69. Dr. Kara Fitzgerald: This Hack Reversed Biological Age by 3 Years in Just 8 Weeks

What if aging isn't just inevitable—but programmable? In this episode of Extend, I sit down with Dr. Kara Fitzgerald, pioneering epigenetic researcher and author of Younger You, to explore how your daily choices—food, movement, sleep, stress—can literally rewire your genes to slow down aging. We unpack her groundbreaking study showing biological age reversal in just 8 weeks without drugs, injections, or extreme protocols. You'll learn how DNA methylation impacts everything from inflammation to longevity, which "epinutrients" flip your genes in the right direction, and why your salad might be more powerful than your supplement stack. Dr. Kara Fitzgerald is a functional medicine physician. Her clinical trial was the first to show biological age reversal through diet and lifestyle alone. She's also the author of Younger You. Let's get into it. We Also Discuss: How she helped reverse biological age in 8 weeks The one test that reveals how fast you're actually aging Can food really reprogram your genes? (Spoiler: yes) Why folate, B12, and mushrooms might be more powerful than your multivitamin The "epinutrients" your aging cells are starving for Why your salad might be more effective than supplements Is the carnivore diet speeding up your biological age? What Yamanaka factors, vitamin D, and plasma exchange mean for your future Thank You to Our Sponsors: TruNiagen: Whether you are looking to stay sharp, feel more energized or simple age better, go to https://www.truniagen.com/Ifit: If you are looking to elevate your home gym fitness experience with the best in fitness tech, choose IFIT. Go to https://www.ifit.com/NextHealth: Your destination for cutting-edge health optimization—from IV therapy to hormone balancing. Explore at https://www.next-health.com/Vitaboom: For supplements you can trust and wellness solutions tailored to your health, visit https://vitaboom.com/https://vitaboom.com Learn more about Dr. Shah: Website: https://www.drshah.com/ Clinic: https://www.next-health.com/ Instagram: https://www.instagram.com/darshanshahmd/ Learn more about Dr. Kara Fitzgerald: Website: https://www.drkarafitzgerald.com/ Instagram: @drkarafitzgerald https://www.instagram.com/drkarafitzgerald/ Book: Younger You https://a.co/d/iQe7d4o

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 0:50Dr. Darshan Shah?

  What if you could reverse your biological age, not using drugs, but using food, movement, and a few overlooked nutrients that we don't normally talk about? In this episode of Extend, I'm joined by Kara Fitzgerald, a groundbreaking researcher and author of Younger You, whose clinical study was the first to show age reversal in humans using nothing but diet, lifestyle, and a few critical nutrients that we'll talk about in this episode. We're going to unpack the science of DNA methylation and how this acts like an on-and-off switch for your genes, and how you can influence it to slow your aging, drop your inflammation levels, and feel radically better in an eight-week program. You'll learn why your biological age matters more than your chronological age,

• 1:35Dr. Darshan Shah?

  how to track it, and which foods, habits, and supplements can actually dial aging in reverse. My friend, Dr. Kara Fitzgerald, is a functional medicine practitioner, and she's a researcher at the forefront of epigenetic medicine. She is doing clinical trials all the time, and she published one of the first clinical trials to show that biological age can be reversed through diet and lifestyle alone. She's also the author of the bestselling book, Younger You. I can't wait for you to hear this conversation with Kara Fitzgerald.

• 2:10Dr. Darshan Shah?

  Dr. Fitzgerald, I'm so excited to finally have this conversation with you. We've been friends for a while now.

• 2:15Speaker 01

  A long time, yeah.

• 2:18Dr. Darshan Shah?

  You know, this is so great to get you on the podcast to talk about your program and the younger you program in general, but also all the research you're doing and how it's evolved over the last few years. It's going to be a huge conversation for me for this podcast, especially because I've been through it myself. I've taken patients through it.

• 2:36Speaker 01

  Yes.

• 2:36Dr. Darshan Shah?

  And I'm excited to talk about it with you.

• 2:38Speaker 01

  Awesome. I'm really happy to be here. Anytime getting to hang out with Dr. Shaw is a good time. It's time well spent.

• 2:44Dr. Darshan Shah?

  Thank you, thank you. So, Dr. Fitzgerald, do you have, like, Cara?

• 2:48Speaker 01

  Of course.

• 2:49Dr. Darshan Shah?

  Cara? Cara, so, you know, your evolution through this is really interesting. I'd love for you to talk a little bit about your, your practice, kind of how you started, and how you happened upon doing your study on the reversal of biological age. Would you talk a little bit about that?

• 3:06Speaker 01

  Yeah, it's, it's a pretty interesting story and I can get into it and get really, really obsessed about it because it's, it's interesting to me as I, you know, just unpacking it over the years, but feel free to interrupt me at any time. I started to think about epigenetics in earnest in around 2013. A lot of papers were crossing my desk, most of it about cancer. So, and we can circle back to this later, but cancer aggressively hijacks epigenetics and gene expression aggressively. And being a functional medicine clinician in a teaching clinic,

• 3:39Dr. Darshan Shah?

  Right.

• 3:40Speaker 01

  I, you know, the big question nagging me was how could functional medicine, this is systems medicine, where this is whole person medicine, how is what we are doing influencing gene expression through epigenetics? And because cancer, the papers on cancer were the one, the primary ones crossing my desk at the time, my question was, you know, simply, are we benefiting? Are we, are we favorable, favorably influencing this? Could anything that we're doing be negatively influencing cancer's ability to take over gene expression? So that was the first question. And with my very smart Nutrition Director, the Director of our Nutrition Programs at the clinic at the time, Romali Hodges, we dove into the science and there wasn't a lot of science. I mean,

• 4:25Speaker 01

  that has changed incredibly. A lot of what we were looking at were cell studies, animals if we were lucky, and we saw that diet had a profound influence on gene expression, in animal studies, in cell studies.

• 4:40Dr. Darshan Shah?

  Because when you were looking at these papers, like, looking at the methylation of the DNA, was something that was rarely done in humans and not at a mass level for sure. So how were you even checking these, how were they back then, running these methylation studies? Was there specialized machinery, specialized labs?

• 5:00Speaker 01

  Well, you know, Illumina, kind of the flagship lab, had smaller arrays back then. So there's, what, 30 million methylation marks on the genome? There's a lot of them. You know, and back then, they were like 27,000. I mean, they were just, they were smaller, they were a little bit more cumbersome, they were a little bit less reliable, but they were there. You know, people were able to do it. Yeah, but most of the data were in cell studies and in animal studies.

• 5:25Dr. Darshan Shah?

  So you're looking at all these studies, and then how did that jump into you actually doing a human study?

• 5:30Speaker 01

  So, that's such a, it's such a great question. So, from our read on the literature, we put together our best hypothesis on what an optimal diet and lifestyle program would look like to meet, to change favorably DNA methylation. So we took all of that literature. There were scant human studies, like some in exercise, or some in meditation, and, but really, the bulk was in, were in animal. And we put together the diet and lifestyle, the methylation diet and lifestyle program that we then rebranded Younger You, but that's the name that we use in research, methylation diet and lifestyle. And we started to do

• 6:10Speaker 01

  it in practice, but we couldn't measure epigenetics at the time. There were no tests to send a specimen into. It was only in the research setting, but we could see patients getting better, we could see people like responding, we could see their antibodies numbers dropping if they had autoimmunity, we could see their numbers dropping, they would lose weight. I mean, we routinely saw people really responding clinically to this dietary pattern over and over and over again. One of our doctors always says it's as impactful for her as the standard elimination diet that we do in functional medicine for, you know, many, many years. So we could see clearly that it was a powerful intervention. But we didn't know if it was changing epigenetics, if it was changing gene expression.

• 6:51Speaker 01

  And it was a conversation that I had with the then CEO of of Metagenics, supplement company around some of our questions around using high dose B vitamins and whether that could negatively influence gene expression. So we were coming at it through that angle. And it grabbed his attention. In fact, at that time, his, his wife was pregnant and she was taking a very high dose, you know, B vitamin prenatal as we, as we always prescribe and as, and as, as is warranted. But knowing that there were some data out there that potentially challenged how and when we used these doses

• 7:30Speaker 01

  just caused him to pause profoundly, you know, enough so that he funded us. He gave, Metagenics gave us an unrestricted grant. They said, you can do this, Cara. You'll own what you guys identify. You can design the study. He put us in the driver's seat entirely. So we were able to hire a clinical research center. Actually, the Health Guard Research Institute at my alma mater, National Institute of Natural Medicine, to run a randomized, controlled clinical study. And in that setting, we were able to look at epigenetics. We could, you know, order all of our test kits from Illumina directly and so on and so forth. So that set it off. Biological age at that time, Darshan,

• 8:11Speaker 01

  was thought to be irreversible, like that you, you couldn't influence it with interventions. That's what Steve Horvath really believed and said. In fact, you know, I saw him lecture at P L M I, you know, you know, saying, I mean, I heard him many times, just really talk about us not having much power over influencing the direction or, you know, changing our biological age. So even though we were Going to have the tools to be able to measure that? I didn't know, I wasn't holding my breath. I was hopeful that we would favorably change gene expression, but I really didn't know what and how. Because again, this was, this was the first of its kind study.

