← Tom Bilyeu's Impact Theory
Tom Bilyeu's Impact Theory
Reduce Your Biological Age, and Live A Longer & Better life | Kara Fitzgerald (Replay)
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- [00:00]
VRBO Narrator
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Dr. Kara Fitzgerald
If the listing says heated pool, but there's actually no pool to heat.
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VRBO Narrator
Definitely a verbocare thing.
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Grainger Narrator
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VRBO Narrator
instead of mom, that's a family thing. Leslie.
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Grainger Narrator
That makes sense.
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Dr. Kara Fitzgerald
Sorry.
- [00:22]
VRBO Narrator
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Grainger Narrator
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Dr. Kara Fitzgerald
People who meditate regularly are biologically younger. People who meditate regularly are biologically younger. But just one meditation experience can still have favorable influence.
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Host (possibly a health podcast host)
Doctor Kara Fitzgerald, welcome to the show.
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Dr. Kara Fitzgerald
Thank you. I am thrilled to be here.
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Host (possibly a health podcast host)
I'm really excited to have you. You are dealing with an area that I have become absolute obsessed with, which. So methylation, which we'll explain to people what that is in a minute. But the idea of my epigenome is really controlling how my genetics express themselves, and that becomes really important. That had been on my radar for a long time, but I couldn't imagine what was actually happening. And so your book is called Younger you, which phenomenal book.
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Dr. Kara Fitzgerald
Thank you.
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Host (possibly a health podcast host)
And it really goes into detail on this idea of what methylation is. And I think even though, like, for anybody hearing that for the first time, I promise we're going to bring you in, you're going to love it by the end of this, and you will understand why it matters. But walk us through what I'll call the three layers. Genetics, epigenetics, and then what methylation is and what brings them all together.
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Dr. Kara Fitzgerald
Yeah, for sure. So, you know, genetic. Our genetic material is static. It's not changing. We inherit some from mom and some from dad, and it's kind of packaged relatively carefully and it doesn't change, you know.
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Host (possibly a health podcast host)
And can you explain the packaging part? That's where this all starts to get interesting. And people that know it well sort of throw that one off the cuff. How. How is one's DNA, which I assume is what you mean packaged.
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Dr. Kara Fitzgerald
Yeah, well, I mean, we have a lot of it. You know, if we end to end, I think it, what, wraps around the world twice. If we did like all, if we spread it all out from all of
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Host (possibly a health podcast host)
our cells, one single strand of DNA,
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Dr. Kara Fitzgerald
each strand within a cell is about six feet. It's, I mean, it's a ton. It's like, it's, you know, but it's, it's, it's microscopic. We have to wrap it up extraordinarily carefully to fit it into a cell. I mean, it's just, it's mind boggling. And so then, so it's wrapped around proteins called histones. And then histones are grouped in four. So there's just wrap, wrap, wrap, rap, rap, grouped in four. And these little groups of four are nucleosomes. And then they're packaged together in what's called a chromatin and then ultimately a chromosome. What's extraordinary is that wrapping helps regulate. So this is the epigenetics that you're talking about. So we need to open it to allow a given gene to be expressed and then we kind of wrap it and tuck it back in or we keep it on. And so again, gene, DNA, genetics, epi, above the gene. So it's all of these variables that go into allowing genes to turn on and turn off. It's all of the, all of the biochemical marks or imprints, whatever you want to call them. And there's, you know, many of them, 100 plus that are working together, engaged in allowing genes to be on and off.
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Host (possibly a health podcast host)
And is it the sirtuins that are doing the actual reading of the DNA and putting the methylation markers on the DNA, Is that what does that.
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Dr. Kara Fitzgerald
No, the methylation markers are placed down on the cytosine nucleotide using DNA methyltransferase. And then it's. And there's a family of DNA methyltransferase enzymes that will do it at different times. I mean, I think this is where we can get in and have our lifestyle actually influence what happens during cell division.
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Host (possibly a health podcast host)
All right, so to bring this back up a level for people that probably now feel like I've drugged them down in the weeds too much. So what became really interesting for me is to, okay, we've got this careful packaging of the DNA and the way that we express or fail to express a gene within our DNA is by wrapping it. So essentially hiding it and saying, don't read this. And in your book, you said something really interesting, which is that if the DNA are the language of our genetics, the methylation is the punctuation. And so it says, stop reading here. Line break. This is a new paragraph. So this is an eye cell, this is a heart cell, this is a skin cell. And oh, by the way, you're in the eye. So eye cell, express yourself. And so you've got all of that in one sort of. Without methylation would be one run on sentence.
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Dr. Kara Fitzgerald
Yeah, that's right.
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Host (possibly a health podcast host)
And so the methylation goes in and says.
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Dr. Kara Fitzgerald
And God knows what would be turned on. Yeah, it would just be a big mess. And we think that this big mess is part of the aging journey.
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Host (possibly a health podcast host)
But yes, that you begin losing your punctuation.
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Dr. Kara Fitzgerald
Yeah, and now I' or it's distorted. It's not where it's supposed to be.
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Host (possibly a health podcast host)
The word is misspelled or out of place in the wrong paragraph. See, that's really helpful for me. So once I had that paradigm, that understanding of, okay, the DNA says your eye should be this big versus my eye is a different size. My heart cell functions like this, yours functions like that. So we each have our own way that all of this is going to express. Like you said, half from mom, half from dad. But then over the process of aging, that gets. Oh, I forget the word wonky. It goes wonky, I think to use the word that you often use. Yeah, my scientific word is wonky. So that begins to break down. When it's breaking down, what exactly is happening? The methylation marks are literally just missing.
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Dr. Kara Fitzgerald
So a few things are happening. And that's an awesome question. I think mechanistically, we have some idea, but why it's happening is a really hot topic right now in the scientific community. So when you look at the epigenome of a younger individual as compared to an older individual, it's fascinating. Like, genes that are on in youth are inhibited in age. And it tends to be that genes that are helpful and beneficial are on in youth. And then genes that are actually. And those same genes are turned off in age. But it's predictable across all of us. I mean, you can't avoid these changes. I think we're working on it right now.
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Host (possibly a health podcast host)
So we can't avoid them yet, right?
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Dr. Kara Fitzgerald
That's right. We can't avoid it. Well, and we're starting to learn. I mean, this is what I wrote about. We're starting to learn. You know, lifestyle interventions that can help prevent the extent of the breakdown and
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Host (possibly a health podcast host)
rewind them in some cases.
