How To Reverse Age Naturally

Kara Fitzgerald, ND, IFMCP

Actually, there were two studies that preceded mine. We were the first to have a randomized control study, and we were the first to have a diet and lifestyle intervention but the TRIIM study using growth hormone, metformin, DHEA, and Zinc came out. That was the first, that was really the first one. And Horvath, you know, the developer of the bio DNA methylation clock, he was an author of that study. And just to give you some context that came out in 2019, our study was underway at that time. But Horvath is on record many, many times saying biological age in humans really can’t be reversed. Like there’s really nothing we can do about it or there’s really not much we can do about it. There was some evidence that a healthy diet and a little more education might slow things down a little but it was pretty equivocal. And so he was just really blown away with that first TRIIM study. We were interested in changing epigenetic expression with our intervention but I wasn’t holding my breath that we would really be moving the needle on bio age. I mean, of course, we were going to look at it but when our study was underway. When we learned that it was even possible. So I guess to your point, it’s incredibly new that we’ve got this evidence in humans now, and ours was really one of the first studies to demonstrate it. 

Dale Bredesen, MD

And so, yeah, you actually used a, I would say, a more physiological approach, but it brings up some really interesting questions. So, you know, when you reverse cognitive decline and it’s pretty easy to say, oh, your MOCA score went from 20. We’ve seen them go from 18 to 30 and your MOCA score improved. So that’s pretty easy. Now, this is why we say reversal of cognitive decline and why I said that in the very first paper. I can’t say that we’re reversing Alzheimer’s per se. We don’t know. We got to have pathology. Now, the good news is we’ve got blood tests. You can look now at PTau. Did you improve your PTau217? Now with aging, it’s quite different because aging involves a whole panoply of things. And so the question obviously comes up. And yours, as I recall you, reduced 3.26 years, if I remember that correctly.

Kara Fitzgerald, ND, IFMCP

Yeah. 2.4.

Dale Bredesen, MD

Little over three years compared to the control group which is huge in a relatively short amount of time.

Kara Fitzgerald, ND, IFMCP

Yeah, very short. Eight weeks.

Dale Bredesen, MD

So the question is if you change the, what you really did was you change the epigenome that gives you biological age. Now, do you know if you change telomeres? So the question is, when you change one thing, let’s just take the epigenome and you change it. Is that really changing organismal aging? It sounds like the sense is that you probably are because these people are healthier. They seem to be doing better overall. What’s your sense about, you know, changing the epigenome for aging? Are you changing global aging?

Kara Fitzgerald, ND, IFMCP

That’s a great question. I mean, so certainly in standard biomarkers and quality of life questionnaires, and so on and so forth. We would say, you know, of course, we are using this intervention in clinical practice, and looking at a broad swath of standard biomarkers and physical parameters we can definitely see that. But like, to your point, you know, really thinking about the physiology of aging and changing epigenetics, changing the clock. I mean, we could ask the question, are we manipulating? Are we favorably augmenting beyond the standard chemistries and so forth? Which are really fundamental and incredibly important, the hallmarks of aging. Getting to sort of like the root of the aging phenomenon itself and we need to continue to research our intervention to demonstrate that and we are continuing to research it. And we’ll fine tune it and have a methylation diet and lifestyle or younger you as we comment. Branded it 2.0 and stuff but what’s extraordinary is that it seems that aging can be just going to the cellular reprogramming conversation that you and I have. Aging can be manifested by manipulating the epigenome. And so when you change epigenetic expression you can see a manipulation of those downstream hallmarks of aging. 

