How you age and how you can age well | Dr. Kara Fitzgerald on Big Bold Immunity #35

Likewise with stress. You know what blew my mind, Jeff, is how 25. So the clock that we looked at, a full 25% of those methylation sites that are measured are influenced by glucocorticoids. They're influenced by stress. They're called glucocorticoid response elements. If that doesn't cause us to want to tune out and meditate or really think about the stress influence on our life as being pro aging, I don't know what does. I mean, that was very profound.

Well, welcome to this extraordinary conversation with the big Bold Immunity podcast. And you know, each of these episodes, I have the chance for exploration with individuals that are life changing. For me, it's a little bit of a very maybe selfish thing that I have the fortune of bringing people that I really consider to be extraordinary guides and thought leaders and that have changed my thinking. And hopefully I can share those with you and they can be powerful ways for you to rethink certain things. And so this podcast with Dr. Kara Fitzgerald is one of those epic moments. It's an epic moment because of her leadership in the field. It's an epic moment because of the years that I've had the pleasure of knowing her as she traveled in her journey, as we are all on our separate journeys. Her journey starting really through health sciences, into her naturopathic degree at Western States in Portland, Oregon, and ultimately into a postdoctoral work with Genova Lab and Metametrics and Dr. Richard Lord, arguably one of the top people in metabolic medicine in our field, and then on into authorship and research and development and clinical practice. And ultimately then her path took her into wanting to advance into the research clinical area in an area that she alone was really starting to pioneer. And that is, you're going to hear more about it, but I'll just kind of summarize it by saying how do we really understand at a molecular reproducible level how people age and how does that relate to biological function of those individuals? So that there's a difference between the age they have in birthdays and the age of their biological system, which we call biological age. And how would we quantify the difference? Most of us would like to think that our age in birthdays would be greater than the age of our biology. We'd like to be younger than that of which our birthdays would tell us. And Dr. Fitzgerald has been on that quest and that understanding through the principles of lifestyle medicine, functional medicine, integrative medicine, natural medicine, all of these concepts that we've heard about, but maybe they appear a little Squishy. We don't have the quantification and the precision to really understand exactly how they all fit together. But she undertook this, this process and this thought process in a way that I would call expansive, courageous, probably against other people's recommendation because they would say, oh, that's not going to work. You know, it's way too problematic. But always look to the people who can do the impossible to see how you're going to carve out new ground. And that's what we see with Dr. Fitzgerald. So, Kara, welcome to the big Immunity podcast, and thank you so much for both who you are, what you're doing, and for being present. So maybe we should just start with me giving you the opportunity to say a little bit about how your journey now through your eyes and experience, have resulted in what now we're going to talk about.

What an honor. And just thank you for that, for that introduction. And, God, it's so nuanced, and you getting it right down to some of the forces against us doing this study or challenging us in our study design and so forth. And, you know, if it wasn't for you, your constant sort of reassuring, calming voice of reason and unwavering faith in what we were doing, you know, who knows if we would have buckled at some point, you know, because as benign as it seems at a glance, we're researching a diet, a very safe diet, and lifestyle intervention it is. I can see in hindsight how radical it was, and I always want to, you know, give credit where credit is due, and thank the foresight of Brent Eck, the CEO at MetaGenics, for being willing to, you know, to. To grant us and, you know, the unrestricted funding to answer this question to embark on this journey. And I deep, deep, deep gratitude. So, you know, I think there's an alchemy of a handful of events going back to, you know, choosing to become a naturopathic physician and being exposed to, you know, nutrition, nutritional biochemistry, you know, just a different lens, you know, kind of a systems lens, you know, looking at physiology and how we address it. And concurrent to that, of course, being becoming aware of your work and seeing you speak, because you were. You're right there in the Pacific Northwest. So I had access to kind of steep in, you know, what you were thinking about then. And of course, it's always rooted in nutritional biochemistry. And I was, you know, enthralled with that and in thinking mechanistically about what it was we were doing and, you know, in influencing physiology and pathways and sort of on and so forth. And so that catapulted me into being able to do this amazing postdoc in a lab, you know, and continue to further that thinking. Of course, we were, you know, moving into the omics revolution where, you know, we were looking at, you know, the genome was mapped and we were looking at organic acids and proteins and fatty acids and so forth. So we were really dancing in a broad investigation of higher throughput