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Dr. Kara Fitzgerald
Yeah, that's right. That's Right. As looking at the biological age clock. So the question, I think, is, with this predictability, is it just damage from wear and tear in life, or is there some sort of a programmed element to this that's driving the aging journey?
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Host (possibly a health podcast host)
Are we programmed to die?
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Dr. Kara Fitzgerald
Exactly. Which is as predictable and sort of elegant in its structure as, you know, developing a human during embryogenesis or early infancy, when we're. When, you know, infants are just aging at this accelerated price. They're like superhumans. You know, I have a toddler at home, and actually she's turning four, but so she's moving out, but. But just watching her. So thinking epigenetically and watching my kid, you know, when she was an infant, sort of heal. Like you can see her skin knitting before. Before your eyes. I mean, it's. Or her learning new language, or her going from sitting to standing to walking. I mean, it's all happening at this record pace. And this developmental. This accelerated developmental place is part of her epigenetic journey. It's part of her aging journey. And that changes over time. And then we hit maturation and sexual maturation, puberty, et cetera. And then women hit pre menopause and peri. And post and on and on. And all these are driven epigenetically. And then we've got this aging phenomena where things break down, where we're at risk of developing cancer and dementia and cardiovascular disease and diabetes, et cetera. And when you look at the epigenome, it looks like it's programmed in there. It's something that all of us thinking about it would like to change and have some control over.
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Host (possibly a health podcast host)
Yeah, so that's a really interesting blend of the philosophy and the science. So if we are pre programmed to die, what are the markers that do that? So I really want to understand this, the. The idea of methylation. So I'm realizing now as I'm formulating this question that I have created an image in my head of like a dollop of glue, basically, that just says, you know, stop. Here one is. Is that what it looks like? Because your book goes into this idea very extensively of methyl donors. So things that you eat that generate. They're building blocks of the goop as I'm imagining it, that creates the ability for the body to put those markers. So you have material needed to put markers, and then you have the placing of the markers in a way that promotes longevity versus dying. So help me understand those two elements. So what is it that gives us the methylation? And then what. In this paradigm where we assume it's pre programmed, even if we're just doing a thought experiment right now.
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Dr. Kara Fitzgerald
Yeah.
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Host (possibly a health podcast host)
Where does it get moved from and to. That begins this experience of aging.
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Dr. Kara Fitzgerald
So methylation. There are hundreds of methyltransferase enzymes. These guys are putting a methylation.
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Host (possibly a health podcast host)
Methylation is a whole bunch of different
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Dr. Kara Fitzgerald
things, like a lot. It's a carbon and three hydrogens. They're ubiquitous in nature. And our body just, you know, we evolved using methyl groups for a lot of things, a lot of really important stuff.
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Host (possibly a health podcast host)
The same at the molecular level. How do they end up being so many different things?
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Dr. Kara Fitzgerald
Well, it depends on what enzyme is using it. So there's a methylation cycle that's worrying in our body all of the time. And this is where we're using B12 and folate and betaine and choline, et cetera, to produce the universal methyl donor. So this is a cofactor, this works with the enzyme and it's called S adenosylmethionine. Methylation cycle is worrying our body. And incidentally, we become less effective at this as we age for a variety of reasons. And we can talk about that. And secondarily, global hypomethylation of the epigenome is actually, is a phenomenon. So if you were to weigh, if you were to weigh all the methyl groups on our DNA, you know, in an aging individual, as opposed to a young individual, they'll have less, a net less.
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Host (possibly a health podcast host)
So globally they're just producing less less. And therefore it's being used on. And one thing, correct me if I'm wrong. Methylation is used to repair DNA. So if it breaks and it broke somewhere where now a missing piece of punctuation is gone, I need to re. Methylate that to say, oh yeah, remember you're an eye cell. So I need to hide.
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Dr. Kara Fitzgerald
Yes, we do in part, yes. And the folate cycle, which is part of the methylation group, gets in there and helps with DNA repair too. There's a lot of, there's a lot of pieces in the DNA repair puzzle. So methylation cycle is always worrying along. We're making this cofactor, CME we call it. And then CME works with the methyltransferase enzymes, all the hundreds of them in the body. And my focus has been DNA methylation. And so CME is used there. So we want to keep this methylation cycle worrying efficiently all the time at any level. Like my kiddo, my toddler, she needs to be accessing loads of methyl groups as well. I mean, this is one of the reasons that we Prescribe folate during pregnancy, you know, and even preconception, like, we really want to be thinking about making sure this is happening. So methylation needs to be moving forward. But we don't. And we'll talk about this. We don't necessarily just want to throw a ton of vitamins at it. You know, we would have already discovered the fountain of youth. Right. If that was going to be successful, we could just take a ton of folate and be 12.
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Host (possibly a health podcast host)
And the reason that we even connect those ideas is because the vitamins are the precursor that allows.
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Dr. Kara Fitzgerald
Yeah, but we want to eat these in our food and in some cases take vitamins. So we want to be thinking about the methyl donor cycle. We want to make sure we've got enough Sam. We want to make sure methylation is happening, and we do that just keeping our methylation cycle humming. And then on the other hand, we want to work on directing where those methyl groups are going. And that is what we think may be the role of polyphenols of the.
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Host (possibly a health podcast host)
What you get from plants.
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Dr. Kara Fitzgerald
Yeah, that's right. They seem to influence the DNA methyltransferase enzymes and perhaps support placement of methyl groups where we want them to.
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Host (possibly a health podcast host)
Just put a point on that for a second. So from an evolutionary standpoint, we have evolved to eat plants, and the idea of thinking of these as signaling molecules, I think becomes very important. So literally, it gets inside your body and it will say. So I've heard it referred to as nutrition partitioning. So it's like nutrient partitioning. So, hey, I'm a traffic cop, right? So I'm saying you go here, you go over here. But it's something I eat. Is it that. It's the presence of certain polyphenols tells my body to do. The direction or the mere presence of those polyphenols do they make. Do polyphenols make it into my bloodstream?
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Dr. Kara Fitzgerald
They influence the behavior of the enzyme. So going back to the DNA method,
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Host (possibly a health podcast host)
polyphenols in my bloodstream.
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Dr. Kara Fitzgerald
Yeah, they should be. Yeah, some of them would be measurable. Yeah, I mean, some of them are transformed by our, Our. Our microbiome and they become secondary compounds. But yeah, it's so weird.
