Reduce Your BIOLOGICAL AGE, and Live A Longer & BETTER LIFE | Kara Fitzgerald on Health Theory

People who meditate regularly are biologically younger. People who meditate regularly are biologically younger, but just one meditation experience can still have favorable influence. Dr. Kara Fitzgerald, welcome to the show. Thank you. I am thrilled to be here. I'm really excited to have you. You are dealing with an area that I have become absolutely obsessed with, which So, methylation, which we'll we'll explain to people what that is in a minute, but the idea of my epigenome is really controlling how my genetics express themselves, and that becomes really important. That had been on my radar for a long time, but I couldn't imagine what was actually happening. And so, your book is called Younger You, which phenomenal book, Thank you. really goes into detail on this idea of what methylation is, and I think even though like for anybody hearing that for the first time, I promise we're going to bring you in, you're going to love it by the end of this, and you'll understand why it matters. But, walk us through the what I'll call the three layers, genetics, epigenetics, and then what methylation is, and what brings them all together. for sure. So, you know, genetic our genetic material is static. It's not changing. We inherit some from mom and some from dad, and and and it's kind of packaged relatively carefully, and and it doesn't change, you know, and and Can you explain the packaging part? That's where this all starts to get interesting, and people that know it well sort of throw that one off the cuff. How how is one's DNA, which I assume is what you mean, packaged? Yes. Yeah, well, I mean, we have a lot of it, you know, if we end-to-end, I think it what wraps around the what world twice if we did like all if we spread it all out from all of our cells, I think One single strand of DNA within a cell is about 6 ft. It's I mean, it's a ton. It's like the It's You know, but it's it's it's microscopic. Um we have to wrap it up extraordinarily carefully to fit it into a cell. I mean, it's just it it's mind-boggling. Uh and so then so it it's it's wrapped around proteins called histones, and then histones are grouped in four. So, there is just wrap wrap wrap wrap wrap grouped in four, and these little groups of four are nucleosomes, and then they're packaged together in what's called a chromatin, and then ultimately a chromosome. What's extraordinary is that wrapping helps regulate. So, this is the epigenetics that you're talking about. So, we have to we need to open it to allow a a given gene to be expressed, and then we kind of wrap it and tuck it back in, or we keep it on, and so again, gene, DNA, genetics, epi, above the gene. So, it's all of these variables that go into um allowing genes to turn on and turn off. It's all of the all of the biochemical marks or imprints, whatever you want to call them, and there's you know, many of them, uh hundred plus, that are in working together, engaged in allowing genes to be on and off. And is it the sirtuins that are doing the actual reading of the DNA and putting the um the methylation markers on the DNA? Is that what does that? N- No. The methylation markers are placed down on the cytosine nucleotide using DNA methyltransferase. Okay. And then it's and and there's a family of DNA methyltransferase enzymes that will do it at different times. I mean, I think this is where we can get in and have our lifestyle actually influence what happens during cell division. All right, so to bring this back up a level for people that probably now feel like I've dragged them down in the weeds too much. So, what what became really interesting for me is to Okay, we've got this careful packaging of the DNA. Yeah. And the way that we express or fail to express um a gene within our DNA is by wrapping it, so essentially hiding it, and saying, "Don't read this." Yes. And in your book, you said something really interesting, which is that if the DNA are the the language of our genetics, the um methylation is the punctuation. And so, it says, "Stop reading here. Line break. This is a new paragraph. So, this is an eye cell. This is a heart cell. This is a skin cell. And oh, by the way, you're in the eye, so eye cell, express yourself." Right. And so, you've got all of that in one sort of without methylation would be one run-on sentence. Yeah, that's right. And so, the methylation goes in and says, knows what would be turned on. Yeah, it would just be a big mess. And we think that this big mess is part of the aging journey, but yeah. begin losing your punctuation. Yeah. And now I'm confused. Or it's or it's distorted. It's not It's not where it's supposed to be. The word is misspelled or out of place in the wrong paragraph. See, that's really helpful for me. So, once I had that paradigm, that understanding of Okay, my the DNA says, you know, "Your eye should be this big." versus my eye's a different size. My heart cell functions like this. Yours functions like that. Yeah. So, we each have our own um way that all of this is going to express, like you said, half from mom, half from dad. But then, over the process of aging, that gets Oh, I forget the word wonky. It goes wonky. I think to use the the word that you use. I I I I I I I I I I I I I I I I I I I I I I I I Mhm. Um when it's breaking down, what exactly is happening? The methylation marks are literally just missing. So, a few things are happening and that's an awesome question. I think mechanistically we have some idea but why it's happening is a really hot topic right now in the scientific community. So, when you look at the epigenome of a younger individual as compared to an older individual, it's it's it's fascinating. Like genes that are on in youth are inhibited in age and um it tends to be that genes that are helpful and beneficial and are on in youth and then genes that are actually and those same genes are turned off in age. But it's predictable across all of us. I mean, you can't avoid these changes. I think unless we're working on it right now. We can't avoid them yet. Right, that's right. We can't avoid it. Well, and we're starting to learn. I mean, this is what I wrote about. We're starting to learn, you know, lifestyle interventions that can help you know, prevent the extent of the breakdown. And rewind them in some cases. Yeah, that's right. That's right. It's as looking at the biological age clock. So, the question I think is with this predictability, is it just damage from wear and tear in life or is there some sort of a programmed element to this that's driving the aging journey? we programmed to die? Exactly. Which is as