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RHR: The Science of Reversing Aging, with Dr. Kara Fitzgerald


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In this episode of Revolution Health Radio, Dr. Kara Fitzgerald, author of Younger You, sits down with Chris Kresser to discuss the results of her landmark study on methylation and anti-aging. Understanding the impact that methylation has and diet behavior and lifestyle inputs that affect methylation is one of the keys to extending our health span and making sure that we age in a graceful way and really can enjoy our health and well-being as we get older. 

In this episode, we discuss:

  • Why discussing aging is so important
  • What methylation is and why it matters
  • How toxin exposure impacts epigenetics and changes in the body and health
  • Dr. Kara Fitzgerald’s study as a multifaceted holistic approach to anti-aging and the results 
  • Where to learn more about the 3 Years Younger program
  • A little background on genes and genetic expression
  • The translation of emotional experience to physiological illness

Show notes:

RHR: The Science of Reversing Aging, with Dr. Kara Fitzgerald
Intro to Dr. Kara Fitzgerald
Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week, I’m really excited to welcome Dr. Kara Fitzgerald as my guest.
Kara has been a guest on the show before. I’m a big fan of her work, and I’m really excited to talk about the evolution of her work on methylation, particularly a new study, a really landmark study that she [and her team have] just published. And then [we discuss] a new book that she has written called Younger You: Reduce Your Bio Age and Live Longer, Better, which is also based on her work on methylation. Dr. Fitzgerald’s the first-ever recipient of the 2018 Emerging Leadership Award from the Personalized Lifestyle Medicine Institute in recognition of her work on DNA methylation. And as a leading voice in the intersection of nutrition, epigenetics, and aging, Dr. Fitzgerald’s work has been featured in media outlets such as Prevention, Fast Company, MSN, Everyday Health, and more.
She received a doctorate from [the] National University of Natural Medicine, and she’s on the faculty for the Institute for Functional Medicine (IFM) and is an IFM-certified practitioner with a clinical practice in Newtown, Connecticut. I think you’ll get a lot out of this [topic of] methylation. It can be a difficult concept to understand at first. But if you’ve been listening to my podcast for any length of time, I think I’ve probably done four or five episodes on it over the years to try to simplify it and break it down. Essentially, it’s one of the most important determinants of how we age because it affects our cellular physiology on every level. And understanding the impact that methylation has and diet behavior and lifestyle inputs that affect methylation is one of the keys to extending our health span and making sure that we age in a graceful way and really can enjoy our health and well-being as we get older.
I think you’ll get a lot out of this episode, and I’m looking forward to diving in. Let’s get started.
Chris Kresser:  Dr. Fitzgerald, Kara, [it’s] great to have you on the show again.
Kara Fitzgerald:  Yeah, it’s great to be here. Thanks for having me.
Chris Kresser:  We’re going to talk a lot about everybody’s favorite complex topic, methylation. I think I’ve done probably five or six shows on it over the years, and you’ve been on the show, as well. We’re going to break it down and make it really simple for people to understand because it’s such an important thing to understand if you’re interested in living a long and healthy life, which I would venture to guess almost everybody listening to the show is interested in. So if we can get past the complexity on the surface of it, I think everyone’s going to find this really fascinating and important information. And I want to talk about the new study you published, a landmark study, [with] really exciting results. And then, of course, your new book, Younger You, which seems to me, correct me if I’m wrong, but really the culmination of a lot of your work on methylation and aging over the last several years.
So, why don’t we jump in first, with why is this important? We know that life expectancy is actually declining for the first time since we’ve measured it, and health span (and we can talk about these terms and break them down) is also declining. So it’s not just a question of how long we live, but if we [live] to 80 [years old] but we spent the last 15 years of that time in a wheelchair or bedridden, that’s not a win, right?
Kara Fitzgerald:  No.
Chris Kresser:  So tell us what inspired you to do this study and write this book.
Why Discussing Aging Is So Important


Kara Fitzgerald:  It’s definitely not a win, Chris. I feel incredibly passionate about that because our statistics are so dismal. We spend the last 16-plus years with significant illness, multiple significant illnesses. And what’s interesting, too, [is that] we’re aging faster biologically, and we get sick. And what’s interesting is that sickness begets sickness. So once you head down that slippery slope, it is indeed a slippery slope.


