#40 Dr. David Sinclair on The Secrets of Longevity Genes

#40 Dr. David Sinclair on The Secrets of Longevity Genes

If you had the chance to slow down the aging process, would you take it? This sci-fi concept may sound like something from a Star Trek episode. But with new research coming to light, anti-aging fiction could very soon be a reality. Maybe it’s all in the genes. 


Dr. David Sinclair is trying to put a stopper in the aging process.

In fact, he’s the one leading the charge. David is the Australian-born Harvard Medical School professor of genetics. He’s also co-director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School. 

On top of all that, he’s also a Professor and Head of the Aging Labs at UNSW, Sydney, and an honorary Professor at the University of Sydney. Like many pioneering scientists, he hasn’t been immune to controversy. But, if you Google his name, you’ll see a laundry list of accolades. Especially within the area he’s best known for is, which are genes and small molecules that delay aging.

He is currently spearheading the research into gene function in the aging process, with a really heavy focus on the Sirtuin genes. 

Dr. Sinclair and his team are also trying to lift the lid on exactly what roles resveratrol and NAD precursors play in the anti-aging process. Alongside this, David has published over a whopping 170 scientific papers, is a co-inventor on over 50 patents, and co-founded multiple biotech companies in the areas of aging and biodefense. 

Oh yeah, and he’s the author of Lifespan: Why We Age and Why We Don’t Have To, which shot him to number 11 on the New York Times bestseller list in just over a week. One of David’s most recent claims to fame was his selection to be one of Time Magazine’s 100 Most Influential People In The World. Now that is impressive. 

In this conversation, Dr. Sinclair and I get right into the fantastic family of proteins known as Sirtuins and their role in the aging process. We also look at how Intermittent Fasting could turn back the clock. We get into how it all started with yeast cells, and why David is so interested in the NMN molecule.

Other great topics we cover:
  • The role Sirtuin genes play and why they’re so bossy
  • Epigenetics and why biological stress isn’t such a bad thing
  • Intermittent fasting and what skipping a meal can do for your body
  • What is Resveratrol and how does it affect the body?
  • Why the NAD molecule is so vital for every living organism
  • The Zombie cells that wreak havoc on your health
  • What David is so excited about for the future of anti-aging science
  • Epigenetic reprogramming and reversing the ticking clock inside us all
  • David’s take on stem cells and how they contribute to the aging process
  • When you should really start taking care of your body

The Darin Olien Show is produced by the team at Must Amplify. If you’re looking to give a voice to your brand, and make sure that it’s heard by the right people, head to www.mustamplify.com/darin to see what Amplify can do for you.

Episode Transcript

Darin: You are listening to the Darin Olien Show. I’m Darin. I spent the last 15 years exploring the planet looking for healthy foods, superfoods, environmental solutions, and I’ve had my mind blown along the way by the people, the far off places I have been, and the life-altering events that have changed my life forever. My goal is to help you dive deep into some of the issues of our modern-day life, society’s fatal conveniences. The things that we do that we’re indoctrinated into thinking we have to, even though those things are negatively affecting us, and in some cases, slowly destroying us and even killing us. Every week, I have honest conversations with people that inspire me. My hope is through their knowledge and unique perspectives they’ll inspire you too. Together, we’ll explore how you can make small tweaks in your life that amount to big changes for you, the people around you and the planet, so let’s do this. This is my show, the Darin Olien Show.