• 8:50Dr. Darshan Shah?

  Right.

• 8:51Speaker 01

  You know, it was by the grace of God, we happened to get funding to go in and do this.

• 8:55Dr. Darshan Shah?

  That's amazing.

• 8:56Speaker 01

  Yeah, so we went in with, we're hoping we're going to change gene expression towards something better. And during the study, it took us a year to run it. The first paper came out showing biological age reversal in humans. And that was the TRIM study in, where is he? He's up near Stanford, Greg Vay and his group. And they had a year-long intervention using growth hormone, metformin, DHEA zinc. And they were able to reverse biological age. And he continues to, you know, research his protocol and refine his protocol and, you know, just get better and better. But time stood still. So those of us doing research in epigenetics were, were really excited about that study. It was extraordinary.

• 9:36Speaker 01

  So, and Steve Orvath, the, you know, the guy who developed the clocks was the, was an author on that paper. I think he was the first author. And, or he was the last, anyway, he shared it with Greg. And he did all the clocks. And so there was just this clear bioage reversal and it was very, very exciting.

• 9:53Dr. Darshan Shah?

  Also surprised by the result?

• 9:54Speaker 01

  Yeah, oh yeah, 100%. Hundred percent. Yes.

• 9:57Dr. Darshan Shah?

  It set off a whole new field. It set off this entirely new direction.

• 10:01Speaker 01

  Yes, that's right.

• 10:02Dr. Darshan Shah?

  Of, I would say healthcare now, you know, if you really look at this.

• 10:05Speaker 01

  And it was just a few years ago.

• 10:07Dr. Darshan Shah?

  Right, yeah, when was the TRIM study?

• 10:09Speaker 01

  2019.

• 10:09Dr. Darshan Shah?

  2019, and your study was published when?

• 10:11Speaker 01

  2021.

• 10:12Dr. Darshan Shah?

  Wow.

• 10:13Speaker 01

  In between those, or it was actually a little bit before, but it was a little bit before Greg's study. But the, there was a vitamin D study. And they showed that D deficiency was associated with an accelerated biological age. And when you repleted vitamin D levels, that the acceleration slowed down. So it wasn't like a randomized clinical trial in the way that, you know, the way that we were doing. But it was able to show deficiency associated with age acceleration and then repletion, you know, slowing it back down.

• 10:42Dr. Darshan Shah?

  I love that. So you saw this data, you got the funding, and back then there were no companies doing biological age testing except for Illumina sending you these special kits.

• 10:52Speaker 01

  They just gave us the kits and then we, we had to have our, we worked with Yale to process all of our study specimen and Horvath has a calculator at UCLA. So we put our data into his system and used all of his tools to actually calculate our clocks. Yeah, it was very different than it is today.

• 11:10Dr. Darshan Shah?

  Right. And the TRiM study was interesting because they use growth hormone. They use some real unconventional, I would say, medical treatments.

• 11:17Speaker 01

  Yeah.

• 11:18Dr. Darshan Shah?

  Whereas you took a dietary and lifestyle approach to the same problem.

• 11:22Speaker 01

  Yeah, that's right. That's right. Yeah. And much shorter timeframe, eight weeks.

• 11:27Dr. Darshan Shah?

  Eight weeks.

• 11:27Speaker 01

  Now, it's an all-in diet and lifestyle, as you know. You know, the diet is, you know, it's a healthy dietary pattern by any measure. There's a lot of veggies, you know, there's some fruit involved in it, there's protein, good fats, a gentle intermittent fasting structure, 12 hours on, 12 hours off.

• 11:45Dr. Darshan Shah?

  Right.

• 11:46Speaker 01

  You know, what else? We have, so we have two, we had two classes of nutrients or have what we call methylation adaptogens and then, you know, methyl donor group foods. And we want people to have lavish amounts of both. So we're specifically looking at DNA methylation here and sweet talking DNA methylation among all of the epigenetic marks.

• 12:06Dr. Darshan Shah?

  Right.

• 12:06Speaker 01

  So we're very interested in that for a number of reasons.

• 12:10Dr. Darshan Shah?

  And what, I mean, before we launched the exact protocol,

• 12:13Speaker 01

  Yeah.

• 12:13Dr. Darshan Shah?

  I'd love to know why you were looking at DNA methylation specifically. And maybe you can tie in a little bit of explanation about DNA methylation, why it's important, and maybe even talk about, a little bit about just methylation and epigenetics globally as well, for the people that are coming into this brand new.

• 12:32Speaker 01

  Yeah.

• 12:33Dr. Darshan Shah?

  That maybe they don't understand epigenetics and what that even is.

• 12:36Speaker 01

  Yeah. So epigenetics, epi above, genetics, your genes. Epigenetics is the field of study that concerns itself with all of the myriad biochemical marks that are on and around this, you know, the double, the double strands of DNA, you know, folding it and, you know, marking it to influence what genes are on and what genes are off, what proteins are expressed and what proteins are inhibited. And, you know, this goes back to Just how a fertilized egg

• 13:07Dr. Darshan Shah?

  Right.

• 13:07Speaker 01

  could develop into a human being of, you know, many, many, many, many different cell types. So your eye cell remains an eye cell. It's not a liver cell. It's not a skin cell or a heart cell. And that's because of epigenetics.

• 13:18Dr. Darshan Shah?

  Uh huh.

• 13:18Speaker 01

  So it's these chemical marks that will turn off certain proteins and allow certain proteins on, you know, to create the unique signature that is you. But there's a, there are regions of epigen, you know, the epigenome that are malleable and changeable based on environmental inputs. So your, so your retina cell isn't going to turn into a hepatocyte anytime soon. Those are very, you know, reliably inhibited. But, you know, there's plenty of the 30 million marks that respond to how we eat, um, what we're breathing, you know, our experience in life, our stress, how we're moving our body and so on and so forth.

• 13:58Dr. Darshan Shah?

  Right.

• 13:58Speaker 01

  And so this area is where we're very interested. The fact that we can influence potently through our choices, gene expression.

• 14:07Dr. Darshan Shah?

  Right.

• 14:08Speaker 01

  And of all of the myriad epigenetic marks, DNA methylation and a methyl group, for anybody who doesn't remember it from, uh, high school biochem, is, is a carbon with three hydrogens. And when these methyl groups are dotted on a promoter region of a gene, that gene is going to be inhibited from being transcribed. So the protein that that gene correlates to won't be produced. If those methyl groups are removed, and we have the machinery to be able to put it down, to remove it, all sorts of stuff. If they're removed, that gene can be turned on. And it's, you know, DNA methylation for a variety of reasons. A is, you know, we can measure it in the laboratory really well and reliably.

• 14:50Dr. Darshan Shah?

  Uh huh.

• 14:50Speaker 01

  It's also, it's lasting. You know, there's enzymes in the body that will keep the patterns going for a number of different reasons. It's just, it's a reliable focus in science than some of the more sort of labile, uh, epigenetic processes.

• 15:05Dr. Darshan Shah?

  Got it, got it. And so for people listening, basically, these are on and off switches for your genes. And then we can look at these on and off switches and what patterns they're in.

• 15:15Speaker 01

  Yes.

• 15:15Dr. Darshan Shah?

  To approximate your biological age using these tests.

• 15:19Speaker 01

  Yeah, so that's one amazing tool.

• 15:21Dr. Darshan Shah?

  Right.

• 15:22Speaker 01

  Of of looking at the epigenome. Yes. So we can identify, like, we could measure a fetus in, you know, in utero and and it would be a negative age.

• 15:32Dr. Darshan Shah?

  Right.

• 15:33Speaker 01

  Or we could look at a centenarian, somebody plus 100, and see a reliable DNA methylation pattern on the epigenome consistent with that age.

• 15:42Dr. Darshan Shah?

  Right.

• 15:42Speaker 01

  And then all points in between. So things change pretty predictably to allow us to see biological age.

• 15:50Dr. Darshan Shah?