Chris Kresser:  Right, we [now] have kids being diagnosed with diabetes, and they’re 8 years old. So we’re not even just talking about the averages where people are, like you pointed out, most people now are getting a serious illness when they’re 63 [years old]. But in fact, obesity and conditions like diabetes are affecting kids who are 8 years old.


Kara Fitzgerald:  Yes, that’s right. And we could skate around this pond for a while, but they’re very pro-aging. When we think about gene expression and my research, they are damaging genetic expression very early on. [Adults with diabetes] are on average, like six to nine years older than their same-age counterparts. So these kinds of illnesses push us to age toward disease, aggressively,


Chris Kresser:  Right. In Functional Medicine, we’ve always talked about why prevention is important. But this adds a little bit more objective evidence for that, right?


Kara Fitzgerald:  Yeah.


Chris Kresser:  It’s not just a conceptual thing, that it’s better to prevent a disease. We actually know that if you have a disease, what you’re saying is, if you have a disease, it drives all kinds of processes that increase your biological age, make it likely that you’re going to live a less healthy life as you get older, and put you at risk for other diseases. So it’s like this whole vicious cycle that starts.


Kara Fitzgerald:  Yes, that’s right. The good news is, it turns out we have a lot we can say about it. But just to go back and answer your first question of why now and why this, we were looking at epigenetic expression. We were thinking about it in our clinic, and I talked to you about it on our podcast some years back, specifically in relation to cancer. And that prompted us to design our diet and lifestyle program that we studied. I want to just say [that] a massive a-ha for me, an extraordinary practice-changing, game-changing thinking-changing for me was seeing the chronic diseases of aging. So age is the biggest risk factor for the chronic diseases of aging, notwithstanding your point that 8-year-olds are being diagnosed with diabetes. Let me just put that over there. But as we age, if we don’t develop those diseases early on, our risk for getting them goes up exponentially. Age is the biggest risk factor.


We had designed this program with an eye toward preventing cancer. But when you look at gene expression, the gene expression changes that happen with aging look a lot like what happens with cancer, diabetes, or heart disease. There are shared genes that are on and genes that are off that are not helpful for us. So when we started our study, a primary endpoint was to actually look at aging. Around the time of our study design, it was not much earlier, the technology to look at biological aging as measured by gene expression became available. And that became a more foundational question for us to answer. Because if we can reverse biological aging, or if we can slow down biological aging at all, then we have the possibility, the potential to reduce risk collectively of all these chronic diseases. And that was a game-changing moment for me in my practice, that focusing more broadly on the aging process, on the physiologic aging process with attention to gene expression, could be the most impactful intervention that we’ve got. So let me stop there and just see if that makes sense and what your thoughts are.


Chris Kresser:  Yeah, absolutely. I think, as we advance in our understanding of all these mechanisms and what really drives the process of chronic disease and aging, we can have a much more sophisticated approach to both understanding inputs that influence those mechanisms and then how we can intervene to slow down that process as much as possible. So with that in mind, why don’t we, since we’re going to be talking a lot about methylation throughout this show, for those [who] are not familiar with that term, what it means and what the significance of it is, why don’t we start there?
What Is Methylation and Why Does It Matter?


Kara Fitzgerald:  MA methyl group is just a carbon in three hydrogens. It’s exquisitely simple, and we just evolved. It’s ubiquitous; carbon and hydrogen are ubiquitous in nature, and I think we just evolved using it, using this lowly molecule to metabolize, to make things in the body, to break things down in the body, to do a lot of processes in the body. It’s a simple way for us to change structure, function, and behavior. So we’ve got a methylation cycle that’s warring around all the time and produces the compound, I’m sure you’ve talked about all this many times, S-adenosylmethionine. This is a relatively large molecule that has that methyl group hanging on, and then it goes to the hundreds of methyltransferase enzymes in the body, and it provides the methyl group for whatever reaction is taking place. So again, we make neurotransmitters, we detox compounds, we metabolize out estrogen, we metabolize histamine, [and] we do all sorts of important physiological processes using methyl groups.


