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Episode 481
The Doctor's Farmacy

How To Reverse Your Biological Age

Open the Podcasts app and search for The Doctor’s Farmacy. If you’re viewing this site on your phone, you can just tap on the

Tap the subscribe button and new shows will be added to your library.

If you’re using a different device, our show is available on the following platforms.

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What if I told you it was possible to reverse your age by three years, in just eight weeks? Well, it is possible, and today you can learn how. 

While this is exciting news overall, perhaps the greatest part is that the changes we can make to reverse biological aging are pretty simple and very accessible. 

The amazing doctor behind this groundbreaking research that has proven our ability to reverse aging is my good friend, colleague, and long-time collaborator Dr. Kara Fitzgerald. I’m thrilled to talk to her about her work on this episode of The Doctor’s Farmacy

If you’ve ever wondered what we can do to stop the aging process, then this episode is for you. We kick off the episode explaining the key concept of the epigenome, which is like the software laid over our genetics controlling their expression. While it used to be thought that our genetics couldn’t be altered, through the study of epigenetics we now know that they can.  

Dr. Fitzgerald is an incredible wealth of knowledge in this area, especially when it comes to the confusing topic of methylation and how it impacts aging. She and I break down the role of methylation in the body and why it’s a powerful regulator of the aging process and a target for eliciting change. 

Through her recent clinical study, Dr. Fitzgerald has identified diet and lifestyle changes that reversed biological aging by three years when followed for just eight weeks. And they don’t even involve anything high-tech or expensive. She shares what kinds of foods participants ate in her high methyl-donor diet as well as the exercise protocol, sleep goals, and stress management practices she saw to be most beneficial. 

We also talk about the power of polyphenols, new methods for testing biological age, which supplements she recommends, and so much more. Aging will never be viewed the same thanks to Dr. Fitzgerald’s work.

This episode is brought to you by Rupa Health, BiOptimizers, and Thrive Market.

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I hope you enjoyed this conversation as much as I did. Wishing you health and happiness,
Mark Hyman, MD
Mark Hyman, MD

Here are more of the details from our interview (audio):

  1. Reversing your biological age through epigenetics
    (6:36)
  2. Initial scientific studies that have shown biological age reversal
    (9:22)
  3. Dr. Fitzgerald’s 8-week age reversal study design
    (11:14)
  4. Seminal research around influencing and regulating gene expression through nutritional intervention
    (25:41)
  5. Using food as medicine
    (30:35)
  6. How exercise, sleep, and meditation were factored into Dr. Fitzgerald’s study
    (40:40)
  7. Primary findings from Dr. Fitzgerald’s research
    (47:12 )
  8. Practical ways to reverse your biological age
    (1:01:43)
  9. Influencing gene expression before conception and during pregnancy and infancy
    (1:04:29 )
  10. Aging without declining in health
    (1:08:06)

Guest

 
Mark Hyman, MD

Mark Hyman, MD is the Founder and Director of The UltraWellness Center, the Head of Strategy and Innovation of Cleveland Clinic's Center for Functional Medicine, and a 13-time New York Times Bestselling author.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

 
Dr. Kara Fitzgerald

Dr. Fitzgerald is on the faculty of the Institute for Functional Medicine, is an IFM Certified Practitioner, and lectures globally on Functional Medicine. She runs a Functional Medicine Clinic Immersion program for professionals and hosts a podcast series, New Frontiers in Functional Medicine, and an active blog on her website. Her clinical practice is in Sandy Hook, Connecticut.

With the Helfgott Research Institute, Dr. Fitzgerald is actively engaged in clinical research on the DNA methylome using a diet and lifestyle intervention developed in her practice. The first publication from the study focuses on the reversal of biological aging and was published this past April in the journal Aging. Her new book, Younger You, as well as her 3 Years Younger Program, have just been released. 

Show Notes

  1. Take her Biological Age Self-Assessment

Transcript

Speaker 1:
Coming up on this episode of The Doctor’s Farmacy.

Dr. Kara Fitzgerald:
I think that’s another cool piece of evidence for our findings. I think if you have a condition, if you’re diabetic or if you’ve got heart disease, et cetera, you’re aging faster and by extension, if you turn that around, you should have even more powerful age reversal.

Dr. Mark Hyman:
Yeah. Welcome to The Doctor’s Farmacy, I’m Dr. Mark Hyman, that’s pharmacy with an F, a place for conversations that matter. If you care about figuring out how long you’re going to live, what your biological clock says and how to reverse biological aging. Well, this is the podcast for you, because I’m so lucky to have my friend, my colleague, my longtime collaborator, Dr. Kara Fitzgerald as a guest today on The Doctor’s Farmacy. And Dr. Kara Fitzgerald has been in the field of functional medicine for decades with me, she’s on the faculty of the Institute for Functional Medicine.

Dr. Mark Hyman:
She’s a naturopathic doctor, but I don’t think that describes really her depth and breadth of knowledge. She’s been a leader in putting forth ideas around aging and methylation, and I actually personally learned so much from her. In fact, we collaborate on a book together which really was the first case study book of functional medicine cases that came out of my practice and my patients and we collaborated to write them up in a way that people could understand how the methodology of functional medicine works.

Dr. Mark Hyman:
I’m just so glad to have you on the podcast and talk of about your new book which is amazing. And also your research which was really the core impetus for the book. And the research really was about how do we reverse biological aging? You actually, I’m going to give you the punchline everybody because it make us I think listen to the podcast. In a very short study, she showed she can reverse biological aging by about three years which is no joke, and her book Younger You, Reverse your Bio Age and Live Longer is out now, I encourage you to get it, and we’re going to talk all about why it’s important to know your biological age and what to do to reverse it. So welcome, Kara.

Dr. Kara Fitzgerald:
It’s really great to be you with you Mark. I’m just giving you a huge virtual hug. I first started, we released an ebook. We were talking about this to professionals back in 2016 and using it in our practice even before then. And you were really an early adopter, you lent your ear on this content way back in the day and it’s you and Jeff Bland, people who just gave me a little nudge along by saying yes, with your interest, with your curiosity, you brought us into Cleveland Clinic Center for Functional Medicine to train the nutritionists early.

Dr. Kara Fitzgerald:
You guys were one of the early earliest adopters of this material and it just means so much to me. So I know we’ve been working together for a long time, since the beginning of my career really, and I’m just grateful. So thank you.

Dr. Mark Hyman:
Well, thanks Kara. It’s great to be working with you. You just make my life easier because I don’t have to do all the work. People are smarter than me working harder, doing the stuff. It’s awesome. So let’s get right into it.

Dr. Kara Fitzgerald:
Yeah. Yeah.

Dr. Mark Hyman:
Your new book is really based on this study that you did that showed a reversal biological age. So we cannot change our chronological age. I’m 62, that ain’t changing, it’s just getting worse every year. Well, maybe not, maybe getting better and, but we can change our biological age which is a new discovery and which means that the youthfulness of our body is not fixed.

Dr. Mark Hyman:
We can literally not only stop it, but we can reverse our biological age which we can measure through objective markers that are now available scientifically. So you look at how this works through this phenomena, what we call epigenetics, and maybe you’ve heard about this people out there. Epigenetics is a really cool idea, and it goes back to the ancient debate between Darwin and Lamarck.

Dr. Mark Hyman:
Darwin believed in the evolution of species and natural selection and Lamarck was like, “Hey, your traits can be actually inherited in a different way and there’s different regulatory things that are having to do with what’s happening in the current life.” And so they’re both right it turns out that that genetics is fixed in the sense of evolution, natural selection, but the epigenome which there’s this super controlled mastery system over your genes, the software, which regulates which of your bazillion genes gets red and which gets transcribed and what proteins get made, that’s completely modifiable and changeable.

Dr. Mark Hyman:
And what’s even more amazing is these epigenetic things we can call the imprintome get carried over generationally. So I just talking to a guy who grew up in the Holocaust and Auschwitz and that embedded trauma in his parents, in his grandparents. That goes down generationally, it can be imprinted on the genes, but they’re not fixed unlike if you get down syndrome, well, that’s fixed, you can’t change that, but you can change the expression even within down syndrome.