  Did you see that recent study about, you know, aging accelerated at age 44 and 62 or something?

• 15:56Speaker 01

  Yeah.

• 15:56Dr. Darshan Shah?

  Was that also using methylation patterns or was that using something different?

• 15:59Speaker 01

  They were looking at multi-omics.

• 16:03Dr. Darshan Shah?

  Got it.

• 16:04Speaker 01

  Yeah.

• 16:04Dr. Darshan Shah?

  That's right. It was something different.

• 16:05Speaker 01

  Yes, it was.

• 16:06Dr. Darshan Shah?

  So and so that highlights the fact there's very, there's a lot of different ways that we can test our biology. And what we're doing now with these tests is that we're using machine learning and algorithms to approximate age based on, I guess, populations and where where their aging is for that particular pattern. And so I think the first person to do this with epigenetics was Horvath. Is that right? And so using using those algorithms is what you used on your patients to see kind of where they fit into this into biological age.

• 16:42Speaker 01

  Yes. Yeah, yeah. There is a hotbed of of research in clocks of all different stripes.

• 16:47Dr. Darshan Shah?

  There are, right.

• 16:48Speaker 01

  Yeah, that's right. I think that the epigenetic clocks are, for myriad reasons, you know, sticking around and important players.

• 16:56Dr. Darshan Shah?

  Right.

• 16:57Speaker 01

  On the on the landscape, but indeed, we're just really tussling with this phenomena of measuring aging. It's interesting and it's complex.

• 17:06Dr. Darshan Shah?

  Right, but what's incredibly, I think, valuable here is for the first time, we have kind of an overall indicator of our current health status in using some of these. And we can use this as kind of a scorecard or a moment in time where we can check our epigenetic age, and then a year from now, check our epigenetic age. And all the things that we did from now till a year from now, how do they add up and stack up in either improving our rate of aging or not improving our rate of aging, right? And so I think that's where we can really use this. That's how I use it clinically, really, with my patients. Is I say, look, this doesn't really mean there's any one specific thing you did right or did

• 17:47Dr. Darshan Shah?

  wrong, but there are ways that you can utilize this to to kind of sum total. How was the last year? I use it every six months. How was the last? How did the last six months add up to affecting your biological age?

• 18:02Speaker 01

  Yeah, I think it's a great tool. And then I think that I think that we're starting to tease out ones that are, you know, changeable with less time and we can, we can lean on those. I like the Doon-Din pace of aging, which is, you know, such a clock. There's new clocks coming out focusing on different organ systems. And, you know, I think those are exciting. It's, yeah, it's a really, it's an interesting field. It doesn't replace our standard testing. It doesn't replace all of the myriad tools that we have in clinical practice, but it enhances, you know, and it can motivate the patient and really give us insight into how we need to work with that individual.

• 18:37Dr. Darshan Shah?

  Right, right. And what's exciting about now, our next topic of discussion here is you've actually figured out a protocol that can positively affect your biological age and utilizing lifestyle, diet as well, and specific items in the diet. And so let's now go into some of the dietary. Methylation adaptogens, you said, was one category? And what was the second category?

• 19:00Speaker 01

  Methyl donors.

• 19:01Dr. Darshan Shah?

  Methyl donors, okay. So what is, what's the definition of a methyl adaptogen and a methyl donor?

• 19:06Speaker 01

  So they're both, we refer to them as a group as epi nutrients. So we know they can influence epigenetic expression. Methylation adaptogens are not, they don't, so the donors, actually, I'll start there. The donors help make the carbon and three hydrogens. So we've got 30 million of them on the genome. We need these guys a lot. You know, we're, we need to, you know, keep them going, replace them, et cetera, et cetera. And methylation is happening elsewhere in the body. We use it for all sorts of important processes in the body. It's just a carbon and three hydrogens. Like, I, I think we were just hardwired to use it because it's ubiquitous. It's easy. So we have this methylation cycle in the body that makes these, these methyl groups, and we need to keep it humming.

• 19:50Speaker 01

  And we become less efficient at it as we age. So the diet needs to be packed with the nutrients to be able to keep the methylation cycle humming and to be able to keep these methyl, these methyl groups being produced and available, doing all the myriad important things they do. So the diet is loaded, loaded, loaded with those foods. And methyl donor nutrients are folate. You know, when you know that folate and B12 are important for you, this is why. Betaine, choline, um, there's a, you know, a variety of different minerals that are important, like zinc, magnesium. We know fish oil even has a, has a regulatory role on the methylation cycle. So the diet is just packed with all of those, as much as we can.

• 20:33Speaker 01

  And we could see in our study participants, they raised their circulating methylfolate. So that was, you know, evidence to us that we said, we achieved what we wanted to achieve with the dietary pattern.

• 20:43Dr. Darshan Shah?

  Are people on the standard American diet deficient in these methyl groups?

• 20:48Speaker 01

  I would say that we, I mean, we definitely see a drop in the ability to methylate as we age. I mean, it's just de rigueur.

• 20:58Dr. Darshan Shah?

  Got it.

• 20:58Speaker 01

  Even when there's a sufficient amount of B12 or folate. But, and you know this as a clinician, the reference range for both of those nutrients is incredibly broad.

• 21:09Dr. Darshan Shah?

  Right.

• 21:09Speaker 01

  We see people with profound B12 deficiency associated, you know, clinical signs and symptoms, but, you know, their B12 is within the reference limit.

• 21:19Dr. Darshan Shah?

  Home reference limit.

• 21:20Speaker 01

  Yeah. So same here, but you'll see somebody's homeless. Systeine rise. I mean, really, homocysteine is a standard marker we get in functional medicine routinely. And we always see it rise in people who are, you know, middle aged and above. And oftentimes, we see it in younger individuals as well, actually. It's just not uncommon to see it high. And it's a much more reliable marker of methylation status, B12 status folate than measuring them directly. So I would say, yeah, you know, we, I mean, we are deficient in these. We don't have enough to maintain, you know, all of the methyl donors that we need. So most of us need more of these nutrients in our lives.

• 21:58Dr. Darshan Shah?

  Yeah. So it's important to know, like, I mean, if you're getting blood testing done, if your doctor is doing homocysteine levels, if your homocysteine level is high, it's an indicator that you're probably not getting enough of this in your diet.

• 22:12Speaker 01

  Yeah, that's right. An elevated homocysteine. Yeah, that's right.

• 22:16Dr. Darshan Shah?

  Very important marker. I test it on all of our patients now.

• 22:18Speaker 01

  Yeah, it's such a great insight. I mean, we, we think about it as being associated with cardiovascular disease, and it is, but it's so much bigger than that.

• 22:26Dr. Darshan Shah?

  Much bigger than that, absolutely. Okay.

• 22:28Speaker 01

  So that's category one.

• 22:30Dr. Darshan Shah?

  And can I just, before we move on from that, can you talk a little bit about MTHFR and people that have a genetic deficiency in methylation as well?

• 22:38Speaker 01

  Yeah. Yeah. So in those individuals, not all genetic issues like MTHFR variant will show up with problems. Not everybody. And maybe this is because they're getting adequate amount in the diet or, you know, they just, they're heterozygous or, you know, they only have one gene variant versus both. You know, for myriad reasons, we don't see everything showing up negatively. But those, those people, so these are lesions, these are, these are genetic variants you're talking about within the methylation cycle itself. So these are people that could have a problem making that methyl, that all important methyl group. You know, I would say preliminary literature and actually even our own study,

• 23:21Speaker 01

  we didn't publish on this, but we saw some background evidence to suggest that people with mutations here seem to be potentially aging at an accelerated rate. I want to be like nuanced in how I say this because the data are pretty scant, but they need more methyl donor support. I mean, that's the bottom line.

• 23:38Dr. Darshan Shah?

  So these are one of those things that if you have a high homocysteine level. Or even if you don't, I think it's valuable to do some sort of genetic testing because if you can't make these on and off switches at a level that your body needs, it doesn't matter sometimes how much of the nutrients you take in, you probably even need higher levels, or you need methylated versions of some of these nutrients, so you kind of bypass some of these pathways.

• 24:01Speaker 01

  That's right. I would say that that's true. It is a continuum. Not everybody is going to need, you know, a really aggressive dose, although some people are. So it is a continuum. But yeah, it's good to know, and it's good to be mindful. Like, I have, my MTHFR is fine, but I have, you know, this sister pathway. I've got a variant in that. And my homocysteine, if I'm not really paying attention, will bump right up. You know, so I'm one of those people. Yeah.

• 24:27Dr. Darshan Shah?

