Pod Insights Extend Podcast with Darshan Shah, MD 67. Chris Mirabile: How to Reverse Your Biological Age (and Why Your Doctor Isn't Talking About It) About this episode What if your real age isn't on your driver's license—but buried in your biology?
In this episode of Extend, I'm joined by Chris Mirabile, founder of NOVOS and one of the few people actually slowing down his pace of aging. We break down why the average person is aging faster than they realize, and how mainstream medicine is decades behind when it comes to prevention.
We get into the 12 hallmarks of aging, why free radicals aren't your enemy, how biological clocks really work, and the lifestyle and supplement strategies that are scientifically shown to make you younger from the inside out.
Chris Mirabile is the founder and CEO of NOVOS, a longevity biotech company backed by leading researchers and data. After surviving a brain tumor at age 16, he became obsessed with the science of living better, longer.
Let's dive in.
We Also Discuss:
Why Healthspan Matters More Than Lifespan
12 Cellular Reasons You're Aging Faster Than You Should
Mitochondria, Free Radicals, and the Truth About Energy Decline
Can We Reprogram Aging? The Science Behind Epigenetics
The Real Pathways to Longevity (That Most Doctors Ignore)
How Your Daily Habits Are Speeding Up—or Slowing Down—Aging
What Your Biological Age Says About Your Future Health
From Supplements to Stem Cells: What Actually Works to Slow Aging
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Transcript 20,148 words · 2 speakers
Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
0:03 Dr. 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.
0:49 Dr. Darshan Shah? Chris, thank you so much for joining us here on the Extend Podcast. Thanks for flying out here and making this happen.
0:55 Speaker 01 Thank you, doctor. It's great. It's great to be here.
0:57 Dr. Darshan Shah? Yeah, so you know, ever since I've met you, I've been very curious about what you do and you as a human, because you've really done kind of what I've been wanting to do for a long time, which is do a crazy deep dive into the hallmarks of aging. And kind of what are the different aspects that we can modify these hallmarks? And I'm really excited to have this conversation with you, because you've done more of a deep dive than almost anyone I know. And it just seems like you have a really good handle on the hallmarks and kind of what affects them and in what direction. So I'm excited to have you.
1:32 Speaker 01 Thank you. Thank you. It's fantastic to be here. I've been looking forward to this for a while.
1:36 Dr. Darshan Shah? Right. And so just so the audience kind of knows your background and why you did all this, would you mind just saying kind of where you came from? And what drove you to this longevity space?
1:46 Speaker 01 Sure. So I grew up in Long Island, New York. And while in high school, I was on a school trip in New York City. And I suddenly got very dizzy and nauseous. And it turned out it was because I was about to have a seizure. And I woke up after that seizure with blood all over my shirt, because I had severed my tongue. And they rushed me to the emergency room. And it turned out that I had a larger-than-golf-ball-sized brain tumor. Was on my left temporal lobe.
2:13 Dr. Darshan Shah? Wow.
2:14 Speaker 01 And they had to do immediate surgery. So they rushed me to NYU Medical Center. And within just a few days, they resected the tumor. And it was a life changing experience for me in every sense of the word. Right? So I, my perspective on life and what I wanted to get out of my life changed. I went from playing on the high school football team to writing poetry in a journal. Uh, cause I couldn't have contact sport anymore.
2:39 Dr. Darshan Shah? Yes, yes.
2:40 Speaker 01 I had so many emotions that I had to, um, you know, sort through.
2:44 Dr. Darshan Shah? How old were you?
2:45 Speaker 01 I was 16 years old.
2:46 Dr. Darshan Shah? So you, yeah, you're like basically a kid going through this. That's so traumatic at that age.
2:50 Speaker 01 It is. And, and it also made me aware of how delicate life really is. And so prior to that, I was already interested in health and nutrition and exercise. So starting from 12, uh, my father helped me install a pull up bar in my basement. And I did pushups and pull ups and started doing curls and stuff at a very young age. And I started to watch what I was eating as well. And so it came as that much more of a shock to me that I would suddenly be struck by a brain tumor. Uh, when I was healthier arguably than almost all of my classmates. And so that's when my thinking about health really transformed. It went from this idea of health being the superficial side of health, which was playing sports well and looking good on the beach.
3:31 Speaker 01 To the real, um, actual health, which is like the biology of, of our bodies, the cellular biology and, uh, organ health and so on. And essentially optimizing our biology to reduce the risk of disease. And thereby also optimize ourselves here and now. So it's a future focus, but it has real world benefits today as well. When you think in that longevity mindset.
3:56 Dr. Darshan Shah? Absolutely. And such a great point because I think a lot of people in general, not just high school students, which I'm actually very passionate about speaking to high school students about health. Because I think there's this misconception that people have that health, as long as you look outwardly healthy, that internally you're also healthy.
4:14 Speaker 01 Right.
4:14 Dr. Darshan Shah? And, you know, that's basically what all we knew for maybe hundreds of years of human civilization. We didn't really know a lot about biology. Biological health and it's kind of, obviously, if you're outwardly healthy, there's a very high chance that you don't have chronic disease going on. But there's also a chance that biologically you are aging faster and there might be something else going on under the hood. And so, you know, at Nex Health, we see a lot of athletes come through. And I can tell you that athletic lifestyle, not only does it lead to things such as metabolic disease, because they're eating just as much as they can to gain muscle and they're eating the wrong foods, but also because of overtraining, you're seeing a lot of inflammation as well.
4:55 Dr. Darshan Shah? And sometimes, like you unfortunately experienced as well, you see people with incidental findings that actually are very consequential, right? And so it's always good to look under the hood further, even if you do live a healthy lifestyle, supposedly, right?
5:12 Speaker 01 Yes, I'm glad you mentioned that because it's something I wanted to mention myself, which is this idea of more is better, which is not actually the case. And it took me a long time to realize this. So I was sometimes going to the gym twice a day, like this is going into my twenties and thinking that exercising more, running more, lifting more and so on is always better. And it wasn't until, I'm 40 now, so it wasn't until I was in my like mid 30s that I came to realize that I was just doing too much. And I needed to prioritize recovery, rest and recovery. And that is equally as important as the actual activity and exercise and so on. So to your point, excess inflammation and the long-term effects of that. And we'll talk later about the mechanisms of aging and inflammaging is one of them.
5:56 Speaker 01 So this chronic inflammation, we want to avoid that as much as possible. And overdoing it is not your friend in that case.
6:03 Dr. Darshan Shah? Yeah, that is so true. And, you know, the more, the more I attend conferences in longevity, I just went to a conference in New York with all the top longevity doctors in the country. This concept of homeostasis comes up a lot, you know? I think our body needs certain levels of stress because it makes our biology more resilient. However, when you push that too far, like to your point, overdoing it, your body just can't catch up. And so reaching that homeostasis is a key factor in all of our health routines, I think.
6:33 Speaker 01 Exactly. So, so what you're talking about is this concept of hormesis, right? So you want to have a A certain amount of stress that our bodies come back more resilient, right? So an example on the topic of physical stress is exercise.
6:49 Dr. Darshan Shah? Right.
6:50 Speaker 01 So if you can only lift five pounds 10 times and you do that today and you do that for a few days, in the future, you might be able to lift five pounds 11 times or six pounds 10 times, right? So you you become a little bit stronger because while you're exercising, you're actually tearing some muscle fibers and the body comes back and says, I need to repair these muscle fibers, but I should make them a little bit stronger next time so that they don't get beat up so much. And that's great when you're doing the right amount of stress. And by the way, it's not only exercise, it's even certain types of foods we eat. So certain antioxidants, for example, aren't actually antioxidants in and of themselves. They're actually these mild toxins.
7:30 Dr. Darshan Shah? Right.
7:30 Speaker 01 Oftentimes, we find them in in plant-based foods. And people will point to them on the internet and say, you don't want to take this because it has a toxin in it. Well, oftentimes, that toxin is actually a healthy toxin because it it induces hormesis where our body comes back stronger and then it produces its own internal antioxidants like glutathione and then superoxide dismutase and so on. So that's the key is to make sure that you get the right amount of stress and you come back stronger and more resilient and you don't have too little stress. You don't want to be like a snowflake and you don't want too much stress where you come back weaker and inflamed.
8:05 Dr. Darshan Shah? It's such a, I'm so glad you mentioned this because it drives me nuts when I'm on Instagram and I see some wellness influencer like demonizing certain vegetables because they have these compounds in them and like how these compounds are going to kill you. And the reality is we have evolved with these plants for millennia. And there's a reason that they're there. And there's a, there's a reason that our human biology is able to eat these plants and come out stronger later. And so even though these might be toxins that can protect the plant from their local environment, it doesn't mean that humans can't eat them and do better with these plants, right?
8:45 Speaker 01 Exactly. And when you look at the scientific studies of people who do eat those plants. Like, take for example, the Mediterranean diet. So you have all of this controversy over which diet is best, and it's almost like religion, and it's tied into politics as well. But putting all of that aside for a second, when you look at the best diet from many, many different studies, it's time and time again, it's the Mediterranean diet, right? And that Mediterranean diet has beans in it, for example, right? A lot of people say you shouldn't eat beans, so it has beans, although they are sprouted, so that is one step you can take. They have lots of vegetables, and they have a moderate amount of protein, and very low animal protein, a moderate amount of, of like fish, seafood, and so on.
9:30 Speaker 01 And when, when we look at that, we see that that is, what's important is to see that that leads to the healthiest outcome. So you can look at it under a microscope, and look at it in a mechanistic way, and say, theoretically, these are toxins that are going to be bad for us, but oftentimes, they actually end up being good for us. And a very quick example of that is, we always think of free radicals as being bad for us, right? But when you exercise, your body produces free radicals. And if you take vitamin C or vitamin E, these healthy antioxidants, after a workout, you're going to counteract a lot of these free radicals. And the result of it, in studies, is that you're going to get less of the benefits from exercise, if you have these antioxidants after a workout, because you're counteracting
10:15 Speaker 01 those free radicals. In this case, the specific case, the free radicals are signals to our bodies to come back stronger, the whole process of hormesis, right? So it's information that's being transmitted to our bodies in the form of the free radicals. So to throw it completely out and say, you don't want any free radicals, it's actually, it's more nuanced than that, as most things in life tend to be.
10:36 Dr. Darshan Shah? Exactly. And another signal that points to the exact same conclusion that you came to there is with hyperbaric oxygen therapy, for example. If you go into hyperbaric oxygen therapy, a lot of the benefit comes from the free radicals that are formed after being in the chamber for a while. And if you take glutathione afterwards, you've basically negated the effect of getting in the chamber. So it's very nuanced, and there's different protocols in hyperbaric oxygen for different things that you're trying to go after. However, they are important. Now, we have glutathione, and we have other free radical scavengers for a reason, and that's because sometimes we do get too much oxidative stress, and... In those moments, it might be a good idea to take some of these, right? In your, what do you, when, when is, when do you think is a good idea to take things like vitamin C
11:21 Dr. Darshan Shah? or glutathione or some of these other free radical oxidative stress kind of scavengers?
11:25 Speaker 01 Yeah, I, I think, um, so we need vitamin C, obviously, otherwise we'll have scurvy, right? So we, we need a certain amount of the vitamin C. I, I do have some vitamin C in a multivitamin that I take, but I intentionally take that multivitamin away from my workout. So I work out in the morning and I'll have the multivitamin in the evening. So as long as there's enough hours separating it, uh, you're still sending those signals to your body now. I don't know to what degree my athletic performance or my muscle growth might be slightly better if I timed it a little bit differently, but there's enough hours where I'm not going to, you know, deal with, with the details like that, right? If I was an Olympic athlete, maybe a different story, but I'm far from that, so.