technology, look, getting to look at a lot of stuff. And, you know, you've always been at that interface of translating science and for clinical application. And we were, We've been sitting at having access to some of these bigger technologies like the epigenetics investigation that I just undertook. So I think. And you've been mentoring me all along. So I think it's just this gift that I was in a position to ask the questions. Like my training led me to think about what are we doing to the epigenome? So what are our interventions doing? And it was clear to me. And so we've been talking about it for a long time. This is nutrigenomic medicine. Of course we're influencing genetic expression. I think we've been pretty confident. But there comes a time when you actually have to say, are you. Are we actually doing it? And we needed to wait for that technology to be available. My entry into seeing it as very important was probably Epigenetics was probably 2013 when I finally, I want to be honest and say I had some resistance to reading the epigenetic literature because it's complicated. You know, that cartoon, you know, just say if it's too complicated, say it's epigenetics. I mean, it is like a whole new science. It is an entirely new paradigm. And I was, you know, I was tucked into my own model and into my own thinking and into my clinical practice and so on and so forth and to. To ingest this new, you know, really revolutionary way of thinking about medicine. It just felt a little bit overwhelming. And yet I knew, I knew it was important. And so I made myself hunker down with papers back then. And a lot of them, the best science was really coming out looking at cancer. And we know that cancer very. The tumor microenvironment very efficiently hijacks the epigenetic machinery and directs gene expression towards its own nefarious end. And we can see. So the area that I was interested in specifically was DNA methylation for a variety of reasons. It's certainly one of the best studied of all of the epigenetic works. And these are the biochemical processes that direct genetic expression. So we've got 23,000 genes, we've got a simple genome as humans, very simple. And then you look at genetic regulation and that's really kind of where the rubber meets the road. And it's as complex as our genome is simple. But of the myriad ways in which we express our genes, probably the best researched and really arguably one of the strongest I think because we see that it's heritable is this is DNA methylation. And very simply it's just, it's methyl groups placed on certain regions of the DNA. And when there are quite a few methyl groups on a promoter region, that gene is generally inhibited. When those methyl groups are removed as they can be or they're inhibited from being placed, that gene can be on simply lots of methyl groups, gene is off, less methyl groups, gene can be turned on. The earlier science was in cancer and we could see that cancer could turn off all important tumor suppressor genes and turn on, which protect us from getting cancer. They would turn those genes off and then they turn on oncogenes. They remove the methyl groups from these genes that promote cancer. In this way they drive cancer forward. We know from research henceforth that epigenetics are incredibly important in an area of not only diagnosing cancer, as with the grail assay, but how we address cancer. So we know this hyper hypomethyl methylation pattern happening in the DNA is extremely important. So as I was reading this Jeff, you can imagine, I mean I was stopped in my tracks. I mean we talked about this back then. What are our interventions doing? How are we influencing this aberrant, this imbalanced methylation pattern? And so that was the first sort of piece that stopped me. Do we always want to supplement, you know, with, with extra B vitamins and folate and B12 and would that be contraindicated in any case? And so we started to have questions here in my clinic and fortunately I've got, you know, I've just got an extraordinarily bright team here of physicians, MDs, ND's as well as nutritionists and my partner Ramili Hodges at Hodges and I, she's the, she, she's the director emeritus, but she was the director of our nutrition programs back then. Decided that we would invest, we would create a food forward plant, actually a food plus diet and lifestyle to attempt to balance DNA methylation as, as, as radical as that was. And we ended up publishing, we put an ebook out as to, you know, our rationale behind it and how we set about doing it. We incorporated it into clinical practice right away, and we saw great results. I think people would feel better. It's a smart dietary pattern. We'll talk a little bit about some of the ways that it's different than other dietary prescriptions. But we saw people get better. We saw homocysteine drop without B vitamins and so forth, and people felt good. But of course, the lingering question is, are we actually influencing genetic expression? Are we doing what we. What we want to be able to do? And as we scratched our heads on being able to research it, you know, we could do a subjective symptom questionnaire, we could measure homocysteine, et cetera. Everything was lacking. I mean, we needed to look at genetic expression if we were going to demonstrate, you know, whether or not our hypotheses had any validity. And, you know, and that's when Brent Eck came in and agreed to sponsor the investigation. Now, I want to say, where does biological aging come into this? Can I make that comment or should I, Should I. Should I keep going or do you want to make any comments?