  Yeah, I have a few patients like that, that, you know, their homocysteine levels are high, and they try to attack it on their own with increasing choline in their diet and taking these more, I guess, methyl group-rich foods. But they still need to be on methylated B vitamins, I think, sometimes.

• 24:45Speaker 01

  Yeah, that's right. That's right. Not everybody, but some of us definitely do. Yeah, yeah.

• 24:50Dr. Darshan Shah?

  Okay. And then the methyl adaptogens, what are those?

• 24:52Speaker 01

  The methylation adaptogens, yeah. So there's this cool body of literature showing that phytochemicals, that plant compounds, the colorful aspects of plants, the polyphenols, so things like curcumin, green tea, ludolin, resveratrol, and on and on. There's many, many, many, many, many, quercetin. These guys seem to be able to regulate the enzymes involved in DNA methylation. So they're not part of the methylation cycle. They're not making the methyl groups, but they are sort of directing traffic, if you will, like where they're going on the gene, to something more favorable. And we got really excited about

• 25:34Speaker 01

  this, and when we were designing the program. And a lot of this science, so this was against cells, we've got some early human data now, looking at it from our group, but it was cancer. So we could see, so cancer would shut down genes that protect us from cancer, from getting cancer. They shut them down by putting these methyl groups on. And these beautiful polyphenol compounds, many, many, many different varieties of them, will turn those genes back on, allow them to kind of get back into, you know, protecting us from cancer. Yeah, just right there, changing methylation on the DNA.

• 26:05Speaker 01

  And so we, every forkful of food in the dietary pattern is both of these. So every single forkful is packed with these epigenetics directing traffic.

• 26:15Dr. Darshan Shah?

  I love that.

• 26:16Speaker 01

  And we believe, and I think the evidence now is coming out that this, you know, that there was, that it was, it was a wise choice for us to focus here because, you know, more, more and more scientists are suggesting that, you know, it's really, if you look at all of the hallmarks of aging, the epigenome is sort of the business, it's like the first step, you know, and if you can get in there and change the epigenome, you can change all of the hallmarks of aging. And I know everything's very interconnected, but, you know, it makes me excited and heartened about this dietary pattern that we just happened to start, you know, with epigenetics.

• 26:55Dr. Darshan Shah?

  Absolutely. I think David Sinclair truly believes that too, that the epigenome is really kind of the centerpiece of the, all the hallmarks of aging. And so that kind of all kind of leads back into epigenetic changes.

• 27:06Speaker 01

  Yes.

• 27:11Dr. Darshan Shah?

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• 27:48Dr. Darshan Shah?

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• 28:27Dr. Darshan Shah?

  Going back to a forkful of methyl adaptogens and a forkful of methyl donors, talk a little bit more about the actual diet and how do we get a forkful of these at home?

• 28:36Speaker 01

  Yeah, yeah, yeah. Like, a well-designed salad, it could be a forkful of both. So, again, it's vegetable-intensive. There's somebody who, Julie Gibson, so she was, she's somebody who's sort of been a rock star in biological age, reversing her own biological age, and she uses our diet. And so she just, she perceives herself as needing to eat a pound of veggies a day. And she talks about how she does that, and smoothies, you know, et cetera. But, you know, lots of greens, lots of cruciferous, and lots of colorful veg. So if you can just get that in, you know, all of it is dense with information. That, that right there is full of methylation adaptogen and methyl donor nutrients.

• 29:20Speaker 01

  And then layer onto that mushrooms, like, any kind of mushrooms. I love shiitake, but my talkie, you know, turkey tail, just you even button, the lowly button mushroom, has a place here. Yeah, yeah, all of them. They're, you know, and it's a superstar because it's both, has the adaptogenic potential and it also has the methyl donor part of it as well. Good quality protein is essential. Fatty, good, clean, fatty fish, you know, chicken, you know, whatever, whatever your protein of choice is, getting a decent amount is essential for the methylation cycle. And, you know, it's important for myriad other reasons as well. Methylation adaptogens are also the spices that we routinely use.

• 30:03Speaker 01

  You know, curcumin, thyme, rosemary, on and on. We've got 30 pages of methylation, methyl donor foods and methylation adaptogen foods. It's my favorite part of the book, this nutrient, epineutrient appendix. And you can go in there and just see, just, you know, almost everything, almost every quality food, whole food, has some element of epineutrients. And so we just really tried to pack the diet full of the ones that have the most bang for your buck.

• 30:31Dr. Darshan Shah?

  Yeah, yeah.

• 30:32Speaker 01

  Green tea.

• 30:33Dr. Darshan Shah?

  And for people that want... To get this dietary program, they just buy the Younger You book, which is the one that I used, and has the entire diet kind of laid out in the eight-week program.

• 30:43Speaker 01

  Yes.

• 30:44Dr. Darshan Shah?

  There are some supplements, though, that can be used as well in this methylation, adaptogen methylation donor program. What are some of those?

• 30:53Speaker 01

  We used a probiotic, lactobacillus plantarum. It's got some data behind it as being able to support the production of folate from the microbiome. So our microbiome, a healthy gut microbiome, makes a multivitamin, basically. I know. It's pretty extraordinary.

• 31:09Dr. Darshan Shah?

  Pretty amazing.

• 31:09Speaker 01

  It is. And the diet is packed with prebiotic foods, so it's going to really be stoking a healthy microbiome. And then we layered into this a probiotic that we were hoping would help increase folate. And we did, in fact, increase circulating folate. But the diet is folate-dense, so we can't say it was one or the other. We also included a greens powder. I'm incredibly bullish on the methylation adaptogen category of epineutrients. So we just packed a little bit more in with a greens powder.

• 31:37Dr. Darshan Shah?

  Got it, got it.

• 31:38Speaker 01

  Yeah.

• 31:38Dr. Darshan Shah?

  And I remember also, there was another supplement that was, was it like a liver supplement or an organ meat supplement?

• 31:46Speaker 01

  Yeah, yeah, yeah, yeah, yeah. So, yeah. Liver, we're huge fans of liver. I mean, we really are. No one wants to eat it, including myself. I don't.

• 31:57Dr. Darshan Shah?

  But it's easier to swallow than a pill.

• 31:59Speaker 01

  It's easier to swallow. It is just, it's a multivitamin mineral in a food matrix. We really believe in this food matrix. So as we were talking about earlier, of course, these, you know, vitamins are essential. I take plenty of vitamins myself. But as much as we can possibly get in a food matrix, it's designed for bioavailability. You know, there's accessory nutrients we don't even understand. There's interactions. There's so much to the complexity of food that we have to respect and lean on it. So, yeah, liver. It's the element of our diet that was least adhered to in both of our publications.

• 32:39Speaker 01

  But we now, you know, we now use supplements. Like, we just, in our first study, we didn't, I wasn't aware that you could get these, you know, freeze-dried liver capsules, and they were super clean. And, you know, I would have had our participants use those. We instead tried to get them to eat liver, and then on adherence data, it was terrible. Nobody really wanted to. But yeah, the capsules are super easy and I love them. I just, I just, I think that they, I think it's an awesome way to get your multivitamin.

• 33:06Dr. Darshan Shah?

  Yeah, it's an easy, it's a, like you said, that food matrix is incredibly powerful and we don't even know how powerful.

• 33:13Speaker 01

  I know.

• 33:14Dr. Darshan Shah?

  And so when you take vitamins as, you know, nature gives it to us in either like a liver capsule or eating vegetables themselves.

• 33:21Speaker 01

  Yeah.

• 33:22Dr. Darshan Shah?

  There's such a synergistic effect there.

• 33:24Speaker 01

  Oh, I know.

• 33:25Dr. Darshan Shah?

  And what we've done with the standard multivitamin is we've broken everything down into individual components and put it together again.

• 33:31Speaker 01

  Yes.

• 33:31Dr. Darshan Shah?

  And we're missing a lot of stuff.

• 33:33Speaker 01

  We're missing a lot.

• 33:34Dr. Darshan Shah?

  Right.

• 33:34Speaker 01

  We are missing a lot. Yeah, we might think, you know, that, and vitamins have their place, multivitamins have their place. There's, you'll get no argument. But yeah, the level of complexity that, you know, a well-designed salad has on that, I mean, it's just, it's, you know, beyond, yeah.

• 33:51Dr. Darshan Shah?

  Beyond, beyond. Okay, so that's the food component slash supplements. And then let's talk about the lifestyle components of the Younger You program. Can you talk about those?