Dr. Mark Hyman:
By the way, I’ve had down syndrome patients and their meta biochemistry metabolism is super screwed up and you can actually work with it to using heroic functional medicine techniques to actually optimize that and improve their function even with a dominant inherited disorder. So epigenome is so cool, and you’re going to explain all what that is, but tell us about how you use this groundbreaking trial to show that we can reverse biological agent. What was the most surprising thing you learned from doing that study?

Dr. Kara Fitzgerald:
Well, let me just say that that was a badass introduction Mark, that’s awesome. I’m so glad you actually brought Lamarck in and oh my God, what a great way to position this conversation. A nice sweep through a good background. Yeah. The most surprising finding for sure was that we reversed biological age by over three years and our participants as compared to the control group.

Dr. Kara Fitzgerald:
Extraordinary because the fourth study, there’s maybe six studies out now, but it was the fourth study at that time to show biological age reversal, and the only study to do it in a control trial and in eight weeks’ time and our interventions are so benign, we did diet and lifestyle. The other study that showed a profound age reversal, really the first and it was written up in nature and published an aging cell and just got an enormous amount of attention was the trim trial, Greg Faye and his colleagues.

Dr. Kara Fitzgerald:
And that was a year long intervention. It was growth hormone injections, Metformin, DHEA and zinc. So growth hormone injections, he was focused on thymus gland regeneration, and they actually did show that, they showed some improvement in T-cell status, et cetera. And that’s been his area of focus in his work and biological age reversal in the study participants by, I think on average, maybe two or three years, but this is over an entire year and it’s using a very aggressive intervention. So by extension, we’re looking at [crosstalk 00:07:16].

Dr. Mark Hyman:
Medications, growth hormone and all this stuff. Yeah. It’s a lot, it’s a lot.

Dr. Kara Fitzgerald:
Yeah, it is a lot. And that’s a black box. Can we just-

Dr. Mark Hyman:
And what was the length of extension they found? What was the length of extension they found on that?

Dr. Kara Fitzgerald:
I think that they did about two years, maybe a bit over two years.

Dr. Mark Hyman:
Okay, so this is really important because you’re talking about a very medication and centric approach.

Dr. Kara Fitzgerald:
Yeah.

Dr. Mark Hyman:
And you did a very foundational approach, a lifestyle.

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
So take us into the study design, what you looked at, who are the participants, what you measured, what the interventions were and what the outcomes were. So we really can understand this in detail because I think it’s worth people listening up to why with some very foundational basic things that we can really arrest and even reverse biological age. And not only that, when you take that as a foundation, then you can layer on top of that all sorts of additional functional medicine approaches to actually go even further. So that’s just foundational, and that was really simple. It’s quite amazing that we achieve those kinds of results with such a simple intervention.

Dr. Kara Fitzgerald:
I know. Well, I want to tell you why I think we did because the Mediterranean diet has been looked at with biological age and there is modest reversal again in a year long study, very modest in just one subgroup. So we used functional medicine principles in our diet design, actually in the whole program designed, we used solid functional medicine/ortho molecular inspired by Bruce Ames, by Linus Pauling, by Jeff where we loaded the diet with things that would influence methylation.

Dr. Kara Fitzgerald:
So everything in the program was designed to move methylation in a favorable and balanced direction. It wasn’t just here’s a turnkey dietary pattern that we think is pretty good. It was very much designed to do that. So our study population, this was … Incidentally, this was run at the Health Gut Research Institute. My co-PIs Ryan Bradley and the Health Gut Research Institute is part of my alma mater, National University of Natural Medicine, and I think they do really good clinical research there.

Dr. Kara Fitzgerald:
And so we recruited men, middle aged, 50 to 72. The reason that we wanted to look specifically at the at middle age is because the scientific term methylation, DNA methylation gets wonky as we age. And we should do a drill down on that as well. And so we wanted to get right in there in the sweet spot when methylation starts to change, starts to look like we’re aging, starts to look like the chronic diseases that we’ll talk about that are associated with aging.

Dr. Kara Fitzgerald:
And that’s where we wanted to investigate. The reason that we only included men, and obviously I’m a woman. We all want to study women and we are doing that now was because it’s a pilot study. We had 20 and 20. We ended up finishing with 18 in our study group and then 20 in our control. If we included women, the age range between 50 and 72, obviously some of them are going to be still menstruating, some of them will be perimenopause and some will be post-menopause, and so that hormonal influence would be difficult to tease out in this size.

Dr. Kara Fitzgerald:
So we needed to start with men which is fine. So eight week intervention and the study, the diet is very plant-forward. All the nutrients that are packed with methyl donors. So a lot of greens, a lot of cruciferous, mushrooms, what else? Nuts and seeds. We did include animal protein, so we wanted folks to have about five to 10 eggs per week for the choline. Beets are in there for the betaine, a great methyl donor nutrient.

Dr. Kara Fitzgerald:
Not a ton of beets because obviously they’re high in sugar, but a couple of beets, a couple of small beets a day. We wanted people to have some liver. Liver is a multivitamin in a food matrix. It is packed with the daily [crosstalk 00:11:36].

Dr. Mark Hyman:
I love that.

Dr. Kara Fitzgerald:
Yeah, it really is. It’s a multi-

Dr. Mark Hyman:
If you all Google liver and nutrition and broccoli or the best vegetables, it makes the vegetables look like cardboard, and the liver is like the superpower of nutrient dense foods. It’s really quite amazing.

Dr. Kara Fitzgerald:
And it’s what we were using before we learned how to synthesize, and isolate B vitamins. We would just emulsify liver and inject it into somebody’s butt, that’s how [crosstalk 00:12:07]

Dr. Mark Hyman:
That’s what indigenous cultures, right? That’s what indigenous cultures always have done. That’s what native American tribes did, they always ate the organ first. It’s what wild animals do when you look at lions or predators, they don’t eat the meat, they eat the organs, and then the scavengers get the meat. It’s pretty interesting.

Dr. Kara Fitzgerald:
Wow. Isn’t that interesting? Yeah, it’s so nutrient dense. So we wanted people to do some liver and we worked, thank God, we have a brilliant nutrition team. And we had some palatable recipes that they could do. And the other option is you can take liver caps, but which I’m honestly doing because I wouldn’t say I’m a great liver cook, but so that was the diet portion. And-

Dr. Mark Hyman:
Wait a minute, wait a minute. Organic chicken livers, organic chicken livers, onions, chop up some onions, stir fry the onions, little oil, chicken liver is in there, fry them up, little salt, pepper, put them on rice.

Dr. Kara Fitzgerald:
Oh my God. It sounds actually really good.

Dr. Mark Hyman:
It’s so good, it’s so good. Well, I grew up on that cause we were very poor. My mother and my sister and I lived in a one bedroom apartment in Queens in New York and I thought this was a gourmet meal because it was so yummy and delicious, but it was actually because we were really poor. My mother was a teacher making 7,000 a year in Harlem, and so basically chicken livers and onions a lot.

Dr. Kara Fitzgerald:
That is so funny Mark.

Dr. Mark Hyman:
It’s super cheap too.

Dr. Kara Fitzgerald:
I remember when we were working on the book, I was snooping around your cabinets. I was in your kitchen. You actually had a really good food down there.

Dr. Mark Hyman:
Sorry to interrupt, but I had to tell that story. Go ahead. Liver capsules. I got it.

Dr. Kara Fitzgerald:
Yeah, great, great. But your liver sounds delicious. I know one of the guys in our study had … He said that they were the new chicken McNuggets for him he actually fell in love with them. I think he must have dipped them in an almond flour or something because there’s no … We don’t do grain in this a week. All right, and then we also … So it’s very methyl donor forward, but the other [crosstalk 00:13:58].

Dr. Mark Hyman:
Hold on, hold on. Before you get, wait, wait before you get into that. I don’t think anybody has a clue what you’re talking about when you say methyl donor. Can you just unpack that?

Dr. Kara Fitzgerald:
Oh, okay. Perfect.

Dr. Mark Hyman:
And why the study was so focused on this idea of improving this phenomena that happens a bazillion times a second in your body called methylation.

