DNA Methylation and Longevity: Can You Influence Your Genetic Future? with Kara Fitzgerald, ND, IFMCP

[00:00:00] Dr. Kara Fitzgerald: Some research really demonstrates that even when we're older, we can get more bang for our buck in certain changes than when we're younger. There is no time like the present to begin to make some tweaks, and definitely saying that you're going to end up where your parents or grandparents were—this inevitable decline—just simply isn't the truth.

[00:00:25] Dr. Melinda Ring: This is Next Level Health. I'm your host, Dr. Melinda Ring, director of the Osher Center for Integrative Health at Northwestern University. On this show, we explore ways to take actionable steps toward optimizing our health with leaders in the integrative, functional, and lifestyle medicine fields who believe in science-backed and time-tested approaches to well-being. Let's take your health to the next level.

[00:00:54] Dr. Melinda Ring: Research on healthy aging has exploded over the last several years, but along with that explosion has come a lot of confusion. There's no shortage of advice promising to slow aging, reverse aging, or biohack your way to longevity; the challenge is knowing which strategies are actually supported by science. My guest today is Dr. Kara Fitzgerald, here to help us separate signals from noise and to share what we can realistically start doing today to support healthy aging based on research into methylation, epigenetics, and measurable changes in biological age. Dr. Fitzgerald is a naturopathic doctor, a certified practitioner and teacher with the Institute for Functional Medicine, and the author of "Younger You: Reduce Your Bio Age and Live Longer, Better," a book grounded in her published clinical research. She was also the first recipient of the Emerging Leadership Award from the Personalized Lifestyle Medicine Institute in recognition of her work on DNA methylation. So, we're going to explore what that is, and why healthy aging isn't about chasing extra years—it's about slowing decline, preserving function, and living well for as long as possible. Kara, welcome. I'm so glad to have you.

[00:02:08] Dr. Kara Fitzgerald: Yeah, I'm so glad to be here.

[00:02:10] Dr. Melinda Ring: If somebody's listening right now and thinking, "Aging's inevitable, I don't really have any control over how time affects my health," what, as we're jumping in, do you want them to understand by the end of our conversation about the power they have over how they age?

[00:02:27] Dr. Kara Fitzgerald: We really are in the driver's seat of how elegantly our journey to the end goes, you know, and whether we get to live it in a very empowered way or whether we fall into the bucket of the average American with multiple diagnoses, multiple medications—where, honestly, the picture's so grim—where we're spending all of our hard-earned savings that we want to pass down on healthcare and nursing homes, etc. The statistics are really pretty grim, and yet we get to choose whether we go on that trajectory or not. So, when we internalize that truth, I think it's incredibly empowering. Some research really demonstrates that even when we're older, we can get more bang for our buck in certain changes than when we're younger. There is no time like the present to begin to make some tweaks, and definitely saying that you're going to end up where your parents or grandparents were—this inevitable decline—just simply isn't the truth.

[00:03:37] Dr. Melinda Ring: I'm aware of this data that says like, never too late kind of thing. are you saying that there's newer research that says that different interventions at different points in our life, or is it really the same? basic principles apply no matter what age we're at.

[00:03:53] Dr. Kara Fitzgerald: In some ways, obviously we don't need the same interventions in our twenties and thirties that we might be thinking about in our forties, fifties, sixties.We have certain kinds of resilience when we're younger we don't necessarily, need to be engaging in some of the interventions. It may not be a great time to be starting, say, rapamycin or thinking about that sort of longevity darling medication. I think that it's fair that there are certain things we're gonna lean into and adopt more aggressively, as we age.There's cool data on gene expression and exercise on methylation and exercise. the Older we get. We can actually affect gene expression, in some cases more potently by incorporating movement than when we were younger. So it's like we get, we can in some ways get more bang for our buck introducing exercise. But the other really cool thing about adopting stuff when we're young is that. If we're a preconception, like if we're gonna have, if we've got kids In our plans, that information that your gene expression has adopted from your healthy dietary pattern and actually, there's a heritability component, so you know your fam, the, your family before you, if that information sits in your genes , and you can definitely hand on those healthy gene expressions. So if you have a decent exercise habit it's really important to think about it during preconception, conception, and pregnancy. Both partners,

[00:05:28] Dr. Melinda Ring: On this podcast we've had a. People talk about this idea of biological age versus chronological age, how old your body behaves, not just how many birthdays you've had, and we cannot change the years on the calendar, but that. The biological age we now know is dynamic and influenced by lifestyle and other things. And one of the main ways that scientists measure biological age is through DNA methylation gene expression. Your research looks directly at whether changing those signals can actually shift biological age. So. I think this term, methylation especially, won't get into all of the M-T-H-F-R and everything, but I think people hear methylation but don't really know what it is. So can you demystify that term for us and explain why it is such a powerful marker?