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Host (possibly a health podcast host)
This is so complicated. This is like some alien invasion type stuff. That's really funny, but really, like, the more I'm beginning to understand it, and trust me, I am well aware my knowledge is so surface compared to yours. But the more I understand this, the more I'm like, God, man, this is like really intricate. And because it's so Intricate and complicated. I'm really surprised that what I eat can have such a profound impact. In fact, I want to give people one of the punchlines of the book. You did an eight week intervention which is like a blip, a blip that's so short. And in eight weeks you were able to get people to see on what they call the Horvath clock, which is a clock of biological age to go backwards three years.
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Dr. Kara Fitzgerald
Yes.
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Host (possibly a health podcast host)
Just insanity. In eight weeks, just based. Did you. I can't remember. Exercise was part of it.
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Dr. Kara Fitzgerald
Yes.
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Host (possibly a health podcast host)
So it was diet and exercise, a
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Dr. Kara Fitzgerald
modest exercise, prescription meditation twice daily, 10 minutes minimum diet. We gave them additional greens powder, some more of those polyphenols, we gave them a probiotic and we wanted them to sleep well, so we focused on sleep hygiene as well. So those five variables we worked with,
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Host (possibly a health podcast host)
that's so bananas to me. And so oftentimes I'll have a conversation with somebody before the camera starts rolling and then we'll hit on something so interesting. I'm like, you know, we should say that on camera. And that's when we'll start. You said I should be testing all of my internal biological markers because I do all this weird stuff. Whether it's cold exposure and you're commit.
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Dr. Kara Fitzgerald
I mean, you do it.
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Host (possibly a health podcast host)
Yes, I do. The reason that I haven't is one time, like if somebody would just show up at my house and draw blood or whatever, I would do it, like no problem. And then the other is I have one really bad strategy and that's I am, I am always trying to ask how much stress can I endure. And so when I think about longevity, I know, like I don't drink, I don't smoke, I don't do drugs, but I do stress.
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Dr. Kara Fitzgerald
Yeah.
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Host (possibly a health podcast host)
And so I'm a little worried about what my Horvath clock is going to be.
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Dr. Kara Fitzgerald
So you haven't done your biological age yet.
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Host (possibly a health podcast host)
I haven't. I do want to. And admittedly it is the friction of having to leave. But if I wasn't worried about the answer, I would have gone out of my way to figure it out. But stress does concern me and I steer by how well I sleep. And so when I get into a period where my. Because I never set an alarm, literally. I mean, if I had a 4am flight, I would set an alarm. But barring that. Yeah, I wake up when I wake up.
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Dr. Kara Fitzgerald
Yes.
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Host (possibly a health podcast host)
But as I get stressed or excited, my sleep will reduce.
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Dr. Kara Fitzgerald
Sure.
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Host (possibly a health podcast host)
And so I'm always a little, especially right now, I am, I am really going hard at this particular moment.
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Dr. Kara Fitzgerald
Yeah.
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Host (possibly a health podcast host)
And so I'm a wee bit.
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Dr. Kara Fitzgerald
Are you meditating though? Like what?
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Host (possibly a health podcast host)
Yeah.
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Dr. Kara Fitzgerald
You do?
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Host (possibly a health podcast host)
Yeah. I don't like when they say if you don't have five minutes to meditate, you're the person who most needs meditation. Yes, I believe in that. So aggressively that. Yeah, I meditate even. In fact, I meditate more in my hyper stressful periods than I do when my life is more even keel because I am so aware one quality of life is so hugely impacted by meditation and then two my performances.
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Dr. Kara Fitzgerald
Yeah, yeah, yeah.
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Host (possibly a health podcast host)
Let's really get deep on it for a second. Let's assume that you're right, that we are pre programmed to die.
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Dr. Kara Fitzgerald
Yeah.
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Host (possibly a health podcast host)
And so now I'm looking at it from an evolutionary standpoint and I'm saying, okay, it's a really stressful environment. If it's a really stressful environment, we gotta get rid of these old fuckers because they're gonna take resources. So let's just speed things up a little bit.
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Dr. Kara Fitzgerald
Yes.
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Host (possibly a health podcast host)
And get them out of the way so that we have enough resources for the next generation. If I'm right, that would make predictions such that people would live for a shorter period of time. Now I'm setting you up. But if I'm right, would it not predict that if you were pregnant, let's say, during a stressful time, that those children would live shorter lives?
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Dr. Kara Fitzgerald
It's been demonstrated. I mean, it's already been demonstrated. Like you can look at the Dutch hunger winter or I mean, of course there was food famine, another kind of a stress. I mean, we certainly see total life stress, you know, maternal stress experience even, you know, a generation out grandparents and probably further out. It will absolutely influence epigenetic expression towards earlier mortality as well as an increased incidence of the chronic diseases of aging. So stress plays a huge role.
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Host (possibly a health podcast host)
We translate stress in the mother, stress
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Dr. Kara Fitzgerald
in the father, both. Dad's right there. So when we talk about stress, I want to say psychic stress, but I also want to include physical stress in there. So physical stress could be changed to eating, you know, excess food or insufficient food. I mean, I just want to kind of expand that. But yes, in the realm of epigenetics, Dad's a big player, Granddad's a big player. Great. Granddad is a big player.
- [20:22]
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- [20:52]
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Host (possibly a health podcast host)
I remember the first time I heard somebody say that trauma can be passed on.
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Dr. Kara Fitzgerald
Yes.
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Host (possibly a health podcast host)
And I was like, huh?
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Dr. Kara Fitzgerald
It's like photosynthesis. I mean, I sort of think about it. It's like, like psychic. This psychic experience is translated into biochemical marks that then influence pass on.
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Host (possibly a health podcast host)
Like, because how it would have to then be encoded in the sperm and the egg.
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Dr. Kara Fitzgerald
Yes. Yes. Onto their DNA.
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Host (possibly a health podcast host)
Is that encoded into the sperm and the egg? And do you predict, if we can't already, will in the future somebody be able to look at sperm and say, ooh, this. You would pass on stress or whatever?
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Dr. Kara Fitzgerald
Yes. So Moshe Sef, who was a co author and an advisor on our study, says that, yes, that there will come a time that we'll be able to predict outcome in offspring by looking at patterns from mom and dad or even looking at patterns in utero, and that we'll be able to actually change those patterns so that we can forego some of the fallout that we would otherwise succumb to.