12:04 Dr. Darshan Shah? It makes total sense. What about taking your multivitamin first thing in the morning before you work out? Is there still an effect that, that could potentially affect your gains afterwards?
12:14 Speaker 01 Yeah, yeah, so there's still like the half-life of, of the vitamin C. And also when it comes to vitamin E, believe it or not, uh, studies have found typically rodent studies, but have actually found that high levels of vitamin E can actually shorten lifespan, which is counterintuitive. And, uh, we don't know exactly why, but most likely it's because of the forms of vitamin E. So what you really want is like the mixed tocopherols and tocotrienols. You don't want a very simple form of vitamin E that you find in a typical cheap multivitamin, right? But to, back to your question, I would say, I personally would try to space it out even more because you have to look at the half-life of these molecules in your blood. And that's going to give you the answer as to how much is still in your blood while you're exercising and post-workout.
12:58 Speaker 01 And you can quickly and easily look that up on, I don't know it off the top of my head for vitamin C, it's probably different for the different forms of vitamin C because you have ascorbic acid, which is commonly found in fruits, but then you've, you've got fat soluble forms and so on. So it's a little bit more technical, but, um, uh, I would personally just try to space it out even more.
13:17 Dr. Darshan Shah? No, that, that makes a lot of sense. So I want to turn the conversation now to the reason we have you on the show. Really focus in on anti-aging and longevity and the entire concept of that. But before I do that, I want to frame this conversation in that when we're talking about longevity and anti-aging, really, you know, it gets a bad rap sometimes because like people assume that we're talking about trying to live to 250 years old. But reality is that what we're really trying to do is increase our health span, the amount of years that we spend feeling vibrant and feeling energetic and having the ability to move and think the way we want to. And through that, the side effect might be that we add more years to our life, which is great.
13:59 Dr. Darshan Shah? I don't think there is a real magic bullet yet to add, you know, decades and decades to our lifespan. And I want to get your opinion on that entire area of research. But just to frame the conversation a little bit, would you mind talking a little bit about the goals of some of the anti-aging and longevity work being done out there?
14:17 Speaker 01 Sure. So it really depends on who you ask. So if you go to a longevity scientist who's really deep in the field, they will say longevity and the most important thing to study is the maximum species lifespan. So that's literally about lifespan and less so about health span. They'll look at health span in the study, but that's a secondary endpoint. The primary endpoint is lifespan. And so in humans, that is, I believe, 124 years. Excuse me, 124 years.
14:47 Dr. Darshan Shah? That's the last thing I read.
14:48 Speaker 01 Jean Calment from France. And so the goal for these researchers and a lot of biotechs in the field is to extend lifespan even beyond that. But if you ask someone who's more pragmatically minded, like I am and like my company happens to be, we focus more on extending health span to your point. And then we expect that by doing so, we're also extending lifespan as well. And I think that that's most important to the vast majority of us. Who wants to live to 150 years if they are, you know,
15:20 Dr. Darshan Shah? In a wheelchair.
15:21 Speaker 01 In a wheelchair. Exactly, exactly. And they're not cognitively sharp and so on, right? So we want to feel like the youngest version of ourselves at any given point in time. That's why at my company, we say be younger for longer. That is our foundational goal. And but that's both, right? So being younger and for longer implies both the health span and the lifespan. So in an ideal world, we are addressing both.
15:46 Dr. Darshan Shah? Well said. And I think this space has advanced incredibly rapidly in the last two decades. First, starting with the identification at a cellular level of what's causing aging. I had the opportunity to meet Dr. Elizabeth Blackburn at TED conference one year when she had first won the Nobel Prize, or first written her book, I can't remember which one, about telomere shortening. And that kind of set off this wave of research at a cellular level of why do people age? And we were talking a little bit earlier about the hallmarks of aging. Would you mind diving into what are the hallmarks of aging just globally? Like, what is that concept? And how has that kind of evolved over the last two decades and where we are now?
16:28 Speaker 01 Sure. So there was a scientific paper that came out just over 10 years ago. And this was an epiphany moment for me when I came across the study. So after my brain tumor, I was very interested in doing everything I could to try to avoid getting another one or any chronic condition for that matter. And so I was constantly on PubMed, trying to get the questions answered. All of these questions I had about health answered directly from the scientific papers rather than through secondary sources. And I stumbled upon this paper called "The Hallmarks of Aging." It was published in a prestigious journal known as Cell. And now it's looked at as a seminal piece in the longevity field. And it essentially broke down the biological reasons why we get older.
17:10 Speaker 01 So it's deconstructing the aging process and looking at everything on a cellular or molecular level that's happening within our bodies. And so at the time, there were nine that were identified. Just last year, those original scientists, those authors, actually republished and added three more. So now there are 12 known mechanisms of aging. There will likely be additional added in the years to come. But we have a pretty firm understanding at this point as to why we are getting older. And then the question turns to, all right, if if aging is the number one risk factor for disease, which it is, that includes cancer, heart disease, dementia and glaucoma, and you go down the list of all of these different diseases, if aging is the number one risk
17:53 Speaker 01 factor, and we're understanding the component parts of the aging process, what can we do to actually slow down the process? And the most logical thing is to try to improve these mechanisms, slow down their degradation. And so to that point, we can talk about the mechanisms, some of the specifically, some of those mechanisms.
18:13 Dr. Darshan Shah? Yes, please, but before we do that, I just want to kind of clarify a thought that I have in my mind about aging as related to chronic disease. So I think I grew up thinking chronic disease is what leads to aging. We start getting Alzheimer's, and we start losing cognitive function, and then that leads to Alzheimer's, which then causes aging. And then we potentially, you know, get cholesterol buildup in our arteries, and that causes heart attacks, which is a symptom of aging. But it's really the opposite kind of thought that I've kind of come to in the last few years, where aging is what is causing us to undergo neurodegeneration, cardiovascular effects, et cetera. And I think that's an important fact, because if we are to look at aging scientifically,
18:58 Dr. Darshan Shah? and we are to address aging from a cellular level, we can potentially avoid chronic disease as well.
19:03 Speaker 01 Yes, 100%. And most people, I think, when they think of aging, they think of this as just something that's part of life.
19:11 Dr. Darshan Shah? Right.
19:11 Speaker 01 Aging is inevitable, right? Maybe they think that it's just the entropy of life. Over time, things get more chaotic, and so even inside of our bodies, and therefore, eventually, things just fall apart and you die. And although there is some truth to that idea of entropy, when we actually break it down into its component parts, we realize that it's actually a lot more to it than that. In fact, if we go back to the 80s, I believe, there was the free radical theory of aging.
19:35 Dr. Darshan Shah? Right.
19:36 Speaker 01 And this was the theory of free radicals, these oxidative stressors actually causing damage in our bodies, and then eventually, there's so much damage, our body can't keep up with it, and we just die, or get disease first and then die. And research have since realized that it's actually much more complex than that. So yes, there is DNA damage that takes place from free radicals and oxidative stress and so on. And that is one of the mechanisms of aging, but it's only one of the 12 mechanisms of aging. So as usual, it's more complex than we first thought it was. But we are getting closer and closer with each day into understanding it. And then also being able to reverse aspects of it. And even on an organ level, and we can talk about some of the experiments in epigenetic reprogramming,
20:19 Speaker 01 where we're able to actually make an old organ young again. So this is more in the future side of longevity. It's not practically available for humans right now, but it's something that can come in the years ahead.
20:30 Dr. Darshan Shah? Wow, that's exciting research that's happening. And let's do that, let's go ahead and dive into a few of the hallmarks of aging. And I know they're kind of split up into different categories as well, right? So maybe you can kind of take us through some of the hallmarks.
20:42 Speaker 01 Sure, sure, happy to. So I'll talk about a few that people are probably most familiar with. At least they're key words that they've heard before. So mitochondrial dysfunction, for example. And this is one that is is a favorite among the wellness community, always talking about, you know, optimizing your mitochondria, right? So what are mitochondria? They are essentially the power plants within our cells. They take the fat and the carbohydrates that we eat and then convert it into energy. Energy currency being ATP, right? Through a process known as the Krebs cycle, which we might talk about again later. And as we age, we have fewer mitochondria. And those mitochondria are not as effective at generating energy anymore.
21:25 Speaker 01 And the result is it's not simply energy. We typically think of energy as like the ability to exercise or think. And that is like the downstream effect of it. But cells have all different functions within our bodies. Some of them are immune cells, some are detoxification and so on. So when you have less energy, you're going to do your job a little bit less well. And that happens from mitochondrial dysfunction. So the question for longevity is how can we optimize these mitochondria? How can we have more of them? And how can we make them more resilient and producing more energy output? Things like exercise are the most obvious ways to do it, but there are also different molecules that can be found in supplements, for example, that can have a hormetic
22:06 Speaker 01 stress on the mitochondria and then lead to more resilient and plentiful mitochondria.
22:12 Dr. Darshan Shah? Now, just to double click on mitochondria for a little bit, what I find incredibly interesting about mitochondria is they were actually separate organisms from unicellular organisms and these organisms teamed up synergistically to form life, basically. And so mitochondria has its own DNA that create more mitochondria within the cell. And so it's just really interesting to me that we have to look at them as a little bit separate and they have their own biology that we can affect.
22:42 Speaker 01 Exactly. Yep, that's a great point. And another interesting fact about it is that all of your mitochondria comes from your mother. So you don't get your mitochondria from your father. So you can either thank your mother or blame her, depending on where you stand with your energy production. So.
22:58 Dr. Darshan Shah? Is the reason for that is because when the ovum and the sperm come together, the ovum is the one that has all the mitochondria already in it. So those are the ones that are replicating in the fetus?
23:08 Speaker 01 I turn that question back to you, Doug. I actually don't know the answer to that.
23:12 Dr. Darshan Shah? I seem to remember that from medical school somewhere, but I'll have to fact check myself on that one. All right. So we know mitochondria is super important and sometimes in my brain, I try to rank these hallmarks of aging, but what I find is every time I try to do that, they all kind of fall into almost equally important. So I don't know how you think of them, but what is your next kind of one that you're focused on more than?
23:36 Speaker 01 Yeah. So you raise a good point, which is that this is a complex web where each of them impact each other, right?
23:43 Dr. Darshan Shah? Exactly.
23:44 Speaker 01 And so looking at them in isolation, although if you improve one, you will probably have reverberating effects across all of the others. In the ideal scenario, you're actually impacting all of them. And that was the insight I had when I first started my company was how can we impact all of the mechanisms of aging? Now, I was focusing first on not necessarily the most important, but on the most commonly known, right? So mitochondria or stem cells are commonly known, right? A lot of people are getting injections of stem cells. But in terms of the most impactful, one of the more impactful ones is the epigenome. So the epigenome is actually, a simple way to think of it is which genes are turned on and off. So we're all born with our genes and they are permanent. They don't change.
24:29 Speaker 01 There is CRISPR technology, which might change that for certain people in the future, but for the sake of discussion, it's permanent. It doesn't change. Then we have our epigenome. So if you think of your genes as being like the piano keys, you're not changing your piano keys, they exist. But the music you play on your piano can be very different, right? So imagine when you're first born, you have, you're playing a beautiful song. Let's just say it's Vivaldi Four Seasons, right? It sounds wonderful. But as you age, you hit the wrong key, or you press it too hard, or too soft, or you miss a key. And so that song doesn't sound as good anymore. And that's essentially what's happening with our genes as we get older. So epigenetically, different genes turn on, that shouldn't, and different genes turn off,
25:14 Speaker 01 that shouldn't, or it's actually more like a dimmer switch, so some might be more dimmed than others. And it's not as optimal. So there's a number of things that come out of the epigenome. One is biological age clocks, which we can talk about, but you can actually measure it by looking at your epigenome, measure your biological age, that is, by looking at your epigenome. But it also impacts the health of the cells and by extension, the organ, that is the epigenetic expression, or the current status of it, right? And so there are researchers, there's actually a Nobel laureate named Yamanaka, who discovered these three enzymes, so they're essentially proteins, that are able to coerce an old
25:56 Speaker 01 cell to get back to its stem cell state again, which is, stem cells, I mentioned it earlier, but very quickly, stem cells are essentially the cells that can then replicate and turn into, create copies of your cells. So you need your stem cells to create new, healthy, resilient cells, because our cells are constantly getting damaged and dying and so on. So bringing it back to like, basically like a fetal state with these Yamanaka factors, which was an amazing discovery.