predictable and sort of elegant in its structure as, you know, developing a human during embryogenesis or early infancy when we're when you know, infants are are just aging at this accelerated pace. They're like superhumans. You know, I have a toddler at home and actually she's turning four but um so, she's moving out but but just watching her so, thinking epigenetically and watching my kid, you know, when she was an infant sort of heal. Like you can see her skin knitting before before your eyes. I mean, it's or her learning new language or her going from sitting to standing to walking. I mean, it's all happening at this record pace. And it's And this developmental uh this accelerated developmental pay- place is part of her epigenetic journey. You know, it's part of her aging journey. And that changes over time. And then we hit maturation and sexual maturation, puberty, etc. And then, you know, women hit premenopause and or and peri and post and on and on. And all these are driven epigenetically. And then we've got this aging phenomena where things break down, where you know, we're at risk of developing cancer and dementia and cardiovascular disease and diabetes, etc. And when you look at the epigenome, it looks like it's fa- It looks like it's programmed in there. It's something that, you know, all of us thinking about it would like to change and have some control over. Yeah, I so that's a really interesting blend of the philosophy and the science. So, if we are pre-programmed to die, what are the markers that do that? So, I really want to understand this the the idea of methylation. So, I'm realizing now as I'm formulating this question that I have created an image in my head of like a dollop of glue, basically, that just says, you know, stop here. Um one is is that what it looks like because your book goes into this idea very extensively of methyl donors. So, things that you eat that generate They're They're building blocks of the goop as I'm imagining it. Yeah. Um that creates the ability for the body to put those markers. So, you have material needed to put markers Yes, that's right. you have the placing of the markers in a way that promotes longevity versus dying. Yeah. So, help me understand those two elements. So, what is it that gives us the methylation? Mhm. And then what in this paradigm where we assume it's pre-programmed, even if we're just doing a thought experiment right now, Yeah. um where does it get moved from and to that begins this experience of aging? So, methylation, there are hundreds of of methyltransferase enzymes. These guys are putting a methyl is a whole bunch of different things. Like a lot. It's a carbon and three hydrogens. They're, you know, ubiquitous in in nature, and our body just, you know, we evolved using methyl methyl groups for a lot of things, a lot of really important stuff. the same at the molecular level, how do they end up being so many different things? Well, by that it depends on what enzyme is is is using it. So, there's a methylation cycle um that's warring in our body all of the time, and and this is where we're using B12 and folate and betaine and and and choline, uh etc. to produce the universal methyl donor. So, this is a cofactor. This works with the enzyme, and it's called S-adenosylmethionine. So, methylation cycle is warring in our body, and incidentally we become less effective at this as we age for a variety of reasons, and we can talk about that. And secondarily, global hypomethylation of the epigenome is actually is a phenomenon. So, if you were to weigh all if you were to weigh all the methyl groups on our DNA, you know, in an aging individual as opposed to a young individual, they'll have less, a net less. So, globally they're just producing less, and therefore it's being used on and one thing, correct me if I'm wrong, methylation is used to repair DNA. So, if it breaks, and it broke somewhere where now a missing piece of punctuation is gone, I need to remethylate that to say, "Oh, yeah, remember you're an eye cell." So, I need to hide Yes, we do, in part, yes. And the folate cycle, which is part of the methylation group, gets in there and helps with DNA repair, too. There's There's There's a lot of There's a lot of pieces in the DNA repair puzzle. So, so methylation cycle is always is always worrying along. We're making this cofactor acid SAM-e we call it and then SAM-e works with the methyltransferase enzymes all the hundreds of them in the body. Um and you know, my focus has been DNA methylation um and so SAM-e is used there. So we want to keep this methylation cycle worrying efficiently all the time at any level. Like my my my kiddo, my toddler, you know, she needs to be accessing loads of methyl groups as well. Like we just all through life. I mean this is one of the reasons that we prescribe folate during pregnancy. You know, and even pre-conception. Like we really want to be thinking about making sure this is happening. So um methylation needs to be moving forward but we we don't and we'll talk about this. We don't necessarily just want to throw a ton of vitamins at it. Um you know, we'd always we we would have already discovered the fountain of youth, right? If that was going to be successful. We could just take a ton of folate and B12. that we even connect those ideas is because the vitamins are the precursor that allows us to actually make it. So So but we want to eat these in our food and in some cases take vitamins. So we want to be thinking about the methyl donor cycle. We want to make sure we've got enough SAM. We want to make sure methylation is happening and we do that, you know, just keeping our methylation cycle humming. And then on the other hand, we want to work on directing where those methyl groups are going. And that is what we think uh maybe the role of polyphenols, you know, of the color What you get from plants. Yeah, that's right. They seem to influence the DNA methyltransferase enzymes and perhaps uh support placement of methyl groups where we want them. To just put a point on that for a second. So from an evolutionary standpoint, we have evolved to eat plants and Yeah. the idea of thinking of these as signaling molecules I think becomes very important. So, literally gets inside your body and it will um say so I've heard it referred to as nutrition partitioning. So, it's like nutrient partitioning. So, hey, it's I'm a traffic cop, right? So, I'm saying you go here, you go over here. But, it's something I eat. Is it that it's the presence of certain polyphenols tells my body to do the direction or the mere presence of those polyphenols do they do polyphenols make it into my bloodstream? They influence the behavior of