Darin: Hey, everybody. Welcome to the show. Thanks for tuning in. Stoked you’re here. We get to share some time and some space together and I get to introduce you to another amazing, unbelievable guest, Dr. David Sinclair. If any of you know him, then you know his brilliance in anti-aging. If you don’t know him, you’re gonna be blown away. He’s an extraordinary gentleman. By the way, this episode is sponsored by Caldera + Lab. I finally found an incredible skincare product botanically-based that I’m going to tell you about a little later in the show. But I’m stoked because I love botanicals, and I love what this product does for me. I’ve been using it for a while. And this is the kind of thing I get excited about when people do the right thing and formulate the right way for things that go on your body have to be safe, effective, and just kick-ass, and I’m going to tell you about that a little bit. So that’s sponsored by Caldera. Today, we’re grateful for them, for the work that they’re doing. But Dr. David Sinclair, holy cow, for the work that he’s been doing and dedicated to. He is literally a world leader in anti-aging research. And he’s the author of The New York Times best-selling book, I love this book, I gobbled it up right away, called Lifespan: Why We Age and Why We Don’t Have To. That’s right. He’s attacking anti-aging. He’s a professor of genetics at Harvard Medical School, a co-director of the Paul F. Glenn Center for Biology and Aging Research at Harvard Medical School. He is best known for his work on genes and small molecules that delay aging. You heard that right. Delaying aging, slowing the biological clock including sirtuin genes, resveratrol, NAD precursors, all of this stuff we’ll get into in the episode. He’s an author and published over 170 scientific papers, co-inventor of over 50 patents, and co-founder of 14 biotech companies. This guy is kickass. He has received numerous honors including being named Time Magazine’s list of 100 most influential people in the world and the top 50 people in healthcare in 2018. Come on. So let’s give it up for this guy, I just have to say that this is an exciting topic because this is everything that we thought we knew about genetics, epidemiology, about just our genes, and this is just what I have, and this is just what I’m dealt with. And we have so much more control of how the environment influences us, what we do with our nutrition, what we do with our sleep, what we do with our exercise, what we do with supplements, all of this stuff we’re going to get into. I got to meet Dr. David Sinclair a few times, and he is just a delight, a human that is doing great work and dedicated, just a bright spirit. So I’m so stoked to have him on the podcast and for you to receive knowledge so that you can kick ass and live the life that you are truly here to live without the limitations of age, without the limitations of aches and pains without the limitations of your own consciousness to expand our education, to expand our knowledge, to expand what it is that we think we know only to challenge that to be open to what we can receive that might possibly blow all of us away in terms of what is actually possible. And so open your minds, open your hearts, take a deep breath, be in gratitude, and welcome my next great guest, Dr. David Sinclair.

Darin: Well, welcome. The last time I saw you is a different world, a lot of things changed, a lot of things are changing. One thing that isn’t changing is we’re aging or at least we’re moving in that direction. And I mean, without getting into the opening up that Pandora’s Box necessarily because I don’t necessarily want to do that, per se. But I mean, let’s just jump into the sirtuin conversation. And so this big discovery you had with the cellular environment realizing this protein, essentially, the sirtuin longevity marker. And then I want to ask about what you’re currently doing today to continue to move the needle.

David: Sounds good. Yeah, so the sirtuins, we have seven of these genes in our body. I first worked on them in little yeast cells back in the 1990s. And so it turns out, most life forms on the planet have these genes, whether they’re plants, bacteria, or even ourselves, of course. And we’ve been along with probably 100 other labs trying to figure out what these genes have been, what are they doing in the body. And in yeast cells, what they do is they promote longevity, they keep the little yeast they use for baking and brewing. They keep them healthier for longer. And it turns out, as a group of scientists, we’ve figured out that they do the same thing in our bodies. So you can think of these genes as making little proteins that are little workers that tell the body how to be healthy. They’re quite bossy. They tell other proteins what to do. They don’t do the work themselves. But they act like the Army Corps of Engineers or traffic cop, think of it that way. Without them, the body doesn’t really know how to take care of itself. And that includes things like digest food well and process it, give the body energy, heal itself, even memory is controlled by the sirtuins. And as we get older, we have less and less of activity of these sirtuins. And this is one of the reasons we believe we become much more susceptible to diseases. We call this process aging, but it’s really just over time losing the ability to fend off, not just internal problems, but as we see now, external infections. And it may be partly the reason why the older population is much more susceptible to COVID is that these inbuilt defenses are just not there anymore or much, much weaker.

Darin: And that’s really where you make that argument of, listen, this is a breakdown of mechanisms. This is kind of a disease pathway, this whole aging thing. That’s kind of your seeing these mechanisms and these sirtuins go down and many other markers, so that’s your argument. So what was the lightbulb moment when you saw these sirtuins and then you realize that it’s expressing in the moment like what was that moment like? And then when did you start to understand that it’s affected in this pleomorphic kind of way how we can stimulate more of them?