26:22 Dr. Darshan Shah? Massive discovery. Yeah. One of the most game changing discoveries ever in human history to be able to take a cell, any cell from your body and turn it back to a pluripotential stem cell is just mind blowing.
26:35 Speaker 01 Exactly, exactly. And then, and then so the work that followed, so Professor Ocampo, who I met with in Lausanne, Switzerland to see his lab and talk to him about his research, he ran a study where he used these yamanaka factors in aged mice and was able to make their livers young again. So imagine having an old mouse that has a serotic liver and they're able to then essentially make it the same equivalent of these young mice. And so then that's, that started a lot of enthusiasm around this idea of yamanaka factors and the epigenome and the possibility, essentially the information theory of aging that Dr. David Sinclair at Harvard has really popularized, that it's actually an information loss issue
27:20 Speaker 01 of the epigenome, almost like a scratched CD is how Dr. Sinclair talks about it, to polish that CD off and then actually make it function properly again. The music plays, back to my analogy, plays properly again, right? And so I know Dr. Sinclair is doing research on, on eye health and aged eyes and trying to cure age related blindness. And so there's a lot of potential behind the epigenome. Now, what I would caution is for people to think that, okay, now we're going to be able to make everyone young again and because our bodies are much more complex than that. And like being able to make one single organ younger again, doesn't mean it's going to be easy or even attainable for us to make everything across our bodies young enough
28:02 Speaker 01 again to make people live much, much longer lives. But on a, on a specific organ level, there's, there's more potential in the midterm, I'd say.
28:12 Dr. Darshan Shah? That's, that's great to hear because I had a conversation with Dr. Peter T about this because he's very practical about. You know, to kind of what's out in the news in science and what can actually be applied. And you had a very important point, which is, you know, yamanaka factors are an incredible discovery, but to be able to apply yamanaka factors to your entire body and expect it to reverse age is kind of science fiction, right? You can't just give someone IV yamanaka factors and somehow they go to every cell and they just stop yourself from reverse aging at exactly the right moment. There's no Benjamin Button kind of science going on here that's going to work. So it takes scientists like Ocampo to really look
28:52 Dr. Darshan Shah? into organ specific aging and how can we target organs and reverse specific cells in reverse when we need them to be. And so my question to you is, how is he applying those cells to the liver of these mice? And how is he controlling that reverse aging process? Do you have any insight into that?
29:13 Speaker 01 I believe that they were injected.
29:15 Dr. Darshan Shah? Directly to the liver.
29:16 Speaker 01 Directly into the liver. And also what's important is to decide which of the yamanaka factors. So there are three, but there are only two that are needed to be used. And what was found is that if you used all three, it might bring the cell back to too young of a state. And a concern becomes that either they lose their identity, they have an identity crisis, right? Or actually, the cells can actually become cancerous and turn into tumors. So it's not this very simple approach of taking yamanaka factors, to your point, like drinking it or injecting it and suddenly get an IV infusion and suddenly become young again. It's a lot more complicated than that. And looking at it on an organ specific basis,
29:58 Speaker 01 even the specific yamanaka factors, the ratios of them, maybe there are other enzymes that can have another additive effect or modulating effect so that it doesn't go over the top. So there's still a lot to learn there. So I don't want people, like you said, the headlines say one thing and they want to sensationalize things. We're a while away from it being practically relevant for them, for most of us. But it's also still something to be very excited about and hopeful for, for the future.
30:26 Dr. Darshan Shah? Yeah, I think the excitement for me comes from the true understanding that these things can do these, at least even in vitro. And we have the ability now to research on pluripotential stem cells, whereas prior is very difficult to get these stem cells to even do research on.
30:42 Speaker 01 Yeah, you're right. I mean, you're reminding me when I was when I was in college, I was planning to start a business to bank stem cells from at the time it was just discovered by an NIH scientist, Dr. Song Tao Shi, I remember acutely, in deciduous and scissors, which were teeth. So it's the technical term for teeth. And formerly, or prior to that, companies were banking it from umbilical cord blood. And this was much more convenient. And so I was planning to launch this business to basically bank baby teeth, only to then hear about the discovery of the ability to coerce cells to become pluripotent again. I was like, oh, this business is going to be outdated in no time. And that was just
31:24 Speaker 01 my being a naive college student and not realizing how long it takes for this to roll out. And now there are plenty of businesses that are banking the baby teeth.
31:34 Dr. Darshan Shah? Yeah, exactly. So funny.
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32:56 Dr. Darshan Shah? You know, we touched on methylation as one of the hallmarks of aging, and I know we're going to come back to that when we have a discussion around biological age clocks. But I would like to go through some more of the hallmarks.
33:07 Speaker 01 Sure.
33:07 Dr. Darshan Shah? You mentioned stem cells, and stem cell exhaustion is one of the hallmarks. And are there ways that you've seen to counteract stem cell exhaustion?
33:14 Speaker 01 Yeah, so just to clarify, when you say methylation, that's specifically the epigenetic approach, right? So the methylation is like the process that takes place for the epigenome, just in case a listener didn't catch that. So, stem cells, yes. So as I mentioned, stem cells are important because they are making replicas of our cells. And we can only make so many replicas. So there's something known as the Hayflick limit. And once you make a certain number of copies, which is a very large number of copies, but once you make a certain number, the stem cell is dying off, or it's not actually able to make perfect copies anymore. And when you start to have a cell that's not functioning properly, you're going to
33:57 Speaker 01 have either a higher risk of that cell turning senescent, or it having flaws in its DNA, and then turning cancerous, and so on. So I would say when it comes to stem cells, a couple of things to consider. One is, the more damage you have to your cells, the more you need to replace your cells, the more you then need to have, you know, use your stem cells which you might exhaust, right? So, living a healthier life and avoiding toxins and smoking and so on, is going to, on its own, have a favorable effect on your stem cells. It will also simultaneously have a favorable effect on what you mentioned earlier, telomeres. So telomere shortening is another mechanism of aging.
34:40 Speaker 01 So your telomeres are the end caps of your chromosomes. Your chromosomes contain your DNA. And so if you think of an analogy would be the the ends of your shoelaces. So your shoelaces have all of these little threads in it and the the caps on your shoelace are what keep everything together essentially and when the, as we all know, you step on on the caps of your shoelace and then eventually comes undone and then all of the threads come out. So imagine that being your DNA being exposed. That's a problem. And so studies have found that although telomere shortening is associated with aging, it's not directly correlated. I mean, there's a correlation, but it's not strong enough of a correlation. So in other words, by looking at my telomere length and your telomere length, we can't conclude how old we are biologically or even chronologically
35:25 Speaker 01 just by looking at that. But what we can see from telomere length is your disease risk. And so, for example, you you can reach something known as the telomeric brink. And that is when your telomeres get too short to the point that you have a higher risk of disease. Say gastrointestinal cancers, for example, are correlated with shortened telomeres. You also have a higher risk of of death once it gets to that point. So for telomeres, it's one of those things that we actually offer a test at my company that looks at both biological age on the epigenetic level, but also telomere length. What we tell our customers is it's about, it's a check off the box metric. It's about making sure you're not in the lower percentiles for your age cohort.
36:08 Speaker 01 So if, in my case, being 40 years old, I want to make sure that compared to other 40 year olds, I'm in, you know, ideally above the 50th percentile, which which I am fortunately. But if you're in like the 20th or the 10th percentile, that's when you should start to get concerned. There's something happening there that you need to keep an eye on because although you're still young at 40, you're in the the the lower end of the range and you need to do something to try to either lengthen the telomeres or slow down their their
36:36 Dr. Darshan Shah? Degradation, right, exactly. You know, and that brings up the next topic, which is another hallmark, was a senescence and cellular senescence. So would you define that for us and just kind of give us your take on that?
36:48 Speaker 01 Sure. Sure, so senescent cells are are becoming more popular. You're seeing, you know, influencers on the web talk about senescent cells and they'll oftentimes call them zombie cells. The reason they call them zombie cells is because these cells are not really alive performing their function. They're actually in this this semi-dead state, but not completely dead, to the point that they're actually secreting a inflammatory molecule.
37:14 Speaker 01 Senescent associated secretory phenotype is what it's known as, or a SASP, S A S P. And so this is actually, the SASP is actually causing damage to nearby cells and increasing inflammation, increasing the risk that they turn senescent and so on. And that's part of the reason why senescent cells, as we age, they go up exponentially. All of these mechanisms actually increase exponentially. But part of the reason is the SASP is impacting nearby cells and thereby turning them into senescent cells. Senescent cells are one of the reasons why our skin wrinkles as we age, it's one of the reasons why our arteries stiffen, along with glycation, for example.
37:55 Speaker 01 And so we want to do what we can to either prevent senescent cells first and foremost, or reduce their spread, essentially preventing, or in some cases, try to destroy those senescent cells. But we need to exercise caution because there's actually some recent research that finds that there might be some beneficial protective effects of the senescent cells. And verdict is still out. We don't know for sure exactly in what cases they're providing a benefit versus not. Now, overall, I will say that senescent cells, you want to eliminate them for the most part, but we don't fully know. Now, one of the things that senescent cells does that's protective, actually, is it can take a, our bodies can take a cancerous cell and turn it senescent.
38:40 Speaker 01 Now, ideally, the immune system is identifying a cancerous cell and just destroying that cell and using autophagy to basically digest it and then recycle its parts. But sometimes it flies under the radar and for one reason or another, it turns senescent. So there's a reason why it exists. Even when women give birth, there's a large number of senescent cells that form from the birthing process. So when you scab your knee, there's senescent cells that accumulate around there. So there is some sort of purpose. But then the question is, for how long do you need them? And do we want to eventually get rid of them because of the damaging effects that they can have?
39:15 Dr. Darshan Shah? Yeah. You know, it's really tied into this whole concept of hormesis again, where, you know, I think doing certain activities like long-term fasting can also help you clear senescent cells, right?
39:26 Speaker 01 Yes, yes, you're right, you're right. And to that point, scientists are also working on creating substances known as senolytics. So seno for senescence and lytic for lysis, like cutting or removing, destroying the senescent cells. There's a very popular cocktail that some biohackers follow, which I would personally never touch, but it's a combination of the statinib, which is a mild chemotherapeutic, plus the natural molecule quercetin. And they will take it, you know, once every six months or so, because for senescent cells, generally speaking, for senolytic, you want to just do one high dose and then to destroy senescent cells and then stop, because you don't want to damage healthy cells, right?
40:07 Speaker 01 But I would be concerned about the possibility of this damaging healthy cells in the process. A very quick fact about one of the products we sell is that we did a mouse study, which if we have time, we can talk more about later, but we actually outperformed lifespan extension of the de-statinib- quercetin combination. So this is something that has been already shown to extend lifespan in my sense, considered one of the most high-tech things, and our natural formulation that you can take over the counter has actually outperformed that.