the enzymes. So, going back to the DNA methyltransferase. in my bloodstream? Yeah, they should be Yeah, some of them would be measurable. Yeah, I mean some of them are transformed by our our our microbiome and they become secondary compounds. But, yeah, mhm. This episode is sponsored by Athletic Greens. Get a free 1-year supply of vitamin D and five free travel packs with your first purchase. Simply visit athleticgreens.com/impacttheory. Now, enjoy the episode. It's so weird. This is so complicated. This is like some alien invasion type stuff. That's really funny. like the more I'm beginning to understand it and trust me I am well aware my knowledge is so surface compared to yours. But, the more I understand this the more I'm like, "God, man, this is like really intricate." Yeah. And because it's so intric- intricate and complicated, I'm really surprised that what I eat can have such a profound impact. In fact, I want to give people one of the punchlines of the book. You did an 8-week intervention, which is like a blip. A blip that's so short. And in 8 weeks, you were able to get people to see on what they call the Horvath clock, Yep. which is a clock of biological age, Yep. uh to go backwards 3 years. Yes. Which is insanity. In 8 weeks just based Did you I can't remember exercise was part of it. Yes. was diet and exercise. exercise prescription, um, meditation twice daily, 10 minutes minimum. Uh, diet we we gave them additional greens powder so more of those polyphenols, we gave them a probiotic, and we wanted them to sleep well. So we focused on sleep hygiene as well. So those five variables we worked with. That's so bananas to me. And so the often times I'll have a conversation with somebody before the camera starts rolling and then we'll hit on something so interesting I'm like, you know, we should say that on camera and that's when we'll start. You said I should be testing all of my, um, internal biological markers cuz I do all this weird stuff whether it's cold exposure or whatever. Yeah, I mean you do you you you do it. Yes, I do. The reason that I haven't is one time. Like if somebody would just show up at my house and draw blood or whatever, I would do it like no problem. And then the other is I have one really bad strategy. And that's I am I am always trying to ask how much stress can I endure. And so when I think about longevity, Mhm. I know like I don't drink, I don't smoke, I don't do drugs, but I do stress. Yeah. And so I'm a little worried about what my Horvath clock is going to say. haven't done your biological age yet. I haven't. I I do want to and admittedly it is the friction of having to leave, but if I wasn't worried about the answer, I would have gone out of my way to figure it out. Um, but stress does concern me and I steer by how well I sleep. And so when I get into a period where my cuz I never set an alarm. Literally, I mean look, if I had a 4:00 a.m. flight, I would set an alarm. Yeah. But barring that, I wake up when I wake up. Yes. But as I get stressed or excited, my sleep will reduce. Sure. And so I'm always a little, especially right now, I am I am really going hard at this particular moment. Yeah. And so I'm a wee bit uh I meditating though? Like what yeah, yeah, yeah. I don't Like when they say if you uh don't have 5 minutes to meditate, you're the person who most needs meditation. Yes. I believe in that so aggressively that yeah, I meditate even In fact, I meditate more in my hyper-stressful periods than I do when my life is more even keel because I'm so aware one quality of life is so hugely impacted by meditation. And then two, my performances. Yeah, yeah, yeah. Let's really get deep on it for a second. Let's assume that you're right, that we are pre-programmed to die. Yeah. And so now I'm looking at it from an evolutionary standpoint and I'm saying, "Okay, it's a really stressful environment. If it's a really stressful environment, we got to get rid of these old [ __ ] because they're going to take resources. So let's just speed things up a little bit Yes. and get them out of the way so that we have enough resources for the next generation." If I'm right, that would make predictions such that people would live for a shorter period of time. Now I'm setting you up, but if I'm right, would it not predict that if you were pregnant, let's say, during a stressful time, that those children would live shorter lives? That it's been demonstrated. I mean, it's already been demonstrated. Like you can look at the Dutch Hunger Winter or I mean, of course there was food famine, another kind of a stress. I mean We certainly see total life stress, you know, maternal stress and experience even, you know, a generation out, grandparents and and probably further out. Um it will absolutely it influence epigenetic expression towards um earlier mortality as well as an increased incidence of the chronic diseases of aging. So stress plays a huge role. We translate Stress in the mother? Stress in the father? Both dads Dad's right there. So, let me when we talk about stress, I want to say psychic stress, but I also want to include physical stress in there. So, physical stress could be changed change to eating, um you know, uh excess food or insufficient food. I mean, I want to I just want to kind of expand that, but but yes, in the realm of epigenetics, dad's a big player. Granddad's a big player. Great-granddad is a big player. So, I remember the first time I heard somebody say that trauma can be passed on. Yes. And I was like, uh-huh. It's like photosynthesis. I mean, I sort of think about it. It's like like psychic this this psychic experience is translated into biochemical marks that then influence on? Like cuz how it would have to then be encoded in the sperm and the egg? Yes. Onto Yes, onto their DNA. in the sperm and the egg? And do you predict if we can't already, will in the future somebody be able to look at sperm and say, "Ooh, this you would you would pass on stress or whatever." Yes. So, Moshe Szyf, who is a co-author and an advisor on our on our study, would says that yes, that there will come a time that we'll be able to predict outcome in offspring by looking at patterns from mom and dad or even looking at patterns in utero. That and that we'll be able to actually change those patterns so that we can forego some of the fallout that we would otherwise succumb to. That is crazy. The thought that I could go in and work with a fertility doctor to say, "Okay, look at my the current state of my sperm and see like is this going to be a problem? Am I going to pass something on?" This is where we're going. Like that's actually going to happen. Yes. Yes. Yes. Yes. That is bananas. So, what's