So you’re sitting, I think, really right in there with root cause aging and so you can do it favorably. When we look at cellular reprogramming or even animal models, some of the work out of Sinclair’s lab, you can see them create age by manipulating epigenetics and then reverse it or, you know, make them younger, biologically younger, physically younger by many different parameters by manipulating favorably epigenetics. A scientist out of Stanford, Vittorio Sebastiano, is demonstrating this in human tissue models and really getting ready for phase one. I mean they’re in FDA talks to actually begin to bring some of this cellular reprogramming technology to clinical trials. I mean, it’s so cool. And so what I want to say is that I think we may be touching on our intervention which is standard diet and lifestyle stuff that we all know is smart. It was intentionally built like you could look at our intervention and say, this looks a lot like a Mediterranean diet. But if you look at it even closer, you’ll see that it’s built brick by brick to influence DNA methylation, which is how we measure bio age. There were very intentional pieces in there. And so the question is, are we touching on sort of root ca aging that can have these downstream effects on all of the hallmarks of aging and that remain to be seen. But I think that quite possibly we’re heading in that direction. 

And there’s actually a new way to measure that. So in Sebastian’s lab, they are seeing that epigenetic reprogramming influences all the downstream hallmarks of aging. I mean, he’s on record saying that he thinks sort of the vis of where you can influence aging sort of the fulcrum is right there in the epigenome. I asked him this, he was on my podcast I asked him, is it the root cause? And he said, I don’t know that it’s the root cause, but if you go in there and you manipulate epigenetics or you’re changing aging downstream, you’re manipulating all the hallmarks of aging. And so they’ve got a clock in their lab that I would like to send our specimen to, where they’re tracking the aging phenomenon across the genome. So it’s a much bigger clock than anything ready in prime time. And they’re showing that caloric restriction has the same, it’s manipulating the same regions as their cellular reprogramming is. And so he and I have been dialoguing about some of the polyphenols, some of the interventions we’ve been using, and whether or not it could have an influence on this clock that’s really capturing, I think, the aging phenomena perhaps more closely. And I would say that you know, it’s possible. I mean, that’s a study that I am just really eager to undertake. But I’ll stop and let you.

Dale Bredesen, MD

Well, that is fascinating. I’ve always considered, for example, when I was at the Buck Institute, so my consideration of aging, you’ve got one person standing with a circle around and one person standing around has got a bow and arrow, one’s got a revolver, one’s got a rifle, one’s got a bazooka. You’ve got to avoid all of these things to age successfully, right? You’ve got to avoid atherosclerosis and you’ve got to avoid cancer. You’ve got all these different things. But let’s talk about some actionable items immediately here. So you brought up something. Everyone’s going to be saying the same thing and I’m thinking the same. Oh, you said you built this brick by brick. You were focusing on methylation. Okay, let’s say that someone wants to use your bricks today.. What sorts of changes in their diets should we make so that we can use your bricks to be a little bit younger, to have to have a younger us?

Kara Fitzgerald, ND, IFMCP

Yeah. So just, you know, going right in there and influencing our gene expression towards something better. We want to be eating, so this comes as no great surprise, we want to be eating a lot of vegetables, of really good quality vegetables. Dark leafy greens, cruciferous. We want to be eating colorful veggies. I get some fruits in there too. Probably lower glycemic stuff like berries and so forth. Mushrooms turn out to be, we call these all epi nutrients.

Dale Bredesen, MD

Most of us are low on it.

Kara Fitzgerald, ND, IFMCP

That’s exactly. Yeah, that’s right. If people are open to doing liver or taking liver in caps, this is another extraordinary nutrient-dense epi-nutrient superstar. We need adequate protein. We need adequate hydration, green tea, curcumin, resveratrol, luteolin, rosmarinic acid in rosemary, turmeric, etc., etc. A lot of the time honored either nutrients used in classic cooking or traditional medicine around the globe are being discovered as having this epi nutrient capacity. And I wonder if that’s why they’re, you know, anti-inflammatory, anti-cancer, brain preserving antioxidant, they’re pleiotropic and maybe it’s because they’re influencing gene expression in such a potent way. So that is anybody can go into their spice cabinet. Easy peasy. Anyone, no matter how picky they are. Chocolate, by the way, coffee. We can all find a bunch of epi nutrients in our kitchen cupboard tonight and in our fridge, really easily.