40:36 Dr. Darshan Shah? Interesting. I'd love to dive into more of those compounds here in a bit, but I want to just finish up the whole conversation around the hallmarks of aging. We haven't touched on nutrient sensing pathways yet, and I'd love to hear your take on, well, first an explanation, because you're so eloquent about explaining these hallmarks, I want to hear how you explain nutrient sensing pathways and degradation of those over time, and how does that happen, and how can we use lifestyle interventions to help, potentially help, turn that process around?
41:04 Speaker 01 Sure. What you're talking about are some common terms that people may have heard of, popularized by people like, for example, Dr. Peter Attia, who you mentioned earlier. Is mTOR, for example, or AMP kinase, right? So let's start, we'll stick with those two to keep it simple. So mTOR is a growth pathway. So when you consume proteins, for example, and to some degree carbohydrates as well, you are stimulating the mTOR pathway, which is that of growth. So we want to create new cells essentially. And that sounds great at first, but we actually don't want to always be creating new cells. And when we live in modern society where we are in a constantly fed state,
41:49 Speaker 01 we never have, you know, periods of famine. And whereas historically we did.
41:55 Dr. Darshan Shah? Right.
41:55 Speaker 01 And all animals go periods where they're not eating, right? We don't really have that anymore. So mTOR is always engaged. And I mentioned earlier, like for example, with stem cells and telomeres, if you're always replicating cells, that can actually have a negative effect.
42:09 Dr. Darshan Shah? Right.
42:09 Speaker 01 So one of the reasons why fasting is actually good for you, also the prescription drug that's popular, rapamycin, which has a lot of scientific research around its ability to extend lifespan across many animal species. Everyone that has been studied.
42:23 Dr. Darshan Shah? Yes.
42:24 Speaker 01 And actually has extended lifespan is because it mutes or down regulates the mTOR pathway.
42:31 Dr. Darshan Shah? Sure.
42:32 Speaker 01 And so that is something that's correlated with longer lifespans is reducing the mTOR. Now AMP kinase, on the other hand, is a pathway that's associated with like nutrient starvation. So when you exercise, for example, your muscle cells, they need more nutrients. And so they will exhibit AMP kinase or they will stimulate that pathway. When you fast, you're actually reducing your levels of nutrients, but then your AMP kinase is stimulated. And this is also associated with longer lifespans and better health spans. So that's the combination of these two are, you know,
43:15 Speaker 01 a good reason why fasting, for example, is going to have favorable effects on your health. You're reducing the mTOR and you're increasing the AMP kinase, both of which are associated with better health. Now you ask, why, why do they, why is our ability, our body's ability?
43:30 Dr. Darshan Shah? Yeah.
43:30 Speaker 01 To sense these degraded over time? And There are multiple reasons for it, but a couple are, for example, and now this is getting into two more mechanisms of aging.
43:40 Dr. Darshan Shah? Yes.
43:41 Speaker 01 One is intercellular communication. So our cells are all communicating with each other. And as we age, they're not able to communicate with each other quite as well as they were before. And as a result, the signals that should be sent across the cells of, you know, whether mTOR or AMP kinase are kind of muted. They are not able to communicate through this vast network of cells that we have in our bodies, right? There's a lot of intelligence within our bodies, crazy amount of intelligence in our bodies that we don't fully even comprehend.
44:14 Dr. Darshan Shah? Right.
44:14 Speaker 01 And so that's an intercellular communication. Then there's also something known as loss of proteostasis. And proteostasis is, so in the word proteo is proteins, is proteins, they, they're these chains of amino acids and they need to fold in a certain way. And that shape then gives it the ability to essentially signal to different cells throughout our bodies, how to behave, how to act. And as we age, we're not able to fold those proteins quite as well anymore. And the result is these proteins aren't stimulating when they should, and that's part of that communication issue. And then they're also sometimes getting stuck like outside of the cell or inside of the cell and they're accumulating.
44:57 Speaker 01 So the, those are the first that come to mind in terms of the possible explanations for the nutrient sensing pathways.
45:06 Dr. Darshan Shah? Yeah. And that's a really good review of the original mechanisms of aging. And now, 10 years later, they came up with another paper adding three more to the list. And I'd love for you to just kind of run me through those real quick.
45:20 Speaker 01 Sure.
45:20 Dr. Darshan Shah? Yeah.
45:21 Speaker 01 So we talked earlier about inflamaging.
45:23 Dr. Darshan Shah? Right.
45:24 Speaker 01 I mentioned it quickly. So inflammation is this process that is actually happening within our bodies. And when we're young, it's pretty much absent. But as we get older, it's like a quiet whisper that turns into a hum that eventually as we're very old, it's this like loud, obnoxious noise of this inflammation within our bodies. And that inflammation is causing damage. And so we want to do everything that we can to try to reduce that inflammation.
45:54 Dr. Darshan Shah? Right.
45:55 Speaker 01 That's the first new hallmark.
45:58 Dr. Darshan Shah? Yeah, and what's important about that is I think that's our immune system actually trying to work to protect us, but because it turns from a hum to a dull roar to a massive flame as we get older, it's actually damaging good tissue and good cells in addition to trying to remove us the toxins from our body and infections, et cetera. And being able to keep that process under control is extremely important as we age because actually more and more relevant as we age.
46:27 Speaker 01 Exactly, yes, yes, you're right. You know, the baby aspirin is one of the, you know, it's associated with longer lifespan or health span. And one way it could potentially be doing that is because it's like a very slight anti-inflammatory dose to help to mute that.
46:43 Dr. Darshan Shah? Exactly, yeah. And so inflammation is one of them, and what are the other two that they've recently identified?
46:48 Speaker 01 Sure, so the next is disabled macroautophagy or reduction in autophagy. So autophagy is a process, again, largely based on the immune system that is essentially looking for cells that are old and not performing their function well and basically digesting them and then recycling their parts. And so this is important in case, for example, we mentioned earlier, there's a cancerous cell or the cell's not performing its job well. So the body needs to recycle that. Autophagy goes up significantly when you fast or you calorically restrict, you have more autophagy that takes place. And so that's like a cellular cleanup process, which is very important for us.
47:31 Speaker 01 But as we get older, our immune systems aren't as strong as they were, they're not as good at identifying the cells or even the threats on an immune system level and removing them. And so that's something that happens as we get older is reduction in the autophagy.
47:48 Dr. Darshan Shah? Got it, got it. And autophagy, I mean, you hear about autophagy a lot with biohackers trying to stimulate autophagy and. There's different molecules that can do that as well. And there are different things you can do to just your wellness routine to stimulate autophagy. And once we get through the last of these hallmarks of aging, I'd really love to talk to you about what are things that people can do to affect all of these hallmarks. So what's the last one? And then we'll touch on the things that we can do.
48:16 Speaker 01 Yeah, sure. So the last one is microbiome dysbiosis. So our microbiomes, everyone is hearing about our microbiomes over the past, say, 10 years or so. It's become more and more popular. It's actually a field that is pretty new. So it's far more complicated than people maybe initially thought. And so there's a lot more research we need to do to fully understand our microbiomes. It's like an entire universe in our guts. And so it's incredibly complex. But as we age, our microbiomes, they become less diverse. So we have fewer bacterial species. And the species that we do have are not as ideal. Some of them are, for example, associated with inflammation.
48:58 Speaker 01 There are certain species that are associated with longer health spans and lifespans. So for example, centenarians have higher, higher levels of Akkermansia, probiotic species. But it's something that's relatively new. But a lot of things actually happen from our guts. We have seven gut organ axes, right? So we have our gut-brain axis, our gut-heart axis, our gut-liver, gut-skin, and so on. And so the things happening in our gut can affect many different organs and how we feel and how we function and so on. So it's, it's an area of like great excitement for researchers to be better understanding
49:38 Speaker 01 to what degree this universe of species within us are actually impacting the full body, the full organism.
49:45 Dr. Darshan Shah? Absolutely. I mean, the gut relatively until recently, it's been kind of hidden inside of us, both, you know, metaphorically and in science. And now this incredible Burst of research around the microbiome has just been so illuminating to doctors especially as to how much the gut really impacts our brain, our heart, all the different seven gut axes that you mentioned. It's just, it's just so exciting because now we can truly affect other organ systems through modifications in our gut microbiome, which is massive, right? Because, and what's really massive about that is that the therapeutics that can be developed through gut microbiome manipulation can be safer and much more effective than
50:30 Dr. Darshan Shah? actual pharmaceuticals.
50:31 Speaker 01 Exactly, yes. There's a tremendous amount of potential behind it. It's just we're at the beginning. We're at the early stages of it. Of course, there's things like fecal microbiota, transplants, and people see improvements in many different issues, whether it be IBS or body fat reduction and so on. But we're just getting started, really.
50:51 Dr. Darshan Shah? Yeah, it's really incredible to see kind of the science kind of blossom in this. But to your point, we are at the very beginnings of this. And so, you know, whenever there's new science out, everyone jumps on the bandwagon and tries to sell you every probiotic and, you know, diet that they can, really without much knowledge of what's really going on in the microbiome, because we just don't have the knowledge right now. There's so much more that needs to be done. So people need to be careful.
51:18 Speaker 01 Exactly. Yeah. So for example, taking probiotics, it doesn't really change your microbiome, right? So acutely, like for the day that you took it, it might have a small effect. But even then, it's so few CFUs, the colony forming units, right? Like the amount is so small that it has relatively, it's like a drop in the bucket. And so, that's not to say all probiotics in all instances. There are cases where, you know, they can be helpful for people. But there's still a lot to be learned about how we can actually have those probiotic strains live and flourish within our guts and for the specific outcomes that we're looking at, whether that be cognitive or skin health and so on and so forth.
51:59 Dr. Darshan Shah? Right, right. And, you know, what I really love about going through these hallmarks with you is it really frames the discussion. Well, it serves as a framework, really, for the overall discussion of aging. And if I were ever to teach a high school biology course, which is actually a dream of mine, is add a chapter in a high school biology book. On health and wellness, I would use this hallmarks of aging structure to frame the entire discussion around the molecules and the lifestyle interventions that you can do to truly affect your health. And so when you go through this list, in your mind, how do you think about how people can affect all of these factors through lifestyle interventions? What are the, what are the big things that people can do to really modify all of these at the same time?
52:45 Speaker 01 Yeah, great question. So it's predominantly our lifestyles, right? So we, we mentioned earlier the idea of our genes and then our epigenome and so on, right? Most people, when they think of aging and health, they think their genes are responsible for their health outcomes. But researchers have found that it's really only 10 to 20% your genes. And it's actually predominantly your lifestyle and your environment in terms of the air you breathe and the things your eyes see and so on. And so I think that for, for those of us who are proactive, that's very empowering because we realize we can take our health into our own hands and our health span and our lifespan are things that we can directly impact here and now. And we can literally, literally slow down our rate of aging. It's
53:27 Speaker 01 scientifically shown that we can accelerate our aging or decelerate our aging. And it comes down to our lifestyles, the foods we eat, the perhaps supplements we take, even prescriptions and so on.
53:39 Dr. Darshan Shah? Right.
53:39 Speaker 01 So the categories, I would say, really come down to nutrition. And when I say nutrition, it's not only what you eat, it's how much you eat, when you eat it, and when you're not eating, right? So meal timing and fasting and all of these things play a role.
53:51 Dr. Darshan Shah? Exactly.
53:52 Speaker 01 Next is activity. We already talked about for most Americans and most people in general, it's about doing more activity. But for some people, as we said, it's about doing less activity.
54:02 Dr. Darshan Shah? Right.
54:02 Speaker 01 Next, I would say is recovery. And in that category, I would include sleep, sleep, which is oftentimes neglected. It's becoming more and more popular for people to focus on sleep. But I, I remember when I graduated college, like people said, like, I'll, I'll sleep when, when I'm dead. And, you know, people were with like a badge of honor that they, they did an all nighter and they worked from until 6am and then they started again at 9am, right? So
54:26 Dr. Darshan Shah? In reality, you just took a week off your life, probably.