And when we look at gene regulation, we see that methylation is huge there in turning genes on and off. Our study focuses on DNA methylation. Methylation is happening elsewhere, like [in] the proteins that DNA is wrapped around; they’re called histones, and those can be methylated. And there are other ways in which it’s happening. But when we put a lot of those carbon and three hydrogens, a lot of those methyl groups down on the promoter region of a gene, that gene is going to not be available for transcription. It won’t be turned on. Conversely, we can remove those methyl groups from the same gene, and then that gene can be turned on. So we are doing that actively in the body, adding methyl groups, removing methyl groups, or inhibiting methyl groups from being laid down. It’s a very active and constant process.


Chris Kresser:  Right. So it has a silencing effect, or one way to think of it [is] like a volume knob turning it up, turning it down. [It’s] probably a better analogy than an on and off switch because there’s …


Kara Fitzgerald:  Yes, that’s right. There’s a continuum.


Chris Kresser:  There’s a spectrum or a continuum with the volume knob; that doesn’t come to mind with the on and off switch. I want to make this even simpler for some folks to understand using some more famous examples of the impact of epigenetics, which is driven, in part, by methylation. The Dutch winter hunger cohort is a great example that I’ve talked about before. During World War II, there was a blockade by the Nazis, and the average calorie intake, I think it dropped to something like 1,300 calories a day. I don’t remember the exact calories. And babies [who] were born during that period ended up later in life having all kinds of health problems. They had higher rates of obesity [and] diabetes because certain epigenetic switches got turned on during that period of famine when they were in utero, [which] caused their bodies to want to conserve calories. And it makes sense.


If you were born in a period of starvation or food scarcity, it would be evolutionarily advantageous to be born into that world with a mechanism for aggressively storing calories as much as you could. And this is just one example of how methylation and epigenetic changes can manifest in our lives. That’s not a genetic change that happened there. It was not an alteration of the underlying genes. Those were environmental circumstances that used that volume knob to turn things up or turn things down and then affected the children [who] were born during that period for their entire lifespan. Not just during the first couple [of] years of life, but during their entire lifespan. So [that’s] an indication of how important this is. [crosstalk 12:00]


Kara Fitzgerald:  In subsequent generations.


Chris Kresser:  Generations. Yeah. We know that these [crosstalk 12:06] [inaudible 12:06] changes can be passed down among at least two, if not more, generations we’re seeing in many of these studies. So I wanted to give people [a] practical example of how this really manifests in our lives.


Kara Fitzgerald:  Can I give a couple more that I think were pretty interesting?


Chris Kresser:  Please, let’s do that.


Kara Fitzgerald:  [In] embryogenesis, the fate of those pluripotent stem cells is determined via methylation. Your eye cell has a certain methylation pattern, and that’s actually going to be sustained. Like, your skin cells aren’t going to randomly turn into liver cells, an eye cell won’t become a heart cell, and so forth. So some methylation patterns on that continuum we talked about earlier are very rigorously preserved over time. So embryogenesis is a time of very active methylation and demethylation.


Interestingly, I podcasted with David Sinclair a few years ago, and he said that, in his opinion, aging, where things really break down, but they do so in a somewhat predictable way, is as robust a zone of methylation change as is embryogenesis. So I think it’s an interesting parallel to draw. So methylation plays a broad and extremely important role in gene expression.
Toxin Exposure and Its Impact on Epigenetic Changes


Chris Kresser:  There are also lots of studies, as you know, that show how exposure to toxins causes epigenetic changes that can be then inheritable through at least two generations, if not more. This is a pretty robust area of research, and it’s actually also one of the ways that we learn that there’s a lot more to toxicity than just acute toxicity. Even still, in some areas of medicine, the idea is you can’t have mercury toxicity or lead toxicity unless you have poisoning essentially. And there’s no such thing as a chronic toxicity that’s caused by exposure to lower levels of those toxins.


But one of the ways that we discovered that that’s not true and that yes, you absolutely can have chronic toxicity from lower levels of exposures through these epigenetic mechanisms and changes cause to methylation by just the dental amalgams, for example, and the vapor[s] that are released from dental amalgams or being exposed to lower levels of lead in water that aren’t enough to cause poisoning or arsenic from certain foods that you might eat. There [are] so many ways that this practically affects us on a day-to-day basis. I think it’s really important for people to understand that because it can get very complex. We start talking about the individual cellular mechanisms.