David: Yeah, we just thought that they were passive genes that were helping. What connected it to me about four years later, I moved from MIT to Harvard and started my own lab, and that’s a scary thing. Because if you’re at Harvard, if you don’t make a big discovery or change the world, you don’t get to keep your job, you’re out of there. So that was stressful. And so what we decided to do is to try and understand how does the body or these yeast cells, either one, how do they, or do they turn on these genes? And if they do, what’s causing them to turn on? And we first turned to yeast because you could do an experiment in a week rather than a century. Now it’s a little bit cheaper as well. So what we found with these yeast cells was that there were a number of ways to turn on the sirtuins, and they’re all related to mild stress. So if we heat it up, the cells to our body temperature, normally they like 30 degrees Celsius, that is, they turned on the sirtuins. They didn’t like too much salt. They didn’t like a lack of amino acids. And they certainly didn’t like a lack of sugar, or what we call yeast calorie restriction or fasting. But the thing that gave us the most excitement at the time, we’re talking 2003, a nature paper that we published, was that there was a single gene that was controlling all the sirtuins. And it has a name, it’s called PNC1. The name is not exciting, but the fact that there was this control gene that was sensing the environment, temperature, that was turning on these defenses, and that fit with the idea that was emerging in the field of health and longevity, which is hormesis, a little bit of what doesn’t kill you will make your body stronger and live longer.

Darin: And epigenetics too, right? So it’s that continued idea that the DNA is not just the stagnant kind of instruction manual, that there’s a listening aspect to this thing. There’s an adaptogenic side of this environment, there’s stimulus. And it makes sense that we have adaptive cellular mechanisms infinitely within the body listening to the stressors. This is such a complicated thing for the mainstream people, and because we hear stress, and we just immediately go to “Yeah, I’m stressed out. I don’t have a job and I don’t have money. Why am I not living longer?” So break down that level of stress because I think, especially now more than ever, what can we do to mitigate because I can only imagine that chronic modern-day stressors over a period of time in that sympathetic response all the time is definitely not going to help this situation. And that the other side of it, this understanding of our friend as stress, and not being too complacent in our modern-day conveniences, we need to actually start getting back to that response of stressing in a good way. So just break that open a little bit so people are really clear between I’m running ragged over here and I’m also not getting out in my natural sense of stress and understanding.

David: Well, unfortunately, stress has two different meanings for the same word. I’m definitely not talking about the chronic stress that almost everybody on the planet right now is feeling, that will not make you live longer, it will age you. That kind of stress leads to molecules like cortisol moving through your body, which are over the long run, very detrimental. So you want to reduce mental psychological stress. But there’s this other type of stress, which is a biological stress, very different. What that really means is, you want your body to think that conditions are becoming adverse, such as not getting enough food for a little time or the temperature’s not optimal, or you’re not getting enough amino acids, for example. That will put your body in a state of alertness and perceived adversity. We know, fortunately, that at least most of us, if we skip a meal or two or even three, we’re not going to run out of food, but our bodies don’t know that. They’ve evolved to panic when we’re not getting enough food, and they turn on these defenses as a result. And that’s why we think that fasting over short periods, not for a really long time. We’re not talking about nutrition here, but short periods of fasting do a world of good for health.

Darin: Yeah, so we can break that down a little bit, but I kind of stick it to myself when we’re talking about these biological stressors because you and I met at Laird and Gabby’s house when you were in the middle of stressing out whether you’re gonna get enough oxygen or not. And also since then, have you seen, I mean, so we’re gonna unpack the fasting and intermittent fasting and how to kind of regulate that. Have you found that being oxygen hungry or breathing starving is also beneficial from the sirtuin’s aspect?

David: That’s unclear. We haven’t made a direct link. Though I’m seeing results from other labs that show that short bursts of hypoxia, well, actually noticed as a fact, will stimulate blood vessel growth. And as you get older, as long as it’s done, absent any tumor in your body, having more blood flow is always a good thing. And the connection that I have to that and the sirtuins is we showed a few years ago that by turning on one of the sirtuin genes, number one out of seven, we could mimic low oxygen. And the mice that we were treating, I had much better blood flow, and their capillaries in their muscle were much greater, more numerous. And then these mice that were elderly now could run like they were young again. And I haven’t proven that if you experience hypoxia the way I was suffering jumping from the bottom of the pool that day that a very similar thing is happening.

Darin: Well, I just talked to Patrick McEwen who wrote the book, The Oxygen Advantage and talking about nose breathing and how some very simple deep breathing exercises of slowing down actually, exhaling breath holds, and then just kind of slowly creating a little bit of a starving sensation obviously increases your CO2 retention, but also potentially mitochondrial production and capillary response. So there’s, definitely this synergy there, potentially. So let’s look at– because intermittent fasting now has been talked about in so many different ways. And now, from your perspective, obviously, you can get into extreme fasting and stuff but that’s not really what you’re talking about, certainly, from like Valter Longo and his work is fasting, mimicking. So it doesn’t have to be– so when people think of fasting, there’s definitely an emotional response if people have never done it because there is an emotional side and the social side of eating. So from your perspective, number one, what does the research say? And then potentially, what is your best kind of recommendation for someone who may not even have done this or can do this but can start tomorrow to help support them living healthier and longer?