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
And it’s very confusing for even doctors, but you Kara are an expert on methylation. You spent your life studying methylation and it really is the regulation of our genes. So explain what methyl donors is, what methylation, just the reader’s digest version and then jump back in [crosstalk 00:14:27].

Dr. Kara Fitzgerald:
Yeah, okay. All right. Perfect. Okay. So methylation cycle produce … A methyl group is just a carbon and three hydrogens. Carbon is you ubiquitous, hydrogens are ubiquitous. We just evolved using this very simple structure everywhere in the body as you said all of the time and we make it in what’s called the methylation cycle, the compound that can deliver methyl groups is called S-Adenosyl methionine or SAMe, people know it as, or SAM.

Dr. Kara Fitzgerald:
And this compound, we were producing all of the time in the body, and then it zooms around and it engages in one of the 300 plus reactions that use an enzyme called methyl transferase. And the SAMe is transferring that methyl group, methyl transferase. So we’re using it in detoxification to make neurotransmitters and to make certain fatty acids, et cetera, just all over the place.

Dr. Mark Hyman:
Energy.

Dr. Kara Fitzgerald:
Yes, yeah.

Dr. Mark Hyman:
Detoxification compounds, everything.

Dr. Kara Fitzgerald:
Right, right. Yeah, all over the place. And so, but my area is specifically now I’m focusing a lot of energy on epigenetic expression, and so methylation is happening there too. So there’s DNA methylation in all of our cells in the mitochondria, there’s methylation happening. There’s other epigenetic methylation processes like his stones, the proteins that DNA is wrapped around.

Dr. Kara Fitzgerald:
They engage in methylation as well, but DNA methylation is unique, and I talk about it in the book. So we’re in, we’re thinking about gene expression and this whole field of study is called epigenetics and we’re using methylation there, but I also want to acknowledge that there are many other epigenetic processes. The reason I’m focusing on DNA methylation and a lot of scientists are is there are a handful of reasons.

Dr. Kara Fitzgerald:
First of all, we can study it. We can map out what they call the whole methylone. So the millions of these little methyl groups that are on genetic material, we can actually analyze and study. When there are a lot of methyl groups on a promoter region of a gene, that gene is generally turned off. In science, if you Google DNA methylation, and you look at your images, you’ll see a strand of DNA, and these little red lollipops, the methyl group is denoted by these lollipops.

Dr. Kara Fitzgerald:
So if there’s a lot of lollipops on a piece on a gene, then that gene is inhibited from bringing transcribed. So a transcription protein can’t land on the DNA and initiate transcription. Conversely, if those meth groups are not present or if there are less methyl groups present, then that gene can be turned on. And as I said in the beginning, as we age, the methylation on our genes is changed and it’s changed unfortunately for the worse.

Dr. Kara Fitzgerald:
So we can see it. The other thing that’s extremely important about DNA methylation is that it can be transferred. So there’s enzymes, there are DNA methyl transferase enzymes that will continue to pass down those marks through cell division after cell division after cell division. And in this way, they’re heritable. So sperm and egg have very complex methylation patterns.

Dr. Kara Fitzgerald:
When the embryo is formed, a lot of those methyl groups are scrubbed off and there’s a family of enzymes that do that, but not all of them are, some of them are preserved, and that’s the imprint home that you mentioned earlier. Methylation is what dictates the fate of pluripotent in embryogenesis. So you’re a liver cell, you’re going to be a heart cell, you’re going to be a skin cell.

Dr. Kara Fitzgerald:
It turns off. So methylation turns off one of the chromosomes and those of us with two X chromosomes. Methylation plays exquisitely important roles. And so for that reason, we’re giving a lot of study attention to it, and I think that ability for it to be a preserved across cell generations and life generations makes it one of the big players in epigenetics, and that’s why we’re putting attention there.

Dr. Mark Hyman:
Yeah, so the idea is basically that you’ve got this molecule carbon three hydrogens. I think of it like the currency of the body. It’s constantly changing chemicals all the time. It’s being transferred, one another molecule and regulating everything in the body. It’s like the central hub of our biochemistry. And if any working your system is screwed, heart disease, cancer, diabetes, Alzheimer’s, autism.

Dr. Mark Hyman:
Everything you could think of pretty much that screws up people is in involved in some way with this process methylation and the DNA part is just fascinating because it’s really the regulator of which genes get turned on or off. And like you said, in every cell, in every cell is the entire blueprint for everything in your body, literally. In your skin cell is a blueprint for your brain or your liver or your kidneys, right?

Dr. Kara Fitzgerald:
That’s right, that’s right, yes.

Dr. Mark Hyman:
Well, how does the skin cell know to be a skin in cell versus a liver cell or a brain cell? Well, it’s these regulatory controls on our genes and which ones gets to compress not, and this is all the methylation stuff. And that really is regulated by B6, B12, folate, you mentioned methionine and all these important molecules that are in our diet and in our food that by the way, Americans are mostly often deficient in or insufficient in.

Dr. Mark Hyman:
And so we’ve got this pandemic of methylation problems, and for those who want a little bit deeper dive on this, I’ve wrote a couple of blogs years ago. And you’ve probably got a ton of information on this, but you can just Google Hyman and methylation and you can learn more about it and all the things, ways to play with it.

Dr. Mark Hyman:
But we’re going to talk about advances even from that article which was now our understanding of epigenetics and just to give people a quick understanding of how the power of this, a lot of this work was initiated by a guy named Randy Journal, who is an amazing scientist. Did he win the Nobel prize? He might have, didn’t he? Or-

Dr. Kara Fitzgerald:
No, but he should. Their very first paper is the most cited paper in the history of science. So there’s a little fact [crosstalk 00:20:53].

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

Dr. Kara Fitzgerald:
And blonde, they’re very visual.

Dr. Mark Hyman:
And yellow. They’re blonde. They’re like these big fat yellow mice that looked like a big piece of fat.

Dr. Kara Fitzgerald:
Geeze.

Dr. Mark Hyman:
Genetically identical. And in one litter of these mice, they just did their normal thing, bred the mice and all that. And this other litter, they gave them methylation factors, B6, folate, B12, and it completely changed their gene expression in such a way that the mice that had the B vitamins and methylation were little, skinny, brown and not diabetic or fat or anything, and so that was just amazing.

Dr. Mark Hyman:
It’s like you’ve got identical genes and you’ve got completely different expression, that’s what Kara is talking about and understanding how to regulate that process is a key to unlocking health and biological aging. So now carry on with your explaining of the study because I want to take that little detour.

Dr. Kara Fitzgerald:
It’s an extraordinarily important and big, big deal what they showed and it’s very visual and he should get the Nobel, and it’s impressive that it’s the most cited paper in the history of science, it’s nuts, but yes. And it really put what the power of nutritional interventions on the map.

Dr. Kara Fitzgerald:
So you know what? One of the interesting things that they cautioned, you probably don’t member this, but at the very end of that abstract, the final sentence is basically a word of caution around appreciating how potent nutrient interventions are. And I think that ushered us into the era of epigenetics, that particular study and nutritional epigenetics in particular because A, we were starting to be able to actually see at that level, epigenetic expression, what they did was they methylated and turned off the agouti gene, but they said, “Look, we’ve introduced B vitamins and we turned a gene off and look at this phenotypical change.”

Dr. Kara Fitzgerald:
It’s favorable, but we need to be mindful in general about the power of our interventions. And for me, as I dove into epigenetics, that was my huge aha. So it was around 2013 and I was tussling with all of the epigenetic literature coming out around cancer, and the thing that just really stopped me and prompted the development of everything was the fact that in the tumor microenvironment, cancer takes over our gene expression for its own survival and shuts down genes we want on, it turns on genes we don’t.

Dr. Kara Fitzgerald:
It is aggressively abnormal methylation in cancer. And my question Mark was if we’re slathering everybody, if we’re going very B vitamin forward, is this what we want to do all of the time? That was my first step.

Dr. Mark Hyman:
I know, you really brought that up because I was like, “Oh, we should be taking all these high doses of B vitamins and methylation factors.” And maybe that’s not always a good idea.