Kara Fitzgerald:  Yes. So multiple low-dose toxins, high-dose single toxin[s], yes, potent, negative influence on gene expression.


Chris Kresser:  Right. And we know that different doses of the toxin can produce totally different effects and sometimes opposite effects. [This] was very confusing for toxicity researchers early on, where they knew what [effects] acute lead poisoning caused. So when they started studying lower levels of lead exposure, they were just looking for lower amounts of those effects, and they missed the other effects that were happening as a result of low levels of that exposure.


Let’s talk a little bit more about your study. Now that people have a general idea of methylation and why it’s so important, tell us about the study you did and what new findings that it produced that were, I think, pretty novel when it comes to the research that has been done on methylation so far.
A Look at Dr. Fitzgerald’s Current Work: A Multi-Faceted Holistic Approach


Kara Fitzgerald:  Yeah, that is pretty novel. It’s the only study out there like this thus far. We will be seeing more, and I’ll welcome it. It’s an area we need to blast into the stratosphere. So we put together a diet and lifestyle program and clinic practice designed to really sweet talk DNA methylation. We scoured the literature and built a diet and lifestyle program specifically for that. And we believe we were influencing it, and it was by the gracious support of Brent Eck at Metagenics, who funded us within an unrestricted grant. We had full say over how we manifested our study. So we hired my alma mater, the Helfgott Research Institute out at [the] National University of Natural Medicine, to run our study. And it was a controlled pilot study. There were about 40 [men], in total. Our study was looking at quite screened healthy, middle-aged men, so 50 to 72 [years old]. And we had a control group that did not receive the intervention and the study group that received the intervention. We’ll talk about the components of diet, but it was very heavy in the methyl donor. So helping that methylation cycle move effectively.


Methylation in DNA becomes less efficient as we age. So we wanted to bathe their cells in lots of methyl donors through food. But there’s also a whole other class of nutrients of epinutrients, we’re calling them. These polyphenol compounds we know and love that seem to have the potential to direct where that methylation happens. So you’re not just throwing a bunch of methyl donors; you’re maybe providing some information. And these polyphenols are green tea, curcumin, quercetin, and luteolin. A lot of the things that you’ve certainly talked about. So colorful fruits and veggies and lots of them. Exercise is an incredibly important epigenetic regulator. Chris, some research, it sounds like it’s describing a polyphenol. It’s really cool how exercise behaves. And what’s interesting is the older we get, we might get more bang for our exercise buck as far as gene expression goes. And we don’t need a lot. We don’t need to jump into the CrossFit gym. In fact, arguably, that will be pro-aging for some of us.


I mean, I was a competitive athlete in college, and I wouldn’t change it for the world. But I was sick after every season, so it had this really immune-suppressive, unhealthy fallout. We prescribed exercise 30 minutes, five days a week at a perceived exertion of 60 to 80 percent. So [it was] not intense. They were maybe sweating a little bit, slight[ly] breathing a little bit heavier but able to carry on a conversation. Sleep is really important in solid, in gene expression and in longevity, and we wanted our participants to sleep well. So we gave them sleep hygiene tips. [Obviously,] you can’t make somebody sleep well, but we just wanted to support them in that. And then [for] meditation, we prescribed a 10-minute relaxation response. Just basic breathing exercise twice per day, 10 to 20 minutes twice daily. The research on stress, damaging gene expression, being pro-aging, being gas on the fire of aging, that research is powerful and clear. And conversely, like exercise, meditating is very favorable for gene expression.


One meditation experience can have some favorable changes, and experienced meditators are biologically younger. It’s really interesting. And then let me say we used a greens powder. So again, more of those really amazing phytochemicals that I think support good gene expression, a greens powder twice a day. And then we gave Lactobacillus plantarum, a probiotic that [will] support a healthy gut microbiome, which is, again, also very important and may specifically help [the] production of microbial folate. So let me stop there. Oh, should I give the findings? Or do you want to?