happening then is you're saying that my there there some global marking on my DNA via the methylation that then or I guess it doesn't have to be global. Although I would assume it will be because it's going to be expressing itself in my body, but then it's also going to express itself in uh pregnancy. Yeah, so here's the thing and let me just say too, there's some cool research on the heritability of exercise habits and how you can hand down some of that to your offspring. So, you can change the methylome, that's what we call the the methylation genome. You know, you can change the methylome favorably or not I suppose if you're a non-exerciser and and and hand down some of those benefits to offspring, yeah. That is fascinating. Um so, here's what here's what happens. This is my understanding. We uh so, our your methylation marks you you and your wife have can see you have a fertilized eggs you egg you know, your methylation marks her methylation marks are handed handed down, but then they're largely removed. So, 10-11 translocation enzymes actually remove methylation marks, you know, from the fertilized eggs um for the most part like we remove the bulk of them, but So, don't be old. That's like the punchline of that moment. just you're just you're cleaning the slate. You're allowing you're allowing the you know, a genesis of a new a new human. There's a But not come Let me just finish this. Not entirely. There's some of you some of your methylation patterns translate over as do your wife's your wife and and that is the heritability portion of of DNA methylation. So, it's not all lost. And so, that might be your exercise habits or you know, some of the stress that you've experienced. And that actually might carry a few generations back. That means that there's what I'll call intelligence imbued in that system where there's a decision-making process. This is remove these, don't remove these. Yeah, so what you know, what gets to stay and what doesn't? There's something called the imprintome and that is um that's being studied by Randy Jirtle. So you know the agouti mice studies probably, right? Because of you, yes. But it's worth telling people important. is so crazy, the most cited thing in science. It's so fascinating. So I'll tell about that paper in a second, but just to kind of wrap this up, the imprintome is some of what can be inherited from mom and dad, some of the methylation patterns that can be inherited from mom and dad. And Randy is actually really interested in studying that now because some of them can translate into pretty serious diseases. So So he wants to work on that, but also in the imprintome can house the benefits of exercise if you've had a good habit, you know, good exercise habit and some you know, some other really cool stuff, too. You said that there is uh a signature for trauma, an epigenetic signa- signature for trauma, but there's also then one for wisdom. Yeah. And that Yeah. That to me is This is so much more complicated than people think. Yeah. Yeah. Yeah, so resilience. So trauma we we've studied trauma. I think that there's a sort of an obsession with studying trauma patterns, not just in the epigenome, but you know, beyond that. And so we know trauma can be carried carried over, trauma can be established in early life and then and then it can translate as chronic disease later on and it can translate to, you know, having a really poor stress tolerance. I mean, can translate into all sorts of things. So yes, trauma has a strong influence. Resilience does, too. Um but we know less about how that translates. That's what we need to study and that goes back to the idea that Moshe Szyf posited where um you know, if we understand these patterns well, we can look at you early on or or or or look at an embryo or or, you know, a fetus and decide, you know, these are resilience patterns and if they're not, we can correct them, etc. I I mean, you know, the era of epigenetics and epigenetic diagnostics is just just just beginning and it's it's just going to continue to grow. Um, but we should be putting energy towards studying um resilience and what that looks like. And then to your point, studying wisdom. So, honestly, we're in such a rabbit hole, but let me just say cuz you talk about the Yamanaka factors quite a bit. I know you I've seen you talk to David Sinclair at least twice and and you're always yammering about his his his Yamanaka research and and and and reversing aging. Causing aging by messing up epigenetics and then reversing aging, cleaning it up with these three of the four Yamanaka factors that clean up methylation specifically. They bring it back to a more youthful pattern. So, we have to ask ourselves in this quest for youth. And this was something that I posed at the very end of my book. If we're going to turn back the hands of time by decades, are we going to by extension, re you know, remove the molecules of wisdom that have have have embedded in our DNA? So, you know, I was listening to you guys talk about if you had a life-threatening illness, you might just go for the Yamanaka factors to see if you can turn it back. Would you learn would you lose some of this extraordinary knowledge that you've obtained on your journey? I mean, you've done some amazing work in your life and some of that is biologically embedded in your epigenome. I mean, what are we doing by turning back the hands of time? Are we at risk of losing some of these um, you know, these marks of wisdom, these these beneficial changes as well? That's one thing I found really interesting about your book and we're not going to forget the mice. So, people following along. Um is in the book you talk about unintended consequences. And so, you lay out this incredible book, which, you know, we'll we'll get into some of the things that you should be eating and all that stuff in a minute, but um you lay out this incredible plan for how people can reverse the biological clock. You'll never be able to reverse the chronological clock, obviously, but um that your biological aging you can move backwards. And then you say, "But hey, be careful because we don't know where all of this is going yet." And so, you do have to be very thoughtful about those unintended consequences. Yeah. Um And you guys have talked a lot about, you know, teratomas or tumors and cancer and so forth, but yeah, I wonder, you know, I wonder about some of the you know, the the less understood shifts that happen with maturation, etc. And this is why I'm obsessed with whole food. So, like I try never I do supplement vitamin D when there's not enough sun, but if there is sun, then I don't supplement and I go get the sun because there's