• 33:59Speaker 01

  Sure. So, we wanted people to be exercising. Exercise is an epineutrient as much as any of the foods. It's an extraordinarily potent regulator of optimal gene expression, as you know. It's just so powerful and the data are so strong. It can act. So going back to our earliest entry into thinking about epigenetics, it was cancer and how the tumor microenvironment turns genes off for its own growth, turns genes on for its own growth. So it just really manipulates. And we can actually look at all of the chronic diseases of aging and see similar patterns. There just happens to be the most research in cancer.

• 34:40Speaker 01

  Well, exercise acts like those epineutrients that reexpress tumor suppressor genes. Like it just gets in there and changes gene expression dynamics towards something more favorable. It's beautiful and it's so powerful.

• 34:53Dr. Darshan Shah?

  Right.

• 34:54Speaker 01

  And, and you know, the one study that I think I love the most, looking at this, is one that demonstrates it's more potent the older we get. So we'll get more epigenetic change bang for our, more epineutrients bang for our buck.

• 35:08Dr. Darshan Shah?

  Well, that's good to hear.

• 35:09Speaker 01

  I know, I know. Yeah, so exercise was an essential part.

• 35:12Dr. Darshan Shah?

  Was there a specific type of exercise?

• 35:14Speaker 01

  No, so we wanted this pad, this whole program to be broadly adaptable. And so we want people to be able to manipulate and do what they want as much as possible. So we just want people to do a minimum of 30 minutes, five days a week. So it's a program for people who aren't exercisers. You know, one who doesn't have a decent exercise habit can step in and do this.

• 35:35Dr. Darshan Shah?

  Yeah.

• 35:35Speaker 01

  We want people to achieve an exertion of 60 to 80% of their maximum. So 60%, you can still carry on a conversation. 80%, you could still have a conversation, but you're breathing heavier. You're probably not talking quite as much. So do whatever you want, achieve that 60 to 80% of perceived max exertion, you know, for a half an hour.

• 35:56Dr. Darshan Shah?

  So that's like zone two.

• 35:58Speaker 01

  Yeah.

• 35:59Dr. Darshan Shah?

  A little bit more than zone two.

• 35:59Speaker 01

  It's a little bit more than, yeah.

• 36:01Dr. Darshan Shah?

  Yeah, okay.

• 36:01Speaker 01

  So that's the foundational intervention for our study. That's what we did in our two research publications. But clearly you can turn the volume up from there. You know, so a younger U2.0 could include resistance training, high intensity interval training. You know, a combination of those that we know have really strong, strong data on them.

• 36:22Dr. Darshan Shah?

  Oh, I love it.

• 36:23Speaker 01

  Yeah.

• 36:23Dr. Darshan Shah?

  So you had the exercise component, the dietary component. Were there any other components?

• 36:27Speaker 01

  Yeah, so we wanted people to be sleeping well. So sleep and stress reduction. Sleep, we, we had nutrition coaches working with our participants, meeting with them weekly. And they would just dialogue about sleep hygiene and, you know, good sleep tips for, you know, making sure you have enough time. I mean, I would say the biggest limitation to me getting adequate sleep is really not going to bed on time. I don't give myself enough runway to achieve seven hours. Seven hours is like my sweet spot. And just, you know, is the room dark? Is it cool enough? You know, is there noise, et cetera, the usual? You know, we recommend a magnesium in the book, a little bit of melatonin, maybe some glycine as needed for sleep.

• 37:10Speaker 01

  But if you're not sleeping, you're definitely accelerating biological age. It's really that simple. And those data are in humans.

• 37:15Dr. Darshan Shah?

  Right.

• 37:16Speaker 01

  And if you're sleeping well, you're preventing all of those things. So, you know, sleep is another exquisitely important epineutrient.

• 37:22Dr. Darshan Shah?

  Sure. On the stress reduction front, were there any specific techniques?

• 37:26Speaker 01

  Yeah, so if you're stressed out, you know, if you're in that toxic stress, you're, you know, you're aging, unfortunately, you know?

• 37:35Dr. Darshan Shah?

  Yeah, absolutely.

• 37:35Speaker 01

  And we can see that via the chronic diseases of aging, but we can also see it's really anchored in these negative epigenetic changes. Stress is quite toxic on the epigenome. So we wanted people to do a simple relaxation response, a breathing, a basic breathing exercise, 10 minutes, twice a day, ideally, created by Herbert Benson many years ago, out of Harvard.

• 38:00Dr. Darshan Shah?

  Oh, okay. And can people find this on the internet?

• 38:03Speaker 01

  Yeah, they can find it in the internet, and it's in the book as well. It's just a super, it's super basic. It's interesting. I think he created it in the 70s, and it was at a time when there was sort of pushback on meditation. So he called it the relaxation response. But that's basically what it is. It's meditation. Now, that's what we used in our study, but there's many ways to get into the zone. You know, one could do yoga. You know, one could do Tai Chi. Like, there's just many, many ways that we could do that. So we've studied the relaxation response as created by Herbert Benson, but really, any kind of exercise to get grounded, you know, yoga nidra could be really important and helpful.

• 38:44Dr. Darshan Shah?

  Got it. So the people in the study underwent these dietary relaxation, sleep coaching, I would say, and 30 minutes factorized five times a day. That was one arm, and then there was, it was a randomized study, right? So the other arm didn't do these things?

• 38:59Speaker 01

  Correct.

• 39:00Dr. Darshan Shah?

  They just had a normal lifestyle?

• 39:01Speaker 01

  They lived, yeah, that's right.

• 39:03Dr. Darshan Shah?

  Their normal lifestyle, okay. And there was a biological age reduction measured by methylation clocks of how many years in your patients?

• 39:10Speaker 01

  Compared to our control group, it was over three years.

• 39:13Dr. Darshan Shah?

  Yeah, and eight weeks.

• 39:14Speaker 01

  In eight weeks' time, yeah, pretty exciting.

• 39:16Dr. Darshan Shah?

  So eight weeks turn back biological age by three, by three years. It's incredibly powerful.

• 39:22Speaker 01

  Yeah.

• 39:22Dr. Darshan Shah?

  And you didn't use any hormone-manipulating drugs or any of these other things? And so I think that just goes to highlight How incredibly important this pathway is and how, you know, to David Sinclair's point, it could be the kind of the the center point of all the other hallmarks of aging.

• 39:41Speaker 01

  Yeah, I, yeah, I mean, so we built, the dietary pattern is good for many reasons, but it was really built brick by brick to influence epigenetics and our, you know, and the other elements were brought in because of their known influence on epigenetics. So yeah, focusing on that, focusing specifically on DNA methylation seemed, you know.

• 40:01Dr. Darshan Shah?

  Seemed like the right move.

• 40:02Speaker 01

  Pretty cool.

• 40:03Dr. Darshan Shah?

  Yeah, you wrote the first book on this and why it's important, and I think many people have used your protocol since then and have seen their epigenome reverse. And now you can get these tests pretty easily.

• 40:15Speaker 01

  Yes.

• 40:15Dr. Darshan Shah?

  Just from a finger stick blood test you mail in now, right?

• 40:18Speaker 01

  Yes.

• 40:18Dr. Darshan Shah?

  So people can do this test on their own before and after the program.

• 40:22Speaker 01

  Yeah, it's fun. Yeah. And we have groups going at our clinic, you know, quarterly, we'll have, we'll have little groups going and you guys are going to be doing groups. It's fun. It's, it's a nice program to do together, you know, especially if this is a change from your usual dietary pattern. It is, it's nice to do that, have that, that, you know, really juicy community support, which is, you know, an epineutrient in and of itself as well. So it's nice to add that element. But yeah, it was really quite exciting. And then the within group comparison, so the, so the guys who underwent the intervention at baseline, their epigenetic, we measured their epigenetic age and compared to themselves at baseline to follow up, their bio age reversed by just over two years. So the within group

• 41:04Speaker 01

  comparison was statistically significant at just over two years. And then compared to the control, we saw a little bit, you know, stronger response. But yeah, very cool.

• 41:14Dr. Darshan Shah?

  Incredibly cool. And I think, I think you mentioned the community aspect of this. I think that's incredibly important as well. Like you said, it's an epigenetic.

• 41:23Speaker 01

  It is.

• 41:23Dr. Darshan Shah?

  A modifier as, as well. And the groups that you run are, are through telemedicine. So anyone can do this from anywhere pretty much, right?

• 41:31Speaker 01

  That's right.

• 41:31Dr. Darshan Shah?

  Yeah. And so all they need is a book. A computer and off you go, reverse your biological age by three years.

• 41:37Speaker 01

  That's right.

• 41:38Dr. Darshan Shah?

  Which is like that, we're super excited to do this as well in our clinic.