Dale Bredesen, MD

You know. So it just says empirically things that people were discovering thousands of years ago that were really wonderful. They weren’t so stupid. They were actually kind of on to some good stuff. And so and what about the fasting part of this? What do you suggest for the best impacts on your aging epigenome?

Kara Fitzgerald, ND, IFMCP

So I know it’s powerful fasting or caloric restriction, you know, just in Sebastiano’s lab and what they’re demonstrating. In our study model, we only suggest a 12-hour on 12-hour off structure. And we’re doing that because it’s doable. You know, this is I mean, and we know the data out there, the economic data on if we slow biological age by a year. You know, there’s where we stand to save trillions and trillions of dollars. So we want as many people adopting these principles as possible and we want them to be doable. So a 12 hour and 12 hour off which a friend of mine just called normal eating, is a good entry point into the conversation. If you can do more, you can go to maybe a 6-18 structure, if that’s comfortable, or 14-10. I mean, play around with it. It needs to be something that is not stress-inducing because you can actually have negative fallout if you move outside of something that’s easy or relatively straightforward and comfortable to do. 

But if we have the other pieces we want, I think a larger fasting window is very beneficial. But here’s the other piece and I think this is missed by a lot of people, scientists included, that window where you’re eating has to be packed, in my opinion, with these epi nutrients. And we outline quite a quite a few targets to attempt to achieve. And so that eating window has to be really important. It can’t be like sushi night at the restaurant for your calories that day. I don’t know that you can anticipate getting the same kind of results with that. So the absence of eating is and certainly is important, but the information on our forks is as important.

Dale Bredesen, MD

Interesting. Okay. This is really helpful. You know, there’s such an interesting relationship between the aging process itself and the various diseases we associate with aging from Alzheimer’s to Parkinson’s to cancers to things like that. So that is really fascinating. Okay. And people sometimes say to me, there’s no reason to work on Alzheimer’s. We’re just going to get rid of aging and then Alzheimer’s will never happen. Well, okay. But then I always point out, yeah, there are changes in the brains of these patients in their twenties sometimes. So it’s not purely aging and yet there’s some absolutely fascinating relationship between the aging process because as you know, you just see this dramatic increase up into your eighties and yet the big increase that people have reported in the last few years is in people in their forties and fifties.

Kara Fitzgerald, ND, IFMCP

So, I mean, what is that? I mean what’s happening? What’s happening? What’s influencing those pathological changes?

Dale Bredesen, MD

I mean, to be honest, I think these are functional medicine societal changes. What has happened since I trained way back in the early eighties is we have more processed food. We have more exposure to toxins than ever before. We have more kind of messed up lifestyles and we have more understanding of living among mycotoxins and things like that. Now, to be fair, air pollution, for example, in L.A. has gone down but we’ve got the California fires. We’ve got a lot of things that are driving us so that the way we look at Alzheimer’s is, you know, too little supply or too much demand. You’re on the wrong side of the curve very much like what Dean Ornish found in atherosclerosis. You know, you got to be on the right side of that equation and so we’ve added negatives to the equation. Unfortunately, at the same time, there are so many people who’ve got some vascular disease, some degree of sleep apnea, some degree in their oral microbiome. This is very much a functional medicine problem.