probably things that we don't understand about the skin is doing something when it actually feels the radiation, you know, on it. Let's talk about Athletic Greens, my friends, the all-in-one daily drink to support better health and peak performance. To help each of us be at our best, AG1 by Athletic Greens simplifies the path to better nutrition by giving you the one thing with all the best things. One tasty scoop of AG1 contains 75 vitamins, minerals, and whole food-sourced ingredients, including a multivitamin, multimineral, probiotic, greens superfood blend, and more in one convenient daily serving. And right now, Athletic Greens is doubling down on supporting your immune system. They're offering our audience a free one-year supply of vitamin D and five free travel packs with your first purchase. Simply visit athleticgreens.com/impacttheory. That's athleticgreens.com/impacttheory and get your free one-year supply of vitamin D and five free travel packs today. athleticgreens.com/impacttheory. All right, guys, take care and be legendary. All right, so walk us through the mice. Yeah. Yeah. Um it's interesting to me in the longevity space um cuz I come from functional medicine. I come from you know I've been nutrition background. I'm a naturopath by training and we're obsessed with these things. Um So nu- nutrition has this extraordinarily profound generationally um uh powerful influence on gene expression and Randy Jirtle showed it. Randy Jirtle and and Waterland in 2003. It's interesting to me because that was when we mapped the genome. We figured out the archi- the human genome in around 2003 and we started to realize it wasn't it didn't house all the answers that our genes aren't our destiny. In that same year, Jirtle and Waterland published their agouti mice study um which incidentally they couldn't publish. I think it took them 16 different journal submissions and finally to a really low-tier journal they were accepted. Yeah, people were like, yeah, whatever. You know, their peer reviewers did not buy what they saw. Wow. Didn't buy it. Didn't accept it. So what they showed they used an agouti mouse which is which has the agouti gene expressed. And in animals in in mice this means that they this when this gene is on they're they're blonde and they're obese. They're very visual. They don't look like a normal you know house mouse. Um they're and they die from you know obesity-related causes. I mean it's just it's pretty extraordinary. So this you can get this mouse and and do research studies on them. And it was actually Waterland. Jirtle credits Waterland for the idea of testing um nutritional intervention in in this mouse model. Like can they methylate and inhibit the gene. And so, that's what they they set out to do. Actually, they initially set out to show They initially wanted to look at what methyl donor deficiency would look like. So, insufficient methyl donors was their first study is and the mice died. They just did They Even faster than normal. They died. Yeah, they just died immediately. Yeah, they didn't survive at all the offspring. So, these were in pregnant agouti mice dams and they gave them they fed them a methyl donor deficient diet and offspring were were dead on arrival. Woah. Yeah. So, that's how important these methyl donors are in our diet. Like they're exquisitely important. So, that was study one and they didn't publish. That was just communication that I had with Randy Jirtle. So, study two was let's increase methyl donors. Let's give these pregnant agouti mice some folate, some B12, some choline, some betaine. Let's give them that. And lo and behold, that agouti gene was hypermethylated and shut off. So, a lot of methyl groups a lot of the the glue or whatever your glue blobs. Shut the gene off. And their offspring were brown like they looked like wild mice. They just like normal wild mice. But here's the kicker. So, these are just nutrients to give to the pregnant um and dams and they reverted the offspring to what they call pseudo agouti and it went on for generations. So, once one laboratory looked at how for how many generations and calculated five. I think Jirtle and Waterland went back three um in their lab. So, nutrients given to the pregnant mouse resulted in a generational influence on gene expression. For five generations. Yes, five generations in one study. no longer had to sort of hypermethylate them and they would keep coming out as normal brown mice. Yeah, or on a continuum. So, it's not an It's not an all or nothing. Like some might have a little speckle of blonde. Like it, you know, it's it's a continuum of how hypermethylated that gene is, but in general, there is a trend towards turning off hypermethylating and inhibiting that gene and therefore restoring these mice to the sort of brown wild-type mice and and and shutting down the the diseases that they were vulnerable to. Whoa. Now this Yeah, big deal. I mean, that's how powerful nutrients are. And that study was ignored at first. They didn't believe it. seemed un didn't seem possible that they could influence genetic expression. Yes, yes, yes. That's so nuts. That's really powerful. tell you another kicker. This is a crazy story. So, another post-doc in Jirtle's lab looked at this same model, so again the agouti mice, the agouti pregnant mice, and gave them genistein, the soy isoflavone. The So, a soy phyto phytochemical. Same effect as the methyl donors. So, a polyphenol, nothing to do with that methylation cycle that I talked to you about at the beginning. Nothing to do with B12 and folate, et cetera, but somehow changed methylation, shut off the agouti gene. Hmm. Riddle me that. I was going to say, so I don't I don't even understand enough to know how weird that is. So, weird because it didn't So, the DNA methyltransferases lay that, you know, use SAMe to put methyl groups onto the gene to shut that gene down, but genistein is a polyphenol. It's It It doesn't influence DNA It doesn't It It It isn't making SAMe. It isn't giving the ingredients to shut it down. So, it's doing something else. And they speculate that it actually repositions the gene, sort of making the the available methyl groups able to get in there and act. So, it's doing something else. And they speculated, yeah, just maybe just like opening it opening that agouti gene up for, you know, ready access to the fewer methyl donors in circulation or something. So, So, Jirtle and his lab said, "Look, you guys, you know, we think nutrients are beneficial. You know, and of course they are." But I was taught we just pee them out, you know, there's no harm. You know, you'll use what you need, you get rid of the rest. Yes. Right? They showed