The Autophagy Molecule That Won a Nobel Prize and Nobody Is Taking It | Ep. 345

And the reason why spermidine is so interesting to me is that we know for certain that spermidine positively impacts or improves a minimum of 9 of those 12 things, if not all 12 of them. And this is based on published scientific literature.

Hey everyone, Dr. Jeffrey Gladden here. I just finished a really great conversation with a woman, Leslie Kenney. She basically has started a company that makes a spermidine product called Primadene, or 2 of them actually, you'll hear us talk about. She has a company called Oxtra. Healthspan, and she's a really fascinating person who has an amazing personal health story and also amazing information about the product spermidine. We're going to go at the root cause of the root cause in this conversation. I think you're going to really enjoy it. It goes deep.

He went from saving hearts as a cardiologist to rewriting the entire aging playbook. Dr. Jeffrey Gladden believes 100 is the new 30, and he's got the science to back it up. This is the Gladden Longevity Podcast.

Leslie, welcome to the Gladden Longevity Podcast. Pleasure to have you here.

Well, it's a real honor for me to be here with a cardiologist of your renown.

Oh, well, okay. Well, I appreciate that. I'm excited for this conversation because you're talking about something kind of near and dear to what we think is really at the root cause of the root cause of health issues, right? So, you know, in our world, we really have a system in terms of how we look at an individual and the life energy circle, the psycho-spiritual spaces on the outside, and then inside is basically a Venn diagram of longevity. And people are a little bit, you know, almost anything can be construed as longevity, right? If we, if we fix your blood pressure, that's a longevity benefit. Well, it is, but it's not the longevity we're talking about there. What we're really talking about in the Longevity Circle are the actual drivers of the aging process, which are both expressions of the aging process, meaning they get worse as we age, but then they also accelerate the aging process. So those are called the hallmarks of aging. And Currently it's accepted that there are 12 of them. We were talking a little bit before the show that I think we both think there are more. I think there are probably 16 and, you know, there will be more in the future identified for sure. But nonetheless, even in those 12 hallmarks, we can even review them if that's helpful to the audience. I can pull up something and kind of run through them. But what's interesting to me is that, you know, when we think about correcting things or turning back the clock, yes, going after health and going after performance and going after the environments, which we also do in our program here in our system are very important. But what's— we think is really absolutely critical is to go after those hallmarks of aging. And I think that's what really distinguishes a true longevity practice from people that are kind of dabbling in some peptides and some cold plunge and some other things like that. So I'm just going to rattle these off and then allow you to start to speak. So just so people understand, so the 12 that we're talking about, one is telomere attrition. This is how telomeres, the end caps on the chromosome, shorten with every cell division. And the telomeres get short enough, they signal the cell to become old and senescent, right? So telomeres are one. Another one is epigenetic alterations, and this has to do with how methyl groups are added or subtracted from the DNA to either upregulate the expression of a gene or downregulate it. And as we go through the aging process, the pattern of methyl group additions and subtractions changes to where our genes are expressing themselves in an older fashion than a more youthful fashion. There's some really interesting things about reprogramming ourselves epigenetically and then loss of proteostasis. This is kind of right at the center of what we're talking about here with spermidine. This is the ability to actually make a protein with fidelity and then have it fold properly and be functioning properly. And then autophagy, which is the ability to actually get rid of that protein and recycle it, if you will, when it's no longer functional. So that's the next one, which is macroautophagy. And then you've got deregulated nutrient sensing. This is a balance between mTOR, how we grow and get strong, and AMPK, how we actually activate this was fast but it's also how we activate autophagy. It's also how we activate DNA repair and telomere repair and things like that. So that is very important, deregulated nutrient sensing. Then mitochondrial dysfunction fits in. I think people can understand that the mitochondria don't work as well. There's mitophagy, which goes along with autophagy, and we'll talk about that as how you get new mitochondria. And then there's cellular senescence. This is kind of where cells go to die, so to speak, except they don't die, they just kind of hang around, and then they become secretory, and now they're spewing inflammatory cytokines into the environment, causing other cells to get old and be inflamed. This really accelerates the process. And there's loss of stem cells. They run out of youthfulness, if you will. There's altered intercellular communication where cells break down in terms of how they synchronize with each other, which leads to dysfunction and inflammation. Then there's chronic inflammation itself. So many ways to have chronic inflammation between the gut, infections, you know, things related to tissues breaking down and all the other ones we've talked about. And then dysbiosis, which is essentially the gut biome shifts as we age as well, which makes us less healthy. And then genomic instability. We don't repair the DNA as well as we used to. And so those are the 12 right there. So that was a little bit of a long-winded intro, quite honestly. I appreciate your patience, Leslie, and letting me walk through that for the audience. But now we're going to talk about a molecule that's near and dear to you called spermidine. So why don't you tell us a little bit about spermidine and how you came to be interested in this molecule and maybe a little of your personal history with it.