- [22:26]
Host (possibly a health podcast host)
That is crazy. The thought that I could go in and work with a fertility doctor to say, okay, look at my. The current state of my sperm and see, like, is this going to be a problem? Am I going to pass something on? This is where we're going. Like that's actually going to happen.
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Dr. Kara Fitzgerald
Yes, yes, yes, yes.
- [22:43]
Host (possibly a health podcast host)
That is bananas.
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Dr. Kara Fitzgerald
Yes.
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Host (possibly a health podcast host)
So what's happening then is you're saying that there is some global marking on my DNA via the methylation that then. Or I guess it doesn't have to be global, although I would assume it will be because it's going to be expressing itself in my body, but then it's also going to express itself in pregnancy.
- [23:13]
Dr. Kara Fitzgerald
Yeah. So here's the thing, and let me just say too, there's some cool research on the heritability of exercise habits and how you can hand down some of that to your offspring. So you can change the methylome. That's what we call the methylation genome. You know, you can change the methylome favorably or not. I suppose if you're a non exerciser and hand down some of those benefits to offspring.
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Host (possibly a health podcast host)
Yeah, that is fascinating.
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Dr. Kara Fitzgerald
So here's what happens. This is my understanding. So your methylation marks. You and your wife conceive, you have a fertilized eggs. Egg, you know, your methylation marks. Her methylation marks are handed down, but then they're largely removed. So 10, 11 translocation enzymes actually remove methylation marks, you know, from the fertilized eggs for the most part. Like we remove the bulk of them.
- [24:09]
Host (possibly a health podcast host)
So don't be old. That's like the punchline of that moment.
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Dr. Kara Fitzgerald
Yeah, you're just, you're just, you're cleaning the slate. You're allowing, you're allowing the, you know, a genesis of a new human. But not completely. Let me just finish this. Not entirely. There's some of you, some of your methylation patterns translate over as do your wives, your wife, and that is the heritability portion of, of DNA methylation. So it's not all lost. And so that might be your exercise habits or some of the stress that you've experienced and that actually might carry a few generations back.
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Host (possibly a health podcast host)
That means that there's what I'll call intelligence imbued in that system where there's a decision making process that says remove these, don't remove these.
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Dr. Kara Fitzgerald
Yeah. So what gets to stay and what doesn't? There's something called the imprintome and that is, that's being studied by Randy Jertle. So you know, the agouti mice studies probably. Right.
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Host (possibly a health podcast host)
Because of you. Yes. But it's worth telling people they're really important because this is so crazy. The most cited thing in science.
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Dr. Kara Fitzgerald
Yes. It's so fascinating. So I'll tell about that paper in a second. But just to kind of wrap this up, the imprintome is some of what can be inherited from mom and dad, some of the methylation patterns that can be inherited from mom and dad. And Randy is actually really interested in studying that now because some of them can translate into pretty serious diseases. So he wants to work on that. But also in the imprint can house the benefits of exercise if you've had a good habit, you know, good exercise habit. And some, you know, some other really cool stuff too.
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Host (possibly a health podcast host)
You said that there is a signature for trauma, an epigenetic signature for trauma, but there's also then one for wisdom.
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Dr. Kara Fitzgerald
And we think so, yeah.
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Host (possibly a health podcast host)
That to Me is this is so much more complicated than people think.
- [26:02]
Dr. Kara Fitzgerald
Yeah, yeah. So resilience, so trauma, we've studied trauma. I think that there's a sort of an obsession with studying trauma patterns, not just in the epigenome, but, you know, beyond that. And so we know trauma can be carried over. Trauma can be established in early life and then it can translate as chronic disease later on and it can translate to, you know, having a really poor stress tolerance. I mean, it can translate into all sorts of things. So yes, trauma has a strong influence. Resilience does too, but, but we know less about how that translates. That's what we need to study. And that goes back to the idea that Moshe Sef posited where if we understand these patterns well, we can look at you early on or look at an embryo or a fetus and decide these are resilience patterns and if they're not, we can correct them, et cetera. The era of epigenetics and epigenetic diagnostics is just beginning. And it's, it's just going to continue to grow. But we should be putting energy towards studying resilience and what that looks like and then to your point, studying wisdom. So honestly, we're in such a rabbit hole. But let me just say, because you talk about the Yamanaka factors quite a bit. I know I've seen you talk to David Sinclair at least twice and you're always yammering about his Yamanaka research and reversing aging, causing aging by messing up epigenetics and then reversing aging, cleaning it with these three of the four Yamanaka factors that clean up methylation specifically, they bring it back to a more youthful pattern. So we have to ask ourselves in this quest for youth. And this was something that I posed at the very end of my book. If we're going to turn back the hands of time by decades, are we going to, by extension remove the molecules of wisdom that have embedded in our DNA? So, you know, I was listening to you guys talk about if you had a life threatening illness, you might just go for the Yamanaka factors to see if you can turn it back. Would you learn? Would you lose some of this extraordinary knowledge that you've obtained on your journey? I mean, you've done some amazing work in your life and some of that is biologically embedded in your epigenome. I mean, what are we doing by turning back the hands of time? Are we at risk of losing some of these, you know, these marks of wisdom, these, these beneficial changes as well,
- [28:25]
Host (possibly a health podcast host)
that's one thing I found really interesting about your book. And we're not going to forget the mice, so people follow along is in the book you talk about unintended consequences. And so you lay out this incredible book which, you know, we'll get into some of the things that you should be eating and all that stuff in a minute. But you lay out this incredible plan for how people can reverse the biological clock. You'll never be able to reverse the chronological clock, obviously, but that your biological aging, you can move backwards. And then you say, but hey, be careful because we don't know where all of this is going yet. And so you do have to be very thoughtful about those unintended consequences.
- [29:03]
Dr. Kara Fitzgerald
Yeah. And you guys have talked a lot about, you know, teratomas or tumors and cancer and so forth. But yeah, I wonder, you know, I wonder about some of the, you know, the less understood shifts that happen with maturation, etc.
- [29:17]
Host (possibly a health podcast host)
And this is why I'm obsessed with whole food. So like, I try never. I do supplement vitamin D when there's not enough sun, but if there is sun, then I don't supplement and I go get the sun because there's probably things that we don't understand about the skin is doing something when it actually feels the radiation, you know, on it. All right, so walk us through the journey.