Kara Fitzgerald, ND, IFMCP

Well, let me say this then because I think that you’ve provocatively said that these things are happening really before the aging curve. But in fact, if we were tracking aging, we would see this as an accelerated aging phenomenon. So I think it falls under that heading. We’re seeing this accelerated aging phenomenon even in kids where we see hypercholesterolemia and so forth. I mean, it’s pretty extraordinary. We see metabolic changes. We see prediabetes. That’s the aging phenomenon kicking in. And I think the more sophisticated clocks we have, the more we’re going to really be able to tap into that. So I think, you know, I think that’s,

Dale Bredesen, MD

What is amazing to me because yes with your measurements, you’re going to be able to say, well, here you are 11 but you actually, you’ve got the age of a 25-year-old. Yeah, that is concerning. You know, you can be aware of, unfortunately, which is really tough. And of course, this is what Robert Lustig has been preaching for years. He actually went into pediatrics to avoid dealing with adult diseases. When he got there, he said, oh, my gosh, I’m seeing type two diabetes. I’m seeing obesity. All the things that I thought I was going to get rid of by going into pediatrics. So it’s actually amazing. And you’re right, I do agree with you. These are 20-somethings that may be aging like 40-somethings. And you see the reverse 40-somethings that may be aging like 20-somethings. So this is as you are able to get these data which haven’t been available in the past, you’re going to see so many remarkable scenarios. So let me ask another piece of this then. When you see people with better epi genomes, do they have better telomere lengths? When you start to do the right thing, does it just stop going down or does it actually get larger? I mean, we always worry about if you’re getting larger, is that going to be related to carcinogenesis. What’s happening with telomere lengths in association with this and what’s happened with senescent cell accumulation?

Kara Fitzgerald, ND, IFMCP

So we are looking at telomere length now. We didn’t look at it in our original study. We’re not looking at senescent cell accumulation, although that would be a lot of fun to it. It would be fun to kind of cast a wider net with some of these labs that you’re proposing. We just need to be mindful about the funding model but yeah, that would be fabulous. Telomeres don’t necessarily change. They don’t change quickly if they change at all. I think a goal would be the preservation of telomere length. That would be a reasonable goal. Like when we look at telomere length and we look at the pace of aging, those are the two tools that we’re using primarily these days, the pace of aging being a third generation and the DNA methylation clock. And I would say that we’re not necessarily seeing telomeres track with slowing the pace of aging. My understanding on the, my read on the literature is that we shouldn’t be telomere preservation is probably the best we can do. But I will say that we’ve certainly seen telomeres increase. I mean, we have but I’m not sure how to explain it. You know, when we do, I don’t know that we can say here’s the recipe for telomere preservation. I mean, there are some products out there like the telomerase inhibitor, a Polyphenol which is probably an epi-nutrient. By the way, I think maybe it is, but so there are some things that we can do that might inhibit them. And yeah, you know, to your point, are we concerned about cancer when we see them very long? I don’t I don’t have a really good answer for that.

Dale Bredesen, MD

Yeah. And then, you know, let me acknowledge the late great Dr. Judith Campisi, who was at the Buck for years. I actually recruited her to the Buck many years ago. She’s an incredible researcher, and she was the one who came up with Senescence Associated Beta Gal and also the one who came up with the idea of or did so much work on analytics and was involved in the unity at the beginning of that company. So just a tremendous researcher over the years. Do you think that the things that you’re using in your patients do have a synergetic effect?

Kara Fitzgerald, ND, IFMCP

Yeah, certainly some of those polyphenols have been identified as such. You know, we’re supplying foods with quercetin and so on and so forth. And I think probably the sort of the entire cocktail of the program plus meditation, plus the exercise component, the fasting window taken together I would anticipate has a favorable influence not just on senility but on multiple hallmarks of aging, dysbiosis being a new one. Inflammation, and mitochondrial health, mitophagy. So I would anticipate that we’re touching on multiple hallmarks of aging in our intervention.

Dale Bredesen, MD

Yeah, really fascinating. Now, one of the things that we found in treating people with Alzheimer’s is when you do the right things. And many of them are very similar to what you’ve been doing. Yeah, that’s an improvement in blood pressure. You see improvements in glycemic index in their glucose control in general. And you see improvements in their lipid panels, things like that. Are you seeing that with your approach to you know, in other words, is that part of getting younger?