David: It’s pretty simple, actually, and if I can do it, probably most people can do it because I’m not as disciplined as you are. There are a few varieties and that the truth is we don’t know which one is best. And it probably depends on the person and even your circadian rhythm and whether you feel hungry in the morning or not. So here’s what I do, I have a very small breakfast, I have a spoon or two full of yogurt. It helps me dissolve the resveratrol, which is one of the supplements I’ve been taking for 13 years. This is the molecule from red wine that we found activated the sirtuin enzyme. So I don’t eat much until late lunch. Sometimes I go all the way through to dinner, and I have drinks in between. And I find that actually really helps me focus. I feel good that way. And I like to eat a decent dinner. And so I do that every day. If I have lunch, it’s usually a very small sandwich or salad, nothing that would fill me up, and I find that works. So that’s called the 16/8 hours of fasting. There are others where people skip food all weekend or two days a week, and I’ve never been good at that, but it’s done. And then there’s the more extreme, so Dr. Peter Attia, who many listeners will know, he goes for a week, sometimes I think four times a year, he’ll do a week of fasting, which is an extraordinarily deep cleanse. And I don’t just mean in the gut. This actually processes– there’s one called autophagy where the cells when they are hungry enough, they actually switched into this state where they start chewing up old proteins. And if you do that for short periods, it seems to be very healthy for animals and ourselves.

Darin: There’s this idea to that if you’re doing types of fasting or a period of time or intermittent consistently that do you think that autophagy is starting to happen over a consistent period of time and that your body’s getting used to and getting ready for and getting more efficient at fasting if you’re not doing it for these long periods of time?

David: I think if you can do these long periods, it’s actually a good thing. Things happen at three days of not eating that don’t happen after one. For instance, there’s a type of autophagy called chaperone-mediated autophagy or CMA. And a good friend of mine down in New York Ana Maria Cuervo discovered this, but you do need really to be quite hungry for that to work. But what she found and she recently reproted this [00:20:03] conference I was at just last week that she can extend the lifespan of a mouse. It looked like it was about 30% at least, which is a dramatic extension just by turning on this CMA process.

Darin: Wow. So what was the protocol to that? How often does that–

David: She did it genetically, so that’s not something we can easily do to ourselves, but the principle is the same, there’s a gene called LAMP, and it actually switches off in the animals as they get older, and she just genetically modified the mice to make sure that didn’t happen.

Darin: Wow. So does she have protocols yet to be able to turn that on naturally or she’s just starting to see that that could potentially happen through long-term fasting?

David: Well, I don’t think she’s explored diet as much in the mice, but herself, she never seems to eat much. She’s always drinking diet sodas and what she lives off. Not healthy but her body doesn’t get a lot of calories as far as I could tell, and maybe that if she outlives all of us, we’ll know that there’s something to it.

Darin: Yeah, well, this restrictive eating seems to show up almost everywhere you even when I was actually in Sardinia with Dr. Longo. And you talked about these sirtuins and they’re definitely, you know, I eat a little bit and very little at night and I kind of go through these phases where they just don’t really eat these huge meals that we’ve kind of bought into in this western world. So there’s definitely something to that. So resveratrol, so this is kind of almost the gasoline or the fuel source for the sirtuins. So how does that mechanism work and what’s the easiest way to do that? Is it a supplement? Is it food? I kind of always stir towards what’s the greatest food source I can get to and use or is it almost impossible to get the doses that we would need to make this significant enough to turn on this sirtuins.