54:29 Speaker 01 Exactly.
54:30 Dr. Darshan Shah? You should have worked half the day and you lived longer, right?
54:33 Speaker 01 Right, exactly. Yep, yep. And so, so at this point, it's, it's encouraging to see the emphasis that's being put on sleep because it's incredibly important. Another category would be psychology. And I would, I would put very close to that psychology is relationships. So when it comes to psychology, having a positive outlook, having purpose in your life, relationships, having strong relationships, being social, having people that you can count on, that you can talk to about anything on your mind, or non-toxic in your life and so on. And then supplementation, I would simplify and say you've got really three categories of supplements. You've got general health supplements.
55:14 Speaker 01 This is really just to maintain the bare necessities for you to be healthy, right? So this is what the government has the RDAs for. The vitamins and minerals that you find in multivitamins and so on.
55:28 Dr. Darshan Shah? Things that are essential for survival and our cellular health fall into this category.
55:33 Speaker 01 Exactly. Vitamin A, the B family, C, D, E, K.
55:36 Dr. Darshan Shah? Like if you don't get them, you'll get into a disease state. Like you don't have enough vitamin C, you get scurvy, et cetera.
55:41 Speaker 01 Exactly, exactly. And there are ideal levels that are oftentimes actually higher than what the government recommends. The recommendations by the government are what you need to avoid scurvy in the short term, right? But it's not about optimizing your biology for the long term. And those levels are typically higher. There was an analysis done of the NHANES data set that looked at the longest-lived people in different cohorts and then like how much of each of the nutrients they were taking in. And essentially what I gathered from that study was that almost 100% of Americans are getting inadequacy of at least one critical nutrient. That might be vitamin D, it might be vitamin K, it might be magnesium, might be choline, the forgotten B vitamin as it's called, right? Which you can find in egg yolks. At least one of them, and most oftentimes it's more than one.
56:26 Speaker 01 So there is something to be said about that. Second category would be a goal-specific outcome, right? So these supplements might focus on, for example, athletic performance or post-workout. It might be for libido enhancement or nootropics for cognitive function and so on. So goal-specific. And then the third category, which is technically within that second category, but for the sake of this discussion, we'll separate it. It's the longevity-specific supplements. So just because something is good for you in the short term for a specific outcome, like focusing better or feeling more energy or performing better in your, you know, running or weightlifting, does not mean it's actually good for you in the long term. And this is something it took me a while to actually come to the realization of.
57:11 Speaker 01 But some things are good for you in the short term, but bad for you in the long term. And so we take the perspective of looking at things that are found to be good for you in the long term, associated with longer health spans and lifespans, but then also ideally are providing short-term health benefits as well. So this is the ultimate form of first do no harm, right? Looking at the long-term effects of the supplements.
57:38 Dr. Darshan Shah? What's an example of something that's good for you in the short term, but bad for you in the long term?
57:42 Speaker 01 Good question. So, well, since you're a doctor, why don't we take like an actual prescription drug, right? So take, um, take something like Nexium.
57:51 Dr. Darshan Shah? I was gonna mention that one. That's so funny that that's the one that you brought up, but perfect example.
57:56 Speaker 01 Okay, great. So, so I'd love for you to chime in with, with your, your doctor perspective on it. But the, the short-term benefits are for gastrointestinal issues, but the long-term, you are reducing the absorption of, of many different nutrients. It can increase the risk of cancer and so on, but you can speak better to the topic than I can.
58:15 Dr. Darshan Shah? I would say, you know, Nexium is a acid reducer for, for symptomatic relief of having gastroesophageal reflux disease, which is, the, the way Western medicine thinks of pharmaceuticals is, it's almost like a, a subscription program, right? That you're just gonna be on this forever, right? And, but all you're doing is covering up the symptoms forever and never getting to why you're having this acid reflux in the first place. And so, yes, it's a much easier way to just cover up the problem and ignore it, but in reality, maybe is the diet that you're eating. Maybe you're having enzyme deficiencies. Maybe you have a actual hiatal hernia in there that needs to be fixed. And so when you look at these prescription medications, and I would
58:57 Dr. Darshan Shah? You know, almost be bold enough to say that most prescription medications should be looked at as a short term fix to a long term root cause issue. And so, look, I, prescription medications are incredible. They've saved many, many, many lives. But just because an antibiotic gets rid of an infection right now, doesn't mean you should be taking that antibiotic every day forever. It's the kind of perspective that we need to have on prescription medications is use them temporarily to take care of an acute issue, but as you're taking them, really start looking into the root cause of the problem simultaneously. So eventually there's a world where you're getting off of this, right?
59:34 Speaker 01 Right, right. And I think you, you raise a good point that I want to emphasize is that the medical establishment has done some amazing things, right? So for example, I wouldn't be here if not for the medical establishment with my brain tumor and curing me of that. And so for these life threatening circumstances, after something negative has happened, to be able to bring somebody back to a healthy state, it's very good. But when it comes to preventative medicine, to, to prevent something from going wrong, or root cause analysis and so on, that's where Western medicine has not really excelled. And so
1:00:10 Dr. Darshan Shah? that's where- It wasn't built for that. It wasn't built for, for that. It was built from treating infections, treating traumas, you know, things that are gonna kill us acutely. And, and I think we, you know, and I have this conversation a lot because I come from both. I come from Western medicine and also the longevity and health and wellness world now, is I think we place too much pressure and emphasis on the Western medical system to keep us healthy, when that's really our own personal responsibility. And that's why it's so important to have conversations like this, because part of personal responsibility is learning all the things that you need to learn to maintain health and to be preventative. And part of that is this conversation that we just had about the hallmarks of aging.
1:00:52 Dr. Darshan Shah? Like, I think most people should have some interest in understanding what these are and how to positively affect them.
1:00:59 Speaker 01 Right, exactly. There was a study once done that looked at the amount of time it takes knowledge transfer to go from a scientific lab into a medical doctor's office. And it was a crazy number. I believe it was around 17 years.
1:01:13 Dr. Darshan Shah? I think even 17 years is a short number because I could tell you that the stuff that I learned in medical school over 30 years ago, they're still teaching with zero up, very little updates, you know? And so it's a long time, but 17 years is about right. And a lot of the things that we're discussing here today, the people that are living today won't be able to really benefit from this, you know? And the knowledge is already here if you're relying on the Western medical establishment to bring this to you.
1:01:42 Speaker 01 Exactly. And that's the perspective I had when I was starting to think about the concept behind my business was going straight to the scientific lab and finding like that is the absolute cutting edge of the field and seeing what they are discovering. And then finding a way to be able to transfer that knowledge and those insights and actual practical therapies, if you will, from that lab directly to the consumer. Because I realized that there's no way that we're going to be able to get the medical establishment to move quickly enough. Now, I will say at the same time that it is encouraging to see how many medical practitioners are now taking it upon themselves to go above and beyond. I mean, you're a case in point example of that, right?
1:02:24 Speaker 01 There's more and more that are doing that, and I think it's growing momentum. And the rate at which people are able to share information now through podcasts and through the internet just in general, and the fact that doctors, yes, they are human as well. And they are also on these different networks and they're learning as well. I think that that's going to actually reduce that 17 or 30 year time horizon into something shorter, but probably still not short enough.
1:02:51 Dr. Darshan Shah? I, you know, I'm really, to your point, I'm encouraged by the kind of groundswell of people in my profession, physicians and also other professions, really taking it upon themselves to understand this space, which is why I super appreciate you being on here to provide that knowledge to us. But I do think, in my opinion, that the Western medical system, the disease care system, the trauma care system is incredibly important. It saved your life, it saved my life as well. It needs to be there and it will always be there. But there's a new system developing, one focus on health, wellness, longevity, health span, that I think will run in parallel to this and people will need to be participating
1:03:34 Dr. Darshan Shah? in both of those, right? And so that's what I'm really excited about seeing happening right now in this moment that we're in today. You know, Dr. Mark Hyman always say, always says, people are sick and tired of being sick and tired. So people are taking it upon themselves to learn and to participate and do these N of one experiments with supplements, with their lifestyle, to see what works for them. I think that's what's really important to, that people are monitoring their biomarkers, do, using things like wearables. I think we both have Oura rings and Apple Watches on, we're in the same camp here, to see what's positively and negatively affecting them. And it's a, it's a really incredible time we're living in.
1:04:11 Speaker 01 It really is. What I would, what I would say in terms of a concern slash a sense of urgency is also trying to make this more accessible and achievable for everyone.
1:04:23 Dr. Darshan Shah? Absolutely.
1:04:24 Speaker 01 Because what, what we see is that, you know, we're well-to-do people in the United States and we care about our health and so we have the, the budgets to be able to afford this and the knowledge and the education and the, the social networks with our friend groups and so on. But what about everyone else? And I feel like there's this bifurcation of the United States and the world in general, where you've got the very healthy, that they tend to aggregate in big cities that are a little bit more superficial, like New York and Miami and Los Angeles and so on. And then you have everyone else who's not really paying attention to it and they're not really into it. And those are the people who are suffering the most. And so then the question turns to, if that's the case, how do we get them more interested? How do we
1:05:06 Speaker 01 use human psychology for like incentivization to get people more interested in making a change in their health, a change in their life, and so on. Something that I'm very passionate about. It's something I'm trying to do with Novos. We founded it as a public benefit corporation specifically for that reason. We create products that are, we believe, addictive in the sense of their taste, so that when you have a choice of an unhealthy sweet, for example, or a super healthy one, you can choose ours. So it's a small-
1:05:34 Dr. Darshan Shah? Using the powers of taste for good instead of negative, like the ultra-processed food industry.
1:05:40 Speaker 01 Exactly, exactly. So these are small steps that we're taking. We have a free mobile app called Novos Life, which, to your question before about lifestyle, this will give people personalized recommendations for what they can do. It also has a free biological age test that's created by AI. A professor at University of Washington, Dr. Suin Lee, along with Dr. Matt Kabreline, a big name in the longevity research field, co-authored the paper, and we imported their work into the app. And then we also have a chatbot that is trained on longevity data and your personal information. And as a public benefit corporation, we make all of this free for anyone in the world to be able to access. So we could easily charge for it, but we want to do what we can to try to get more
1:06:22 Speaker 01 and more people interested and aware that most of the things you can do to slow down your aging don't cost you a cent. And when it comes to fasting, you'll even save money because you have less food that you're eating, right? So it is something that can be economically accessible to people. We just need to find a way to do it.
1:06:38 Dr. Darshan Shah? That's incredible work that you're doing. And it's so great that you're putting this out there at no cost for people. I can't wait to download the app. I think, is this the app that you also have the skin age calculator on?
1:06:49 Speaker 01 So that's separate, but we're actually integrating it into the app very soon. So Novos Life will soon have FaceAge. So FaceAge is something that you can find on our website. If you go to novoslabs.com/faceage. It's an AI technology that's trained on millions of people's photographs. And we're able to tell you how young or old you look right now. And then we can also tell you skin health markers, for example, pore size, skin inflammation levels, skin wrinkles, eye age, and so on. And then we give you personalized recommendations for what you can do to improve all of these scores. Now, we started the conversation where we talked about how like the superficial side, how we look in some ways is not a reflection of what's happening inside.
1:07:32 Speaker 01 But at the same time, in some ways, it actually is. And there is a study done called the Dunedin Study that looked at people from, I believe, five years old until now, they're, I think, fifty-six years old now, and over a thousand people in New Zealand. And also, more recently, about six years ago, they ran an epigenetic test on these people. And they created an epigenetic test called the Dunedin Pace Clock, right? To measure the speed at which you're aging at this point in time, based more or less on the last six months of your life, but also aspects of even your childhood might impact your pace of aging. And they were then able to categorize people into the slowest agers, average agers, and the fastest agers.