- [29:40]
Dr. Kara Fitzgerald
Yeah, yeah. It's interesting to me in the longevity space because I come from functional medicine. I come from, you know, I have a nutrition background. I'm a naturopath by training and we're obsessed with these things. So nutrition has this extraordinarily profound, generationally powerful influence on gene expression. And Randy Girdle showed it, Randy Jertel and Waterland in 2003. It's interesting to me because that was when we mapped the genome. We figured out the human genome in around 2003 and we started to realize it didn't house all the answers, that our genes are in our destiny. In that same year, Girdle and Waterland published their Agouti mass study, which incidentally, they couldn't publish. I think it took them 16 different journal submissions and finally to a really low tier journal. They were accepted. Yeah, people were like, yeah, whatever. You know, their peer reviewers did not buy what they saw.
- [30:38]
Host (possibly a health podcast host)
Wow.
- [30:39]
Dr. Kara Fitzgerald
Didn't buy it, didn't accept it. So what they showed, they used an agouti mouse which has the agouti gene expressed. And in animals, in mice, this means that when this gene is on, they're blonde and they're obese. They're very Visual, they don't look like a normal house mouse and they die from obesity related causes. I mean, it's pretty extraordinary. So this, you can get this mouse and do research studies on them. And it was actually Waterlin Journal credits Waterland for the idea of testing nutritional intervention in this mouse model. Like can they methylate and inhibit the gene? And so that's what they set out to do. Actually. They initially set out to show they initially wanted to look at what methyl donor deficiency would look like. So insufficient methyl donors was their first study. And the mice died. They just did.
- [31:34]
Host (possibly a health podcast host)
We didn't.
- [31:34]
Dr. Kara Fitzgerald
Faster than normal. They died. Yeah, they just died immediately. Yeah, they didn't survive at all the offspring. So these were in pregnant agouti mice, dams, and they gave them, they fed them a methyl donor deficient diet and offspring were dead on arrival.
- [31:49]
Host (possibly a health podcast host)
Whoa.
- [31:49]
Dr. Kara Fitzgerald
Yeah. So that's how important these methyl donors are in our diet. Like they're exquisitely important. So that was study one and they didn't publish. That was just communication that I had with Randy Jerdle. So study two was, let's increase methyl donors. Let's give these pregnant agouti mice some folate, some B12, some choline, some betaine. Let's give them that. And lo and behold, that agouti gene was hypermethylated and shut off. So a lot of methyl groups, a lot of the glue or whatever your glue blobs, shut the gene off. And their offspring were brown. Like they look like wild mice. They just like normal wild mice. But here's the kicker. So these are just nutrients that give to the pregnant dams and they reverted the offspring to what they call pseudo agouti and it went on for generations. So one laboratory looked at how, for how many generations and calculated five, I think Girdle and Waterland went back three in their lab. So nutrients given to the pregnant mouse resulted in a generational influence on gene
- [32:55]
Host (possibly a health podcast host)
expression for five generations.
- [32:58]
Dr. Kara Fitzgerald
Yes, five generations in one.
- [33:00]
Host (possibly a health podcast host)
So I no longer had to sort of hyper methylate them and they would keep coming out as normal brown mice.
- [33:07]
Dr. Kara Fitzgerald
Yeah. Or on a continuum. So it's not an, it's not an all or nothing. Like some might have a little speckle of blind, like it, you know, it's, it's a continuum of how hypermethylated that gene is. But, but in general there was a trend towards turning off, hypermethylating and inhibiting that gene and therefore restoring these mice to the sort of brown wild type mice and shutting down the diseases that they were vulnerable to.
- [33:30]
Host (possibly a health podcast host)
Whoa now.
- [33:31]
Dr. Kara Fitzgerald
Yeah, big deal. I Mean, that's how powerful nutrients are. And that study was ignored. At first, they didn't believe it.
- [33:38]
Host (possibly a health podcast host)
It just seemed un.
- [33:39]
Dr. Kara Fitzgerald
It just didn't seem possible they could influence genetic expression. Yes, yes, yes, yes.
- [33:44]
Host (possibly a health podcast host)
That's so nuts. That's really.
- [33:47]
Dr. Kara Fitzgerald
Let me tell you another kicker. This is a crazy story. So another postdoc in Girdle's lab looked at this same model. So again, the goody mice, the goody pregnant mice, and gave them genistein, the soy isoflavone. So a soy phytochemical, same effect as the methyl donors. So a polyphenol, nothing to do with that methylation cycle that I talked to you about at the beginning. Nothing to do with B12 and folate, et cetera, but somehow changed methylation, shut off the agouti gene. Riddle me that.
- [34:18]
Host (possibly a health podcast host)
I was gonna say so I don't even understand enough to know how weird that is.
- [34:22]
Dr. Kara Fitzgerald
It's pretty weird because it didn't. So the DNA methyltransferases lay that, you know, use CME to put methyl groups onto the gene to shut that gene down. But genistein is a polyphenol. It doesn't influence DNA. It isn't making same. It isn't giving the ingredients to shut it down. So it's doing something else. And they speculate that it actually repositions the gene, sort of making the available methyl groups able to get in there and act. So it's doing something else. And they speculated, yeah, just maybe just like opening it, opening that agouti gene up for ready access to the fewer methyl donors in circulation or something. So Girdle in his lab said, look, you guys, you know, we think nutrients are beneficial, you know, and of course they are, but I was taught we just peed them out, you know, there's no harm, you know, you'll use what you need, you get rid of the reptile, right? They showed five generations that these nutrients influenced. And so their conclusion in that 2003, well, it had this powerful favorable influence on these, on these mice, on these good things.
- [35:33]
Host (possibly a health podcast host)
Then it's doing bad things.