Kara Fitzgerald, ND, IFMCP

Yeah, for sure. So there are two cohorts that we work with. We have the population, you know, we’ve researched and so far those people are extremely healthy and our intervention is getting healthier. In fact, our two publications, Biological Age, were younger than chronological age at the start, which is kind of cool. So I mean, they were just really healthy and there was evidence that, you know, demonstrating that they were helping and they got and they got younger still. So our cohorts right now are sort of, we’re focusing on looking at the healthy population because we’re interested in kind of isolating the aging phenomena. So that’s been really pretty exciting. We studied, and we published a case series on women who outperformed the guys. They were a series of six women. They got on average about 4.6 years younger using the same clock. However, it was done in blood and our first study was done in saliva so it’s not quite an apples-to-apples comparison but I think it is really cool. And these women, they were biohackers. I mean, they really started, they came to us excited to be early adopters in this. So they were very healthy at the start and biologically younger as well. 

When we use this in the clinical practice, in our clinical practice, where people are coming to us with different with autoimmunity, with cardiometabolic diseases, and with cognitive impairments of varying degrees. Yeah, we see those parameters. We see people lose weight, we see blood pressure improve, and we see antibodies and autoimmune diseases drop. I mean, really not dissimilar from the kind of changes that you see in your protocol. So yeah, we do in the clinical setting, we just haven’t studied it yet and it would be fun. I mean, I would honestly, I would anticipate if we look in a population presenting with like if we were to look in type 2 diabetics and run this program that we know already. Nathan Price published on this, that they have a pretty profoundly accelerated biological age. I mean, the chronic diseases of aging routinely are commensurate with an accelerated biological age. So I think diabetes was the most severe and so I would anticipate our cohort would start out older. But, you know, we would get them that window, that change would be much bigger.

Dale Bredesen, MD

Yeah, that’s a great point. So I guess that brings up the question of, you know, are these people who have these age-related diseases, is it because I mean, is the disease causing the aging or is the aging causing the disease or are they actually both doing you know, is it both or neither?

Kara Fitzgerald, ND, IFMCP

I know that’s such a great question. You know, that’s a two-beer question. I don’t actually drink. But I mean, that’s such a great question. I mean, it gets to the heart of what is aging and it’s a question that I asked you when I interviewed you a couple of years ago. What is it? I mean, I think that there’s the wear and tear of life. The influences on the epigenome. Those changes prompt the aging phenomena. I think that we’re also hardwired. You know, I think there’s probably two paths we’re hard-wired after we’re past reproductive maturity. I mean things begin to change epigenetically. So I think there are two paths of information that we need to tease out to really answer that. However, that’s where you get into Yamanaka factors and cellular reprogramming. I mean, they’re touching on both of those paths. They’re reversing. I mean Yamanaka can reverse age to to pluripotent stem cell status. I mean that’s a real reversal of the aging phenomena. But we’ve got plenty of runways just addressing environmental inputs on the epigenome without even getting to sort of some of the aging phenomena that are probably baked into our genome slash epigenome. We’ve got plenty to do just getting ourselves moving, eating right, paying attention to pollution, stress, and our environmental inputs will keep us plenty busy. Be able to help allow us to experience a health span commensurate with our lifespan and allow us to have a robust lifespan. I mean, we know humans can live a good 120 years. I mean, we know we know that and we know that certain population organs like loose ends populations have a health span commensurate with their lifespan. We also know that those blue zone populations they’ve done a couple of studies, and actually there was a really cool French study, our biologically younger and actually up to 30 years biologically younger. And so sometimes I joke that 100 is the new 70. I mean, so we’ve just by living a good life here and now, we can reverse and slow down biological age and allow our health span to be right in lockstep with our lifespan and extend both of them. And then after that, we can talk about some of the, what my friend refers to Sergey Young is the longevity bridge where we start tweaking cellular reprogramming and, you know, Yamanaka Factor interventions and some of the more radical stuff that’s happening in the, you know, in the research setting.