1:08:13 Speaker 01 Then they used computer software to merge the faces of the ten slowest agers, ten average agers, and the ten fastest agers, for both males and females. And when you look at the photographs of these people, actually, I'm going to correct myself, they're forty-six years old, and so this was done at, I believe, when they were forty years old, or forty-five years old. When you look at the photographs, you see the slowest aging people look like they're in their late thirties, and the fastest aging people look like they're probably fifty-seven, fifty-eight years old. So it's almost a twenty-year gap in the perceived age of these people. So what's happening inside of us is actually impacting our skin aging, the adipose tissue, so the fat on our face, and how young we look, our skeletal structure and so on, our
1:08:58 Speaker 01 hairline. All of these things are being impacted by the rate at which you're aging. And so all of the things we've been talking about, these lifestyle changes, even certain supplements, they can all have a favorable effect on that. So those who are a little bit more superficially inclined can also get the added benefit that they have a lower risk of disease and mortality as they're aging, when they're focusing on longevity, but they can also... So look better in the process too.
1:09:21 Dr. Darshan Shah? Right, so true. You know, I just recently brought a memory for me. A couple of years ago, I went to a medical school reunion and I looked at all the people that went to medical school with me. And there was about a 20 year gap in the ones that looked the youngest versus the ones that looked the oldest. And you can really, you know, we're all the same age going through medical school at the same time. And so it's really poignant to see how people age from an outwardly standpoint by looking in the mirror has has can differentiate so much as you kind of go down, go through life, you know?
1:09:55 Speaker 01 Yeah. Did the critical care and ER doctors look the oldest and the plastic surgeons look the youngest?
1:10:02 Dr. Darshan Shah? That I would say that you could definitely see the impacts of stress and your professional stress, how much it impacts the way you look. It's it's a huge factor, I think. Absolutely. And you know, stress impacts a lot of aspects of our life. I think if you have a stressed life, and I was a victim of this, you don't exercise as much, you don't move around as much, you don't eat well, you just kind of eat whatever's around. It's usually ultra-processed garbage. You don't sleep well when you're stressed. And all those things kind of come together to cause aging, right?
1:10:32 Speaker 01 Not only that. So I think it was as recent as around 2010 or so, maybe just before it. The medical establishment didn't accept the idea that that stress could cause health issues. And it took some time to do studies and find like the glucocorticoid receptor stimulation and essentially increases in cortisol and the effects that high chronic cortisol can have on organ function and blood pressure and heart attack risk. And even more recently, finding that like hair graying is not only caused by stress, but stress can actually cause your hair to turn gray. And when you remove that stressor, the melanin returns and the hair goes back to the proper color.
1:11:13 Speaker 01 Now, there could be other reasons too. Aging does cause it. Nutrient deficiencies, especially copper and zinc and so on can cause it. It's not the only cause, but the stress is having a direct impact on our physiology.
1:11:24 Dr. Darshan Shah? Absolutely. You know, my previous life, I used to do hair transplant surgery. And you almost every single person that I talked to that had lost their hair, there was a stressful period of their life that that they can point to that led to that hair loss. They could say, I started losing hair when I started this new job. I started graying and losing hair when I had my child, those kind of things. And so it's it's not an old wives' tale where, you know, where your mom might have told you, you you gave them gray hair. It's it's it's real. The stress does cause real changes in in the hair color and the amount of hair that you have.
1:12:02 Speaker 01 Yeah, it was once thought of as as that. And as only after research has now proved it, it's actually it's it's shown. Yeah, there's a lot of truth in in the things our parents have taught us.
1:12:11 Dr. Darshan Shah? Absolutely. So going back to the aging clock, because I know you have a lot of specific, deep knowledge here. I remember getting from Elizabeth Blackburn, actually, my first telomere age score done of almost like two decades ago now, I think. Wow, it was a long time ago. And I was really happy with the results. And then I was a bit bummed when I found out that telomere age really is not is not a real indicator of true biological age. And so I started going down the rabbit hole of biological age tests. And I took the Horvath test when it first came out. What is the current status of biological age testing? And what is your perception around how the accuracy of it and what do you use it for?
1:12:48 Speaker 01 Yeah. So I feel your pain, first of all. My telomere length was that of an eight year old. And how much I would love to have the biology, not the brain, not the mind, but the biology of an eight year old. But I don't, believe me, I don't. But with that said, yeah, so so people are going to hear people throwing around carelessly this this concept known as biological age. You hear it everywhere now. And oftentimes, it's not actually based on anything with strong scientific backing. So someone might say, oh, my biological age is 10 years younger. And I ask, well, what's that based on? Usually, they don't know. But when we dig into it, it's like, oh, based on my resting heart rate. It's like, OK, that's not actually your biological age, right?
1:13:31 Speaker 01 So it might be or your HRV or like these individual data points that companies are trying very hard to associate with longevity, but it's not actually true longevity measures. So when it comes to biological age.
1:13:44 Dr. Darshan Shah? On that point, to your point, I'm so sorry, one of the scales that. I had a while ago would give me a biological age every time I stepped on it. I was like, how is this thing giving me a biological age?
1:13:55 Speaker 01 Absolutely not.
1:13:56 Dr. Darshan Shah? You know, through electrical current going through my body. There's just no way.
1:13:59 Speaker 01 Absolutely.
1:14:00 Dr. Darshan Shah? And so people do need to be very knowledgeable about where is that being calculated from? Before they put a lot of stock in it, right?
1:14:07 Speaker 01 Yes, definitely. Yes. Yeah. So, so let's, let's give the high level overview of how biological age can be best measured, actually what it is in the first place. So biological age is essentially how old we are biologically, which is at least now being calculated as the, the risk of morbidity, mortality, and also like how high your quality of life is. And it's going to be based on the average of people of a certain chronological age. So me being 40, if I am biologically 30, that means my risk of getting a disease or dying. And also like my quality of life. So my cognition and physical abilities and so on should be that of an average 30 year old. And so that is great because every seven to eight years, your risk of death doubles. And that's an exponential curve. And that's why so many, so few people are left when you hit 90.
1:14:52 Dr. Darshan Shah? Right. That's an important point to double click on because as you age, if your biological age is older than your chronological age, it's actually a much higher risk of death as you go, go through this aging process. So tracking your biological age becomes even more important as you age. And so I'm 52 now right now. I get my biological age test done every six months to a year. Cause I, I just need, I just want to know.
1:15:18 Speaker 01 Yeah.
1:15:18 Dr. Darshan Shah? Cause I know how important it is now to track it.
1:15:21 Speaker 01 And the fact that 80% approximately is your lifestyle and your environment. So you can control it, right?
1:15:26 Dr. Darshan Shah? Exactly.
1:15:27 Speaker 01 So yeah, that's a great point. So being 40, if my biological age was 47 versus it being say 33, that would mean four times higher risk of death or a disease at this point in time than it would be if it was lower. And so that should instill a sense of urgency, light a fire underneath you to like change your lifestyle to try to get it lower. So how are biological ages measured, at least in the more effective way? Well, we'll talk about very quickly this idea of the omics, the omic sciences, right? So we, we talked a little bit about this. We have our genomics, so those are our genes. Then we have our epigenomics, so that's our epigenome. From there, you have your transcriptomics.
1:16:07 Speaker 01 This is creating messenger RNA from your genes and based on what's exposed from your epigenome, which lights are turned on, let's say. And that's then going to lead to protein creation, which is your proteome. Proteins are what's all of these messages are communicating across our bodies. The enzymes that are catalyzing reactions, so on and so forth. Proteins are essentially what any drug or supplements is really modulating. It's the proteins in our bodies, right? Like altering the shape of that protein or what it what it docks to and so on. So proteins are incredibly important. And then you have something known as your metabolome. Metabolome is all of the molecules in our blood, right? It can include the microplastics.
1:16:52 Speaker 01 It includes everything, right? The cholesterol, the lipids. And then from there, you also have your microbiome. And so all of these are being investigated for ways to try to measure biological age and disease risk and mortality risk and so on. With that said, currently, the most advanced form of biological age measuring is the epigenome. And within the epigenome, you have some clocks. They're called biological age clocks that are more effective than others. So you mentioned the Horvath clock. The Horvath clock was the first biological age clock, but it was based, it was tracking chronological age. It was trained based on chronological age,
1:17:35 Speaker 01 as opposed to being trained on morbidity and mortality and quality of life and so on. So it was an amazing accomplishment to create this clock in the first place. But in terms of practical use today, it's really best for, say, a crime scene. Like there's a murder mystery and you're trying to figure out how old the culprit potentially was, right? And so you use this Horvath clock to approximate how old they were chronologically. But for practical and medical reasons, it's not nearly as powerful. And so second generation clocks came out. And these were trained on morbidity and mortality. And these are clocks like the Pheno age clock, the Grimm age clock, and so on. And these were a major upgrade. Then there were third generation clocks that came out, or really just one.
1:18:19 Speaker 01 And this is the Dunedin pace clock that I mentioned earlier. The Dunedin pace clock actually gives a different measure. It is your rate of aging at this point in time. Lower is better. So one means you're aging at the average rate for someone at any given point in time. For point six nine, which is my biological rate of aging, that means I'm aging thirty one percent slower than the average person. So each year I'm aging only point six nine years potentially. At least that's what this clock is approximating. That also means a lower risk of morbidity, mortality, et cetera. It's a really powerful measurement because it's essentially looking at your trajectory of aging.
1:19:00 Speaker 01 It's like based on predominantly the last six months of my life and my lifestyle. Is this causing me to age faster than I was before or slower than I was before? Whereas
1:19:11 Dr. Darshan Shah? I was gonna sorry to interrupt you, but I just want to say this is where I find these aging clocks the most useful. It's a scorecard of all of the things you've done in the last six months. And so that's why I measure mine every six months. And it creates a sense of urgency. It creates a sense of investigation into your habits, into your lifestyle, into new interventions you might have put into place over the last six months to see what is the sum total of what you've done. If your age pace of aging goes down, you did something right. You need to keep doing that, whatever you did in the last six months. But if it goes up, really it's time to turn your attention to your health again and your and your overall habits. And so I think it's so important and critical to highlight this as a more of a scorecard
1:19:55 Dr. Darshan Shah? rather than anything that you should look at as being a scorecard for yourself rather than anything you should look at as a kind of like a detrimental thing that your pace of aging is so high. And now you're just a bad human being. It's really in to that point. I think it's also very important to do these on a consistent schedule, right? And so if you can afford to do these every six months, I think it's a good pace of doing these.
1:20:22 Speaker 01 Yes, yes.
1:20:23 Dr. Darshan Shah? Do you agree with that?
1:20:23 Speaker 01 I do agree. I look at it as a North Star metric. It's one single metric that tells you if overall the aggregate of everything you've been doing is actually good for you and it's leading to a better potential health outcome, or if it's not so good for you. And when we get typical blood labs completed, we're always looking to see if something is in range, but we actually don't know what is fully optimal. And there's so many different blood biomarkers that like, nobody, even the best doctor, doesn't know exactly what the combination of all of these factors together actually equates to. This is something that requires mathematics and AI to really try to figure out what all of this means. And that's where these clocks come in. Now, those blood labs are still very important,
1:21:06 Speaker 01 but that's more for, you know, a specific condition or, you know, someone has cardiovascular issues. So you need to look at their APOB and their LDL and LP little a and so on, right?
1:21:16 Dr. Darshan Shah? And they're more like lagging indicators too. Like, once those start getting abnormal, it means you're accumulating damage for a long period of time, right? And so this is more temporally significant by something over the last six months versus years of damage now leading to metabolic disease, heart disease, et cetera.