Yeah, let me take a break just for a second, Ben, so you can oxygenate those frontal lobes, because we're going to have another run at it here. But I want the people that are fortunate to experience what you've just said to take a kind of a pause and ask the question, what is it that is within the human spirit that creates our ability to do something great? Because that potential resides in all of us. How does that actually happen? And how does a person go from a state of inquiry to a state of becoming an expert? What are the driving forces that create that? If in fact our genes are there to be capable of expressing the full potential that we inherited through those 23 pairs of chromosomes, how do we squeeze out the maximum value? And you just gave a classic example of how that occurs in a person's life. This isn't abstract. It's not some hairy fairy, blue sky, all thing. This is real person living a real life who has then created an impetus in their need to know that finds solutions to problems that maybe at first level would have seen, maybe impossible or overwhelming or, gee, I don't even think I want to try this because there are too many barriers and blocks in the road. And I'd like to take a different path. It's easier. I don't believe that probably ever. In this process that you just described, and the oratory eloquence in which you describe your own learning in ways that is deep and wide that you ever really felt that there are insurmountable barriers to you learning this information and gaining some ability to ultimately help people. Right? That was a driving force. And I think that power, that energy resides in all of us at some level. It doesn't always have to be out epidemic genetics. It can be anything, right? Anything. A person then sees in their life as a need to know that is so powerful that it goes to sleep with them, they awake with them. It becomes, as Salinger said in Franny and Zoe, with every beat of their heart, it becomes part of their being. And that is that. Dr. Fitzgerald, I've known and had the pleasure of knowing as I've watched you mature and developed your career in that you've been a model, not just a model as a woman, but as a model as a person in our field that is establishing a tone of excellence in your pursuit. Because there's always the chance along the road that you'll end up in blind alleys, and then you have to find a way out of those blind alleys. It's a natural process through discovery that you're going to end up in places that you got to back out of and find a new place. And you've just described it sounds like a smooth process. It was not a smooth process of your own education or the pursuit of your research or the ultimate oversight of how that was conducted and the final assembly of the data. And being the person to be a principal author on the first study ever published showing how nutrition and diet and lifestyle influences then the epigenetic aging of cells. That, to me, is a success story that models across all sorts of other applications, not just this one singular endeavor. So I just want to take a moment to acknowledge that because often in our life, we all need champions upon which we can model ourselves. And you are one of those. And your colleagues, I know you would say you didn't do this all by yourself, but someone has to lead the band, right? And you certainly have. So I just want to take a breath, oxygenate our neurons, and acknowledge that. Now, for those individuals who maybe got lost in a lot of the very, very eloquent and complicated discussion you shared with us. There was a lot of density of material. It reminded me of Jeff Bland on steroids, the way you were describing that, that this concept of epigenetics, just to remind people, was resisted for years as a feature of importance in anything other than developmental embryos. And because it sounded a little bit like what we were saying is that a Person could adapt to their environment. And adaptation to an environment was just stricken from all medical health sciences curriculum. It was all around natural selection, Darwinian natural selection. There was no such thing as adaptation. Now suddenly we have reintroduced the concept that there are these different tuning knobs. There's a coarse tuning knob, that's genetic selection, and there's a fine tuning knob that's epigenetic modeling. And this has come to life, and now it's being seen as a major driver for how every person changes their architecture in the way their genes are expressed as they age, depending upon the experiences that they've had in their life, including things like post traumatic stress syndrome or exposure to chemical pollutants, or all these variables that imprint our genes. So I just want to acknowledge that what you've just described is a paradigm shift of epic proportions that quite honestly changed the whole of healthcare in the 21st century. And I authored an article on this not too long ago saying that if we were to categorize all the discoveries that have been made over the last hundred years, this concept of epigenomic patterning through intervention by exposure to the environment is a major agent of change that will ultimately change all the way we see healthcare. So that's a pretty big deal. And you're right at the forefront of that now. I'll turn it back over to you to talk about the study and this extraordinary work.