• 41:41Speaker 01

  Yeah, it's awesome. And I should just add, I mentioned this in the beginning, but in our research study, we saw, you know, not only did we see circulating folate increase without supplements, triglycerides dropped, LDL dropped, weight, people lost weight, a significant amount of weight. And we didn't report that in our first study. We have a, we have a paper in peer review right now where we talk about the weight change. In our clinic practice, we see inflammation drop. I mean, we just really see lives changed using this intervention.

• 42:09Dr. Darshan Shah?

  Yeah, I mean, that can, dropping inflammation, dropping triglyceride levels, all these immediate blood biomarkers of actual, not just age reversal, but chronic disease avoidance is incredibly important.

• 42:23Speaker 01

  Yeah.

• 42:23Dr. Darshan Shah?

  So I think this is really important for, it's important for everybody, but really for people that are looking to make a change relatively quickly in, in their biology. And maybe, you know, I mean, do you almost look at it as something that someone who needs a jump start can do something like this?

• 42:42Speaker 01

  Yeah, for sure. Yes. In our practice, we used it with some people who were really, you know, struggling. In fact, in fact, originally, we were using it with that very sensitive population, and I'm sure you know, who can't tolerate anything, you know, that, you know, you give them a, you know, your most gentle vitamin and they have a reaction to it. And when we originally enrolled this, we were using it with, with that group and people responded.

• 43:07Dr. Darshan Shah?

  Wow.

• 43:08Speaker 01

  I know, it was amazing. And they responded profoundly. And if they really hung in there with it, you know, we would see remarkable change, not only in how they felt, but in their various biomarkers. It's an awesome jump start. It's an awesome way to get engaged in this. And then after you've finished the eight weeks, you know, you can take elements and incorporate into your regular lifestyle. You can continue to use this EpiNutrient information. Like you will never eat a forkful of food without thinking about what kind of information you're putting into your body. And do you want to actually give your body that information or not? You know, it's just, there's such a different and empowering relationship you can have with food and with your lifestyle choices.

• 43:46Dr. Darshan Shah?

  Absolutely. I mean, I think. You know, as far as the testing goes, let's talk about that real quick. You don't need to do the testing to put this into play in your life. You'll actually feel the difference after eight weeks.

• 43:57Speaker 01

  Yeah, that's right. So in the book, two cool pieces. We have a BioAge quiz that people can take that's in the book, or you can just go to my website and do it for free there. You don't even have to get the book. And we have found, cool enough, and this will hopefully be another paper, or white paper, or something, that it correlates significantly with the doomed and pace of aging.

• 44:19Dr. Darshan Shah?

  I mean, that's amazing.

• 44:19Speaker 01

  I know. We've got a group of just over 70 individuals who've done both our quiz plus the pace of aging, and we can see that it tightly correlates. So the quiz actually has a little bit of evidence behind it now that, you know, that it's not a bad quiz, that it's not just a pop quiz.

• 44:34Dr. Darshan Shah?

  And this is a quick, like, 10-minute quiz from what I remember on your website. And you get the score right away.

• 44:39Speaker 01

  You get the score right away.

• 44:40Dr. Darshan Shah?

  So this is a great way to test yourself and it costs you nothing except 10 minutes.

• 44:46Speaker 01

  That's right, that's right. And then there's something that you use in practice as well called the multi-symptom questionnaire, the MSQ. And we have that in the book as well. It's the smartest thing. If you're going to do this, the whole program, do an MSQ at baseline. It's just a careful exploration of your various symptoms. And then do it at the end and see what the difference is. Chances are really good that your score at the end is going to be lower.

• 45:12Dr. Darshan Shah?

  Sure.

• 45:12Speaker 01

  You know, it's just that, it's that simple. People feel good on this dietary pattern.

• 45:16Dr. Darshan Shah?

  Yeah.

• 45:17Speaker 01

  So those aches and pains, the headache, the allergies, you know, we can just see the GI stuff. We can see that clear.

• 45:23Dr. Darshan Shah?

  Right. Which just goes to speak to the functional kind of root cause methodology of how this program is affecting our health. Because when you affect the root causes, inflammation, epigenetic expression, et cetera, can lead to less symptoms all over your body. And whether it be migraines, or like you said, joint pain, et cetera, this is really working at a root cause level.

• 45:48Speaker 01

  Yeah.

• 45:48Dr. Darshan Shah?

  Right. Amazing.

• 45:54Dr. Darshan Shah?

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• 46:39Dr. Darshan Shah?

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• 46:53Dr. Darshan Shah?

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• 47:37Dr. Darshan Shah?

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• 47:44Dr. Darshan Shah?

  You had mentioned something a little bit earlier where you're going to do Younger U 2.0, or you've done Younger U 2.0.

• 47:49Speaker 01

  We have iterations of Younger U 2.0. So, you know, having the advantage of using it in clinical practice for a long time, we know how to do a Younger U, we know how to individualize it for the person sitting in front of us to make sure that it's just the best dietary pattern for them. So, maybe they need to turn the ketone volume up, you know, or maybe they need, they're working on muscle mass and we can tweak it, or maybe they've got inflammatory bowel disease and can't tolerate certain foods. So, we've really learned how to individualize it in clinical practice, but we're excited also about turning the volume up ever so slightly on protein, you know, and really supporting people in doing resistance training along with the Younger U, so that's a 2.0. Maybe turning

• 48:34Speaker 01

  the volume up a little bit on that intermittent fasting window, because we know the research on that is just so, so, so strong. The other piece that we learned recently, a group of scientists in the UK out of a group called NetMind undertook the program themselves in the middle of the winter in London, so dark and rainy, and they did a full supplement washout. They stopped all of their supplements two weeks before and continued off of them through the duration of the study, and all of them became vitamin D deficient. And we don't want that. In our original study, and unfortunately they missed this, people who came into it on vitamin D were allowed to remain on their vitamin D, but the research on vitamin D as deficiency

• 49:17Speaker 01

  as an age accelerant and then repletion as an age decelerant is, you know, study after study, it's pretty strong at this point. So, even though this group got younger as measured by the pace of aging, that's awesome, they all became D deficient. So, who knows? If they didn't, maybe they'd be even younger. But our lesson, my lesson, is D will be a part of the, of the pattern going forward.

• 49:41Dr. Darshan Shah?

  So, that'll be a supplement that should be continued throughout the entire thing.

• 49:44Speaker 01

  Yeah, that's right.

• 49:45Dr. Darshan Shah?

  Are there any other supplements that you would continue through the program, like omega-3 supplement, for example?

• 49:50Speaker 01

  I think, yeah, I think that that's fair. So we, in our first study, we had them do a washout, but in the second case series that we published on women, we just had them stay with their supplements. So we, whatever they started on, they continued on. And then I cover a lot of those foundational supplements. And of course, magnesium, fish oil, you know, are key players. So, yeah, I mean, there, people, you know, we'll see, you will see. We're working on funding right now to do, to do a few different arms of younger you iterations. But, yeah, those are really important nutrients.

• 50:25Dr. Darshan Shah?

  Yeah. And also, I think it'll be interesting to kind of suss out where most of the effect is coming from by doing all these different.

• 50:31Speaker 01

  Well, that's in, that is a paper that is in peer review right now.

• 50:35Dr. Darshan Shah?

  Oh, okay.

• 50:36Speaker 01

  So we did, we did do that, actually. Somebody, yeah, it's pretty interesting. And we have an idea. I mean, the reality is the overall dietary pattern and the lifestyle changes, they're all good. And they're all really strongly anchored in good science. But it does seem like some of those, those so-called methylation adaptogens, those polyphenols, were extra important.

• 50:59Dr. Darshan Shah?

  Wow.

• 50:59Speaker 01

  I know. It's pretty cool.

• 51:00Dr. Darshan Shah?

  That's so incredible to, to know, because, you know, I think as far as polyphenols go, in the standard diet that I see most people eating, I mean, there's very few polyphenols in people's diets.

• 51:12Speaker 01

  Yeah.

• 51:12Dr. Darshan Shah?

  And, I mean, you have certain people doing things like the carnivore diet that are getting zero polyphenols. And so there might be, you know, I wonder if anyone's ever done any epigenetic clocks on people on the carnivore diet?