1:21:33 Speaker 01 Yes, yes, I couldn't say it better myself.
1:21:40 Dr. Darshan Shah? This episode was brought to you by Nex Health, a health optimization and longevity clinic located in Los Angeles, Manhattan, and soon to be opening in Montecito, Nashville, Miami, and many other cities in the United States and Canada. Nex Health is the Apple Store of wellness, where you can optimize your health span and lifespan using cutting-edge technology. I actually founded Nex Health eight years ago to give my patients a place to go get extensive biomarker testing done and provide them with all the tools that I use to get my health in order. The longevity circuit in Nex Health using hyperbaric oxygen, sauna, cryotherapy, and LED light is a game changer. In addition, the doctors at Nex Health measure thousands of biomarkers
1:22:24 Dr. Darshan Shah? and put into place a longevity optimization plan using advanced tools like ozone, plasma exchange, and peptides. Go to www.nex.health to check it out.
1:22:38 Dr. Darshan Shah? This episode was also brought to you by Vitaboom. Vitaboom is a revolutionary company that sends you a custom supplement protocol based on your needs using blood-based biomarkers. You could either send them your latest blood test, or they will send you a fingerstick test for blood analysis. Vitaboom then curates and ships you an extremely convenient monthly box of daily supplement packs that have your custom protocol in them. What's great is that they also provide all the best brands like Timeline, TruNiagen, and many others for your custom daily packs. I love mine especially for travel, since I don't have to bring 10 bottles of supplements with me and just open up a daily pack for every day that I'm taking
1:23:23 Dr. Darshan Shah? my vitamins and supplements. Go to vitaboom.com and check it out.
1:23:30 Dr. Darshan Shah? So I'm really excited about these aging clocks because, and you provide an aging clock as well. And you were saying you do this in partnership with True Diagnostic Laboratories? Is that correct?
1:23:41 Speaker 01 Yeah, so we're partnered with them, but we offer a different customer experience. I would say True excels with working with doctors directly. We excel working with consumers and making very consumer-friendly products. And the price point is also more affordable, what we offer. So we've got, for example, the pace of aging. So we can tell you how fast or slow you're aging. We have the Symphony Age Clock integrated, which would be the newest clock coming out of Yale University that will tell you your biological age. But even more interesting, I think, is organ-specific ages. Because, you know, overall, as a whole body, I might be in my late twenties biologically. That's what the tests, many tests have come out to for me. But what about my liver or my heart?
1:24:25 Speaker 01 Or maybe there's a specific organ that's lagging the others, and that one I should focus more on. And then we also offer a fourth output, which is the telomere length I mentioned earlier. So we get all four of those in the Nova's age.
1:24:38 Dr. Darshan Shah? That's fantastic, because those are the four that I look at with all my patients, actually. I think these are all four incredible metrics to be able to track on a frequent basis, especially when you've got the basics in order, right? Like, I feel it's probably overkill to start doing this if you're eating ultra-processed food every day and you're, you know, maybe in metabolic disease, many pounds in the obese category, maybe you're not sleeping at all. What I try to recommend to our patients that come is let's clean up all of that first, right? And then we're going to start doing a deeper dive into things like biological age and even utilizing supplements that can affect biological age, right?
1:25:17 Speaker 01 Sure, sure, yeah. Yeah, it is great to see the baseline, at least for motivation, if someone is very unhealthy and seeing that they're aging like 1.2, 20% faster than the average person.
1:25:27 Dr. Darshan Shah? That's a good point. It does. It's good to see where you're at at the first moment of going through a health journey, because it's also very motivating when you put things in place, because guaranteed this will come down a lot by doing the basics right.
1:25:40 Speaker 01 Right, exactly. Yeah, you can go a very long way with your biological aging, just getting those basics, like reducing your body weight, eating healthier diets, sleeping better, being more physically active. Yeah, you can go theoretically from 1.2 to 0.9 in a year's time, which is a tremendous change.
1:25:57 Dr. Darshan Shah? Absolutely. So I do want to now talk about also, like, say you're at 0.9, you want to get to 0.7, right? You're doing all the things, but what are some of the compounds that can potentially push you over the edge of even getting slower biological aging? And, you know, when I think about this, I also think about our conversation about science then becoming mainstream, and it takes a long time. And a really good example of that is the interventions testing program run by the NIH, right? And so for those of you who don't know, the intervention testing program is an NIH program where they're actually testing different interventions on specific population of mice in two different laboratories. Is that correct?
1:26:35 Speaker 01 Three.
1:26:36 Dr. Darshan Shah? Three different laboratories. Amazing. And, I mean, as far as validated mouse studies goes, this is one of the best, right? And maybe you can talk about the program, some of the interventions, and what your thoughts are around them.
1:26:50 Speaker 01 Yeah, sure. So, I mean, I think you summarized it nicely. So they're doing it in multiple places. They're doing it at the same time. And that's important just to, you know, scientists oftentimes say we need to replicate the study to to confirm that it actually is having this effect. And so the fact that in this case, it a substance succeeds if it is replicated three times is a very, very high scientific standard.
1:27:14 Dr. Darshan Shah? Exactly.
1:27:15 Speaker 01 And so I will caution to say that simply because it doesn't succeed doesn't mean that it isn't actually having a favorable effect. It really depends on, you have to then dig into the study, like, did it fail in all three studies? Okay, well, then that's an issue. Did it succeed in one or two? Well, why might it have succeeded in one or two? Or why did it fail in only one or two? Right? So then that's when you have to start investigating and trying to better understand, right? So it's not always clean cut. But with that said, some substances that have been found to have a favorable effect are, for example, rapamycin, which we mentioned earlier. Rapamycin is a immunomodulatory drug, so it's something that is intended to turn off your immune system in the case of an organ transplant, transplant.
1:27:58 Speaker 01 But it's also been found largely because of, it's believed, the reduction in mTOR stimulation that we discussed earlier, to extend lifespan and health span in practically every single animal species ever studied. And there are a lot of human biohackers and even scientists in the field that off the record, and some on the record, take rapamycin, right? So they'll take a large dose, say five milligrams is the typical dose, like, once every week or once every other week. And there are potential side effects and there's a lot of risks and you, as a medical doctor, can say it better than I can, but it's not something I would suggest that people just do on their own, have medical supervision.
1:28:34 Dr. Darshan Shah? Well, they can't, they have to, it's a prescription medication, right? And so I know there are some online vendors selling it without a prescription, but you have to be very suspect of that because it is a prescription medication to do this.
1:28:45 Speaker 01 Right, exactly. But it's, so it's a very promising compound. Scientists typically compare results of other interventions to the rapamycin to see where it falls relative to rapamycin. So that's kind of like the gold standard, if you will, in the longevity field currently for something ingestible to extend health span and lifespan.
1:29:03 Dr. Darshan Shah? What are some of the others?
1:29:04 Speaker 01 So, one that's actually commonly taken, and most people don't even know that it has this effect when they're taking it, is Aztexanthin. So Aztexanthin is an over-the-counter supplement. It's something that causes shrimp to be pink and salmon to be pink. Oftentimes, it's actually even added as a food additive to make farmed salmon artificially look more pink than it actually is. Ironically, this is like one case where it could actually be health-promoting, right? It's not like a negative chemical.
1:29:31 Dr. Darshan Shah? It's so ironic, right?
1:29:31 Speaker 01 Some positive chemical.
1:29:32 Dr. Darshan Shah? Most food colorings are very bad for you.
1:29:35 Speaker 01 Yep, yep, yep. I'm sure they were not thinking that. Like, oh, let's use a healthy compound. But it just so happens to be a very healthy compound. I believe it's a carotenoid family. It oftentimes finds itself in your skin tissue, for example. It's been studied for things like improvements in athletic performance, but also improvements in skin health, potentially. I can't make this claim officially, but a lot of anecdotes, people say that from sun exposure, it can reduce the damage and reduce the risk of getting a sunburn, and more likely to tan as a result of it. And again, the carotenoids are these antioxidants that sit in your skin, and they're protective. So, but it's also been shown in the ITP to extend lifespan in the mice.
1:30:19 Speaker 01 So, that's a very accessible, yeah, compound. Seventeen beta, is it seventeen beta or seventeen alpha? Seventeen beta estradiol.
1:30:28 Dr. Darshan Shah? Yeah, I forgot too, so we'll look it up and put it in the show notes, but I'm pretty sure it is beta.
1:30:33 Speaker 01 I know the Greek character, but I think that's beta. So seventeen beta estradiol, it's a hormone. It's a feminine hormone, being in the estrogen family, but it's actually not a feminizing hormone, so to speak. That's also been shown to extend lifespan. I'm very proud that the mouse study that we ran on one of our products actually outperformed that, as well as the Dostatinib that I mentioned, and every other supplement ever studied, we have outperformed in terms of extending aged mouse lifespan, so including nicotinamide riboside NR, which is very popular. So, both every supplement, as well as many of these most advanced interventions that are being done in the scientific laboratory, many of them, even TERT genetic therapy, we outperformed. So...
1:31:19 Dr. Darshan Shah? Yeah, so I mean, I'd love to dive a little bit more into the substances that you've found that moved the needle and have outperformed even some of the interventions in ITP. Can you talk about some of those a little bit?
1:31:29 Speaker 01 Yeah, so I'll talk about the individual ingredients.
1:31:33 Dr. Darshan Shah? Yeah.
1:31:33 Speaker 01 But what I'll also emphasize is what's perhaps even more important is the effect that the combinations of ingredients can have. Professor Brian Kennedy at National University of Singapore, he's a world-renowned longevity researcher. He has spoken about many times at different events about how in his research, he finds that when you take one healthy longevity ingredient and you add another healthy longevity ingredient, you would think they would be additive. More often than not, they actually exhibit the same effect or actually even a worse effect. And in a few cases, it actually has a negative effect on the lifespan or health span of the animal. So it's not as simple as like A plus B equals C, or that that is going to be a greater outcome.
1:32:18 Dr. Darshan Shah? And this is a huge problem I see a lot because I have a lot of patients that find supplements that promote longevity and they buy all these sup- they have a huge supplement cabinet of longevity supplements. And the fact is that a lot of these, when given simultaneously, can also can, like you said, either counteract each other, actually cause a negative effect. And testing them together, it's incredibly important on your own biological age, but also in the laboratory, before you start combining random ingredients.
1:32:50 Speaker 01 Yeah, exactly. I think it's just overall, it's an overly simplistic comprehension of biology. There's actually a very well-known longevity influencer that is very popular, I won't say by name, but one of the things that he does is restrict caloric intake. So he's hypocaloric, has a low calorie intake, but then also takes hormone therapies like TRT, and I believe at some point, HGH. And so that's testosterone replacement therapy and human growth hormone. And we believe that that is an overly simplistic perception of aging because one of the reasons why caloric restriction probably extends health span and lifespan, among many,
1:33:33 Speaker 01 is that you are actually reducing these growth hormones, androgynous hormones, right? And so if you're then replacing them with injections, you're probably counteracting the benefits of that fasting in the first place. So it's erroneous to think that because one thing works, that you should then add that to your routine without understanding the biological mechanisms by which it is working in the first place, right? So that also applies to stacking supplements. And I'd say for basic, general multivitamin types of ingredients, as long as you're getting the dosages right and so on, you can stack those. Like, we know that these are essential. But when you're getting more complex with things like longevity, like are you over-stimulating hormesis, which then it becomes toxic?
1:34:18 Speaker 01 Are you over-stimulating AMP kinase or not stimulating mTOR enough? And then the different mechanisms of aging? I mean, it's incredibly complex.