Dale Bredesen, MD

Yeah, that’s going to be really interesting to see what happens with that. So, you know, when I was on the National Aging Council years ago, there was a report that came out from one of the other people on the council who showed that we in the United States get our first complex chronic illness, our first chronic illness about ten years before people in the UK, typically in our forties, whereas in the UK you get your first one in the fifties and so you end up with a relatively short health span and a relatively long sick span just to get guess where we stand with our life span. So let me ask you then, let’s say we have let’s say someone’s coming to you. They have a 30-year-old person and a 70-year-old person, let’s say could be even father-son or mother-daughter. Are you going to be able to have a similar effect on the two of them in terms of the reduction of their epigenome? Or is there a point where you say I really can’t do it, you are beyond X age?

Kara Fitzgerald, ND, IFMCP

God, I’m, you know, there was a really cool study that came out looking at the influence of exercise on the epigenome. Exercise is really one of our most potent epi-nutrients. You know, it’s probably right up there with kale. It’s so potent and pleiotropic and its influence. And one of the things that they identified and I love to talk about this is the older the individual was, the more epigenetic change, the more bang for their epigenetic change they got. They actually had more impactful epigenetic changes. Specifically, they were looking at tumor suppressor genes. So tumor suppressor genes protect us from cancer and they become hypermethylated as we age, which increases our vulnerability to developing cancer. I mean, it’s just this like, why does that happen? You know, like this raw deal, and then oncogenes are turned on, you know, what’s that about? You know, is it just sloppy epigenetics because of an environment or is there some sort of a baked-in program? But it just it doesn’t seem cool at all. And incidentally, that’s reflected in the tumor microenvironment. So like the tumor microenvironment looks like aging. But it was so exciting to me to see that older individuals actually achieved more bang for their buck by doing epigenetically and exercising. So 100%, I would say we absolutely start wherever you are. You’re with a robust commitment and anticipate seeing benefit.

Dale Bredesen, MD

Okay. Very interesting. So of course, with respect to cognitive decline, one of the things that has an important benefit happens to be BHRT, a bioidentical hormone replacement. Have you looked at that and what is happening with your epigenomic age when you are including BHRT?

Kara Fitzgerald, ND, IFMCP

So I know that the absence of BHRT is or certainly estrogen. I mean, if we look at menopause, we can see that what we can see physiologically once women hit menopause their risk of developing all of the various chronic diseases of aging increases. And we can see that epigenetically as well using HRT or bioidentical HRT has that, to my knowledge, we don’t have any specific publications on that yet. However, it would be an easy data mining project for one of the labs, and my guess is that bioidentical HRT would be associated with a younger biological age. But I could actually get that answered and I’ll email you. You can put it in the show notes for my talk because I don’t have the answer.

Dale Bredesen, MD

This is always an issue because people say, well, you know, I had menopause 10 years ago. And so I’m told, don’t don’t even think about BHRT. But one of the things that fascinated me in our experiments was that you can actually look at estradiol binding to its receptor has an effect on hundreds of genes and one of the ones that increase is the alpha-secretase that cleaves APP in the connection direction. So we think of this now, it can go connection or protection and the protection side is associated with Alzheimer’s disease and connection is associated with making and keeping memories. So estradiol definitely drives it in the connection direction, whereas NFKB drives it in the protection direction, it’s an inflammatory marker, etc. So you can really follow these molecular pathways beautifully to see why these things should or should not work, though. All right.

Kara Fitzgerald, ND, IFMCP

Yeah. And I think we could conclude that there’s a strong place for BHRT.

Dale Bredesen, MD

Yeah, sure. And in your studies, you look at all these wonderful things like their epigenome. They’re they’re biological aging. One of the things that’s been fascinating to me is how do you look at it since we quantify so many different things. How do you look at skin? Skin is one of the most important things to so many people. Does my skin look better? You know, that sort of thing? And so how do you quantitate aging of the skin? Is there a measurement that you do or something you do to say, okay, your skin is three years younger than it was becoming?