David: Well, we can activate it a few ways we’ve discovered. There is the resveratrol molecule, which we’ve worked on for over a decade. It’s hard to get a lot of resveratrol to the body. It’s very insoluble. That’s why I take with yogurt that may help it to be absorbed. We’ve done some studies in humans and other stuff too, and it’s very improtant to make sure it’s absorbed otherwise, these trials can tend to fail. But it does seem to be antiinflammatory in people’s as well as in mice. And especially if you’re having a high-fat diet, let’s say you’re a fat mouse, resveratrol extends the lifespan of those mice very  effectively. For some reason we also found it extended the life of mice if they were skipping meals every other day. We don’t yet understand that. But anyway, to jump to the chase, I take a gram of resveratrol with my morning yogurt everyday. And I’m still doing okay physically so that’s a long-time experiment with what we call an [00:23:35] But it’s hard to do it with resveratrol. There’s another discovery that’s interesting that came out of another lab, the Merzenich Lab. And they discovered just what was the end of last that olive oil component, one particular olive oil component called oleic acid, which is a monounsaturated fatty acid, activates just the same way that resveratrol does when it touches and interacts with this CERT1 enzyme in the cell. And there’s a protein that grabs the oleic acid and concentrates it by pushing it into CERT1. So this may be one of the reasons I think, and so to others that when you eat a lot of olive oil, it has some benefits. Who knew that it was turning on the body’s defenses against adversity. And then there’s a third way, just briefly, which is that the sirtuins need fuel. They don’t just work without it. And if you don’t have this fuel, they’re dead, and it’s called NAD. Now NAD is a ubiquitous molecule. It’s in every form of life in every cell, and we need it for many chemical reactions. But what was discovered by my colleagues, Lenny Guarente at MIT deserves a lot of credit for discovering and [00:24:56] a good friend of mine at WashU that NAD is the fuel for sirtuins. Now, our bodies have a certain amount of NAD. We needed to survive. And without NAD, we’re dead in about 30 seconds, we need this stuff. And our bodies are always making more, but as we get older, it looks like we make less and less. But you can supplement with precursors to NAD. We’ve done a lot of work as [00:25:20] on supplementing mice, old mice with NAD. And that was one of the ways we made those mice run further was to give them some NAD booster. One of the NAD boosters that we’ve used a lot is called NMM. It’s short for nicotinamide mononucleotide. Just be careful not to mix it up with m&ms because m&ms are probably not going to make you live longer. I can’t prove it, but that’s my suspicion. But yeah, so those are the three main ways that we know to activate sirtuins. There are a whole bunch of other polyphenols that are in plants that can activate sirtuins and we’ve known this for a decade. There’s a new one that’s on the scene called fisetin. There’s another one called quercetin. I think people pronounce them differently sometimes. But these are increasingly of interest to people in part because of our work but also because other labs have found that they have health properties, one of which is that they kill off or help kill off senescent cells. And senescent cells is a whole different story. Senescent cells are old cells that just accumulate in our body. Think of them as zombie cells, they sit there and wreak havoc and make other cells dysfunctional. They cause inflammation, they can even cause cancer. So we don’t like senescent cells. We’re trying to find ways to kill them off in the body. And these molecules seem to have some of those facts.

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Darin: If there was like 12 of you, and we had unlimited funding, could you imagine the kind of work that could be done on just spending enough time on one plant and extracting all of the different aspects that it has? I mean, because it’s like we talked about one molecule doing all of these things. Well, sometimes there’s moringa aloe vera, for example, who’s got 36 antioxidants very powerfully in it. And so I’m like, man, we need to stay longer, we need to live longer just so that we can actually study this natural part of our world so we can discover I think more of what is out there. So from your perspective right now, number one, what are you excited about, like you put up this book NAD, resveratrol, eat less, good amount of biological stress, I would add in have people lift heavy, try to lift heavy every day, just increase that natural growth hormone and several other things, obviously sleep and hydration and sensible eating and all of that stuff. What are you now focused on, and most excited about in your research and maybe whatever you can share, but please share with me because I’m kind of cheating here a little bit. I want to know what you’re doing because I also have my hand in a bunch of other stuff and obviously in the plant world and potentially one day we could bump up against each other on some stuff.

David: Sounds good.

Darin: So what are you excited about?

David: Well, we’re always interested in new molecules. We coined the term xenohermesis. It’s a long word, Conrad Howards, a colleague of mine and I coined it. So xenohermesis is the term that means if you eat plants that are under adversity, you will sense that and get the benefits. You’re exactly right. Resveratrol is the the ultimate example of that. And also you’re right, I tried to eat foods that have not been grown under perfect conditions, usually they have a lot more color. They might have a few holes in them from insects, but that’s fine. That means that they’re the plants that are defending themselves with these molecules and we, I think, reap the benefits. But the big one that’s coming down the line in the aging field is what’s called epigenetic reprogramming. And you mentioned earlier, Darin, the epigenome. It’s really important to know all about that. The genome is the DNA, the epigenome, other structures in the cell that controls which genes in the DNA get turned on and off. And when you’re young, it’s a perfect symphony of which genes get played in every cell essentially different than every other. But as we get older, cells, it becomes a cacophony, and the music isn’t played well, the genes get switched on and off in the wrong way. And I believe that’s a major part of why we age. And we can actually measure that quite accurately and predict how long someone will age. And we’re not all the same age, of course, even if we’re all biologically, I’m 51, all 51 year olds are not the same biological age by any means. Some people are still in their late 30s and some people are in their 60s. And that very accurately predicts what diseases you’ll get or how soon you’ll become morbid and sick and eventually die, which is an interesting but scary thought that there is a clock in our bodies that’s run by the epigenome. But what’s really interesting is that we’ve just discovered that you can reset the epigenome and get those genes to to be turned on and off. And the sirtuins, at least three of them, numbers one, six and seven are intimately involved in controlling that process. So that might be one of the reasons why sirtuins are so good for us is that they slow down the aging of that clock.