five generations that these nutrients influenced. And so their conclusion in that 2003 Well, it had this powerful favorable influence on these on on these mice on these offspring. So So that's what they said, you know, we long thought these were basically inconsequential, right? I mean, medicine, we evolved not even paying attention, you know, physicians aren't even trained with nutritional train like we just don't even think nutrition nutrients are a big deal at all. And these guys completely changed that conversation. And in their abstract, the end sentence was, "We need to pay attention to how powerful these are, you know, because they can have unintended consequences." So And then they showed genistein does the same thing, and it's not even a methyl donor. And so in that study, the post-doc who wrote who wrote who conducted that study said, "Well, you've got a vegan mom who's eating a whole lot of soy, so, you know, loaded up on genistein, maybe she's eating grains with folic acid, you know, fortified grains, which were riddled with in this country, you know, and layer in a multivitamin, a prenatal, and you've got a ton of methyl donors or or or or nutrients acting like methyl donors, and and that may not be a safe phenomena. Now, we know we need methyl donors in pregnancy, no doubt about it. Um we need them throughout our lives. We really need to be bathing our our genes in in in healthy methylation, but yeah, it can get a little squirrely when we're using isolated micronutrients and dosing really high and layering them in layering in with other nutrients that have an influence on methylation that we don't even understand yet, like genistein and So it goes back to your original point of diet, you know, whole food matrix, eating how we evolved, you know, getting some vitamin D from the sun. I mean, just sort of having that be our touchstone, sort of, you know, our foundation. And then layering on some of these interventions if we need them, if there's a reason. Man, being a pregnant woman does not sound stress-free. It's like you can't be stressed because that's going to pass on. You've got to be hyper careful about what you eat. You can't just blast your system with all these vitamins. Damn. Uh yeah. Well, the There is some cool research, actually. The The The folks at Grow Baby Health are friends of mine, and they've used They're using our program and layering it in into what they're doing, and they've got extraordinary birth outcomes. Like, their incidence of common childhood illnesses or um you know, gestational diabetes, some of the complications of pregnancy, they're like nil. Their incidence of autism in offspring from this from this clinic are I think I you know, maybe one if I I I put the stats in. Yeah, they've published on them, and they are using micronutrients. They are using a prenatal. So, I want to clarify. I don't want I don't want anybody to get anxious. There absolutely is a place for these micronutrients in pregnancy, and you get them from a whole foods diet, and you avoid folic acid fortification. Um and you know, just pay attention to how much soy you're eating you eating etc. So, there's some some ducks to put in a row, um but we still, you know, micronutrients are generally healthy in pregnancy. Wow. All right, let's get into the the do's and don'ts. So, let's set aside exercise for now and just talk about uh diet. What should people be eating? Yeah. So, we want to we want methyl donors, like up the wazoo. Loads of methyl donors. So, we want to be doing um greens, lots of greens. We want to be doing, you know, leafy, good greens. Spinach and kale. Yeah. Yeah, totally. We want to be doing, um, we want to be eating some beets. Not a ton, but maybe a couple of small beets. They're pretty high in sugar and we just we don't need a ton of them. Um, But betaine is a red gives us something? Betaine. Yeah, betaine will help ward the methylation cycle. It will help with methylation. Beets. Uh, seeds, mushrooms, shiitake, enoki, maitake. Um, these are rich with choline, folate. They're like they're Mushrooms are really extraordinary. Wild mushrooms. Mushrooms are so gross. Are they gross? I can't deal. So, Okay, fine. So, for those folks who like mushrooms, eat mushrooms. There are alternatives. Like So, mushrooms are rich in choline. You can't Or you can take them Or you can take them encapsulated if you want to, which mushroom just like ground up? Yeah. Okay. So, it's not like it's a isolated compound from the mushroom. It's actually just encapsulated shredded mushroom. Yeah. Got it. Yeah, you can. You can get that. can get that with liver as well, right? Yes. In fact, that's how I ingest my liver cuz I don't cook it. Fair. Yeah. Liver is a multivitamin in a food matrix. It is so extraordinary. You don't need You don't need to eat a ton of it. You don't have to have it every day. If you get three servings a week, you're getting just a massive amount of good folate and B12, et cetera. Is there a encapsulated liver that you recommend? Yes. It is I have a whole list of products that I like in the in the resource section that we vetted for for purity. New Zealand sourced liver tends to has in my research the cleanest reputation. They seem to be doing a really good job. So, methyl donors, eggs, another beautiful source of choline that you want to be getting. Yeah, so greens, seeds, some nuts, fats from fish. nuts have to be raw? You know, raw is better. But I would Because I'm cooking out some of the micronutrients or because they the delicate fats. So you know, they're more beneficial in the raw state. Cuz like raw pumpkin seeds sounds pretty gnarly. They're not bad. pumpkin seeds are really good. Yeah, that's right. Go with what you're going to consume. So it's not like baked becomes bad for me, it's just not as good. Don't eat like charred, obviously. Don't eat really poor quality. Try to get a good quality, but I use I eat roasted pumpkin seeds. I love them. I throw them on my salad. You're going to get some nutrient for your bang for your buck in that structure. And do we have like a short seed list of the good ones? We really like pumpkin. We really like sunflower. Um sesame. Those are good. So seeds, mushrooms, liver, greens, eggs, salmon or other really fatty fish. And those are going to keep that methylation cycle warring. Those are some of the key ingredients that will keep methylation warring, mushrooms. And then we've got these traffic directors, the polyphenols. And so those are all your colorful fruit and veg. I mean, some of our favorites are curcumin. Curcumin, turmeric. Turmeric. Curcumin is an extraordinary Those are the same thing. Turmeric is the spice that houses