Thank you. Go ahead. So that's very, very, very meaningful to me. I mean, I'm glad that my camera's a little blurry because I'm like, I'm tearing up with, with what you've said. I mean, I just want to. I don't want to talk about it too much because then I'll just, I won't be able to continue to dialogue. I'll be so teared up. But I've just had very important humans, I mean, including you, walking with me, saying yes, you know, just saying yes to me. Like, that thought is a good thought. That's a, that's a reasonable thought. You know, continue on that trajectory. I had such a good relationship with Richard Lord, my mentor and postdoc advisor. He would ask me, well, he always needed to get me out of his office, I'll say that, because we were in there dialoguing and he couldn't get anything done. And so he would send me off with almost like a biochemistry co on. It would be a challenging question, like, what is the amino acid that sits in the aconitase, you know, the center of the econitase? You Know, the catalytic center of the aconitase enzyme, you know, and why is that amino acid there? And then he would shut his door and that would take me a long time to actually figure that out. And of course it was, it was, it was cysteine, it was a sulfur amino acid, and that's because it complex with the iron and blah, blah, blah. But, and I got it wrong, I actually said histidine. But that's. And I think that that's why it's with me now as strongly as it is, because I got it wrong. But to have people in my universe who are bright, big thinkers, encouraging me consistently to continue to think. And the other thing that Richard told us often was to embrace the uncertainty. And so there's some value in, I mean, that's one of the most sage pieces of advice I've gotten. If you can sit with the uncertainty, there's so much possibility in that. And perhaps that really informed my ability to move forward with this question. And the other thing he said to me that was it's extremely important, and I continue to share that with the folks that I mentor, is that if you train your eyes, you will see, you'll see the way before you. But there's a lot of opportunity, there's a lot of low hanging fruit. We have access in our field still. Our field is not so big that you don't get to speak directly with or connect with big thinkers. In our field there is, and there is much opportunity and much to do. And I believe that my foundation, both intellectually, with the intellectual rigor that I was exposed to and sort of the support and the belief, really put forth this possibility. And there's just no question that you've been a big piece of that for me throughout my career.

Okay, okay, so let me then just quickly respond by saying what you've done is then to share this wisdom that you've accrued through all these efforts and these associations, you're forming a younger universe of collaboration thinkers. This is how we spread ideas. Ideas grow geometrically. They're like a virus in the nervous systems, and they ultimately serve the test of time when people feel that they're of value enough that they tell them to somebody else. And that's what great ideas do. No one owns ideas. Ideas are free to change the universe by test in the great cauldron of human society. And that's what you're doing. You're collecting together like minds to move forward this concept. And I want to say this concept is extraordinarily powerful because if you believe that societies change on belief systems of the aggregated, then what we can say about this is that if people believe that how they think, act, and behave marks their genes with messages that create their outcome as human beings, how they see their lives, is it a happy life? Is it a fulfilled life? Is it a life of peace? Is it a life of grace? Or is it a life in terror, in fear, in harm, in hostility, in war? I mean, those are all available, accessed emotions within the human nervous system that get partitioned based upon the experiences that we have that start with our inquiry of how we, as human beings, live in the world about us. And so this epigenetic principle is not just a younger you, it is a resilient you. It is a resilient related to your connection to others. It is a communication of I can be better because my genes will serve me better if I treat them right. That is a powerful concept. And you are. You're building that concept through the studies that you're doing at Basic Science.