Darin: You know, a few years ago, I forget how many, I’m just now thinking of the clock right and our clock and our biological clock. And there’s a couple things I want to kind of open up here and that is stem cells. And also the telomeres and the telomerase. So there was that evidence that came out and I don’t know. I kind of want to pick your brain on the accuracy of measuring the telomerase and measuring the rate at which we’re losing the ends of our chromosomes as an accurate way of measuring our biological age. So I want to get your thoughts on that. Is that coming to be more and more accurate? Or is there other ways that are number one more accurate? Or is it needing to be a little more expanded than just looking at telomerase?

David: Yeah, so telomere is definitely shortened as we get older, you can measure that. And people have had this as a clock up until about five years ago. But the new epigenetic clock is fast taking over from that because it’s bound to be more stable and more or accurate. Although he’s biased, Steve Horvath, another good friend of mine at UCLA. He was looking at the telomerase clock or telomere length clock versus what we now call the epigenetic Horvath clock. And he said the telomeres are so variable that they don’t serve as a good a marker as his clock. And if you’re wondering, if you’re listening, and you want to get into the detail, Steve Horvath’s clock is based on little chemicals called methyls that will be added and subtracted physically to our DNA molecules. And he can read that, we can read that in my lab. And we can do that pretty easily for a few hundred bucks. And there are even companies now that are offering our services to have these measures from [00:35:34] 

Darin: Is that specifically methylation, the methylation process of the body?

David: Yes, it is. But what we’re finding is with the epigenetic reset, and we focused on resetting the old eye, the eye of a mouse that’s old or damaged, we could reset the epigenetic clock, the methyl clock, the Horvath clock is it’s also known. But we also think that we’re reactivating polymerase. We have some evidence that the cells are not as old in that regard as well. So that’s what’s exciting about the epigenetic angle is that it might be able to reverse many of the different causes of aging that we scientists have been arguing for 20 years, which is the most important. Fortunately, about I think it was close to 10 years ago, we at least agreed that there is more than one cause of aging. We have nine of them. Epigenetics is one, telomeres is the other, there’s autophagy and proteostasis go together. There’s nutrient sensing, stem cells, you mentioned, mitochondrial function, or energy production in the body. So the list is a little bit longer, but you get the idea. But what I’m excited about is that reversing the epigenetic changes seems to reset many of those and we’re just ticking them off the list including, we think, resetting telomeres.

Darin: It’s very interesting. It’s just really cool the fact that you’re at this point where you’re understanding the different systems. I remember when the research came out about the telomeres and it just blew my mind. But now you’re like, well, that’s one piece of this bigger kind of system and to describe this new way of seeing a clock biologically and then starting to peek into it in terms of its susceptibility and it’s also reset ability, that’s super exciting and must wake you up in the day, in the morning.

David: It’s one of the most exciting things I’ve seen, and I was very fortunate that a PhD student in my lab made this discovery. What I should mention is that it doesn’t just reset the clock in the node cells in the back of the eye, those eyes in the mouse, the mouse was blind and then three weeks later, they can see again, which to me just is an incredible finding. And the thing that’s also surprising is there are proteins in the cell that get rid of these methyl chemicals on your DNA. Similar to when a dentist will scrape or dental technician will scrape your teeth and get the plaque off, that’s what these proteins do. And when we remove those proteins from the eye, we have technology gene therapy to get rid of those, now the clock didn’t go back and the eyesight didn’t recover. So what does that say? It says that the clock or at least these methyls are part of potentially part of the aging process and the resets.