curcumin. Curcumin. Um So curry, do you like curry? Can you do a curry? I eat curry frequently. Awesome. Golden milk is one of my favorites. I love curry. Golden milk is is a turmeric drink. Turmeric and a little bit of coconut milk and you know, a little pepper and some other spices and it's just delicious. It's a very It's a time immemorial drink in India. All right. It's delicious. Um So, methyl donors plus these polyphenol compounds that um appear to direct what where methylation is happening. And we want to load up and you know, again, blueberries, curcumin, um EGCG and the other cate- catechins in green tea. I don't know what that is. I know what green tea is, though. green tea. So, green tea is loaded with these phyto- chemicals that are, you know, gene reservers, DNA methylation adaptogens, whatever you want to call them. I mean, just helping with optimal epigenetic expression. That's what we think. And most of the research at the time of our book um is in vitro. So, in cell studies or in animal studies, but they seem to be able to turn back on some of the genes that are shut off in the aging journey. So, these compounds have far-reaching beneficial effects. They're anti-cancer, they are anti-inflammatory, they're anti-microbial, and you know, beneficial to our microbiome. Um they're anti-aging in a lot of ways, senolytics like quercetin. Um What's a senolytic? Senolytic helps helps uh inhibit production of the zombie cells, those pro-inflammatory Yeah. So, just just think colorful elements of your fruits and vegetables far and wide have this methylation adaptogenic effect. Seem to be able to direct DNA methylation. What's your take on fruit? I think of fruit and vegetables as being so different. I even think of berries as different from fruits. Yeah, yeah. Most of the fruits have important compounds, but we don't, obviously, because of the sugar impact, you don't want to be eating tons of them. So, you need to be mindful. Um Can I eat as many raspberries as I want? You know, if your blood sugar is in reasonable control, I mean, do you wear a continuous glucose monitor? I have many times. Yep. I'm not currently. Yep. But yes. So pay attention. You know, just pay attention to how your body responds. Like I we recommend blueberries on a daily basis as one of the or any dark berries. Raspberries would be in there. Um if you're going to load up on them, you know, you might want to just pay attention to your sugar and see how much you can tolerate. It's going to be different for for all of us. But if you have your raspberries maybe on a salad and you've got a higher fat dressing and some fiber in there, you know, each of it it'll be different for each of us. Um but super important information is contained in raspberries and all of these. And we're just starting to understand how sophisticated the information is. Like I was reading a this is a cell study, but curcumin in turmeric can inhibit mTOR in multiple myeloma cells. So in a can't I know. In it and it's a cell study. So it can it can hypermethylate an M the mTOR gene in multiple myeloma cells in a cell study. By ex- by comparison, curcumin has also been shown in cell studies to turn on a hypermethylated BRCA gene. So BRCA the BRCA um genes are major highly important tumor suppressor genes. So they keep us clear of cancer. A functioning BRCA gene keeps us clear of of cancer, takes care of DNA repair, etc. It does a lot of stuff. The BRCA a functioning BRCA we're not talking about the BRCA mutation, but a functioning BRCA gene can actually be hypermethylated and inhibited and then it's associated with all sorts of cancers. So It by getting hypermethylated or hypomethylated? So it's shut down and no longer um available to do its work. Hypermethylation, lots of methyl groups inhibit it from being on. So curcumin will allow that to be re-expressed. So, in mTOR, it can shut it off in a multiple myeloma cell, but BRCA, it can turn back on to go do its good work. All right, so let me say that in layman's terms. So, mTOR, which is basically grow. So, hey buddy, grow. Grow muscle, grow tumors. Yes. So, we're shutting down mTOR, and then we are removing the errant punctuation that is making the the sentence impossible to read in the BRCA gene. We're turning the BRCA back on and allowing it to function. That's a So, it does two two opposite things. Curcumin and turmeric does two opposite opposite things in cell studies. It's amazing. So do some of the other players like luteolin or um quercetin. Um what else? Genistein. So, going back to soy. That's a really important polyphenol that of soy as being bad. Yeah, I would say that if you can get a an organic and perhaps fermented soy, it's an important polyphenol. I mean, it's just got important potent power benefit for the most part beneficial power. I just wouldn't overdo it. need to worry about the estrogen? No, I don't think that there's there's enough and you don't want to swim in it. You know, have a serving of it every now and again if you if you like it. We don't use it in the intensive part of the program, but we do um allow it for vegans in the program or uh when you transition off of the intensive eight weeks, you can include it and and they're important polyphenols. So, these guys are the traffic directors. So, we want to load our body up with this collection of compounds and there's a 30-page nutrition um appendix that will give you the details like all of the foods that you can access to get some of these really important epi-nutrients as a category. Both of them we're calling them epi-nutrients. Woo. Okay, so there's a reason that your book is robust. Uh it is not brief in its um incredible description of what's going on and what we need to do to combat all of that stuff. This is really really incredible stuff to me. Uh I want to run through just a synopsis and there's been a few things that we haven't gone really deep on that's probably worth just reminding people that they should be doing. But so all right, we've got our genetic code which isn't changing, it's not going anywhere, but you have the epigenome which is probably way more important. Like when you look at the genetics of a plant, it's way more robust than the genetics of a human. And yet humans are pretty damn complicated. Right. Because of this epigenetics of what is expressed, what's not expressed. Yes. What you eat Yes. has a huge Yes. impact on what's expressed. Going back to the mice study, it's pretty crazy that you can alter the pregnant mother's uh diet and it has a five-generational impact. That's so crazy. I really think that's going to give women heart palpitations. But if I can help them reframe it that it can be a negative