Kara Fitzgerald, ND, IFMCP

I think there’s a measurement coming. So there are some, you know, pretty neat scientists a skincare company that was started by four PhDs who developed a skin biological age clock and they’ve published on it. And they’ve actually used it to test various peptides. They used it to pull together a product that they developed which they’re in there researching it and they’re publishing on it and they’re, you know, they’re looking at beyond biological age, mechanistically what’s occurring. I mean, there’s some just really cool science. There’s another there’s another company that’s doing something similar in skin science as well and looking at mitochondrial fitness, you know, and skin health and just showing some cool results. So there, you know, some tools can measure, you know, wrinkles and sun damage and so forth that that could give predict that can produce a biological age like Matty spores have these tools. These tools actually have been used in different research settings. So I think there’s a place for those. But I’m very excited for skin bio age clocks to be available to us clinically. I think that would be really fun.

Dale Bredesen, MD

Yeah. And we clearly different parts of skins are going to have different effects, but you know, it’s something that really impacts people. People know if my skin is going to be looking better, that sort of thing. Yes Very.

Kara Fitzgerald, ND, IFMCP

And I mean we know certainly anybody who adopts a healthy lifestyle habit will see these changes anecdotally. I mean, the fact of the matter is we are hardwired biologically to be able to predict somebody’s age. So we can look. I mean, that’s been published so we can look at another individual and say your X age and your why Y age. And we can look at the, you know, in your why age. I mean, we can actually perceive accelerated biological aging or decelerated aging. So adopting the healthy lifestyle, which, you know, when people say you look great, you look younger, it’s probably actually a trip. It would be fun to actually test it, you know, and to have that hard evidence that’s awesome for people. But really, when people notice why you look great. Wow, what are you doing? The reality is they’re they’re picking up that they’re biologically younger. I mean, there there’s just evidence for that.

Dale Bredesen, MD

Yeah, such a great point. Okay. And then the other thing is, is cognition, of course. Did you do have you done any studies when you’re looking at younger age? Do they seem to be better cognitively or do they even mention, hey, my memory is better? Hey, this is better or what? What’s your sense about that?

Kara Fitzgerald, ND, IFMCP

So this would be more in the clinic setting and not what we’re studying in the research setting. Certainly, we can see that in our MCI patients where we’re tracking with MOCA and in other tools that you’ve been advocating forever. In fact, one of our clinicians is trained in your model for sure. And I mean, I think all of us are using components of it. But one of our clinicians who does it primarily really follows in lockstep your program. And we layering in younger you nutrients and so we will see that in that population for sure but we haven’t we haven’t studied it in the research setting. If you go back to the if you’re at the Buck Institute again, maybe you can bring us on board and we can somehow lock into practice and be able to be able to really answer your great questions because it would it would be so fun.

Dale Bredesen, MD

Yeah, as I say, it is, we have gone from the dark ages, a decade ago where there’s nothing you can do about these things. You know, as Linda Marsh of the science writer said, I don’t think we’ve ever seen a failure on such a level before when you talk about neurodegenerative disease. And of course, the same issue was true for aging where like, what can you do about it? It’s just, you know, it’s going to happen. And now suddenly all these things have opened up and you’re seeing people get better. You’re seeing people stay better. We just have a paper that’s coming out, showing over 10 years of sustained improvement in some of the patients. So I’m really excited about that. You’re reversing biological age so that brings up the other question, which would be the next obvious question. If you’re reversing the age, how much of a Benjamin Button effect can you have? You know, 3.2, four years. Yeah, can you go farther if you keep going? You showed that. As you said, you showed it quickly. What if someone does this for five years? Can they get five, six, seven, eight years? You’re where do you where what is the max?