Darin: Wow. That’s incredible. So then it leads me into my next question then. So what I’m hearing is that potentially it’s turning this on and cleaning things up in a certain sense so that the eyesight can come back, but where is the repairing side of it because I just want to set a stage a little bit. So I’ve worked with Dr. Henry Young who discovered the totipotent stem cell and then pluripotent and all of this stuff, and he was at Mercer University and he’s discovered that and essentially, working withsalamanders and all of this stuff in the late ’70s. And then in the ’80s, the Mercer University said basically you’re crazy, you can keep that, so they gave him the IP. And so he stuck it in a NGO, essentially and continue to do the work. And what he found was obviously totipotent is kind of like that has no blueprint but can turn itself into any tissue or any organ, even the zygote, even at the basis of all levels. And there’s ways to endogenously induce a high amount of activated totipotent stem cells. And for everyone, I’ll just keep it really simple. There’s a lot of stem cells, and stem cells, once they’ve been given instruction, they can’t go the opposite, they can’t go back. So if you have a bunch of totipotent stem cells, meaning they have the ability to repair the body in levels that can blow your mind and having worked with Dr. Young for a while, it’s kind of astonishing if you flood the body full of someone’s– so he did a couple of things and I won’t make this too long. He did a couple of things, he was able to take circulating totipotent stem cells, that was patent number one, take it out of your body and blood. He was then able to find that totipotent and no one else could even understand what that was or looked like. He could then proliferate billions of them. So they were your own. And he made more of them and injected them back in your body just via the blood, and then the body turned into a healing incubator. And then as he saw that there was a huge amount of telomerase and telomeres that was kind of an off gassing of the process of this healing. And he regenerated knees and joints and everything within weeks within one injection of this stuff. And then there’s also things I realized through compounds and certain lifestyle things that you could tweak and you could turn on your endogenous totipotent stem cells. So blueberries, a cup of blueberries, and low to no caffeine and alcohol, and then blue green algae. It turned on your totipotent stem cells by over 10 times. So this is all in research, he’s written 200 different papers on all of this stuff. So my question then there has to be this intersection between what you’re talking about potentially, and the availability or the access of stem cells as a way of repairing and being available because it’s kind of the same, I would love to see the bell curve of this because it’s kind of the same thing as you cruise in your life and you don’t take care of yourself, your stem cell activity goes down and your ability to repair goes down. So what are your thoughts on, sorry for the long haul, but I just wanted you to have a little bit of understanding of where I’m coming from, I just want to understand that intersection because there has to be a strong correlation between what you’re talking about and this–

David: Yeah, there is actually, very well predicted. The technology that we use to reverse aging and reprogram cells is related to the technology that people use to turn adult cells back into stem cells, and use those cells, pluripotent stem cells to make organs and skin, this kind of thing. But you don’t want to use something that’s so strong that you’re going to turn the eyeball or any part of your body into new stem cells because it could easily lead to cancer. In fact, it’s known if you try that, you will get a mouse that has cancer. You can even kill it within two days if you do it too hard. So we had to figure out a way to do it safely to take the cells back in age so that they’re not stem cells, but they’ve got the health and vitality of stem cells, which we know lasts a lot longer than a lot of other cells in the body. And so what we took was a subset of what are called Yamanaka genes or Yamanaka factors, the three of them. One is called Oct4, Sox2, and last one’s Klf4. These are factors that like the sirtuins direct other genes how to behave. And we found to set off this cascade of a program that involves probably hundreds of other genes that go to work and reset the cell, but we’re very fortunate that we didn’t cause any cancer. We’ve tested this for over a year. It’s very, at least an animal’s very safe. We’ll see in people hopefully in the next couple of years. But we were excited because the genes that we left out, we’ve now shown with the toxic ones, you don’t don’t need those. And I think that what we’re doing is tapping into what salamanders naturally do. Those animals that can rebuild things like lizards tail, they can do that. We mammals, primates have lost that ability. I think finally, we’re gonna have the ability to do that again.

Darin: Let’s do it, man. That’s incredible. But when you start breaking down the mechanisms, and then you start understanding this stuff, it’s almost like just what you said, it’s kind of like, I love that you just said that because it’s almost this dormant ability that we have in us that potentially it’s available. We just haven’t evolved or maybe we d evolved, or whatever that part is. And I love your sense of this stuff because I’m sure you’ve been looked at sideways more than you’ve been looked at straight on and believed by your colleagues. So I can only imagine, here’s this, you know, your demeanor is so calm and peaceful, but at the same time, you’re kind of an ass-kicker. You’re pushing envelopes. And now I think you’re probably, correct me if I’m wrong, but there’s more and more research, and you probably surrounded yourself with a lot of great other colleagues that are now getting the attention. Just a snippet, what was it like for you pushing into these areas when maybe at Harvard and all of these places, people kind of thought you were a little nuts?

