And I talk about some of the science there, and we want to be nourishing our children's epigenome at those times. And I talk about the research actually through the life, through the lifespan and it's cool like boy.

How do I get in the randomized controlled trial on cuddling? Because I want to be in that study.

It's so funny. It's a big, it's very, it's important. It's just really important. If there were, if there was one additional piece in this study that I would have put in if I could have, that would have been a community element and we'll build that out in the app. Yeah.

I mean, you could call that sociogenomics. Yeah, sociogenomics, I call it. Right. How our social interactions regulate our genes.

Yes, it's a big deal. It is. And that's heritable. A lot of it.

Eat your medicine, exercise a little, don't stress too much, and do a lot of cuddling. It's basically what you're saying.

Yeah.

And, and you have any.

Yeah.

And, and I think this is great. This is such great advice. I also think that, you know, there's a, another layer of sophistication that you haven't even touched on in the study. And I think it was really smart to do the basics first. But I, I can imagine designing a study where you layer in a real functional medicine approach, looking at all the biological systems in the body, optimizing for each of them, and then checking on what happens. How do you optimize your microbiome, your hormone balance, and all these things? Yes, the self factors do regulate all those things, but there's also supplements. There's also different kinds of exercises, all kinds of stuff that you can do to regulate those. And, I think that's going to even.

Show a bigger reversal.

That's right. And, by the way, for people that are listening, you might go, oh, three years, what's the big deal? Blah, blah, blah. If we eliminated cancer from the face of the planet, our life expectancy would go up two years. If we eliminated heart disease, I think it would maybe go up three years. So you're talking about like that, that's a staggering, that's a staggering result in a study. So I really applaud you in eight weeks, in eight weeks, in eight weeks, like this, you know, you spend, you spend 50 years screwing up your system and the body is so freaking smart that when eight weeks, you can literally reverse the damage that you've done your whole freaking life on your biology. Imagine if you just sort of started early and kept going where we're headed. I just think we're in this exciting moment around aging longevity and And your work is just so important in that. I really congratulate you.

Can I give a statistic? I know we need to wrap up, but let me just get this. Because what you just said about cancer just prompted me thinking about again, Sinclair. He published with some colleagues a work looking at the economics of biological age reversal. So we always silo ourselves in research and we focus on cancer and we focus on heart disease. And there's an argument, a logical argument, just really putting biological age at the front and center because it is the biggest risk factor for all of these chronic diseases. So if we lower biological age by extension, we're lowering risk of all of the diseases of aging. I just, I want to underscore that a big time and also say that when you look at DNA methylation patterns, you know, just like I started this conversation thinking about cancer, well it turns out the cancer epigenome looks very similar to the aging epigenome to the cardiovascular disease epigenome to the dementia epigenome. So when you correct it together, and you lower biological age, and by extension you're reducing risk. So they did this study crunching economics, and if we were to improve lifespan by just a mere year, one year, they estimate that to be like a $38 trillion savings. And if 10 years, an order of magnitude more, $380 trillion, so the cost savings staggering.

But it's sort of counterintuitive, right? You think, oh, people are gonna live longer, they're gonna be a bigger burden, it's gonna be more Social Security, more Medicare, more, all the expenses are not working, they're not productive.

How, how does that work? Because it's just intuitively, it seems like Betty White, we're gonna be like Betty White. We're gonna just leave this beautiful, healthy. So we're going to have healthy longevity.

And, you know, and pass gracefully and simply. so in other words, yeah, I think that's a really important point. So the data is really there. We learned about this from Jeff Plan years and years ago. James Freese from Stanford did a very seminal study where he looked at what we called a very few simple lifestyle doctors and how they influence our longevity and death. And what they found was that if you exercised, if you didn't smoke, and if you kept your ideal body weight, super simple, those three things, and you kind of followed those the ones who exercised ideal body weight didn't smoke, they lived long, healthy lives and then dropped dead. The people who didn't follow those three parameters actually had long, slow declines and died early, painful, expensive deaths where the people who died older died cheaply, painlessly, and quickly. quickly, right? Yes. They went from, I'm like, okay, I'm having dinner with everybody. Like, Jeff Bland tells a story about, I think his mother or grandfather or some grandfather or something. He, they all had, like, Thanksgiving dinner. He's like, oh, I've been spending a great ride with you all. I love you all. I'm going out. I'll see you later. And, like, he literally went to bed and didn't wake up. That was it. He knew he was going. He's like, I'm done.

And he literally was like, fine. He was, I had dinner. And then, like, okay, I'm, I'm always over. I'm checking out. And that was it. I was like, that's just amazing, right? That's, that's how to go. Yeah, absolutely. Absolutely. We, in this country, we are aging fast. We're actually aging faster than other Western countries. The last 16 years, here's some horror statistics. The last 16 years on average in this country are spent with at least one diagnosis. And most of us have two poly pharmacy. We're giving all of our money to pharmacies, to skilled nursing facilities, we're giving all of our money to hospitals. and our family members are taxed with the burden of the shell of us living these really poor quality existence. And we have the power to change that. So, we need to. I mean, it's an imperative.