1:34:26 Dr. Darshan Shah? Exactly. And also, to your point, you know, what time of day do you take these as well, right? Because if you're doing exercise and then you're taking certain supplements, it's completely counteracting each other. You're blunting the effect of the exercise and you're blunting the effect of the compounds that you're taking. So you have to be able to time these correctly. And just to double-click on the point of, you know, doing multiple interventions at the same time, you're affecting these pathways in completely opposite directions. And so you're pulling the pathway in one direction and pushing it in another direction at the same time. And this further emphasizes why people need to understand some of these pathways like mTOR, because certain interventions can push it or pull it.
1:35:12 Dr. Darshan Shah? And you have to at least temporally or time-wise separate those interventions. And yeah, so I just wanted to make further emphasis on this point because it's very important.
1:35:22 Speaker 01 Yes, and I don't want people to feel discouraged at the same time. So what can they do? I think number one is to refer to experts in the field that that understand the full span of longevity research. And we try to do it at Novos and we try to put that information out there in blog posts and in our mobile app and so on. And even in our formulations, we work very hard on those formulations. But we're not the only ones out there. And of course, Next Health and you and what you've created here as well. But I'd say the second thing is is data, right? So get the biological age test done or get the blood labs done. See how these different interventions are affecting you with objective data and then subjective data, like, are you feeling better? Are you feeling more energized?
1:36:06 Speaker 01 Are you sleeping better? All of these things that are associated with health span. Now, not everything that, as I said before, that's good for you in the short term is going to be good for you in the long term. But generally speaking, if you're sleeping better and more soundly, if you don't feel as agitated and stressed and anxious and so on, these things are associated with a healthier life. So on the subjective level, that's probably also something that more likely than not is moving in the right direction.
1:36:32 Dr. Darshan Shah? Absolutely. So what are some of the compounds you found and you put into your product that you feel are the most beneficial?
1:36:38 Speaker 01 Sure. So I'll start with the most controversial one. The most controversial one is a trace dose of lithium. So lithium, people, when they hear it, they either think of exploding batteries on airplanes or they think of like psychiatric drug, you know, for bipolar disorder or schizophrenia. But in that case, the dosage is 200, 300 times greater than we're talking about. We're at the one milligram dosage level. So San Pellegrino Water brand, for example, if you have a couple of liters of that, you're actually getting in the neighborhood of around one milligram. It's high in lithium. Lithium is actually something that we evolved with. It's in our water supply, right? So it's it's an element, it's in rocks and it leaches through into the water.
1:37:22 Dr. Darshan Shah? Yeah, and to be clear, it's been in our water supply since caveman days.
1:37:25 Speaker 01 Exactly. We've always been drinking it. The salmon we eat is, the lithium is in their tissue. And now with farm-raised salmon and municipal water supply and bottled waters and so on, we're getting very, very low levels of it. Studies have been done looking at populations that have higher levels of lithium in their water supply. And there are correlations with, for example, lower rates of depression, suicide, murder, bipolar, schizophrenia, Alzheimer's, dementia. All of these neurocognitive-related issues, lower rates. Some scientists have even gone as far as saying that it should be considered a vitamin or a mineral, an essential mineral, to integrate into the water, water supply, to get people drinking more of it again.
1:38:10 Speaker 01 It has favorable effects on the epigenome, which we talked about earlier. It has, again, these cognitive benefits. So we included that in our formula at the one-milligram level.
1:38:20 Dr. Darshan Shah? Great.
1:38:20 Speaker 01 So very small, but high enough level to be associated with these positive effects.
1:38:26 Dr. Darshan Shah? Great. What are the next couple that you've incorporated that you believe in?
1:38:30 Speaker 01 Yeah, let's, let's talk about terastilbene. This is also not controversial, but it brings up a controversy, which is resveratrol. So resveratrol is an ingredient that Dr. David Sinclair, who we mentioned earlier for the Yamanaka factors at Harvard, he wrote the book Lifespan, a New York Times bestseller. He has popularized resveratrol, but a lot of people are critical of that. And they don't think that resveratrol does quite what it has been worked up to be. Specifically, there haven't really been replicated studies to show lifespan-extending effects of resveratrol. Also, the dosage is incredibly high. And then in the mice that have been studied, where there was an effect from Dr. Sinclair's lab,
1:39:11 Speaker 01 It was in obese mice, so it wasn't a normal, healthy mouse. And terastilbene, on the other hand, so resveratrol comes from grapes and it's in red wine. That's part of the reason it's famous. Terastilbene is found in blueberries and it's, it's a very similar molecule. It just has three methyl groups attached, so it actually has a better oral bioavailability. So when you ingest it, you absorb a lot more of it and it has a much longer half-life in, in the blood. So it sticks around in our blood and it can exhibit the, its effects even longer. And scientific studies have fantastic results from it. In fact, David Sinclair's former lab supervisor, Dr. Leonard Garanti at MIT,
1:39:55 Speaker 01 suggests terastilbene over resveratrol. So that, that's another ingredient that we have in our formula. Calcium alpha-ketoglutarate is a, is a very powerful ingredient. Alpha-ketoglutarate is something that's in our bodies, part of the Krebs cycle, levels decline as we age. And the calcium form specifically was found at Brian Kennedy's lab in Singapore to have a favorable effect on mouse lifespan as well as on epigenetic age. So not other forms, there's like arginine, alpha-ketoglutarate, which bodybuilders oftentimes take, but the calcium form specifically, we don't know exactly why, but presumably, or hypothesis, is that it's something to do with the rate of absorption, slows down the absorption,
1:40:40 Speaker 01 which turns out to actually be a good thing in this case. And so it extended mouse lifespan, but it also in humans was associated with a lower biological age as measured by the epigenome. So that's something that we have a hefty dose of 1100 milligrams in one packet of our flagship product, Novo Core. Phycetin.
1:41:01 Dr. Darshan Shah? Phycetin.
1:41:02 Speaker 01 Phytin is found in strawberries and it was looked at as being a senolytic. So something that would destroy the senescent cells that we mentioned earlier. Well, recent research has found that it actually doesn't exhibit that effect. But we're very happy with its inclusion because we've done a couple of studies, actually at different labs, which have found really great benefits of our combined formula, largely because phytin is in it, but the effects of all of the other ingredients combined. So this is the synergy. So I'll give you two examples. One is on the senescent side of things. So at Newcastle University, they looked at human senescent cells, I believe it was in keratinocytes, so these are skin cells, and looked at the effects that our product,
1:41:46 Speaker 01 NovoScor, could have on those senescent cells. And we were able to reduce the size of those senescent cells by approximately 50%, which was at the same order of magnitude approximately as the prescription drug rapamycin. The second study was done at the Salk Institute here in California. Dr. Pamela Maher, who advises us, she ran a study with a prescription R and D drug, it's not yet out for the public, it's still being studied, that specifically targets this process known as oxytocosis-ferreptosis. And it's an inflammatory process. It's associated with Alzheimer's, dementia, as well as certain types of cancer. And compared the phytin to that drug, and then also compared our combined formula to that drug.
1:42:31 Speaker 01 And phytin performed well, but our combined formula performed 50% as well, or sorry, 50% in between the phytin and that prescription drug. So significantly more powerful by combining the ingredients. And the other ingredients are not known as senolytic. And so it's this combination, the combinatorial effects that we are seeing, having this really great effect in the in vitro studies, as well as the in vivo mouse study that we did, and even a human case study where we showed three quarters of the people that took our product for six months, reduced their pace of aging by the equivalent of one month per year. So imagine like one free month of life per year is how we like to think of it.
1:43:11 Dr. Darshan Shah? Right.
1:43:11 Speaker 01 And then the quarter that did not slow down, they also didn't speed up. So you would expect in this group, there would have been some people whose pace of aging should have sped up. Like lifestyle stressors, not living as healthy as they were and so on, but they didn't. So that leaves us hopeful that the effects of our formula are actually protecting those people. And those who are maintaining their healthy lifestyles are actually slowing down their pace. That's a case study when we have a clinical trial that's underway right now.
1:43:38 Dr. Darshan Shah? So exciting. Yeah. Well, I'm personally so excited for all the research that you're doing and to see what you come up with next. You're doing incredible work and I really appreciate all of your knowledge for our listeners that come on our show. It's, uh, it's really important for people to know this information. And I know we kind of got a lot of very sciency at some points. However, I think this is important science because it can really affect our health and it's accessible for people, even for free through things like your app. So it's, uh, it's really important stuff and I thank you for doing this with us.
1:44:09 Speaker 01 Thank you. I really appreciate being here. For anyone who's interested in learning more, there's novoslabs.com. We're on social as novoslabs. Then I have a blog, slowmyage.com where I post my results, my lifestyle and just my perspective on the field in general. And I'm also on social media, especially Instagram and X as slowmyage.
1:44:28 Dr. Darshan Shah? Yeah, I've learned a lot from the slow my age blog. So thank you for doing that.
1:44:31 Speaker 01 Thank you.
1:44:32 Dr. Darshan Shah? What are you most excited about coming up?
1:44:35 Speaker 01 Oh, wow. Uh, we have a lot of great things happening within, within our company. So we were just recently accepted into the longevity biotech association. It's run by Dr. Nir Barzalai, prominent researcher in the field at Albert Einstein. And, um, we're the only direct to consumer, we're the only over the counter formula company in that group. Everything else is this advanced biotech. And the reason we're inducted into it is because of number one, the meticulous science that we follow, working with the best scientists in the world to validate our products and to help us formulate. And then to that point, our future formulations and the things we're doing are true biotech. Like experimenting with many different compounds and combinations in all different animal species to figure out what is probably going to be the most
1:45:17 Speaker 01 Most effective in humans and then bringing that research to humans to then validate it. So we're taking that biotech approach, but applying it to a consumer company that's venture capital funded. It's it's it's new. It's not done this way. It has not been done this way before. But we're really excited about the potential because there's a lot to learn from biotech. There's also a lot to learn from going direct to consumer and enabling people in the short term rather than having to wait the long, you know, in the long term. We're using natural ingredients, safe ingredients in the process.
1:45:47 Dr. Darshan Shah? Yeah, I mean, if the entire supplement industry started off that way, we'd be in a much different situation than we are now with the kind of wild, wild west of supplements everyone refers it to, which you have no idea what these products are doing or if they even have the right ingredients in the bottle that you're taking. That's what's so scary. You can buy a bottle of supplements now and you don't even know what's really inside of there.
1:46:09 Speaker 01 Oh, my God. Yes, you you remind me very quickly. I went to Airwan yesterday here in L A because we sell our product there. And I was just checking the store shelves and there is a drink that's sold as an energy drink. It has caffeine in it, but it has a high dose of something called L D O P A. And as a doctor, you know what L D O P A is, and it was used in studies for people with Alzheimer's and so on. But it's basically something that will immediately raise your dopamine levels. But it there's really no safeguard on it and you can, when you stop taking it, your dopamine receptor sites can be significantly downregulated and then you can lose the effects of dopamine. Right? And so you don't want to take this chronically. Like I had tried it once or twice as a supplement and I was like, wow, I feel great. But I don't want to take any chances. It's sold on the store shelf.
1:46:52 Dr. Darshan Shah? Yeah, anyone can buy it. They have no idea. No one's going to look at the ingredients and see L D O P A and understand what it truly does to your receptors and downregulation of them over the long term. And then you need bigger and bigger dopamine hits to get to the same effect, et cetera. And so, yeah, it's it's a it's buyer beware all the time, right?
1:47:11 Speaker 01 Yes, yes.
1:47:11 Dr. Darshan Shah? But anyway, Chris, this was a great conversation. Thank you so much for joining us and I can't wait to have you on again.
1:47:16 Speaker 01 Thank you. It was fantastic to be here. Great questions. It was really enjoyable.
1:47:22 Dr. 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.
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