- [35:35]
Dr. Kara Fitzgerald
So that's what they said. You know, we long thought these were basically inconsequential, right? I mean, medicine, we evolved not even paying attention. You know, physicians aren't even trained with nutritional training. Like, we just don't even think nutrients are a big deal at all. And these guys completely changed that conversation. And in their abstract, the end sentence was, we need to pay attention to how powerful these are, you know, because they can have unintended consequences. So, and then they show genistein does the same thing, and it's not even a methyl donor. And so in that study, the postdoc who conducted that study said, well, you've got a vegan mom who's eating a whole lot of soy. So, you know, loaded up on genistein, maybe she's eating grains with folic acid, you know, fortified grains, which we're riddled with in this country, you know, and layer in a multivitamin, a prenatal, and you've got a ton of methyl donors or nutrients acting like methyl donors. And that may not be a safe phenomena. Now, we know we need methyl donors in pregnancy. No doubt about it, we need them throughout our lives. We really need to be bathing our genes in healthy methylation. But yeah, it can get a little squirrely when we're using isolated micronutrients and dosing really high and layering in with other nutrients that have an influence on methylation that we don't even understand yet, like genistein. And so it goes back to your original point of diet, you know, whole food matrix, eating how we evolved, you know, getting some vitamin D from the sun. I mean, just sort of having that be our touch point, sort of, you know, our foundation, and then layering on some of these interventions if we need them. If there's a reason.
- [37:19]
Host (possibly a health podcast host)
Man, being a pregnant woman does not sound stress free. It's like you can't be stressed because that's gonna pass on. You've gotta be hyper careful about what you eat. You can't just blast your system with all these vitamins. Vitamins, Damn. Yeah.
- [37:34]
Dr. Kara Fitzgerald
Well, there is some cool research, actually. The folks that grow Baby health are friends of mine and they're using our program and layering it into what they're doing. And they've got extraordinary birth outcomes, like their incidence of common childhood illnesses or gestational diabetes, some of the complications of pregnancy. They're like nil. Their incidence of autism in offspring from this, from this clinic are maybe one. I put the stats in. Yeah, they've published on them. And they are using micronutrients. They are using a prenatal. So I want to clarify, I don't want anybody to get anxious. There absolutely is a place for these micronutrients in pregnancy. And you get them from a whole foods diet and you avoid folic acid fortification and just pay attention to how much soy you're eating, eating, et cetera. So there's some, some ducks to put in a row. But we still, you know, micronutrients are generally healthy in pregnancy.
- [38:37]
Host (possibly a health podcast host)
Wow. All right, let's get into the. The do's and don'ts. So let's set aside exercise for now and just talk about diet. What should people be eating?
- [38:49]
Dr. Kara Fitzgerald
Yeah, so we want to. We want methyl donors, like, up the wazo. Loads of methyl donors. So we want to be doing greens. Lots of greens. We want to be doing, you know, leafy, good greens. Spinach, kale. Yeah, yeah, totally. We want to be doing. We want to be eating some beets. Not a ton, but maybe a couple of small beets. They're pretty high in sugar, and we just. We don't need a ton of them.
- [39:15]
Host (possibly a health podcast host)
But deep red gives us something.
- [39:18]
Dr. Kara Fitzgerald
Betaine. Yeah, Betaine will help whir the methylation cycle. It will help with methylation. Beets, seeds, mushrooms, shiitake, enoki, maitake. These are rich with choline folate. They're like. They're. Mushrooms are really extraordinary. Wild mushrooms. Are they gross?
- [39:37]
Host (possibly a health podcast host)
I can't deal, so.
- [39:39]
Dr. Kara Fitzgerald
Okay, fine. So for those folks who like mushrooms, eat mushrooms, there are alternatives, like. So mushrooms are rich.
- [39:47]
Host (possibly a health podcast host)
I'd hide them in food if I have to.
- [39:49]
Dr. Kara Fitzgerald
Or you can take them. Or you can take them encapsulated if you want to, or if we can.
- [39:52]
Host (possibly a health podcast host)
But is it a whole mushroom just, like, ground up?
- [39:56]
Dr. Kara Fitzgerald
Up. Yeah.
- [39:56]
Host (possibly a health podcast host)
Okay, so it's not like it's a isolated compound from the mushroom, actually just encapsulated shredded mushroom. Yeah, got it.
- [40:07]
Dr. Kara Fitzgerald
Yeah, you can. You can get that.
- [40:08]
Host (possibly a health podcast host)
You do that with liver as well, right?
- [40:10]
Dr. Kara Fitzgerald
Yes. In fact, that's how I ingest my liver, because I don't cook it.
- [40:13]
Host (possibly a health podcast host)
Fair.
- [40:14]
Dr. Kara Fitzgerald
Yeah. Liver is a multivitamin in a food matrix. It is so extraordinary. You don't need. You don't need to eat a ton of it. You don't have to have it every day. If you get three servings a week, you're getting just a massive amount of good folate and B12, etc.
- [40:28]
Host (possibly a health podcast host)
Is there a encapsulated liver that you recommend?
- [40:31]
Dr. Kara Fitzgerald
Yes, it is. I have a whole list of products that I like in the resource section that we vetted for purity. New Zealand source liver has, in my research, the cleanest reputation. They seem to be doing a really good job. So methyl donors, eggs, another beautiful source of choline that you want to be getting. Yeah. So greens, seeds, some nuts, fats from
- [41:00]
Host (possibly a health podcast host)
fish and nuts have to be raw.
- [41:03]
Dr. Kara Fitzgerald
You know, raw is better, but I
- [41:06]
Host (possibly a health podcast host)
wouldn't because I'm cooking out some of the micronutrients or because they.
- [41:09]
Dr. Kara Fitzgerald
Yeah. In the delicate fats. So you know, they're more beneficial in
- [41:13]
Host (possibly a health podcast host)
the raw state because like raw pumpkin seed sounds pretty gnarly.
- [41:16]
Dr. Kara Fitzgerald
They're not bad.
- [41:17]
Host (possibly a health podcast host)
Baked pumpkin seeds are really good.
- [41:19]
Dr. Kara Fitzgerald
Yeah, that's right. I go with what you're going to consume.
- [41:24]
Host (possibly a health podcast host)
So it's not like baked becomes bad for me. It's just not as good.
- [41:28]
Dr. Kara Fitzgerald
Don't eat like charred obviously. Don't eat really poor quality. Try to get a good quality. But I use, I eat roasted pumpkin seeds. I love them, I throw them on my salad. You're going to get some nutrient for your bang, for your buck in that structure.
- [41:41]
Host (possibly a health podcast host)
And do we have like a short seed list of the good ones?
- [41:44]
Dr. Kara Fitzgerald
We really like pumpkin, we really like sunflower, sesame. Those are good. So seeds, mushrooms, liver greens, eggs, salmon or other really fatty fish. And those are going to keep that methylation cycle whirring. Those are some of the key ingredients that will keep methylation wearing mushrooms. And then we've got these traffic directors, the polyphenols. And so those are all your colorful fruit and veg. I mean some of our favorites are curcumin. Curcumin, Turmeric. Turmeric. Curcumin is an extraordinary.