Dr. Kara Fitzgerald:
That’s right. And now that we can see at this level, I think we want to be a little bit more nuanced in how we approach, and there are without question times we need to go and go hard with B vitamins. Actually, there’s a study in glioma using very high dose folate we can talk about later that had some interesting, good outcome.

Dr. Kara Fitzgerald:
So the point is is that our interventions, we’re not just going to pee those B vitamins out and not have to worry about it. We need to just think a little bit more nuanced. So but we know we need methyl donors. We know as we age, basically our genome becomes generally speaking, less methylated. So we need to just consume as many meth donors in our diet as possible. So that was our first piece.

Dr. Kara Fitzgerald:
There’s no evidence in the literature that there’s anything negative with a high methyl donor diet. So in that at food matrix, go for it, binge on kale all day long, have a couple of the chicken fried livers that mark is talking about, and you’re good. That’s a really amazing thing. So that’s item number one, food forward always works.

Dr. Kara Fitzgerald:
But the other piece, the other huge aha for me in this journey was looking at the literature on polyphenols. It turns out that these beautiful compounds that have time and memorial use histories like the catechins in green tea or corcumin or luteolin or resveratrol or quercetin, all of these compounds that we know and love and use and eat and prescribe, et cetera, et cetera. They appear to direct methylation traffic. At least that’s what our findings suggest.

Dr. Kara Fitzgerald:
So when I first started to read about it, again, we’re looking at this oncology literature and so in cancer, actually in aging as well, tumor suppressor gene which are important genes we want on get hypermethylated and shut off which is not a good thing. The in-vitro studies were showing routinely that these polyphenols will allow for the re-expression of these inhibited genes. So that’s cool.

Dr. Kara Fitzgerald:
So polyphenols seem important in in-vitro. Yes. And there’s a whole table in my book that walks through various tumor suppressor genes and the polyphenols that have been studied. This has also been demonstrated in the animal studies as well. And diindolylmethane, sulforaphane, we know these things to help us detox, et cetera, but you know what? I think they’re doing the heavy lifting mark at the level of the epigenome.

Dr. Kara Fitzgerald:
I think they’re changing genetic expression, and then we’re studying the downstream effects and saying, “Oh, they’re anti-inflammatory, they’re anti-cancer, they’re antioxidant, they’re detoxification.” But I think as we tease it out more and more, we’re going to see its gene expression. So as packed into this methylation donor-based diet is all of these polyphenols. So it’s a very dense polyphenol diet. So again, lots of cruciferous, lots of colorful veggies, we wanted people to consume green tea, we had a curcumin requirement and actually in my book-

Dr. Mark Hyman:
Wait, are you saying food is medicine? What are you saying?

Dr. Kara Fitzgerald:
No, I wouldn’t go there.

Dr. Mark Hyman:
Listen folks, this is just … You’ve got to tune into what she’s actually saying. What she’s saying is she designed a way of eating, picking certain foods that have very particular compounds in them, both methyl donors like choline and betaine, things like B vitamins, but also these phytochemicals that also regulate our genes and regulate enzymes and regulate our biology and inflammation and detoxification.

Dr. Mark Hyman:
And so when you’re eating, it’s so far more than calories. Food as Jeffrey Bland taught us all is information, it’s code, and it’s going to upgrade or downgrade your biological software literally with every bite. And that’s really quite amazing, and you showed it. Yeah, that’s what you showed. You didn’t have to take these fancy expensive drugs with side effects and this and that. It’s like what’s the side effect of eating sardines? Nothing except good side effects. You get choline, you get Omega-3 fats, you get protein, you get all these wonderful stuff, right?

Dr. Kara Fitzgerald:
I think that that’s why … That has to be why we were able to move things as rapidly as we were because we looked at it through a ortho, molecular functional medicine.

Dr. Mark Hyman:
Functional medicine lens.

Dr. Kara Fitzgerald:
This is true functional/ortho molecular of medicine where we’re doing the right amount of a nutrient for the right effect and I have-

Dr. Mark Hyman:
Ortho molecular means to correct, to straighten or correct molecule. Orthopedics is to straighten or correct bones, ortho molecular is to correct and, or straighten your molecules, right? That’s where functional medicine is essentially derived from.

Dr. Kara Fitzgerald:
And I think that that’s why we were able to make a difference. And when you look at other studies where they’re doing some caloric restriction, data out now which is beneficial for sure or the Mediterranean diet or there’s a study that showed some modest stage reduction with just general healthy eating patterns. You’re going to get no argument.

Dr. Mark Hyman:
It’s all an upgrade, right? It’s upgrade from fast food and junk food, right?

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

Dr. Mark Hyman:
So were you using supplements and exercise and stuff in the study as well?

Dr. Kara Fitzgerald:
Yeah, yeah, so let’s talk about that. The only supplements that we used because I didn’t want to use isolated nutrients. We did a greens powder to extra hit home those all important polyphenols. So a couple of hit green powder a couple times a day and we used a probiotic. We used lactobacillus plantarum. The reason that we did that is multifold, but a healthy gut microbiome makes a B complex.

Dr. Kara Fitzgerald:
You want a natural B complex take care of your gut. Seriously. And so lactobacillus plantarum has been shown to increase endogenous, microbial production of natural folates, and so we introduce that, but a healthy microbiome.

Dr. Mark Hyman:
Okay, in English that means your gut bacteria make B vitamins like folic acid?

Dr. Kara Fitzgerald:
Yeah.

Dr. Mark Hyman:
She likes to use big words, but.

Dr. Kara Fitzgerald:
So funny, you’re so funny.

Dr. Mark Hyman:
My mother is always like, “Use the KISS method. Keep It Simple, Stupid.”

Dr. Kara Fitzgerald:
Yeah, for sure. Okay. I’m cool with that.

Dr. Mark Hyman:
I can be your translator. Obama had his anger translator, I’ll be your translator.

Dr. Kara Fitzgerald:
Oh my God, that’s so funny Mark. Yeah, for sure. Yes. So and the other piece is that our gut bugs regulate us, and when they … They’re playing an intimate role in healthy genetic expression. So we need to love on our gut bugs. And so in this study, we did, we kept it simple and we just used lactobacillus plantarum and we significantly increased circulating methyl folate. There were no B vitamins to be found, but we did increase that in our participants actually by quite a bit.

Dr. Mark Hyman:
Amazing.

Dr. Kara Fitzgerald:
So that’s the diet and then, oh, actually the diet is low glycemic, it’s antiinflammatory, no grains, no legumes, no dairy. And listen, I am a big fan of blue zone data and I know they’re loading up on certain grain and they certainly eat beans and stuff. And I want to say that this is a finite period of time. This is not a lifetime diet. It could be if you wanted it, it’s a healthy eating pattern, but I’m all about transitioning back in and bringing the legumes in, but we wanted to really control glycemic cycling.

Dr. Mark Hyman:
Well, the other thing you did by the way, the other thing you did by doing that diet and just clarify for people, getting rid of dairy, gluten, sugar, processed food.

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
Right? Grains and beans.

Dr. Kara Fitzgerald:
No alcohol, mm-hmm (affirmative).

Dr. Mark Hyman:
No alcohol, that’s exactly my 10-day detox diet which I use all the time to help people quickly recover from all problems. And the reason it works is not only because it contains all these nutrient dense phytochemicals and all the B vitamins and all this stuff that you’re talking about, but it also eliminates the inflammatory foods and inflammation is a cornerstone hallmark of aging. In fact, it’s often called inflammaging.

Dr. Kara Fitzgerald:
Yeah, that’s right.

Dr. Mark Hyman:
So you were doing a double whammy. You were power housing all these food as medicine compounds, at the same time you were taking away because I believe if you gave all that stuff and people were eating still in addition to that, a lot of processed foods or even gluten and dairy or sugar, it might not have worked.

Dr. Kara Fitzgerald:
Right, yup, yup. I think that’s a reasonable supposition and hopefully as we continue to investigate it, we’ll see, we’ll see, and we’ll be able to layer in individualization and all exciting stuff. But yeah, I think that’s possible. It’s like Sid Baker, right? Get rid, add this, get rid of this.