David: Well, it hasn’t been an easy career, I’ll put it that way. A lot of work that we’ve put out over the years starts out with some healthy skepticism, but it’s okay. I tell people in my lab that if it’s not a surprising discovery then it’s not worth working on. And so what we try to do is to do things that are unexpected. That’s really what the best science is about. If you can predict what’s going to happen, then that’s not so exciting. We want to push the boundaries. And actually at Harvard, we are encouraged to do that kind of research. It’s just that the field of aging has had a bad rap for many years. It’s changing now, but when I first started, it wasn’t considered a real form of biology. It’s certainly changed since I started. But I also speak out, I say things that a lot of doctors don’t believe, which is that aging should be considered a medical condition. We should try to treat aging, not just individual diseases. And unfortunately, yeah, things are changing, and the book that I wrote has helped sway a lot of people that it’s just a no brainer once you lay out the facts. But it has been tough and I’ve come up against pharmaceutical companies who’ve said that our work was wrong. And I’m still standing. I haven’t had anything yet that blew up. But it’s a scary thing having someone published that it’s wrong. And then typically you have to spend three to five years working on it to see if they’re right or you’re right. And actually, the best attitude that I could have and teach my students is the answer doesn’t matter whether, honestly, whether we’re right or wrong, of course. It’s better if we’re right, but what’s more important is we figure out what’s true, and then move on. And as long as you’ve got that attitude, it’s not that stressful. Just tell me the truth, and you go and do it.

Darin: Yeah, exactly. And that’s why I applaud you for doing that. And we unfortunately have conflicts of interest in so many different ways. And pharmaceuticals have bet that this type of model and this type of understanding of health is best not to come out because it doesn’t keep their model of sick people activated. But I love the fact and I think that this should be, I think aging should be packaged differently too because if we actually understand that the research is supported in your daily habits, and that daily habits is contributing you to the seat that you’ll be sitting in in the future, but it’s actually going to give you gifts now. And that’s where you don’t think of that because if you’re 50 or 60 or 70, you’re like now I’m thinking about anti-aging, but we really should think about is kicking ass every day of your life. It just so happens that if you line up some of these principles, all of these principles that you’re talking about is going to give you benefits now, and it’s going to lay the foundation for you to live a long, healthy life. And that’s the change of our culture. Jumping out of this quick fix idea, but it’s actually quick because we know making one shift, sleeping well one night or not sleeping well one night is gonna mess anyone up. So these things are actually fast, but we need to kind of package this whole thing differently. You know what I’m saying?

David: You’re totally right that you cannot just decide at 60, I’m gonna live a long time. It’ll help if you turn your life around. But the biggest bang for the buck is if you live your whole life like that, and the clock ticks slowly every day. Until we figure out how to reverse aging an entire body, and that’s definitely a decade away, we have to do these things every day so that clock ticks slowly.

Darin: Yeah, so let’s slow it down so that David can get to that point where he’s figured it out to literally turn back the clock, and then we can put a lot of tension on the good that we need to put in the world and help some of these crazy things that are going on. But hey, I wanna thank you for your time. I know you got a board meeting so I’ll let you get your head around that. David, I just appreciate you. I appreciate the work you’re doing. I appreciate the spirit at which you’re doing it. And we just need more health, more positivity, more people looking at life from a way that is– I mean, there’s so many other questions that I wanted to ask you too, in terms of attitude but let’s let’s save that one because I think that’s a secret as well. So let’s save that and we’ll dig into that maybe in person when we’re able to move around a little better, but I appreciate you, man. Totally stoked.

David: Thanks. But it’s good to see you again, and I’m a big admirer of your work too. It’s really been amazing to see that your voice is out there now too. Thanks for having me on. I appreciate it.

Darin: You got it, brother.

Darin: That was a fantastic episode. What was the one thing that you got out of today’s conversation? If today’s episode struck a chord with you, and you want to dive a little deeper on a variety of topics, check out my live deep dives on darinolien.com/deepdive. More episodes are available on darinolien.com as well. Keep diving my friends, keep diving.

Darin: This episode is produced by my team at Must Amplify, an audio marketing company that specializes in giving a voice to a brand and making sure the right people hear it. If you would like or are thinking about doing a podcast or even would like a strategy session to add your voice to your brand in a powerful way, go to www.mustamplify.com/darin. That’s www.mustamplify.com/darin.

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