- [42:22]
Host (possibly a health podcast host)
Those are the same thing.
- [42:24]
Dr. Kara Fitzgerald
Turmeric is the spice that houses curcumin. So curry, do you like curry? Can you do a curry?
- [42:31]
Host (possibly a health podcast host)
I eat curry frequently.
- [42:33]
Dr. Kara Fitzgerald
Awesome. Golden milk is one of my favorites. I love curry. Golden milk is a turmeric drink. Turmeric and a little bit of coconut milk and you know, a little pepper and some other spices and it's just delicious. It's a very, it's a time immemorial drink in India. It's delicious. So methyl donors plus these polyphenol compounds that appear to direct what, where methylation is happening and we want to load up and you know, again, blueberries, curcumin, EGCG and the other catechins in green tea.
- [43:10]
Host (possibly a health podcast host)
I don't know what that is. I know what green tea is.
- [43:12]
Dr. Kara Fitzgerald
You know, green tea. So green tea is loaded with these phytochemicals that are, you know, gene whisperers, DNA methylation adaptogens, whatever you want to call them. I mean, just helping with optimal epigenetic expression. That's what we think. And most of the research at the time of our book is in vitro, so in cell studies or in animal studies. But they seem to be able to turn back on some of the genes that are shut off in the aging journey. So these compounds have far reaching beneficial effect. They're anti cancer, they are anti inflammatory, they're antimicrobial and beneficial to our microbiome. They're anti aging in a lot of ways. Senolytics like quercetin.
- [43:56]
Host (possibly a health podcast host)
What's a senolytic?
- [43:57]
Dr. Kara Fitzgerald
Senolytic Helps inhibit production of the zombie cells. Those pro inflammatory cells. Yeah. So just, just think colorful elements of your fruits and vegetables far and wide have this methylation adaptogenic effect. Seem to be able to direct DNA methylation.
- [44:16]
Host (possibly a health podcast host)
What's your take on fruit? I think of fruit and vegetables as being so different. I even think of berries as different from fruits.
- [44:23]
Dr. Kara Fitzgerald
Yeah, yeah. Most of the fruits have important compounds, but we don't obviously because of the sugar impact, you don't want to be eating tons of them, so you need to be mindful.
- [44:34]
Host (possibly a health podcast host)
Can I eat as many raspberries as I want?
- [44:37]
Dr. Kara Fitzgerald
You know, if your blood sugar is in reasonable control. I mean, do you wear a continuous glucose monitor?
- [44:42]
Host (possibly a health podcast host)
I have many times.
- [44:43]
Dr. Kara Fitzgerald
Yep.
- [44:44]
Host (possibly a health podcast host)
I'm not currently.
- [44:45]
Dr. Kara Fitzgerald
Yep.
- [44:46]
Host (possibly a health podcast host)
But yes.
- [44:46]
Dr. Kara Fitzgerald
So pay attention, you know, just pay attention to how your body responds. Like we recommend blueberries on a daily basis as one of the. Or any dark berries, raspberries would be in there. If you're going to load up on them, you know, you might want to just pay attention to your sugar and see how much you can tolerate. It's going to be different for all of us. But if you have your raspberries, maybe on a salad, and you've got a higher fat dressing and some fiber in there, you know, each of it, it'll be different for each of us. But super important information is contained in raspberries and all of these. And, and we're just starting to understand how sophisticated the information is. Like I was reading, this is a cell study, but curcumin in turmeric can inhibit MTOR in multiple myeloma cells. So. I know, and it's a cell study, so it can hypermethylate the MTOR gene in multiple myeloma cells in a cell study. By comparison, curcumin has also been shown in cell studies to turn on a hypermethylated BRCA gene. So brca, the BRCA genes are major, highly important tumor suppressor genes. So they keep us clear of cancer. A functioning BRCA gene keeps us clear of cancer, takes care of DNA repair, et cetera. It does a lot of stuff. A functioning brca, we're not talking about the BRCA mutation, but a functioning BRCA gene can actually be hypermethylated and inhibited and then it's associated with all sorts
- [46:21]
Host (possibly a health podcast host)
of cancers by getting hypermethylated or hypomethylated hyper.
- [46:26]
Dr. Kara Fitzgerald
So it's shut down and no longer available to do its work. Hypermethylation, lots of methyl groups inhibit it from being on, so curcumin will allow that to be re expressed. So in mtor, it can shut it off in a multiple myeloma cell, but brca, it can turn back on to go do its good work.
- [46:47]
Host (possibly a health podcast host)
All right, so let me say that in layman's terms. So mtor, which is basically grow. So hey, body grow. Grow. Muscle grow. Tumors.
- [46:54]
Dr. Kara Fitzgerald
Yes.
- [46:54]
Host (possibly a health podcast host)
So we're shutting down MTOR and then we are removing the errant punctuation that is making the sentence impossible to read in the BRCA G. We're turning the
- [47:07]
Dr. Kara Fitzgerald
BRCA back on and allowing it to function. So it does two opposite things. Curcumin and turmeric. Does two opposite things in cell studies. It's amazing. So do some of the other players, like luteolin or quercetin. What else? Genistein. So going back to soy, that's a really important polyphenol.
- [47:28]
Host (possibly a health podcast host)
I think of soy as being bad.
- [47:30]
Dr. Kara Fitzgerald
Yeah, I would say that if you can get an organic and perhaps fermented soy, it's an important polyphenol. I mean, it's just got important potent power for the most part, beneficial power. I just wouldn't.
- [47:43]
Host (possibly a health podcast host)
Do I as a guy need to worry about the estrogen?
- [47:46]
Dr. Kara Fitzgerald
No, I don't think that there's enough. And you don't want to swim in it. You know, have a serving of it every now and again if you like it. We don't use it in the intensive part of the program, but we do allow it for vegans in the program or when you transition off of the intensive eight weeks, you can include it. And they're important polyphenols. So these guys are the traffic director. So we want to load our body up with this collection of compounds and there's a 30 page nutrition appendix that will give you the details. Like all of the foods that you can access to get some of these really important EPI nutrients as a category, both of them, we're calling them epinutrients.