Chris Kresser:  Yeah, that’s a lot. And it’s cool because I think one of my frustrations with a lot of research is the whole randomized controlled trial [design], which, of course, has benefits and there are pluses. But there are also minuses because the way of designing research is predicated on the idea that a pill of some sort is going to be the answer for every problem that we might study. Whereas, really, what you did is much more of a multifaceted intervention, right? With diet changes, stress management, sleep hygiene tips, and more. And to me, that reflects more of what we are really going for. If you’re using lifestyle, medicine, and a holistic approach to health, we’re not just trying to find what is the impact of an isolated chemical versus the placebo. So, that’s one thing that stands out to me about this research.


And one of my pet peeves when someone says, we can only look at randomized controlled trials, placebo-controlled, randomized controlled trials, and I’m like, okay, well, I guess you’re only going to be considering medication as the answer for every problem that we might have in terms of human health.


Kara Fitzgerald:  Or you’re going to look at a supplement through the medication lens and reduce it basically to a drug.


Chris Kresser:  Exactly. To a single nutrient. Yeah. So kudos to you for doing that. And yeah, I would love to hear what were the results of this multifaceted intervention.
The Results of the Study: Reverse Aging


Kara Fitzgerald:  The thing that really got us a ton of attention to cut to the chase was the fact that our control group, excuse me, our study group, were 3.24 years younger biologically using the original Horvath bio age clock, as compared to our control group. So our study group got significantly biologically younger in a very, very short period of time. That hasn’t been shown. This is very, very new.


Chris Kresser:  Yeah, that’s amazing. So let’s just reiterate that. Using the measures that we know of right now to determine biological age, participants in the study reduced their age by three years, did you say? Three, 3.2?


Kara Fitzgerald:  3.24.


Chris Kresser:  3.2[4] years. And how long was [the study period], just to repeat for the folks who might have missed it?


Kara Fitzgerald:  Eight weeks.


Chris Kresser:  Eight weeks, so two months and you reduced your biological age by 3.2[4] years. That is remarkable.


Kara Fitzgerald:  It’s extraordinary. It got us very, very excited, too. And we’re embarking on our next studies now that we can talk about later.


Chris Kresser:  Yeah, it makes you wonder what might happen in six months or a year, or two years. Yeah, absolutely. It’s really exciting.


Kara Fitzgerald:  Or what will happen with people [who have] diabetes or cardiovascular disease? These were healthy [men]. They were not on medications. They didn’t have hypertension. It took us a long time to run the study because we did some pretty hefty screening.


Chris Kresser:  Yeah.


Kara Fitzgerald:  So if we can reverse bio age in healthy individuals, there’s no doubt in my mind that using these interventions in individuals with various diseases where we should see more significant change. I want to say one more thing, Chris, because I think it’s important.


Chris Kresser:  Please.


Kara Fitzgerald:  We used nutritionists. I’ve got a big nutrition team in my practice. We have a nutrition internship here. [The] key to this program being successful was having our nutritionists very well trained in the program, meeting with our study participants weekly or more if they requested it. But there was a requirement for at least four encounters once weekly for the first month. They didn’t get to practice medicine or be nutritionists or coaches; they didn’t get to cheer them on. They had to follow a pre-approved script, so it was dry. But I do think that contact and support, so our participants were not just given a bunch of printed handouts and hustled off to go and do this intervention. They were supported every stage of the way with our nutritionists. And I’m sure that that is a big deal.


My co-PI (Principal Investigator) Ryan Bradley at Helfgott [Research] Institute said to me early in the study, I love saying this because I think it’s so funny that he would be paying attention to our intervention. He would be studying us administering this intervention because of its complexity and the fact that these kinds of studies are difficult to pull off. So he was studying us. And we did it because of the nutritionists. So I’m sure that that was impactful.


Chris Kresser:  Yeah, you’re preaching to the choir. With our [ADAPT] Health Coach Training Program and [Functional Medicine] Practitioner [Training] Program, I’m a huge believer in that, as well. There [are] lots and lots of studies, as you know, Kara, that just have looked at the impact of that kind of support alone where they’ve randomized people to two groups, and then one group, and both are receiving sham treatments. But the only difference is the effect of the practitioner where the doctor comes in and is really brusque and doesn’t really give the patient the time of day and walks out. And then [in] the other group, there’s a much more caring and kind interaction. They’re both receiving either a placebo and, in some cases, even a sham surgery; they’ve done trials like that. And not surprisingly, the ones who have a more considerate, empathetic connection with the provider get much better results.