It's so true. David Sinclair who wrote Lifespan is one of the leading researchers in longevity and you mentioned him earlier. I know he's a great guy and essentially, he's He said that aging is not what we think it is, this normal process that inexorably proceeds until we die, that it's actually a disease. And that we don't understand the fact that all the chronic diseases that we see, that we treat in silos, heart disease, cancer, diabetes, dementia, et cetera, et cetera, they're all reflections of underlying problems in our biology, in our biology that is actually embedded in certain root causes around lifestyle, environment and so forth. And what you did was you addressed those root causes and worked way upstream so you don't actually have to find the cure for cancer or heart disease or diabetes or Alzheimer's. That is just a dumbass way to go about it. Look at the upstream mechanisms. And I think this is a breakthrough idea that aging is actually a disease that we need to think about as as a dysfunction that we can correct. And that's what you did in your study. And I think that's what's gonna sort of change the face of this and not allow us to sort of continue in this dumb siloed way. And even the hallmarks of aging, which are talked about as the root causes of aging, right? The hallmarks of aging, inflammation, oxidative stress, epigenetic changes, you know, mitochondrial dysfunction, on and on, insulin resistance. These are not, they're downstream. They're downstream. And so, oh, this is the root cause of aging. no, these are upstream from the diseases. Yes. But what's upstream to the hallmarks of aging, right? That's where functional medicine comes in because it actually helps us to understand the biological networks that are driving these hallmarks of aging. What causes mitochondrial dysfunction? What causes inflammation? What causes alterations in the microbiome? What causes hormonal dysregulation? That what causes epigenetic changes, that's what's interesting to me. And that's really what your sort of work is doing.

That's right. That's right. And I would say that this is just such an important area. This is the tussle right here. I think we want to be putting attention towards addressing those epigenetic imbalances and that, I mean, there's a debate in the field of biogerontology now whether or not there's some, there's a where whether aging is a programmed event, a programmed evolutionary event into the epigenome. And I think that that's, I think it's a possibility. I mean, obviously we do have the weight of environment and our lifestyle choices, et cetera, but we've got a predictable lifespan. The healthy of us, the healthiest among us generally aren't going to go past 120 years. So there's something, anyway, it's an interesting sort of next generation conversation in the longevity space.

I mean, it is because people are talking about longevity escape velocity, which means we live long enough, enough advances will happen understanding of aging science that we can apply those concepts and actually escape death. Now, I'm not so sure that's true, but it's a fascinating idea. And then very, very prominent scientists are having this like George Church at Harvard and others. So it's very cool. Well, this is so fantastic. You are doing such important work. I'm so glad that you've kind of taken this to the next level. Everybody should go out and get a copy of Younger youg Reverse youe Bioage and Live Longer. You've got an online community. Go to Younger youg Universe. You can go on your website, which is tell us where to go to find all that stuff.

Just go to youngeryouprogram.com, youngeryouprogram.com, you'll get the book. You can find out about the app. and if you go to youngeryouprogram.com/BASA, you can grab the, you can take our biological subjective age questionnaire, which is awesome, and you can take that as many times as you want and we'll email you the results so that you can see the areas you need to tweak. It's a cool start and then, you know, join us in on the app and get your epigenetic biological age and just hang out with with us in there and we can all get younger together. Well, Kara, I learned so much today.

I hope you all out there learned a lot. This is a game-changing study and your book is really fantastic. So, thank you for the work you're doing. Everybody who's listening, if you love this podcast, please share with your friends and family and social media or everywhere else you want to share it. Subscribe where you get your podcast and leave a comment. What did you learn? What excites you? What have you done to reverse your biological age? Tell about it. And please come next week and we'll see you there on the Doctor's Pharmacy for another episode. Hey, everybody, it's Dr. Hyman. Thanks for tuning into the Doctor's Pharmacy. I hope you're loving this podcast. It's one of my favorite things to do and introduce to you all the experts that I know and I love and that I've learned so much from. And I want to tell you about something else I'm doing, which is called Mark's picks. It's my weekly newsletter. and in it I share my favorite stuff from foods to supplements to gadgets to tools to enhance your health. It's all the cool stuff that I use and that my team uses to optimize and enhance our health. And I'd love you to sign up for the weekly newsletter. I'll only send it to you once a week on Fridays. Nothing else, I promise. And all you have to do is go to drhyman.com/picks to sign up. That's drhyman.com/picks, P-I-C-K-S, and sign up for the newsletter and I'll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger longer.

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