Thank you. I have to say, I'm curious about. I would love to have Siddhartha Mukherjee come back to a PLMI and talk to him about this, because I know he has to embrace it as a big thinker, but he's also challenged the power of epigenetics as well. So just Note to you, Dr. Blanche, maybe Dr. Mukherjee could. Could come back to him. So we. So to move to biological aging. So I want to say a couple things. So my entry into really thinking strongly about epigenetics and translating it into this diet and lifestyle program and starting to think about it, clinical practice was through the lens of cancer. But one of the things that we know about biological aging is that it is the number one risk factor, or we can just say aging more broadly for all the chronic diseases, including cancer and heart disease and diabetes and autoimmune disease and even infectious disease like Covid. So the. So aging itself is. Well, it's been posited that maybe aging itself is a disease, but it's certainly the number one risk factor for all of these. So we started over here thinking about cancer, but what we ended up uncovering, a huge aha for me that I actually talk about in the book that's coming out in January, where I kind of outline this trajectory, is that changes to epigenetics, in particular, DNA methylation, is where I put my focus, are really shared across these chronic diseases. If you look at the changes that drive aging forward on the epigenome, they're the same that Move cancer forward. They're the same that move cardiovascular disease forward or immune system degeneration, deterioration, stem cell changes. The stem cell microenvironment of an older individual doesn't look that dissimilar from cancer. It's crazy. It's really extraordinary. We realized that we may be changing the aging journey itself with this intervention. So that huge aha for us. And the first question we really set out to answer. So we saw that our participants did well on the study. It's an eight week intervention again. Diet, exercise, a meditation, prescription, sleep, hygiene, encouragement to get at least seven hours. We did a greens powder and we had a probiotic Lactobacillus plantarium. But the first thing we looked at when we unpacked our DNA methylation data was whether or not we influenced biological age. Because that sort of, that underpins really everything else. And I was confident, Jeff, that we shifted epigenetics. I mean, my read on the literature was things can change quickly. Even though that was, I was challenged. People certainly challenged our duration of our study and thought we should have done it for six months. But, you know, try to do a nutrition and lifestyle intervention on any human for six months, I mean, we would lose them. So these are scientists talking, people without clinic experience and they're coming from, you know, a different kind of vantage point. As a clinician, I knew eight weeks was, you know, really the far end of time. We were going to get people to adhere and we wanted them to adhere. We actually had nutritionists tracking with them, supporting them in their adherence journey because it was very important. But the first question we unpacked was, did we influence biological aging? Because if we did, then these other questions, the suggested answer is that we're reducing the risk of all chronic diseases. It was hugely exciting when we saw that. We changed it profoundly at that time. When we crunched our data in 2019, as compared to our control group, our subjects got 3.24 years younger as compared to our control group. And it was, you know, it was. I remember talking to Brent about it and it was at night and I was pacing back and forth and you know, it was a mic drop, it was a phone drop moment. It was very, very powerful and telling you. And just being up at, you know, at McGill University with Moshe Sef, who is, you know, again, a huge supporter of our work and has walked with us closely on us on this journey. And I met him through you. I met him at plmi and he's been, he's one of our authors. And anyway, it was just a spine tingling, extraordinary moment to see that we had done that with, with the then main biological age clock, the Horvath 2013 clock. So it was one of the first biological age clocks in our pattern. You know, clearly suggested that these folks got, you know, over three years younger in just eight weeks. Well, even to this day, you know, we're only in 2021, but that, that study hasn't been repeated nor have we really seen our study with had a control group which is, which is unique. I mean this is a new, a new field and so we were first for a lot of things but including having a randomized control trial. I just want to stop and see if you've got any comments before I continue.

Well, my only comment of course is Yahoo. And I think that it's very important for those individuals who may not be so steeped in some of this science jargonesque to know that your book Younger your Reversing youg Bio Age really demythologizes a lot of this and makes it consumer friendly. And that comes out in January. So I think that's going to be a great tool for people who may be a little bit geeky but not maybe as steeped in some of the deep science that we're discussing right now. So I think the book is going to make a significant contribution to spreading this message and giving news to you that people can apply. The other thing that I think is really important is when you look at, at your diet construction, you might want to just comment on how you were designing the diet relative to certain foods that had certain principles that were at least implicated as having epigenetic influences.