• 51:24Speaker 01

  That's a really good question. Yeah. And, you know, like, if you're a di, so if you're diabetic and you start the carnivore diet, you know, if you're diabetic, your age is accelerating. I mean, unfortunately, any chronic disease, we're going to see age acceleration. But diabetes is really, I think it's on average, Nathan Price published on it, being like six years old. It's definitely an age accelerant. If you go on the carnivore diet, you're going to drop your sugar, you're going to drop your insulin. So it's a short-term intervention. So in that setting, you would probably see a biological age deceleration. You would see a beneficial change. But, you know, measure that same person, you know, a year from now when their microbiome has radically changed and, you know, my guess is that we might be seeing, you know, it creeping forward. And we're going to see micronutrient deficiencies and all sorts of stuff.

• 52:09Dr. Darshan Shah?

  Absolutely. I mean, you know, I'm not knocking the carnivore diet at all. I've seen a lot of success and a lot of patients with it, not just for diabetes reversal, but also for weight loss, et cetera. But I do think, you know, it's so individual. You have to do an N of one experiment on yourself when you're going through these experiments and having tests available like blood biomarkers, like methylation, DNA tests, et cetera. I think people need to look at those on an individual basis and see how these different interventions are affecting them.

• 52:39Speaker 01

  That's right. That's right. And then in the long term, you know, the long-term outcome of a carnivore dietary pattern, I just, you know, I think it's unsustainable. And I think to your point, you know, there's, you're going to really aggressively change the microbiome. And so the microbiome is acting on those polyphenols and producing all these postbiotic compounds that are just wonderkins. You know, they're just doing all sorts of extraordinary important work in the body. And you won't, and you won't get those and you'll get a die-off on the bacteria that are actually producing them and, you know, the whole ratio will change. So I think for the long term, you know, we're looking at a difficulty with that. But yeah, you know, I'm a believer in the N of one.

• 53:19Dr. Darshan Shah?

  Absolutely. Are you testing the microbiome before and after the Younger You program?

• 53:23Speaker 01

  In the clinic, yeah. That's a, that's a, that's a standard part of it. And you do see in somebody on a carnivore diet, a more prone inflammatory pattern, you know, especially, I should say, carnivore diet, you know, over a period of time. You know, and you see, you know, favorable changes on a veggie-dense diet. Interestingly, there was a study, you saw that you, the omnivore and the vegan study, they got so much PR. And they saw favorable short-term changes in the vegan diet. They lost a little bit of weight, you know, their clock seemed to slow down relative to the omnivore. But same kind of complaint with that dietary pattern, like for the long haul, you're going to see micronutrient deficiencies. You know, you'll see a change to the microbiome and so forth.

• 54:05Speaker 01

  So in the short term, you know, some good benefit, but some possible, you know, fallout with long-term use.

• 54:11Dr. Darshan Shah?

  Yeah, you know, we, this dietary debate will probably go on past our lifetimes.

• 54:16Speaker 01

  Yeah, yeah, yeah. That's right.

• 54:20Dr. Darshan Shah?

  You know, I think, once again, it's N of one, like somewhere in the middle is probably right for most people where you have that meta-training diet with, you know, a good amount of vegetables, good amount of protein.

• 54:30Speaker 01

  Yeah.

• 54:30Dr. Darshan Shah?

  All has to be well sourced, of course, you know, and, and some good fats. And then some people are going to do better with more vegetables, some are going to be better with more protein.

• 54:39Speaker 01

  That's right.

• 54:39Dr. Darshan Shah?

  And maybe there's different points in your life where you do better on one and the other one, too, right?

• 54:43Speaker 01

  Yeah, that's a very good, yeah, I mean, if you're doing a bunch of high intensity interval training, you know, you're going to need some readily accessible carbs.

• 54:50Dr. Darshan Shah?

  Right.

• 54:51Speaker 01

  If you kick those to the carb and you're just doing, you know, something with almost no carbs, like carnivore, you're, yeah, you're going to feel that when you really try to hit those heights with exercise. So to your point, yes.

• 55:02Dr. Darshan Shah?

  Like your days you're doing your two hour, two hour bike rides, I'm sure you need some carbs.

• 55:06Speaker 01

  Well, it just made me think of when I was competing, I would, there was a, there was a burrito shop around the corner and I'd always have a big burrito with the wrapper and chips. You know, that's what, that was my, my night before my race meal.

• 55:21Dr. Darshan Shah?

  The night before the race.

• 55:22Speaker 01

  But those chips were like really essential. I needed that.

• 55:26Dr. Darshan Shah?

  I love it. Yeah, those night before the race meals are always.

• 55:29Speaker 01

  They're good.

• 55:29Dr. Darshan Shah?

  They're really good. It's kind of like, just eat as much as you can.

• 55:32Speaker 01

  Yes.

• 55:34Dr. Darshan Shah?

  That's awesome. So you're still in clinical practice, right? Are you still seeing patients as well?

• 55:41Speaker 01

  I am, I have a micro, I have a micro practice. At least I'm keeping my tone upon, yeah, I, but I do.

• 55:46Dr. Darshan Shah?

  I think it's important, I do the same thing. You know, it's always good to see patients and see how different people react differently. I learned so much from.

• 55:55Speaker 01

  Yes.

• 55:55Dr. Darshan Shah?

  Patients and having, that's why they call it a practice.

• 55:58Speaker 01

  I know. It really is. It's important to kind of just to keep our head in that game.

• 56:03Dr. Darshan Shah?

  Right.

• 56:03Speaker 01

  You know, as providers, so yeah.

• 56:05Dr. Darshan Shah?

  Exactly. And you're one of these people, Cara, that you, you're always keeping your finger on the pulse of what's going on in the research. You're so well read, you're looking at the research all the time. What are you seeing as some of the things that are really piquing your interest in biological age reversal?

• 56:23Speaker 01

  Wow. I mean, I know that, you know, you're big on therapeutic plasma exchange and I just had my first one. I'm so excited. I think the research coming out on it is ridiculously exciting, you know, and I think it's, it's, it's a safe intervention. There's just so many pluses to it. I have clinical experience seeing some extraordinary turnaround in some of my patients with, with inflammatory conditions, but doing it as a wellness intervention, I'm pretty excited about. But aside from that, so there's a few things that I'm, I'm very interested in. One is there's a clock that isn't available in the clinical setting, it's in the research setting, that appears to capture all of the hallmarks of aging.

• 57:02Dr. Darshan Shah?

  Ah.

• 57:03Speaker 01

  So a lot of the clocks that we're using now, if not all of them, are surrogate markers. So they may not be capturing the aging phenomena itself, but they're, you know, they're suggesting it. But this clock, which is out of Vittorio Sebastiano's lab, you know, you know of, of Vittorio.

• 57:18Dr. Darshan Shah?

  He's in San Francisco, right?

• 57:19Speaker 01

  Yeah. And this really seems to be capturing, so when, so when, when there's a favorable influence on the clock, it seems to, it seems to track with all of the hallmarks. And the, and the intervention that does it in their laboratory is a yamanaka factor intervention. So it's directly, yamanaka factors, as you know, directly addresses the epigenome. So it's another piece of evidence and it's similar to what David Sinclair is doing in his lab. So they're changing gene expression vis a vis the epigenome, using these yamanaka factors. And, and, you know, and heavily DNA methylation is, is there. They're changing DNA methylation and they're able to see all of the downstream hallmarks change. They

• 58:02Speaker 01

  also demonstrated that caloric restriction, this is still in animals, so we need to get into humans, had similar changes to the yamanaka factors on this particular clock, which I think is really exciting. And looking at the elements of the clock. There's some evidence that these beautiful polyphenols might play a role and might be able to favorably influence the clock. So I'm excited to hopefully, you know, have access to that clock in our research. We are, we totaled up the phytochemicals, the polyphenol specifically in our intervention. There's about three grams, which is really, it's kind of dwarfs any other sort of polyphenol dense dietary pattern. And I would like to

• 58:44Speaker 01

  do some work with that clock to see, like, can we, are we touching, is this dietary pattern at all touching on, you know, what the yamanaka factors are doing?

• 58:53Dr. Darshan Shah?

  Yeah.

• 58:54Speaker 01

  I know that Vittorio Sebastiano is working, is sort of jumping the FDA hoops to bring a yamanaka-based intervention to clinical trials, which is ridiculously exciting.

• 59:05Dr. Darshan Shah?

  That's exciting.

• 59:06Speaker 01

  Mm-hmm. And it's going to start with skin. Like, I'll do it.

• 59:09Dr. Darshan Shah?

  Exactly.

• 59:11Speaker 01

  So, you know, we need to, as Sergey Young talks about, he's a, he has a longevity fund that invests in all sorts of, including the X Prize, all sorts of really cool businesses in the longevity space and biotechs and so forth. He talks about the longevity bridge. You know, we need to get to the other side when some of these interventions will be ready. And we need to be taking care of ourselves now. We need, you know, therapeutic plasma exchange using some version of the younger you dietary pattern, you know, exercise, adequate sleep. So all of those things I think are important. I'm bullish on rapamycin, quite frankly.