[00:06:21] Dr. Kara Fitzgerald: Methylation is the process of adding or removing a little, bitty, ubiquitous compound—a carbon with three hydrogens—from a molecule. By doing this, you change the structure and behavior of that molecule. Methylation is happening everywhere in the body for myriad reasons all the time. It is incredibly foundational, and we need to be doing a decent job of it. It is true that as we age, we don't methylate as efficiently as we did when we were younger. This carbon with three hydrogens is produced in the methylation cycle. The universal methyl donor—where that carbon with three hydrogens sits—is something called S-adenosylmethionine, or SAMe for short. SAMe just whirls around the body, helping us to make a billion different compounds or, again, change the structure and function of compounds. It is involved with lots of neurotransmitters and hormones, detoxifying hormones, and changing the structure of fatty acids that are important in brain chemistry. It also engages in a lot of detoxification of various environmental toxins and metallotoxins, like arsenic. So, it is just buzzing around doing tons of stuff. There are hundreds of enzymes that facilitate these methylation reactions that SAMe is a part of; it helps us make adrenaline, dopamine, et cetera. My area of interest is DNA methylation. Adding or subtracting methyl groups is a huge player in gene expression—turning genes on and off. In DNA methylation, when there are a lot of methyl groups—and anyone who looks in the scientific literature will see that these methyl groups are usually denoted by a red lollipop—if a promoter region of a gene is dotted with these red lollipops, that gene is basically inhibited from being turned on. If the red lollipops are gone, then that gene can be expressed. They can be added or subtracted through enzymes, and in this way, it is one of the fundamental ways we regulate gene expression. Our research, and the research of others, demonstrates there is a lot we can do to optimize gene expression through the window of methylation. I want to back up and talk about the methylation cycle itself. The process of making S-adenosylmethionine (SAMe) is very nutrient-dense. It is the reason we want to have enough folate in our diet, and why we need B12 and choline from eggs. When you are told eggs are incredibly important, know that choline is a huge player in healthy methylation. Betaine from beets is another thing, as are downstream compounds like glutathione, which is a workhorse for detoxifying compounds. The process of methylation has its tentacles all over healthy physiology.

[00:09:40] Dr. Melinda Ring: when people are like, well, am I a good methylator? Do I need to worry about it? are you a proponent of. Biological age testing. And if so what do we need to think about for that versus say some of, should we be testing these nutrient levels, like you said, the bees, homocysteine, et cetera. Like should everybody be getting those?

[00:10:03] Dr. Kara Fitzgerald: If people come to our practice we're a small sort of boutique practice and by the time folks end up there, they're either very avid longevity seekers and they've come across our research or. They need an in-depth functional medicine analysis. So people who come to, to, see us, we do tend to cast a wide net with regard to laboratory testing. My background training is in laboratory science, and so I'm very comfortable. Sort of looking under the metabolic hood, and I can I, I, think that it can inform treatment just really allow us to practice precision treatment. So, to that end, yeah. Looking at all the essential and unconditionally essential nutrients including those in the methylation cycle. Looking at fatty acids, organic acids, like the whole thing, stool sample.

[00:10:55] Dr. Melinda Ring: Some of these other tests, again, maybe falling a little bit more in the biohacking type test about, for biological age, like telomere tests and DNA methylation and, do you use those in your practice either as a motivator or a tracker? Just through the research lens? I've seen the same patient have two different types of tests and get drastically different results. Where one was like, oh man, I'm like 20 years older than my chronological age. And then they did another test and it was like, I'm five years younger than my biological age. outside of a research setting, is there, what should people look for if they are even thinking about doing that?

[00:11:37] Dr. Kara Fitzgerald: one that we're using is called the Dunedin pace of aging. So if you're aging at a rate of one, you are aging consistent with your chronological age. If your your rate is greater than one, you're aging faster than the rate of your chronological age. If you're less than one, then you're in a good spot in your aging slower than your chronological age. So obviously we wanna be less than one . The cool thing about this test, there's just like a lot of really nice science on it. we can affect it. So we can definitely change it with the interventions that we use in functional practice, and we can get change relatively quickly. You could do a baseline pace of aging test, and if you wanted to in as little as eight weeks , you could do a follow up. We've used this in clinic practice. We'll use it in groups where we're doing the dietary pattern that we research. Using epigenetic measures like these, looking at biological age. While I like it, it certainly has not. Supplanted, good foundational functional medicine and good foundational laboratory testing. All of our standard, labs still have a really important place to play. And this is this is an additional kind of fun level. I should, we have a quiz for free. It's in the book, so if you have the book, the quizzes there, you work

[00:13:05] Dr. Melinda Ring: That's a very low tech kind of a way

[00:13:07] Dr. Kara Fitzgerald: Super low tech.