Yes, I mean, so we really kind of hedged our bets that if we work, if we design a diet to optimize DNA methylation expression that we were getting to root cause, you know, in 2017 that wasn't quite as conclusive as it is now. But we knew that in general it was a healthy eating pattern. But we wanted to load it up with nutrients that help with, with DNA methylation. So they're methyl donor nutrients. These are nutrients like leafy greens, you know, seeds, pumpkin seeds, sunflower seeds, sesame seeds, some nuts, betaine from beets. So beets are important choline helps in methylation and that comes from eggs. So that's one of the reasons eggs are so good for us. And liver, the often maligned liver is a beautiful multivitamin in a food matrix. Our read on the literature is that is delivering things in a food matrix, delivering these nutrients in a Whole food matrix yields more bang for our buck for a variety of reasons, not just because it's so safe to do this, but the synergistic interaction among nutrients just help transform their behavior in the body and their ability to influence genetic expression. And I know you'll have thoughts on that. Our diet was packed with these methyl donors to move methylation forward. But if you recall from my comment on cancer, we don't want to push methylation too far forward. There is hypermethylation that can be negative. And so we needed to be mindful about that. We want balanced methylation. And so preliminary research again at the time, a lot of it was in vitro. So in cell studies or animal studies suggested that polyphenols, so the, you know, the colors, the nutrients we find in fruits and vegetables, good examples include curcumin and turmeric or EGCG and green tea, or quercetin and rutin and you know, the beautiful packed polyphenols of Himalayan tartery buckwheat. I just am so excited to see what it, what Himalayan tartary buckwheat actually does to the epigenome because it is just, it's an extraordinary nutrient, really almost on par with what I just described liver to be. It's just so packed with so many important nutrients. But the research on these guys suggest that they maybe direct how methylation happens, that it's happening on the right gene. And I'm extrapolating somewhat. Research, in vitro research has shown that these beautiful polyphenols help turn on genes we want on. And in some cases there's less research here, but help turn off genes we don't want on, but to keep expression going of those all important tumor suppressor genes to protect us against cancer and so forth. We see polyphenols are very important here and we know from their time immemorial use, curcumin and green tea, for example, that they are all important anti cancer molecules. And it probably has to do, I would say in significant part with their ability to help regulate genetic expression. So we wanted our diet absolutely drenched as much as possible in these all important polyphenol compounds. And to that end, our participants had at least 7 cups of fruits and veggies a day, you know, with extra for bonus points if they wanted them. And then additionally, and additionally we gave them the greens powder. So I just. And oh, and let me make one comment. So in our data it does suggest that we found that like because our participants got biologically younger, as measured by DNA methylation, it Looks like there was a rearrangement of how methylation was happening towards a more favorable pattern. So we didn't put push net methylation higher on the genome, we rearranged it. And you know, I would argue that, you know, that suggests exactly what we speculated.

Well, I think that you said so many things there that are just like, wow, we could go on, on a riff here playing in B flat for many, many bars because there is a tremendous amount of density in what you said. But one, one that I want to, to stop for a moment because I think that and this is a shame on me, so I'm acknowledging a mea culpa here that 10 or so years ago when we first started really talking about methylation as a process that regulated gene expression, I was a pretty strong believer that this process was regulated principally through the folate methyltransferase pathways and that we really, the regulation points, the pinch points could be related to factors that influence directly the metabolism through the folate cycle into the principal methylating downstream component of that path, of that network. And I do believe that's still important. So I don't want to discount that and throw the baby out of the bathwater. But I think what you've said is really the frontier of what we have learned over those last 10 years and that is upstream to that are the regulators that maybe these specific polyphenols have based on their structure, function, relationships with certain cell signaling processes that regulate the gene expression or the activity of enzymes that are involved with the architecture of where methyl groups are to be put. And so it's really who organizes how methylation is going to occur and then do we have the available methyls to go where you need them to go? So it's a combination of those two factors. And then we add to that of course the discoveries that are now with the microbiome where we say but when we eat stuff, that stuff doesn't go directly into our bloodstream, it has an effect by its metabolic influence by gut microbes that then influence our gut immune system that then influence factors related to it. And so it's a much more complex orchestrated web. And that's why what you said about food based delivery systems versus one nutrient at a time, because it's an orchestral process, it's not like the best first violinist playing by themselves. So I really, there's so many takeaways from your study and I know you've read that because I've had a, the privilege of reading a pre print version of your book. You've really discussed this beautifully in the new book coming out in the first of the year. So all of this is made user friendly in a way that we start accessing this extraordinary new science that you're discovering.