That’s just how we’re wired as human beings. We need that kind of support and interaction. And it’s not just a luxury or some kind of touchy-feely thing. That’s another issue with the way that trials are often designed, right? They don’t account for that. They’re trying to eliminate all of that, all those parts of medicine and just focus on the impact of the isolated chemical on the body, which is a huge mistake. And I totally agree [that it’s] the right approach. And that’s actually what we need to be building into clinical interactions even more so that people have that support in between appointments and can actually be successful in making those changes.


Kara Fitzgerald:  Yeah. Nutrition studies are notoriously horrible. You just can’t give somebody a program and say, okay, go do it. That’s a recipe for failure. I absolutely agree [with] everything that you’re saying.


Chris Kresser:  Yeah. Cool. Well, that is really a groundbreaking study. Tell us a little bit about what you might, I mean, you may or may not be able to talk about it. But what’s next on the research side?


Where to Learn More: Younger You Program


Kara Fitzgerald:  I can definitely talk about it. So we’ve built out a digital platform that houses the whole program that people can access now. Just go to YoungerYouProgram.com, and the book is there. And then [for] the program, which we’re calling 3 Years Younger (3YY), there’s a link just below the book. One arm of the digital platform, you can just go and do as you wish. Actually, let me say that the structure of the study is built out in this. So everything that you need, including our nutritionists, these really amazing human beings, are there and part of the program. So you’ll continue to get those touchpoints with the nutritionists who were either in the study or trained by those who ran our study. You’ll get the same supplements that we used, and you’ll also get biological age, baseline biological age, and then biological age at the end. We have a biological age subjective assessment, too, which you can get at the website. And that’s a fun self-test that you can administer. It’s not validated. We designed it with a lot of attention, but it hasn’t been validated. But that can be a fun and free starting point.


You can just go and do the app as you wish or you can choose the research arm, and you just have to fill out the various forms, sign your name on the dotted line that you understand what you’re doing, and that you will allow us access to your anonymized data and will continue to study it. We are not defining the population; anybody can participate. It is a high-oxalate diet. So if you’re a stone former, you need to get pre-approval from your physician. But I think that would be the only issue and probably not for many of us. And then we’ll continue to look at it. And as long as we have good size numbers, which we will over time, we’ll be able to look at [a] younger population, we’ll be able to look at people with different conditions, [and] we’ll, of course, be able to look at women and different ages. And we’ll be able to look at the influence of the diet through the lens of what supplements people might be taking because we’re not going to control for certain things. So, it’ll be cool for us to go through [those] data.


Chris Kresser:  Yeah, and now we have the capacity for the first time in human history to collect these data and then really make sense of them. And that ability is only going to improve over the coming years. So I want to talk about some of the concepts in your book that have informed your work and my work for a long time. And one of them is, I think, really important for people to understand. And I think there’s a lot of misconceptions about it, which is the relationship between genetics and health.


I think a pretty common idea is [that as] we get older, we just start getting diseases, and it’s just bad luck. I even hear people say just bad genes, just the luck of the draw. It’s a really disempowering point of view. And it’s actually one that’s not really supported by the evidence. So let’s talk a little bit about genes, epigenetics and health. What’s most important? What do we know about this?
A Little Background in Genes and Genetic Expression


Kara Fitzgerald:  Yeah. It’s so important. So we did think our genes were it, right? We did think it. In fact, epigenetics and the fact that you talked about [the Dutch Hunger Study] and the heritability component. That was like blasphemy for the fact that it wasn’t accepted or respected. And I think some scientists very stuck in these old paradigms might still challenge it, even though the evidence screams otherwise.


Chris Kresser:  Overwhelming, yeah.


Kara Fitzgerald:  Yeah. So, we did think that, right? We thought that when we mapped [out] the human genome in the early 2000s, we were going to be able to identify basically one or two genes [that] cause a given disease, like we would crack the disease code. We figured we would do it. A, we discovered we didn’t have that many genes, a lot less than we thought we would. And then B, we discovered that, in fact, no, genes do not seem to be playing a massive role in the disease process at all. And I know I want to say that they’re continuing to analyze genes in different ways and we will find useful patterns. But by and large, I think the overwhelming discovery was genes just aren’t that big of a deal. In the longevity space, they’ve been hunting for the “longevity gene” forever and ever and ever and just failing.