Dr. Mark Hyman:
Yeah, so basically diet you did, you did the greens powder and what else?

Dr. Kara Fitzgerald:
Yes. So, and so yeah, a little bit keto leaning, a little modest, very modest time restricted eating, just 12 hours on, 12 hours off. We didn’t want to make it onerous, and we also didn’t want to just study time restricted eating, but we wanted it to be doable for our participants. We had nutritionists meet with our participants weekly.

Dr. Kara Fitzgerald:
They didn’t cheer lead them, they had to read from a very stale script that was IRB-approved, but just basically do any questions, do you need recipes? Yeah, it was very structured what they were able to do, but I will say so when we first designed this study, Ryan over at Health Gut Institute was dubious that we would be able to have such a sophisticated multi-variable study really be successful and have it participant adherent, and I think that it was our nutritionists being there being present that was the difference in our success, and we do have adherence data that are very good.

Dr. Kara Fitzgerald:
And it’s something that we’ll need to write up on. But Mark, I was like, “This is my big chance to engage in clinical research.” This is going to be successful. These guys are sticking to it. And then the nutritionists has made that difference. And incidentally for folks who want that kind of support, we’ve got a digital platform that has the nutritionists we used in our study available and all other stuff to really have pull the branch down for folks who want that.

Dr. Kara Fitzgerald:
And that’s also where we’re going to continue to study it if anybody wants to participate in contributing their data to research. So that’s diet, and then we had other interventions, and this is where we need to think about in our world, we’re focused on the methylation cycle. Anybody who studies functional medicine knows biochemistry in an extraordinary way. And they know a lot about the methylation cycle, but when you get into the science, you will see that methylation is regulated by far more than whether we’ve got that little cycle is humming along.

Dr. Kara Fitzgerald:
So exercise, the data on exercise and methylation and specifically DNA methylation is extraordinary and exercise and biological age is extraordinary. And there’s a handful of things. So exercise is as a rule potently, anti-aging, but if we overdo exercising, then that can be pro-aging. And I talk about that side of handful of studies in the book there.

Dr. Kara Fitzgerald:
So we want to realistic amount of exercise. In our program, it was a modest and easy. We wanted it to be doable, we wanted people to adhere to it, and it was just 30 minutes, five days a week at a perceived exertion of 60 to 80% doing whatever they want to do. So it’s your perceived exertion of 60 to 80% which is going to be different than mine. 60% is going to be maybe a little bit of a light sweat.

Dr. Kara Fitzgerald:
Your breathing is increasing a little bit and then 80%, 20% more than that, 60%. So a little bit more, sweating a little bit more, heavy breathing, but you’re still able to have some level of a conversation and do whatever you want. Our participants, let me say, and I think this is another cool piece about our findings. Our participants were extremely healthy. They couldn’t be on medications or come in with diagnosed conditions, even high blood pressure.

Dr. Kara Fitzgerald:
We wanted to look at healthy men. We wanted to really study DNA methylation in healthy men. So in aging healthy men. So we were really isolating the influence of the aging journey. And I think that’s another cool piece of evidence for our findings. I think if you have a condition, if you’re diabetic or if you’ve got heart disease, et cetera, you’re aging faster and by extension, if you turn that around, you should have even more powerful age reversal.

Dr. Mark Hyman:
Yeah, right. So basically what you’re saying is you took healthy guys or healthy study participants that did have a chronic illness and you saw this massive change?

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
But actually, what I always say is if you don’t have a headache and aspirin doesn’t do anything. Right? So if you actually … I remember this patient Janice often talked about. She came into Cleveland Clinic in one of our group programs Functioning For Life. She was a BMI of 43 I think, which is a massive, she was just a massive woman, Type 2 diabetic, on insulin, heart failure, kidneys failing, liver failing, high blood pressure and tons of meds, stents, angio, cardiac disease, the whole thing.

Dr. Kara Fitzgerald:
Wow.

Dr. Mark Hyman:
In three days, three days she was off her insulin, three weeks, she was off all her medications, heart failure reversed, kidney failure reverse, diabetes was gone, A1C from 11 to five which is like our five and a half which is ridiculous, that never happens. If you get a drug that has a 1% drop in A1C, that’s like a “Hallelujah, this was a blockbuster drug.”

Dr. Mark Hyman:
We’re talking about not only a 1%, but a 6% reduction which is a logarithmic scale. So it’s a huge thing. And then a year she lost 116 pounds and reversed everything. Her biological age I’m sure went back 20 years, not three. So anyway, go ahead.

Dr. Kara Fitzgerald:
Yes, yes. That is awesome.

Dr. Mark Hyman:
So you did diet, you did exercise, you did the greens, what else was it? What else did you do?

Dr. Kara Fitzgerald:
We did. So we wanted our participants to sleep. So the data on sleep, it’s strong and specifically relating to DNA methylation. If you’re not sleeping, you’re aging. That’s really the bottom line now. And you’re walking out DNA methylation and this is strongest we can see in animals where you can actually dissect and take a look at what’s happening in the central nervous system and the damage to the neurons with just like one sleepless event.

Dr. Kara Fitzgerald:
It’s extraordinary how nourishing sleep is on genetic expression on DNA methylation specifically. But more broadly, we know poor sleep is the risk factor for all of the chronic diseases of aging. So we wanted our participants to get at least seven hours and they would … We gave them sleep tips and they would check in with the nutritionist as part of that structured IRB document that they would … The checklist.

Dr. Kara Fitzgerald:
So at least seven hours, exercise, we prescribed meditation. One of a massive aha for me, it is specifically relating to the clock that we used. We used the flagship Horvath … The first biological age clock on the map by Steve Horvath at UCLA, another Nobel prize to be winner because he’s changed the longevity field with his extraordinary work out of his laboratory.

Dr. Kara Fitzgerald:
So we used that original clock. There are second and third generation clocks now that have come out subsequent to our study, the field is galloping forward. And if you want to, we can talk about that, but it’s this original clock is still badass and it’s got the most science on it, and just loads of publications. It is 353 of these methylation sites are measured in it. A full 25% of those are associated with glucocorticoid response elements, meaning, they are driven by stress, driven by cortisol. So think about it, the biological age clock, 25% of it is driven by stress, isn’t that nuts? 25%.

Dr. Mark Hyman:
Yeah, so this is quite amazing what you’re saying. Let me slow down for a minute because you’re saying basically using these very expensive high tech interventions like eating better, sleeping, meditating, and walking, taking a green powder, right? And everybody is looking at these expensive drug trials and all these mechanisms, very intense interventions and you’re saying eat better, exercise a little, sleep better, relax. And basically, you can reverse your biological age.

Dr. Mark Hyman:
This is profound because it doesn’t even layer in to me all the things that we do in functional medicine that are about upgrading everything in a different way. Yes, this is just the foundational lifestyle factors, but we got a whole other toolkit to optimize the immune system and detoxification, the microbiome, and the mitochondria and on and on and on. So it’s just stunning.

Dr. Mark Hyman:
So tell us, when you start looking at what were the outcome measures, so we know what the intervention, what were the outcome measures? What did you find? And what are the things people looked at that actually that you saw this biological age change? So what were the primary and secondary outcome measures?

Dr. Kara Fitzgerald:
So we looked at quality of life changes, the subjective questionnaires which didn’t in this healthy population change appreciably. There was some trend towards more energy, et cetera, but really nothing much. But we wouldn’t expect a lot in this population like you would say in looking at some in a population with IBS or whatever.

Dr. Kara Fitzgerald:
Their cholesterol dropped, their LDL dropped, but again, they weren’t particularly hyperlipidemic, but they were just eating healthier, more fiber, triglycerides dropped which suggests to me that they … Were in fact keto-leaning. And so we did achieve that which was nice because we didn’t measure ketones. We didn’t change. So we looked at a host of methylation biomarkers, classic methylation biomarkers, homocysteine, adenosylmethionine, et cetera.

Dr. Kara Fitzgerald:
We didn’t change those appreciably. So that’s an interesting piece in our study. We changed where methylation was happening on the genome. We didn’t push methylation forward. We changed where it’s happening on the genome which I think is really cool. We moved it around, and so in this first publication and there’ll be subsequent publications to this.