[00:13:09] Dr. Melinda Ring: Super low tech. So you've published several articles now on your younger, you protocol and the impact that it had reducing biological age. And there's the diet you mentioned, and then of course almost so like in terms of similar lifestyle type things with movement and stress and sleep and all those kinds of things. But I think what I. Like to dive into, it is what you've mentioned about the diet. So you have a specific dietary protocol that you recommend, and I think there's two phases of it can you go through what recommended diet. Was for your or, and remains for your patients and for listeners who are interested in a younger you.

[00:14:00] Dr. Kara Fitzgerald: Yeah. And again, the cool thing is that this is available, this is free. You can access this dietary pattern without needing to put out any money. It's in our research, every, every publication that we've, that we've had so far, it just includes a snapshot of what the diet looks like. It's got a ton of polyphenols , it's got a ton. And those are plant phytochemicals. They're just extraordinarily potent and powerful for keeping the body healthy in many different ways. And really for optimizing gene expression, they're super important players. So the dietary pattern is very dense in those. We actually call, we call those in our research, methylation, adaptogens . And now we're calling them epi-nutrients or epi-nutrients , superfoods or something a little bit more general. There's lots of cool human data coming out, really corroborating the power of our dietary pattern with their own studies. Like we can see the Mediterranean dietary pattern. We can see that a high polyphenol diet dietary pattern is just incredibly smart.

[00:15:09] Dr. Melinda Ring: Yeah, every, every day another study. Published about, pops up in my email every day prevents stroke, prevents this. Yeah. It's pretty amazing. But, but yours is a little I mean, I noticed, so maybe in, in the intro there was some traditional foods like liver, eggs you mentioned as being the choline rich and then grass fed meat. And I think those are.

[00:15:38] Dr. Kara Fitzgerald: A little bit different. Yeah.

[00:15:41] Dr. Melinda Ring: In what we think of as a traditional Mediterranean style diet. Can you

[00:15:45] Dr. Kara Fitzgerald: Yes.

[00:15:46] Dr. Melinda Ring: about why those are included? I know you mentioned the eggs a bit and the eggs. The choline is in the yolk, right? It's,

[00:15:52] Dr. Kara Fitzgerald: that's right

[00:15:53] Dr. Melinda Ring: So for my egg white omelets, you gotta actually do the yolk. So maybe talk

[00:15:58] Dr. Kara Fitzgerald: Talk about

[00:15:59] Dr. Melinda Ring: those ended up in yours versus just saying like, eat a Mediterranean diet.

[00:16:04] Dr. Kara Fitzgerald: Yeah. So, we wanted to do a potently anti-inflammatory diet when talking about DNA methylation. Our goal was specifically to optimize gene expression and DNA methylation, so we scoured the literature. Most of it was animal and cell studies, but we put the dietary pattern together based on our clinical experience, training, and best read of the literature. There are two classes of dietary components in it. First, there are the methylation adaptogens, or epi-nutrients. These are the polyphenol-rich compounds that we share with the Mediterranean diet. Then, we were a little bit to the left of the Mediterranean dietary pattern in that we want people to be eating a lot of foods rich in methyl donors. Going back to the beginning of our conversation, the methylation cycle is very nutrient-dense and demanding; it is happening all the time in basically all cells of the body and is very important for gene expression. We wanted that cycle to be actively making S-adenosylmethionine (SAMe), and we know that we do that less effectively as we age. As a physician, you know your older patients are more likely to have higher homocysteine, which is a classic blood marker of whether the methylation cycle is functioning. It is standard that we see homocysteine creep up over the years. That is a surrogate suggestion that methylation elsewhere, including on gene expression, isn't happening well. So, we wanted to pack the diet as full as we could. Liver is a superfood; it is basically a multivitamin-mineral in a food matrix, which makes it more bioavailable than just taking a hard tablet and hoping your stomach acid adequately breaks it down. So, we recommend lots of liver and eggs, specifically for the choline. Mushrooms are dense in methylation adaptogens and plant phytochemicals, but also choline and even folate. We wanted meat because of the B12 and the minerals involved in methylation. We just wanted to support methylation from all angles, so those foods help keep the methylation cycle functioning, and then the phytochemicals can help direct how and where methylation happens. Another thing that happens as we age is we stop methylating as efficiently. Methylation on the genome starts to become what we call aberrant. We start to turn off genes that would be better left on, and we allow genes to turn on that promote the chronic diseases of aging. In particular, there is a lot of science in cancer. When we look at cancer gene expression, we see that cancer will hijack epigenetic expression in the tumor microenvironment; it will turn off certain genes that protect us—the tumor-suppressive genes—and it will turn on classic genes called oncogenes, which push cancer forward. When you look at an aging epigenome, you actually see the same thing. As we age, we hypermethylate tumor-suppressive genes and turn on these oncogenes. That is a big reason that biological aging is the biggest risk factor for developing cancer, all of the chronic diseases of aging, and even infectious diseases like COVID. There is this aberrant DNA methylation process happening as we age, and we wanted to pull out all the stops with the dietary pattern and lifestyle interventions to help cut that off at the pass. We were able to show in our research that we did do that. We will have a study coming out in the not-so-distant future, looking beyond the clocks to more broad gene expression in our study cohort, and we can see that we changed it favorably.