• 59:47Dr. Darshan Shah?

  Yeah.

• 59:47Speaker 01

  I'm less excited about metformin, I think, for some of the negative fallout. But I think, you know, I think there's interventions we have right now that will take us a long way, you know, over the longevity bridge until we get to really some of these exciting interventions that scientists are working on right now. So, you know, it's a good, it's a good time to be alive.

• 1:00:06Dr. Darshan Shah?

  I agree. I agree. I, you know, I think the yamanaka factors, for the listeners who don't know what they are, they're a Nobel Prize-winning discovery of certain proteins that can actually turn around or reverse cellular aging. We have no control over this process, other than to give one, two, or three of the yamanaka factors. And so there's a lot of research that needs to get done.

• 1:00:26Speaker 01

  Yeah. Actually, they time it. So there's, yeah, and they can shut down. So that's kind of the, the, the delivery of the aminaka factors and, you know, the intervention that will time it and stop it. Cause it will, if you, you know, left to its own devices, it will take a somatic cell. So it will take that retinal cell or, you know, a cardiomyocyte and restore and turn it back to pluripotent stem cell. So it's like as young as you get. And you don't want that. So, so all, there's a lot of energy going on, the delivery and the intervention used to stop it and how long the exposure is and all of that.

• 1:01:00Dr. Darshan Shah?

  But it's almost like science fiction type of discovery. And you think about that, like, I could take a skin cell from you and turn it back into a pluripotent stem cell. And, you know, David Sinclair is talking about then taking that and cloning that into another you. I mean, there's, there's like, we're in the realm of science fiction right now. And obviously some of it's like a little bit overblown, but just the fact that we're there and people, I mean, this is legitimate science. People are winning Nobel prizes for these things. I mean, there's, there's, there's work to be done, which is incredibly more exciting than, we just don't know. There's no work to be done because we have no direction ahead in.

• 1:01:36Speaker 01

  Yeah, it's, it is. It's very exciting. It's super disruptive.

• 1:01:40Dr. Darshan Shah?

  Right.

• 1:01:41Speaker 01

  I think people are taking to heart the fact that we spend, you know, our final 16 plus years sick, you know, with, with multiple diseases on polypharmacy. I mean, it's dismal. You know, the health trajectory or the, or the disease trajectory that we're on is, is depressing, but you know, the sun is right there. I mean, the possibility is right there. And people are getting it and taking charge. And to your point, when we were talking off air earlier, you know, the mission, I was actually reading the mission statement of Next Health over there. It's just really cool. You know, you, you want to disrupt this whole, like all of us want to disrupt the slumber that the, you know, the medical system is in, in this country and really the world. So, you know, it's exciting. And the possibilities

• 1:02:26Speaker 01

  are, they're like, they're science fiction, but, um, you know, just very exciting science fiction.

• 1:02:31Dr. Darshan Shah?

  Yeah. The key is to stay healthy long enough and alive long enough to see what science fiction actually comes true, you know? Stayed alive long enough to see a self-driving car actually work. Have you taken a Waymo yet?

• 1:02:44Speaker 01

  No, I haven't.

• 1:02:44Dr. Darshan Shah?

  You can get them in L.A., right down the street over here. Yeah, it's a car that'll drive you around Los Angeles with no driver.

• 1:02:51Speaker 01

  How do you like it?

• 1:02:52Dr. Darshan Shah?

  It is actually really cool. I mean, it's science fiction come to life. And these things are happening during our lifetime.

• 1:02:59Speaker 01

  I think, you know, when when Victoria Sebastiano was talking about it and he he, I mean, it was just the way that he structured it. So, you know, a lot of us think we're going to take a cocktail of yamanaka factors and, you know, turn back to 20. And that is, you know, out there and likely won't land. But rejuvenating the ovaries, you know, exposing the ovaries, because each organ system is different. It's going to need its own cocktail and its own timeframe, et cetera. Rejuvenating the ovaries in a woman, allowing her to, you know, make estrogen for longer and progesterone and so forth, will take care of, you know, not just ovarian function and, you know, her fertility, should she want to have a kid, but, you know, bone health, skin health, brain health, heart health.

• 1:03:43Speaker 01

  So it's like this local application in an organ where you can get this full system leverage effect, I think, makes sense to me.

• 1:03:50Dr. Darshan Shah?

  Absolutely. And there are scientists that are injecting yamanaka factors into livers of animals and causing liver regeneration, which could be incredibly helpful for people that have

• 1:04:01Speaker 01

  Yes.

• 1:04:02Dr. Darshan Shah?

  maybe fatty or fibrous liver disease, right? So these kind of things can be

• 1:04:06Speaker 01

  Yes.

• 1:04:06Dr. Darshan Shah?

  therapeutic in the near future.

• 1:04:08Speaker 01

  Totally.

• 1:04:09Dr. Darshan Shah?

  So exciting.

• 1:04:09Speaker 01

  It's very exciting.

• 1:04:11Dr. Darshan Shah?

  Right, right. And plasma exchange is exciting because it actually, for those of you who don't know what that is, that's a therapy that can be done to remove your blood of 150 cc's at a time, remove the plasma and then reinject it into the other arm, your blood cells. But in the plasmas, where all the negative toxins and the cytokines, that inflammatory cytokines live, and just kind of removing and giving your body a break from these toxins and cytokines can allow your body time to heal. And so these are therapies that have been FDA-approved, that have been in the hospital for a long time, that we're bringing out into the wellness and health care world, the health world.

• 1:04:48Speaker 01

  Yes.

• 1:04:48Dr. Darshan Shah?

  And I think using Things like the Younger You program, combined with plasma exchange, all together can keep us healthier long enough to experience some of these incredible, mind-blowing technologies. But, you know, these things cost money, but what moves the needle more than even all of the things that we talk about that cost money are the things that don't cost money, and putting those into your lifestyle first.

• 1:05:11Speaker 01

  Yeah, that's right. Yeah. Get a good night's sleep, do a little meditation, get your body moving, you know, give someone a hug.

• 1:05:18Dr. Darshan Shah?

  Right. What I love about the Younger You program is it's also free, pretty much. I mean, you can do it for free. You can get the book, you can take your test online and institute it into your life. And it is a sustainable program, actually.

• 1:05:30Speaker 01

  I think it is. Yeah. You can transition the habit and, you know, just transition into that and sort of get used to the targets. And yeah, it is sustainable. And it's nutritionally replete.

• 1:05:40Dr. Darshan Shah?

  Yeah. That's fantastic. Well, thank you for all the work that you're doing, Dr. Fitzgerald, and more to come, I'm sure.

• 1:05:47Speaker 01

  Yes.

• 1:05:48Dr. Darshan Shah?

  The next time you're in Los Angeles, I'd love to have you back on the show to talk about the new things that you're doing.

• 1:05:53Speaker 01

  I'd love to be here and go back to the clinic. It was so fun.

• 1:05:56Dr. Darshan Shah?

  Thank you, Dr. Fitzgerald.

• 1:05:58Speaker 01

  Yeah, absolutely.

• 1:05:59Dr. Darshan Shah?

  Oh, one more thing. Where can people find you? Tell us all the ways.

• 1:06:02Speaker 01

  You can find me, you can find our whole team at drkarafitzgerald.com. Super easy.

• 1:06:07Dr. Darshan Shah?

  And doesn't YoungerYou.com work as well?

• 1:06:08Speaker 01

  Yeah, YoungerYou.com, yeah. You can get to the book.

• 1:06:11Dr. Darshan Shah?

  That takes you to the book and the testing. And DrFitzgerald.com is where people can interact with their clinical team.

• 1:06:16Speaker 01

  Yes.

• 1:06:17Dr. Darshan Shah?

  And if they want to join a Younger You intensive program through telemedicine, they can do that also on drkarafitzgerald.com?

• 1:06:24Speaker 01

  Yes, and they can access the Younger You world through drkarafitzgerald.com. So it's if you need to remember just one, just drkarafitzgerald.com. Newsletters over there, you know, recipes, et cetera, et cetera.

• 1:06:35Dr. Darshan Shah?

  Yeah, your newsletter is great, actually. I really enjoy it. Thank you so much for joining us today.

• 1:06:39Speaker 01

  Thank you. It's great to be here.

• 1:06:41Dr. Darshan Shah?

  Thank you.

• 1:06:44Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you liked this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best and it's always important to seek their guidance.