- [48:30]
Host (possibly a health podcast host)
Okay, so there's a reason that your book is robust. It is not brief in its incredible description of what's going on and what we need to do to combat all of that stuff. This is really, really incredible stuff to me. I want to run through just a synopsis and there's been a few things that we haven't gone really deep on that is probably worth just reminding people that they should be doing. But so, all right, we've got our genetic code, which isn't changing. It's not going anywhere. But you have the epigenome, which is probably way more important. Like when you look at the genetics of a plant, it's way more robust than the genetics of a human. And yet humans are pretty damn complicated.
- [49:12]
Dr. Kara Fitzgerald
Right.
- [49:13]
Host (possibly a health podcast host)
Because of this epigenetics of what is expressed, what's not expressed.
- [49:18]
Dr. Kara Fitzgerald
Yes.
- [49:18]
Host (possibly a health podcast host)
What you eat has a huge impact on what's expressed. Going back to the mice study, it's pretty crazy that you can alter the pregnant mother's diet and it has a five generational impact. That's so crazy. I really think that's going to give women heart palpitations. But if I can help them reframe it, that it can be a negative impact or it can be a positive impact. As in the study was looking at the good things that you can pass on, which is pretty incredible. Okay, so we've talked about all that. Now let's give a quick breakdown. What is the role of stress, sleep and exercise?
- [49:56]
Dr. Kara Fitzgerald
Incidentally, we have what we call the younger U hybrid in here for pregnant women and preconception. So we put together what we think is a good eating pattern. So if you have palpitations, ladies, and if you need it, just take a look at the book because you can totally eat for your genes, your genes and your offspring. So if we're not sleeping, we're aging. I mean, you know, sleep is an essential component of good epigenetic expression. Insomnia ages people, and that's been demonstrated looking again at DNA methylation, but it's a lot better. So I just walk through all the hacks that I've used. Cold room, you know, going to bed on time, not setting my alarm. That's a big thing for me. I use melatonin and magnesium. I find both to be helpful. I use meditation, so I do meditation. Sometimes I'll listen to rain. Like I'll just all sorts of different very dark rooms. So we need to sleep, we need to figure out how to get it. It's really important with repair and anyway, on and on. Stress is potently pro aging. And again, as we've been talking about, it can be generational and it will influence morbidity and mortality. But I think stress is one of the most pro aging experiences that we can have and that we need to be paying attention to, to turning it off and not allowing it to drag us by the hair. So stress is very pro aging. I think the clock that we used the Horvath 2013 like the flagship sort of gold standard clock that we used in our study. A full 25% of those methylation sites are influenced by the stress response. 25%. There's no other factor that influenced this singularly influences the clock as these what they call glucocorticoid response elements on the clock. So that, to me, suggests that stress plays a huge role, huge sleep stress. Conversely, the data on meditation on Tai chi, on yoga, is extraordinary. Even a single exercise can have favorable changes. Like, we can make a difference pretty quick if we continue to do it over time. I mean, just think cell division after cell division after cell division, you can hand down these favorable changes. So if we continue with our good habits, we can have these lasting and really powerful improvements. People who meditate regularly are biologically younger. People who meditate regularly are biologically younger. But just one meditation experience can still have favorable influence. Even yoga, like a weekly yoga habit, showed beneficial changes on the epigenome. A weekly yoga habit. So we got this. We can do it. You don't have to retire to the mountain and enter a Zen monastery and practice eight hours a day. You just start wherever you are and you can make favorable changes, but understand that the habit is obviously better. Same thing with exercise. Like, a single exercise event can change DNA methylation, epigenetic expression favorably, like one single time. Keep doing it, and it's, you know, the benefit of it is so far reaching. There was a paper that came out not too long ago, really arguing that all of the benefits of exercise come from the epigenetic influence. As I said, we can pass some of those down. And the older you are, the more bang for your buck you get. With exercise, exercise will turn back on those previously inhibited tumor suppressor genes. As we age, our risk for cancer rises exponentially. And a piece of that is, you know, and again, this goes back to the program aging conversation is that we reliably shut down our tumor suppressor genes, like these genes that keep us clear of cancer. We start to hypermethylate them and inhibit them. I mean, what the heck is that about? Exercise turns them back on, as do these polyphenols. It's like exercise is like a physical polyphenol. Isn't that wild? Isn't that wild? Exercise is like eating a vegetable.
- [54:06]
Host (possibly a health podcast host)
That's crazy.
- [54:06]
Dr. Kara Fitzgerald
I know. It's so cool. And it doesn't take a lot. So one exercise event can be beneficial. But then again, the habit, the lasting habit, is good. And we could have a whole Other conversation of are we doing high intensity? Are we doing something low and slow? I mean, what are we doing? Are we doing weights, resistance training? There was a study that came out not too long ago, specifically beneficial for mitochondrial DNA methylation. So pretty cool. I think we do what we love, what we're good at, what we're consistent with. And our study, a very gentle prescription of 30 minutes, five days a week, minimum perceived exertions, 60 to 80% of max. So not intense, but it was the consistency that we thought was important. Over exercising can be pro aging. I mean, anybody who is a competitive athlete, I mean, I know when I was a cyclist in med school, I was racing competitively and I would always crash at the end of my season. I'd always have upper respiratory infection. Always. You just wear yourself down with the stress of repetitive, really high intensity events. And it's pretty common that you get a cold or you get sick for a while. So over exercising can be a pro aging. But I still love high intensity interval training. I just, you know, I'm just a little bit more mindful about it and I do pay attention to my biological age. And we can talk about that as well.
- [55:33]
Host (possibly a health podcast host)
That will have to be on round two. I cannot believe how fast this went. That's. This is so fascinating to me. Where can people follow you? Where can they get the book youngeryouprogram.com
- [55:44]
Dr. Kara Fitzgerald
or drkara fitzgerald.com so clinic and everything else. Drkara fitzgerald.com book youngeryouprogram.com and we also have an app where we have IRB. We're researching IRB. Institutional Review Board means we have permission to continue to do research. So in our app, which you can find at younger your program, you can jump in and join us on this continued research. And the next data that we're looking at is awesome. It's exciting and I just look forward to publishing on it soon.
- [56:13]
Host (possibly a health podcast host)
I can't wait. That'll be a lot of fun, guys. You will love the book. Check it out. If you're as obsessed with aging backwards as I am, this is another fun one. Be sure to check it out. And speaking of things that you should check out, if you haven't already, be sure to subscribe. And until next time, my friends, be legendary. Take care. Peace.