Thank you. It's so exciting and I want to say so you and I have dialogued about say the New Age trial. There are studies looking at nutrition and they're very, very important looking at and how it implements how nutrition influences the epigenome and it is favorable. The volume is not quite as turned up as we saw with our study. So using a Mediterranean eating pattern is favorable on epigenetic expression. I do not. I mean there's. It seems pretty unequivocal at this point and I'm sure we'll have more and more research as time moves on. But I'm excited to see that our design which has Mediterranean components but really thinks about what the methyl donors are and those the all important polyphenol epinutrients which we call methyl donor adaptogens are how they are influencing and we turn those volumes up perhaps beyond a typical Mediterranean diet pattern. I also want to throw one other thing out there because I'm with you in being very educated on the methylation cycle and, and the folate vitamin cycle and thinking there. I think it's been a little bit myopic and we are blowing out. So we had lifestyle components, meditation twice daily, sleep and exercise. Exercise is behaves. Folks, this is going to sound crazy like a polyphenol. There's a fabulous study that I wrote about in the book where it talks about exercise influencing tumor suppressor genes, allowing them to get turned back on. Like we see some of these beautiful polyphenols doing as well. And actually there's a heritability component. We can hand the benefits of our hard work of our, you know, getting on that peloton every day or you going out in Bainbridge, your beautiful neck of the woods. But those hard efforts, if, if we're preconception we can hand some of those patterns down. It's amazing. So exercise, correct exercise, not get up off the couch and start crossfitting tomorrow. But balanced exercise is remarkably epigenetically potent and it addresses DNA methylation and it is not in the DNA methylation, it's not in the methylation cycle. Likewise with stress. What blew my mind, Jeff, is how 25 so the clock that we looked at a full 25% of those methylation sites that are measured are influenced by glucocorticoids. They're influenced by Stress, they're called glucocorticoid response elements. If that doesn't cause us to want to tune out and meditate or really think about the stress influence on our life as being pro aging, I don't know what does. I mean, that was very profound. And there's more literature where that comes from. And likewise, we see people, you know, meditators, experienced meditators, have a younger biological age, but heartening for those of us who aren't, you know, living in a. In a ashram or a monastery. One single meditation episode can have favorable epigenetic marks. Obviously, they accumulate, and you get more benefit if you really engage in this activity over time. And the same with sleep. We see insomnia as being very pro aging and likewise, better sleep as being balancing. So we brought in all of these because we wanted to hedge our bets. We knew they were important for a variety of reasons, but our read on the literature in terms of epigenetic expression was clear that they're very important.

So obviously, you have left us with a trail of extraordinary ideas for which we could now spend hours, at least hours, probably days, to really fully describe and explicate. But I think we want to titillate our viewers and give them the opportunity to go to your book younger, your reversing your bio age. And I think there's an acknowledgement I want to make which I have not acknowledged until this moment, but I think it's the appropriate time. The whole reason that I came out of kind of what I want to say, a period where I was more serving in mentorship and from an educational model and listening to what you were doing and how you were doing it, and then hopping onto this Himalayan tartary buck story. It was because of you and your work that I said, you know, I need to really get involved with Himalayan tartery, buckwheat, regenerative agriculture. I need to bring this crop back in America. It was really the motivation of your work that stimulated me to now become a gentleman farmer. And our farms in upstate New York and all this whole process that we're now resurrecting this crop that has been lost since colonial America, that has probably the highest level of these immune active epigenetic modulators of any single fruit seed that is available. So I just want to thank you because it set me on a whole nother journey to interface in this latter phase of my career what we might be able to give back to the system. So that's how we build our community. Right? So thank you and to all of the listeners of this, you've just been graced with one of the most extraordinary forces of nature, Dr. Kara Fitzgerald. And if this is a model for all of us, how to pursue our dreams and to stay at task and to collect the right people around us to make our dreams become reality, then you miss the intention and the outcome of this extraordinary podcast. So thank you, Dr. Fitzgerald, for all, all that you've done.