impact or it can be a positive impact as in the study was looking at the good things that you can pass on which is pretty incredible. Okay, so we've talked about all that. Now let's give a quick breakdown. What is the role of stress, sleep, and exercise? Right. Um incidentally, we have what we call the Younger You Hybrid in here for pregnant women and pre-conception. So we put together what we think is a good eating pattern. So if you have palpitations, ladies, and you're if you need it, just take a look at the book because you can totally eat for your genes, your genes and your offspring. So if we're not sleeping, we're aging. I mean, you know, sleep is an essential component of good epigenetic expression. Insomnia ages people. And that's been demonstrated looking again at DNA methylation. Um but it's a lot better. So I just walked through all the hacks that I've used. Cold room, you know, going to bed on time, not setting my alarm. That's a big thing for me. I use melatonin and magnesium. I find both to be helpful. I use meditation. So I do meditation. Sometimes I'll listen to rain. Like I'll just all sorts of different very dark room. So we need to sleep. We need to figure out how to get it. It's it's really important with repair and anyway, on and on. Stress is potently pro-aging. And again, as you as as as we've been talking about it, it can be generational. And it can it will influence mortality morbidity and mortality. But I think stress is one of the most pro-aging um experiences that we can have and that we need to be paying attention to turning it off and not allowing it to drag us by the hair. Um so stress is very pro-aging. I think it the clock that we used, the Horvath 2013, like the flagship sort of gold standard clock that we used in our study, a full 25% of those methylation sites are influenced by the stress response. 25%. There's no other factor that influence that this so singularly influences the clock as these what they call glucocorticoid response elements on the clock. So that to me suggests that stress plays a huge role. Huge. Um sleep, stress. Conversely, the data on meditation, on tai chi, on yoga is extraordinary. Even a single exercise can have favorable changes. Like we can make a difference pretty quick if we continue to do it over time. I mean, just think cell division after cell division after cell division, you can hand down these favorable changes. So if we continue with our good habits, we can have these lasting and really powerful improvements. People who meditate regularly are biologically younger. People who meditate regularly are biologically younger. But, just one meditation experience can still have favorable influence. Even yoga, like a weekly yoga habit showed beneficial changes in the epigenome. A weekly yoga habit. So, you know, we got this. We can we can do it. You don't have to retire to the mountain, you know, and and and and to a Zen monastery and practice 8 hours a day. Like, you just start wherever you are, and you can make favorable changes, but understand that the habit is obviously better. Same thing with exercise. Like, a single exercise event can change DNA methylation, epigenetic expression favorably. Like, one single time. Keep doing it, and it's, you know, the benefit of it is so far-reaching. There was a paper that came out not too long ago really arguing that all of the benefits of exercise come from the epigenetic influence. As I said, we can pass some of those down. And the older you are, the more bang for your buck you get with exercise. Exercise will turn back on those previously inhibited tumor suppressor genes. As we age, our risk for cancer rises exponentially. And a piece of that is, you know, and again, this is goes back to the program aging conversation, is that we reliably shut down our tumor suppressor genes. Like, these genes that keep keep us clear of cancer, we start to hypermethylate them and inhibit them. I mean, what the heck is that about? Exercise turns them back on. As do these polyphenols. It's like, exercise is like a physical polyphenol. Isn't that wild? Isn't that wild? It's like It's like Exercise is like eating a vegetable. That's crazy. I know. It's so cool. And it doesn't take a lot. So, one exercise event can be beneficial, but then again, the habit, the lasting habit is good. And And could have a whole 'nother conversation of are we doing high intensity? Are we, you know, doing something low and slow? I mean, what are we doing? Are we doing weights, resistance training? There was a study that came out not too long ago specifically beneficial for mitochondrial DNA methylation. So, pretty cool. Um I think we do what we love, what we're good at, what we're consistent with. In our study, a very gentle prescription of um 30 minutes, 5 days a week minimum, perceived uh exertion 60 to 80% of max. So, not intense, but it was the consistency that we thought was important. Over-exercising can be pro-aging. I mean, anybody who is is a competitive athlete, I mean, I know when I was I was a cyclist in in med school, I was racing competitively, and I would always crash at the end of my season. You know, I'd always have a upper respiratory infection, always. You know, you just wear your yourself down with the stress of of repetitive, you know, really high intensity events, and you know, it's it's pretty common that you get a cold or you get sick for a while. So, over-exercising can be a pro-aging, but you know, I still love high intensity interval training. I just, you know, I'm just a little bit more mindful about it. And I do pay attention to my biological age, and we can talk about that as well. That will have to be on round two. I cannot believe how fast this went. That's This is so fascinating to me. Where can people follow you? Where can they get the book? youngeryouprogram.com or drkarafitzgerald.com. So, clinic and everything else, drkarafitzgerald.com. Book, youngeryouprogram.com. And we also have an app where we're we have IRB We're researching. IRB Institutional Review Board means we have permission to continue to do research. So, in our app, which you can find at youngeryouprogram, you can jump in and join us on this continued research. And the next, you know, data that we're looking at is awesome. It's exciting, and I just, you know, look forward to publishing on it soon. I can't wait. That'll be a lot of fun. Guys, you will love the book. Check it out. If you're as obsessed with aging backwards as I am, this is another fun one. Be sure to check it out. And speaking of things that you should check out, if you haven't already, be sure to subscribe. And until next time, my friends, be legendary. Take care. Peace.