Kara Fitzgerald, ND, IFMCP

Okay, so I want to make two comments. One is that we can see that Alzheimer’s is an age-acceleration phenomenon. We can see that standard blood biomarkers that have been you know, that have been associated with biological age. So they’re weighted in an algorithm to capture biological age and standard blood biomarkers. We can also see that in DNA, methylation, and biological age clock. So we can see the aging phenomena. And therefore, it stands to reason that we can absolutely get in there and change in reverse bio age as I mean, it’s got it just has to track with the work that you’re doing. And I know you’re bringing these measurements into your research. You just must be looking at epigenetics at this moment.

Dale Bredesen, MD

Thanks to you. So we are working with True Diagnostics to look at epigenetic biological age basically. And we will see where things stand at the beginning of the trial and the end of the trial.

Kara Fitzgerald, ND, IFMCP

I’m so excited to see that. And even beyond the clock, there’s the methyl loam is far greater than the clock. So there’s much else to look at and we’re doing that now. We’re actually working on what they call an epigenome-wide association study with our first cohort and we see that we’ve influenced the course of hundreds of genes, and that’s going to be just really fun. And I think that gets into the nitty gritty of metabolism. And what’s happening preclinical. It’s just very exciting to me. So yeah. So Benjamin Button, like how far can we go?

Dale Bredesen, MD

How far do you go?

Kara Fitzgerald, ND, IFMCP

Yeah. So with the diet people ask me that question. I just it’s so funny. With our diet and lifestyle intervention, we aren’t going back to pluripotent stem cells, you know with our diet and lifestyle intervention. I think what we get to do, to your point, is shut down that sick span and we get to extend. So let’s have a very robust lifespan and have our health span walk in lockstep with that. You know, let’s all live to 120 and be vibrant and strong and active and cognitively intact and just all of that. I think that is one of the potentials for this diet and lifestyle program perhaps layering in some of the like rapamycin, some of the Senolytics combinations that people are using, and some of the other slightly more radical, if you will. Interventions maybe exercise some stem cells and so forth. There are a lot of tools that are nearing that are ready for primetime or nearing. And then at some point, you know, the Yamanaka Factor intervention, you know, will very likely, you know, enter use clinically.

Dale Bredesen, MD

Yeah. And I gather from David Sinclair’s work that as he’s saying if you wait too long it doesn’t seem to do what you’d like it to. I guess you may be able to go from 40 to 20. You probably can’t go from 70 to 30, that sort of thing. Now, we’ll see. Time will tell and maybe ultimately these cars that we drive around called human organisms are going to be you know, you keep on replacing the right parts. You keep on doing the right thing, checking the oil, etc. And that you can keep them going for a very long time. We’ll see. I think this is why I say we are going from the dark ages to a golden age where we’ve got blood tests now for Alzheimer’s. We’ve got better ways to do it. We’ve got the measurements of biological age. We are beginning to understand the relationship between biological age and chronic illness. We’re starting to understand why it’s going awry, what’s happening, what we’re exposed to, where we live, where we eat. I was just talking earlier to Brian Carr about changing the way we build homes. As he points out, he’s driving down the road, it’s pouring rain and all these houses that are being built, all the wood is just sitting out there in the in just wet. And so, of course, they use the same stuff. And now you’re living in mold food. Do you really want to do that? I mean, is that really the best way? So I do think that you know, public health measures. Reducing the processed food, reducing the fire, all that sort of stuff is going to help. So we’re kind of getting to that point of it’s not just about taking antihypertensive and everything will be fine. So this is really a golden era and obviously, you’re contributing hugely to it. And so, Kara, just absolutely great to talk to you, as always. Please keep up the fantastic work. I look forward to hearing more and I’m very interested in everything you’re doing with reversing age. Obviously, you’ve got the stuff, you’ve got the book Younger You. You’ve got the studies on women, you’ve got the studies on both. It obviously works for everyone. And as you’ve pointed out, it seems to work just fine for older people like me, as well as younger people like you. So that’s so fantastic to hear. So thank you very much for your great work. Thank you for joining me.