There are some genes that seem to be perhaps a little more significant than others, but not always, and not across the board. It’s pretty crazy. So that really catapulted us into the era of epigenetics. Epigenetics [has] been around, the science has been around for a long time. But our attention really turned to there in a strong way. So it’s not about the gene. It’s about the regulation of the gene that interfaced between the genetic material and environment. So it turns out that how we live, who we are, what we’re thinking, what we’re eating, what we’re being, doing, saying, all of that has [a] potent impact. We were so wrong about it. It’s amazing. In fact, we get to drive the gene car. We have a lot of say, and therefore a lot of responsibility, over our path and our health.


Chris Kresser:  Right. This is sort of good news, bad news. I think it’s mostly good news. But yeah, it comes down to, I think this is hard to quantify exactly, but there are studies that suggest that 90 percent of what the risk of chronic disease and, of course, the converse of that of what drives our health comes down to diet, lifestyle, and behavior. The choices we make on a day-to-day basis, and all the other factors of the exposome. Air quality, water quality, exposure to toxins, food, stress, sleep, etc. And only 10 percent of what determines our health are the underlying genes themselves.


Now, of course, there are always exceptions like cystic fibrosis. If you have that gene, you’re going to have that disease. But for most chronic diseases, which is what plagues our health, seven of 10 deaths are caused by chronic disease. We know now that epigenetics and gene expression and the choices we make have a much bigger influence.


Kara Fitzgerald:  Yes.


The Translation of Emotional Experience to Physiological Illness


Chris Kresser:  One of the things that I think we’re learning a lot more about that’s interesting, [and] you talk about [it] in your work, is this concept of biological embedding, which explains how our emotional and psychological experiences and imprinting could be adverse childhood experience, could be [post-traumatic stress disorder], could be a car accident, could be something that has a profound impact on our nervous system, and our emotional and psychological health, then impacts our physiological health. And everybody listening to this has had their own personal experience of it in some way or another and knows that it is a real thing. But in medicine, up until very recently, that was all just sort of put under the psychosomatic label, right? Now we know that methylation is one of the mechanisms that actually connect those things. So can you talk a little bit about that?


Kara Fitzgerald:  Yeah, it’s fascinating. And it’s heritable. It’s the translation of psychic experience into biochemical marks that then turn genes on and off. That’s basically it. Our psychic experience translated into biochemical marks. It’s like photosynthesis or something. It’s so extraordinary. So our thoughts become biochemistry and influence gene expression or our experiences. But I guess the other piece, or not, I guess, extraordinarily, we can inherit this through generations and it will dictate our stress response. How some of us could have the same experience and have a very different response to it, emotional sort of physical response to an experience. One person may have a lot of resilience. One person may not. And the individual who doesn’t has less methyl groups on the glucocorticoid system. So they’re going to be dumping out stress hormones more quickly.


This has been demonstrated in one of our co-author’s research for many, many years since the ‘80s, Dr. Moshe Szyf, in his animal studies. Actually, there’s some human corollaries. But this will increase, so this will push aging forward, and this will increase the risk of the chronic diseases of aging. We can see difficult experiences. Hypermethylating, important feel-good hormones, or hormone receptors, or I should say the genes of these hormones like oxytocin. And that can be associated with depression, including postpartum depression. We can see far-reaching influence from our psychic experience on genetic expression.


We have not done a good job in studying what resilience looks like, and we have to. One of the very interesting things, Moshe Szyf has been on my podcast. He’s a brilliant epigeneticist and has been in this arena a long time. He’s looked at the influence of experience in orphanages or he’s looked at the experience of Holocaust survivors in subsequent generations. And his belief is that we will be able to take a methylation fingerprint, if you will, of an infant or even in utero and shift those patterns before they become significant before they play out. Think about that; think about getting in there. And so one of the areas that he looked at, he was part of Project Ice Storm out of Quebec, where there was a bad weather event. I think it lasted a couple of weeks. Women who were pregnant gave birth to kids who had higher rates of autism, higher rates of asthma, because of the stress. And it was either the emotional stress or the physical stress, or both. It didn’t matter, is the point. But his thinking is that we will arrive at a place where we can tweak methylation patterns before they’re even an issue. Before the kid has to go through it or spend endless time in therapy or whatever kind of journey that they need to take, we’ll be able to turn it around. So I think the possibility of where we’re heading could be extraordinary.