Dr. Kara Fitzgerald:
We showed that as compared to the control group, the biological age clock reflected a biological age that was 3.24 years younger in our control group, in our study group at the end of eight weeks as compared to our control group and the within group comparison. So comparing study group to themselves at baseline, it was about two years younger.

Dr. Mark Hyman:
That’s amazing. So help us stand the idea of this biological age clock and how it’s measured, why we should care, why is it relevant? Why is this new idea that we can look at? We all knew that DNA methylation was a thing, but it’s not something you can like go to the lab and get a test for. Now, there’s a lot of companies offering diagnostic tests where you can actually measure by likely.

Dr. Mark Hyman:
So I’m actually doing this myself. I’m working on another book yep on longevity as well. And I word all the methylation kit, I’m going to do them and I’m going to implement all kinds of strategies that I’m going to retest it. I’m going to use myself as a guinea pig. But I think that it’s important for people understand what are these biological clocks? What is the biological age? How is it defined and how do people understand it better? Because what you showed through these interventions was this reversal and improvement in all these biomarkers, but what is it exactly?

Dr. Kara Fitzgerald:
Yeah, good question. Well, I’m going to just jump in and you’ll clarify and interrupt as needed.

Dr. Mark Hyman:
Sorry, I don’t mean to interrupt. I’m listening, I’m going, “I don’t think that everybody who’s listening is going to get that so I got to just slow this down a bit.”

Dr. Kara Fitzgerald:
I know, listen, I don’t say that facetiously at all. I’m completely cool with that. And you and I have been talking for many, many years now, so I’m completely cool with it and I know it’s complex. And so it really helps to have almost another set of eyes on what you’re saying, so I appreciate that. And I had somebody actually help me write the book who did a lot of this heavy lifting around the translation because that’s the hardest piece, expressing this content in a clear way.

Dr. Kara Fitzgerald:
So Steve Horvath, back in about 2013 or so was asked to take methylone data, all of these, the DNA methylation sites and figure out patterns that correlate with chronological age. So the first clocks were trained against chronological age. So from embryogenesis, so from pregnancy all the way up to centenarians, he had these massive data sets and he looked at methylation patterns and crunched huge numbers with big computers.

Dr. Kara Fitzgerald:
He’s a biostatistician and was able to fig pull out 353 methylation sites from these massive data sets that correlate with a 0.96 degree of accuracy with chronological age. So the first clocks are just like in lockstep, by comparison, telomeres correlate to about 0.4. And prior to the advent of DNA methylation, biological age clocks, telomeres were gold standard. And there’s still a place for telomeres, nobody’s getting rid of telomeres, but we’re thinking about them in a different lens.

Dr. Mark Hyman:
I did mine a few years ago and the time I think I was 58 or something, and my biological age was 39 on the telomeres. Does that-

Dr. Kara Fitzgerald:
Which I’ll take. I’m not going to argue with that.

Dr. Mark Hyman:
I’ll take it. I’ll take it. I’ll take it. I wish my gray hair would know that actually, but anyway [crosstalk 00:47:04].

Dr. Kara Fitzgerald:
Right, right, that’s right, all the wrinkles. Yeah, for sure.

Dr. Mark Hyman:
But you’re saying this is actually a better marker and it’s more accurate?

Dr. Kara Fitzgerald:
Oh yeah, its changed, it’s changed the face, the field of bio gerontology. Yeah, having these markers of biological age are … They’re just going to transform science. I think we already see that my study, people going forward and doing nutritional research are probably going to try to get epigenetic data in there now, hopefully going forward, but I think in general with these clocks and the next generation clocks, yes, they’re extraordinary.

Dr. Mark Hyman:
So what is it actually measuring?

Dr. Kara Fitzgerald:
So that’s what he was able … Yeah, so the pattern of methylation on certain genes changes predictably, predictably over time. So in utero, there’s a pattern that’s consistent with a negative age. I guess you’re not born yet. And then obviously it goes up, orders, the magnitude and change structure, and when you’re a centenarian plus. So there’s just these predictable, reliable changes that correlate with chronological age.

Dr. Kara Fitzgerald:
What’s interesting though is that in this very first clock, it’s a better predictor of health and mortality than chronological age itself. So very early on in the biological clock journey, the DNA methylation biological clock journey, we could see that they were better predictors of health outcome very early on, and that’s only improved and grown and become more robust and more insightful.

Dr. Kara Fitzgerald:
It’s interesting, there’s a DNA methylation telomere clock, so it’s looking at the DNA methylation expression on telomere. It’s actually more reliable than directly measuring telomere. So we can see DNA methylation patterns are more reliable of around biological age in your health and your longevity potential than your chronological age. So it’s really a new era of science, and I want to say another thing.

Dr. Kara Fitzgerald:
So after that, your thinking could logically be, “Well, these are surrogate markers of biological aging, these are surrogate markers of another process happening of the inflammation or the hallmarks of aging, the loss of DNA patency or the loss of antioxidants or the increase in inflammation, et cetera, the whole hallmarks of aging.”

Dr. Kara Fitzgerald:
So you might think they’re surrogate, but research I think is starting to suggest especially out of Sinclair’s lab at Harvard that they’re not just suggestive of aging, that DNA methylation patterns are probably fundamental to actually driving aging. So and that is another cool thing for us because we put our eggs in the DNA methylation basket. We really want to change that.

Dr. Kara Fitzgerald:
So two studies out of Sinclair’s lab that are extraordinary. The first one is looking at an age associated optic neuropathy in a mouse model. And so they created this age associated optic neuropathy by damaging DNA methylation. I think that’s how they initiated it, doesn’t matter, but the way that they were able to restore vision and reverse aging in the optic neurons was by changing DNA methylation and demethylation.

Dr. Mark Hyman:
It just sounds biblical. You make the blind to see, right?

Dr. Kara Fitzgerald:
Yeah.

Dr. Mark Hyman:
You take a mouse and blind them, and then you give a bunch of stuff that is pretty, pretty simple and cheap. And then you bring back their vision like Jesus.

Dr. Kara Fitzgerald:
Yes,. So they used something called Yamanaka factors, they used three of the four.

Dr. Mark Hyman:
Yes.

Dr. Kara Fitzgerald:
Yamanaka factors are famous because, well, Yamanaka and actually one other guy.

Dr. Mark Hyman:
The Japanese doctor, scientist.

Dr. Kara Fitzgerald:
Yup. He discovered them and they did get the Nobel, but he had and the co-discover, the co-scientist in that. Anyway, Yamanaka factors change methylation. And in so doing, you can take a somatic cell and just turn it back into a defined cell and turn it back into a pluripotent stem cell. So you can take cell X, a brain cell or whatever, and douse it with some Yamanaka factors and bring it all the way back to an undefined stem cell, and they do that by [crosstalk 00:51:54].

Dr. Mark Hyman:
Which then can become anything?

Dr. Kara Fitzgerald:
Then can go on, yes. So that brain cell [crosstalk 00:51:58].

Dr. Mark Hyman:
It’s like a super power, superhero trick. Imagine like taking a person and then completely reversing them to their embryo and then restarting again to become another person, it’s pretty freaking cool.

Dr. Kara Fitzgerald:
It’s crazy, yeah, it’s crazy. If you think about it too much, yeah, it’s nuts. I see a person and then they’re like a little puddle of booze on a chair, I don’t know. It’s weird. Yeah, you’re back to a pluripotent state. Yeah, you’re an undefined entity.

Dr. Mark Hyman:
And pluripotent means you get to be anything you want?

Dr. Kara Fitzgerald:
That’s right.

Dr. Mark Hyman:
If you’re a pluripotent cell, you can be a skin cell, an eye cell, a brain cell, a heart cell, that’s what that means?

Dr. Kara Fitzgerald:
Yeah, that’s right. Oh my God. Anyway, so they used three of the four in this study and they restored the neurons to a younger state and they also restored vision in the study, it’s amazing. And they did it by specifically changing epigenetic expression and DNA methylation in particular. Then in 2021, they published another study looking at aging in general, exploring the Genesis of aging in general and a mouse model and reversing that, and it was the same thing.