[00:20:44] Dr. Melinda Ring: Let's focus on women for a second and maybe the role of organ specific aging and ovarian health and things like that. What do we need to be thinking about and how does that play into women's long-term health?

[00:20:59] Dr. Kara Fitzgerald: Polyphenols, these plant phytochemicals are just no joke. We can see that our dietary pattern is incredibly helpful for ovarian health. For women's health more broadly, for protecting us again, from cancer, from the chronic diseases of aging breast cancer you know, keeping our tumor suppressive genes on and humming. There's cool research on just the power of polyphenols. The diet is low glycemic. It's a good foundational, very helpful dietary pattern that is helpful for us as women in keeping us strong, keeping our bones strong, and helping us through the transition. We're clinicians first before we became clinical researchers, and we used this diet and practice for years. So one of them, you'll see a table in the book on how you can adapt the dietary pattern for the human being sitting in front of you so you can individualize it, you can add it if you're vegan, if you're not. Allergic to food X, if you've got small intestinal bacterial overgrowth, if you have ms,

[00:22:12] Dr. Melinda Ring: Yeah.

[00:22:12] Dr. Kara Fitzgerald: dietary pattern is the foundation. put the methylation information in there, and then you mix it for this human in front of you. If it's somebody working on conception or if it's a woman carrying a child, obviously you wanna turn the volume up, heavy duty on protein, you wanna turn the volume up on certain types of methyl donors. And, we just cover how to individualize using the core tenets of it in the book. And we've got a lot of experience doing that in practice. So.

[00:22:44] Dr. Melinda Ring: ovarian rejuvenation, you're not talking about implants and things like that. You're saying we can rejuvenate our health and our OV ovaries and hormones through a good diet and polyphenol intake and things like that.

[00:22:59] Dr. Kara Fitzgerald: This dietary pattern can help us stay strong and balanced. It's not going to supplant HRT. You can modify the dietary pattern to turn the volume up on phytochemicals that have estrogenic benefits, et cetera, et cetera. So you could tweak it as needed. So it's a foundationally useful dietary pattern for women. And then on top of that, you layer in what you need for individual needs; this is not going to take over HRT. However, we know that hot flashes, we know that some of the downfall of the menopausal journey is. Is exacerbated considerably by poor diet and lifestyle. So certainly using this can help with the transition journey for sure.

[00:23:52] Dr. Melinda Ring: I always like to end with this question, which is if you could share one piece of personal wisdom or. One small doable practice that listeners could start today to support their biological age and reach their own next level of health, what would it be?

[00:24:09] Dr. Kara Fitzgerald: I would say that we wanna be thinking about getting phytochemicals into our dietary pattern on a daily basis. Like if I really, honestly have to whittle it down to one thing, I have at my side here on the floor. I have a giant, pretty well designed salad. All of that is information. It's dense in polyphenols and there's some chicken on top, so I've got a decent chuck of protein on there as well. The salad dressing is rich in herbs. Herbs are phytonutrients extraordinaire and I think. We are coming into an era where the power of polyphenols, the power of phytochemicals, is being recognized and appreciated, in a more powerful way than before. Because we have the tools to see what they're doing. We can see how they're transformed by the microbiome and what they're doing systemically, and we just, we can't underestimate the power of them. So I always am mindful to put that information in my body. And when I can't get it in, diet, I will pop some supplements. Like I'm known to take some green tea . I'm known to take some Himalayan and tar buck weed or some curcumin and so forth. So just be them. I'm bullish on the power of that information on physiology.

[00:25:35] Dr. Melinda Ring: So Kara, thank you for such a hopeful conversation. It. For me it really reframes methylation, not as just something abstract or technical, but a reminder that our biology is listening. It's listening to the food, especially to stress, to sleep, to how we live. That gives people more agency than many of them realize. For everyone listening, we'll link to Kara's research and writings in this show notes. And as always, remember, longevity isn't about chasing youth. It's about preserving vitality, curiosity and capacity for the long run. Thanks and I'll see you next time on Next Level Health. Thank you for joining me on this episode of Next Level Health. I hope you found some inspiration and practical insights to enhance your wellness journey. Don't forget to leave a comment on YouTube or review on Apple Podcasts. I'd love to hear your thoughts and suggestions for future topics or speakers. Be sure to follow Next Level Health with me, Dr. Melinda Ring as we continue exploring the path to healthier, happier lives together.