Chris Kresser:  That’s really fascinating. I think another interesting part of this is, it comes back to this idea you mentioned earlier, like when you realize the impact that these epigenetic changes have, it comes with a lot of responsibility on the one hand. Because it means that our choices are even more important because they’re the primary determinant of our own health span. How long we’re going to live, but how well we’ll live during that time and how well we’ll age. But not just that; there [is] also the determinant of the impact [on] our offspring, our children’s health span, and even our children’s children’s health span if we’re of childbearing age. So that’s another reason to consider that. So there’s a lot of responsibility there.


On the other hand, I think it has an effect of lessening the guilt, blame, and shame that some people feel who struggle with things like anxiety or depression or difficulties with mental or behavioral health in any way. Because often, those problems come with that added layer of this is my fault, there’s something wrong with me, there’s something I’m not doing right, [and] this is why I feel this way. But in reality, a large part of that is something that was inherited, or in epigenetic patterns that started with your parents or even grandparents and, essentially, the impacts of some trauma that are passed down among generations that you have essentially, your nervous system received that imprint. So you were starting from that place. And again, the intention here is not to shift people into a victim mentality. It’s the opposite. But it’s to also help us understand that we’re part of an ecosystem and we’re subject to a lot of influences, some of which we have control over and some of which we don’t. And, when I explain things to patients, my hope is that that softens that guilt, blame, and shame layer because that’s often what prevents people from taking effective action. Because they get stuck in that cycle of blame and self-recrimination. Whereas if they see it as something that wasn’t all their doing, then they can mobilize to take the right actions in the present moment to move to a healthier place. I think that’s a really important piece.


Kara Fitzgerald:  Yeah, it’s extremely important. I think continuing that thread, if we are gentle with ourselves, if our anxiety threshold is lower, we’ve got to respect that and allow for that. And yes, it may come from our parents, our grandparents, or our earliest childhood experience, and it changed our genetic expression. We have to respect it. And I want to say that we do have some capacity to change that. We need to study this area. It doesn’t have sufficient science on it yet. But our cells are dividing all the time. And we can maintain those methylation patterns, or we have an opportunity for renewal.


Some I talked about stem cells are, once a heart cell is going to stay a heart cell. But there [are] other regions that are labile and that are very responsive to our influence. And so the more, and as I said earlier with regard to meditation and the favorable changes we see in glucocorticoid gene activity or glucocorticoid response elements, it could be on another gene, but it’s influenced by glucocorticoids. Or some of our feel-good hormones or our longevity, the longevity patterns, etc. Like the things that we want, we can change those in meditation. We can change things with diet, with exercise. So with patience of who we are and what we’ve inherited epigenetically, I think that we’ve got some tools. Tools are emerging for how we can work with them and change those and build resilience.


Chris Kresser:  That’s so great. This is a really exciting field, and you’re pioneering new pathways forward. I love the work you’re doing and the research. And your book, Younger You: Reduce Your Bio Age and Live Longer, Better, is phenomenal. It’s really a blueprint for how we can improve our health span and enjoy the quality of our life as much as possible, which is really what this is all about. Tell people where they can learn more about the book and the program and your work.


Kara Fitzgerald:  Just come on over to YoungerYouProgram.com. You will see the book there; there’s a bunch of free stuff that you can get, and then just below that is the digital program 3YY that you can access. You can join our continuing research study or just jump in and do it as you wish.


Chris Kresser:  Awesome. Thanks, Kara. It’s always a pleasure to speak with you. I look forward to hearing about the next round of research and have you back on the show.


Kara Fitzgerald:  Yeah, cool. Thanks so much for your support, Chris. I really appreciate it.


Chris Kresser:  It’s a pleasure. Thanks, everyone, for listening. Keep sending your questions in to ChrisKresser.com/podcastquestion. We’ll see you next time.

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