Dr. Kara Fitzgerald:
So aging is as they outline in epigenetic dysregulation, and they reversed aging again using Yamanaka factor. So they went from an optic neuropathy model to just aging in general and analyzed it and reversed it, again, using three of the four Yamanaka factors. And what they said in their paper is that we all retain a youthful epigenetic pattern on our epigenome, and we can uncover that, yeah.

Dr. Mark Hyman:
Okay, wait a minute, wait a minute. So what you’re saying is there’s a younger you locked inside of you?

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
And you have to unlock it? And this is where the science of aging and longevity is going. We’re learning how to actually create a younger you that’s already there locked inside of you ready to come out if you take away the crap and put in the good stuff?

Dr. Kara Fitzgerald:
Yes, isn’t that amazing?

Dr. Mark Hyman:
It is pretty cool.

Dr. Kara Fitzgerald:
That’s tingly, right? It’s extraordinary.

Dr. Mark Hyman:
I’m so excited about it because I’m 62. So I’m way more interested than I was 10 years ago.

Dr. Kara Fitzgerald:
I know, I know. I am too. Well, I became a mom, I’m 54 and I became a mom at 50.

Dr. Mark Hyman:
No you’re not, come on. You’re not.

Dr. Kara Fitzgerald:
I am, I’m 54.

Dr. Mark Hyman:
What? No way. Oh my God. I thought you were like 35, maybe 40. Okay. You are ageless, you look no different than when I met you 20 years ago, really?

Dr. Kara Fitzgerald:
Well, I need glasses now though. Well, I needed glasses then, but not as [crosstalk 00:54:36].

Dr. Mark Hyman:
Well, maybe I do too, that’s why [crosstalk 00:54:37].

Dr. Kara Fitzgerald:
Yeah, that’s right. That’s why I look so good.

Dr. Mark Hyman:
Anyway, let’s keep going. So I’m still not quite sure about this biological clock thing. What is the test actually measuring? It’s measuring where the methyl groups are on the genes and how does it know how old you are based on those methylation texts?

Dr. Kara Fitzgerald:
Because you know what? You need to just get Horvath on your podcast or you need to just get a biostatistician on your podcast because there are predictable [crosstalk 00:55:03].

Dr. Mark Hyman:
Okay, introduce me to him. I want to have a, yeah.

Dr. Kara Fitzgerald:
Okay, okay, okay. Because there are predictable changes that happened with biological age. So I’ve got my methylation sites at 54 on 1221 and 72 and yours are on 1613. There are predictable changes that happen over time. I love it. We were talking at the beginning how you were pelting me with these same questions and my very first lecture, I think, as a newly minted physician, I did a lunch and learn at a conference at an IFM conference, and you were pelting me with these same questions. It’s great.

Dr. Kara Fitzgerald:
It’s a great question, and I think the answer is a bio statistical one about just the predictable pattern changes. Let me tell you this. When we did our study, we had extra kits left over. The kits by the way back then were, this was just a few years ago, were over a thousand dollars per on discount, but we had a couple kits left over. And so we gathered them here and I got my Isabella who was two at the time, and her epigenome was wildly different.

Dr. Kara Fitzgerald:
And it’s just a bunch of numbers on this massive, massive, insane spreadsheet. But when you crunch those numbers and you can look at it, she’s got the epigenome of a two year old at that time, it’s really cool. Everybody else is an adult, and it’s just glaringly different.

Dr. Mark Hyman:
Very cool. So taking all the conclusions from your study, how can you advise people to optimize their epigenome? What are the things we can do practically? Because this is really awesome science. And encourage people we’re going to have in the show notes, we’re going to have a link to the study, Kara’s new book, Younger You, we’re going to provide all that and also various ways to access her subjective, biological aging questionnaire, how to get the methylation test. All that’s going to be there. But tell us in a nutshell what are the take homes for people around? How do we live to optimize our epigenome and hence reverse our biological age?

Dr. Kara Fitzgerald:
So for those of us who are adults and are wanting to remain optimal or a teen, an optimal biological age, we want to be dousing our DNA methylation with the nutrients that needs to perform optimally. And I would argue that it’s our diet or some variation of our diet which layers well with anything actually.

Dr. Kara Fitzgerald:
You can make a keto if you want to, you can make it phone map friendly and whatever you need to do, take the fundamental principles of what we figured out and layer them in to whatever it is you’re doing. And if you’re an Uber biohacker who’s doing growth hormone injections and not Greg Fay’s next study, awesome. Layer these principles into what you’re eating because you still need to consume calories. Just layer these principles in.

Dr. Kara Fitzgerald:
Take stress seriously and the pro-aging effect of stress which is … Stress is gasoline on the aging fire and take that seriously and take some time out. There are a lot of amazing apps out there. I love the Healthy Minds app out of University of Wisconsin and I just use it all the time. They have these micro meditations you can just pop on your phone and take a couple of breaths and bring yourself down a notch, that’s an anti-aging intervention right there.

Dr. Kara Fitzgerald:
Have some green tea, have some curcumin, all of those polyphenols you know and love, they are important. And they’re probably epigenetically active. In the back of the book I have this massive nutrient appendix of epinutrients and you can … It lists the polyphenol and then it lists the foods that they’re found in. And all of us can go in there and eat a ton of those every day. It’s doable.

Dr. Mark Hyman:
Amazing.

Dr. Kara Fitzgerald:
So I would take it seriously, and the other piece in our book Mark that I think is important is that we talk about epigenetic changes through of the lifespan. And I tweak the diet a little bit around some of those thoughts. So for instance, because pregnancy is so important, actually in pre-pregnancy and conception, and we talked about the heritability potential, we want to be thinking about these.

Dr. Kara Fitzgerald:
So not just as an anti-aging intervention, but if you’re going to be conceiving, men are on this hot seat as well. This is not in a women’s domain. This is where we see the impact of a man’s epigenome on offspring right here in DNA methylation patterns. You want to be adopting these principles. I created a Younger You hybrid is what I’m calling in the book because I would’ve felt remiss if I didn’t give preconception and pregnancy and postpartum and … Here’s what you can do.

Dr. Kara Fitzgerald:
You bump up this nutrient, continue with this, it’s more protein, there’s more carbs, there’s actually more calories in general. But all of that is in there. And when we’re in … So in infancy, so the data and infancy and early infancy, there is quite a bit on needing cuddling. There’s no time, obviously we don’t need cuddling, but in terms of epigenetic expression, early infancy is a big deal.

Dr. Kara Fitzgerald:
And I talk about some of the science there and we want to be nourishing our children’s epigenome at those times. And I talk about the research actually through the lifespan and it’s cool, like boy.

Dr. Mark Hyman:
How do I get in, how do I get in the randomized controlled trial on cuddling? Because I want to be in that study.

Dr. Kara Fitzgerald:
I know, I know, I know. Cuddling community, it’s so funny. It’s important. It’s just really important. If there was one additional piece in this study that I would’ve put in if I could’ve, that would’ve been a community element and we’ll build that out in the app. Yeah, you know that. You guys published on that.

Dr. Mark Hyman:
We call that sociogenomics yeah. Sociogenomics I call it. How our social interactions and regulator genes, right.

Dr. Kara Fitzgerald:
Yes. It’s a big deal. It is, and that’s heritable.

Dr. Mark Hyman:
So eat your medicine, exercise a little, don’t stress too much and do a lot of cuddling, that’s basically what you’re saying.

Dr. Kara Fitzgerald:
Yeah, yeah.

Dr. Mark Hyman:
And I think this is great, this is such great advice. I also think that there is another layer of sophistication that you haven’t even touched on in this study, and I think it was really smart to do the basics first, but I can imagine designing a study where you layer in a real functional medicine approach, looking at all the biological systems in the body, optimizing for each of them, and then checking on what happens?

Dr. Mark Hyman:
How do you optimize your microbiome? Your hormone balance and all these. The lifestyle factors do regulate all those things, but there’s also supplements. There’s also different kinds of exercises, all kinds of stuff that you can do that’s to regulate those. And I think that’s going to even show a bigger reversal.

Dr. Kara Fitzgerald:
Yes, that’s right.

Dr. Mark Hyman:
And by the way, for people that are listening, all three years, what’s the big deal? Blah-blah-blah. If we eliminated cancer from the face of the planet, our life expectancy would go up two years. If we eliminated heart disease, I think it would maybe go up three years. So you’re talking about that’s a staggering result in a study.

Dr. Mark Hyman:
So I really applaud you in eight weeks, in eight weeks. You spend 50 years screwing up your system and the body is so freaking smart that in eight weeks, you can literally reverse the damage that you’ve done on your whole freaking life on your biology. Imagine if you just started early and kept going where we’re headed. I just think we’re in this exciting moment around aging longevity and your work is so important in that. I really congratulate you.

Dr. Kara Fitzgerald:
Can I give a statistic? I know we need to wrap up, but let me just get this because what you just said about cancer just prompted me thinking about again, Sinclair. He published with some colleagues a work looking at the economics of biological age reversal. So we always silo ourselves in research and we focus on cancer and we focus on heart disease, and there’s an argument, a logical argument for risk, just really putting biological age at the front and center because it is the biggest risk factor for all of these chronic diseases.

Dr. Kara Fitzgerald:
So if we lower biological age by extension, we’re lowering risk of all of the diseases of aging. I want to for that a big time. And also say that when you look at DNA methylation patterns, just like I started this conversation thinking about cancer, well, it turns out the cancer epigenome looks very similar to the aging epigenome to the cardiovascular disease epigenome to the dementia epigenome.

Dr. Kara Fitzgerald:
So when you correct it together and you lower biological age and by extension you’re reducing risk, but so they did this study crunching economics. And if we were to improve lifespan by just a mere year, one year, they estimate that to be a 38 trillion savings. And if 10 years in order of magnitude more, $380 trillion. So the cost savings are staggering.

Dr. Mark Hyman:
But it’s counterintuitive, right? You think people are going to live longer, they’re going to be a bigger burden, it’s going to be more social security, more Medicare, more, all the expenses are not working, they’re not productive. How does that work? Because it’s just intuitively it seems like the opposite.

Dr. Kara Fitzgerald:
Well, we’re going to be like Betty White, we’re going to just leave this beautiful, healthy. So we’re going to have health longevity and pass gracefully and simply.

Dr. Mark Hyman:
So in other words, yeah, I think that’s really important point. So the data’s really there. We learned about this from Jeff Plain years and years ago. James Freeze from Stanford did a very seminal study where he looked at what we called a very few simple lifestyle doctors and how they influence our longevity and death.

Dr. Mark Hyman:
And what they found was that if you exercised, if you didn’t smoke and if you kept your ideal body weight, super simple, those three things, and you follow those people, the ones who exercised, ideal body weight, didn’t smoke, they lived long healthy lives and then dropped dead’s. The people who didn’t follow those three parameters actually had long, slow declines and died early painful, expensive deaths where the people who died older, died cheaply, painlessly, and quickly, right?

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
They went from, I’m like, “Okay, I’m having dinner with everybody.” Jeff Bland tells a story, I think his mother or grandfather, or some grandfather or something, he’s like, they all had like Thanksgiving dinner. He’s like, “Oh, it’s been a great ride with you all. I love you all. I’m going out, I’ll see you later.” And he literally went to bed and didn’t wake up. And that was it, he knew he was going, he was like, “I’m done.” And he literally was fine, had dinner. And like, “I’m always over. I’m checking out.” And that was it. I was like, “That’s just amazing. That’s how I want to go.”

Dr. Kara Fitzgerald:
Yeah, absolutely, absolutely. In this country, we are aging fast, we’re actually aging faster than other Western countries. The last 16 years, here’s some horror statistics. The last 16 years on average in this country are spent with at least one diagnosis, and most of us have two, polypharmacy. We’re giving all of our money to pharmacies, to skilled nursing facilities, we’re giving all of our money to hospitals and our family members are taxed with the burden of the shell of us living these really poor quality existence, and we have the power to change that. So we need to, it’s an imperative.

Dr. Mark Hyman:
It’s so true. David Sinclair who wrote Lifespan is one of the leading researchers in longevity, and you mentioned him earlier. I know him, he’s a great guy. And essentially, he said that aging is not what we think it is at this normal process that proceeds until we die, that it’s actually a disease. And that we don’t understand the fact that all the chronic diseases that we see that we treat in silos, heart disease, cancer, diabetes, dementia, et cetera, et cetera, they’re all reflections of underlying problems in our biology dysfunction in our biology that is actually in embedded in a certain root causes around lifestyle, environment and so forth.

Dr. Mark Hyman:
And what you did was you addressed those root causes and worked way upstream so you don’t actually have to find the cure for cancer or heart disease or diabetes or Alzheimer’s. That is just a dumbass way to go about it.

Dr. Kara Fitzgerald:
Yes. Yes.

Dr. Mark Hyman:
Look at the upstream mechanisms, and I think this is a breakthrough idea that aging is actually a disease that we need to think about as a dysfunction that we can correct, and that’s what you did in your study. And I think that’s what’s going to change the face of this and not allow us to continue in this dumb, siloed way.

Dr. Mark Hyman:
And even the hallmarks of aging which are talked about as the root causes of aging, the hallmarks of aging. Inflammation, oxidative stress, epigenetic changes, mitochondrial dysfunction, on and on, insulin resistance. They’re downstream. And so, “Oh, this is the root cause of aging.” No, these are upstream from the diseases.

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
But what’s upstream to the hallmarks of aging, right?

Dr. Kara Fitzgerald:
Yes.

Dr. Mark Hyman:
That’s where functional medicine comes in because it actually helps us to understand the biological networks that are driving these hallmarks of aging. What causes mitochondrial dysfunction? What causes inflammation? What causes alterations in the microbiome? What causes hormonal dysregulation? What causes epigenetic changes? That’s what’s interesting to me, and that’s really what your work is doing.

Dr. Kara Fitzgerald:
That’s right, that’s right. And I would say that this is just such an important area. This is the tussle right here. I think we want to be putting attention towards addressing those epigenetic imbalances and that … There’s a debate in field of biogerontology now whether aging is a programed event, a programmed evolutionary event into the epigenome.

Dr. Kara Fitzgerald:
And I think it’s a possibility. Obviously, we do have the weight of environment and our lifestyle choices, et cetera, but we’ve got a predictable lifespan. The healthy of us, the healthiest among us, generally aren’t going to go past 120 years. So there’s something … Anyway, it’s an interesting next generation conversation in the longevity space.

Dr. Mark Hyman:
It is because people are talking about longevity escape velocity which means we live long enough and enough advances will happen understanding of aging science that we can apply those concepts and actually escape death. Now, I’m not so sure that’s true, but it’s a fascinating idea.

Dr. Kara Fitzgerald:
That’s a conversation, that’s a big [crosstalk 01:10:08].

Dr. Mark Hyman:
Very prominent scientists are having this like George Church or Harvard and others, so it’s very cool. Well, Kara, this is so fantastic. You are doing such important work. I am so glad that you’ve taken this to the next level. Everybody should go out and get a copy of Younger You, Reverse Your Bio Age and Live Longer. You’ve got an online community, go to Younger You Universe. You can go on your website, which is tell us where to go to find all that stuff.

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

Dr. Mark Hyman:
Oh Kara, I learned so much today. I hope you all out there learned a lot. This is a game changing study and your book is really fantastic. So thank you for the work you’re doing. Everybody listening, if you love this podcast, please share it with your friends and family and social media or everywhere else you want to share it. Subscribe where you get your podcast and leave a comment. What did you learn? What excites you? What have you done to reverse your biological age? Tell us about it, and please, come next week and we’ll see you there on The Doctor’s Farmacy for another episode.
Speaker 1:
Hi everyone, I hope you enjoyed this week’s episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services.
Speaker 1:
If you’re looking for help in your journey, seek out a qualified medical practitioner. If you’re looking for a functional medicine practitioner, you can visit ifm.org and search their find a practitioner database. It’s important that you have someone in your corner who’s trained, who’s a licensed healthcare practitioner and can help you make changes, especially when it comes to your health.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

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