Well, I'll do a sort of helicopter view because you've given us that wonderful introduction to the levers that we can actually push or pull in order to slow or hasten our aging process. And obviously we wanna slow it. And the reason why spermidine is so interesting to me is that we know for certain that spermidine positively impacts or improves a minimum of 9 of those 12 things, if not all 12 of them. And, uh, we can go into the nuts and bolts of this, but this is based on published scientific literature. And so because of the fact that there is a lot of crosstalk between these hallmarks of aging, it's kind of like at home when you clean one room in your house, suddenly you feel better about everything else and the ability to clean the other rooms in the house. Simply by improving autophagy itself, you will have a positive spillover effect on another hallmark. Let's say that's mitochondrial dysfunction, or maybe that's protein folding. But this crosstalk is real. And, you know, if I think about the most impactful things that I can do as an individual to slow the aging process, I want more bang for my buck, and I want to hit as many of those hallmarks as possible. And spermidine really does that.

Yeah, I think it's, it's a really good point that you make, this idea of crosstalk. I think this is something just to reiterate for the audience. So one of the things that's important to notice about these 12 hallmarks is that they all play together. And so when telomeres get short, it's not just that the telomeres get short and not just they increase the incidence of senescent cells. When your telomeres get short, they actually decrease mitochondrial function, so you're making less ATP. When you make less ATP, you're less able to repair your DNA, you see. And so they're all playing off of each other. And when you don't have good autophagy, then your proteins are increasing inflammation. And so all of this plays together and they sort of spin up. And it's one of the reasons that one of the most critical things to understand about aging is that it's exponential and not linear. Chronologically, it's linear, right? Every year we're another year older, but biologically it's an acceleration. And between the ages of 63 and 80, is a massive, massive increase in the pace of aging. So if you're not, if you don't have an exponential strategy to deal with an exponential problem, right? Then you're gonna be falling behind. And this is why it's so important when you're thinking about your own longevity to really focus on these hallmarks because this is where the exponential acceleration is happening. The beautiful thing about spermidine is that with the crosstalk that it engenders between these hallmarks, it's actually slowing down the whole cycling up process, right? It's like, it's like stepping into a tornado that's spinning up and slowing down the spin. It's like, oh, okay, well, now we have the opportunity to kind of get ahead of it in some other ways, right? So anyway, it's a fascinating molecule and it's a fascinating process. So you have some personal history with this as I understand, is that correct?

Yes, that's right. So about 21 years ago in 2004, so 22 years ago now, good heavens, I was diagnosed with multiple autoimmune conditions, lupus, rheumatoid arthritis. They didn't catch the Hashimoto's thyroiditis, but that was diagnosed. Um, that was there at the same time because I had destroyed most of my thyroid. This was all going on while I was trying to conceive my first child using IVF. I'd been told initially that I had idiopathic infertility, which is just the fancy word for we don't know.

We don't know.

We don't know, but it sounds, it sounds good. To the patient. And forgive me for saying that. And then at age 39, they said, you're too old and you need donor eggs. So now we know why you're not getting pregnant. So take these donor eggs. And it was a bit of a, a bit of a tornado for me emotionally to give up this idea of having a baby. And at the same time, think, wait, I was just trying to bring new life into the world. And now you're telling me my own life might be at uh, I don't understand. The folks in the white coats are the experts. And I think that for some consumers, consumers, patients in the United States, we think, and I think this is wrong, that our doctors can do everything. Even when we present, when all the wheels have fallen off, you know, fix me. And my doctor looked at me when I said, wait a second, you have to fix this. I can't go into embryo transfer with lupus, rheumatoid arthritis, and all of these injectable immune suppressants, my doctor simply looked at me and said, I wouldn't do this IVF. Even if you're successful, you've only got a good 5 years left.

Goodness gracious.

Yeah. And I think, you know, we have to think back in 2004, we didn't have treatments, certainly no cure for lupus. And she told me that this was a doctor in Boulder, Colorado, that I, would need to expect it to get worse over time and manage my expectations on what life, you know, could provide for me. For patients, this is, this can be really traumatic. And in the same way that you often tell your own clients, now, wait a second, wake up as if you're 27 years old. Do not wake up thinking you're, you're 70, right? Mindset is very important. And I think I was very lucky to, to have had a, kind of ornery grandmother from the American Midwest. She had already died, but her voice came to me in that moment where, you know, the doctor said, "There's really nothing we can do." And her voice came to me and she said, "Let's throw the kitchen sink at it, Leslie." And I thought, that's right, that's the pioneering spirit. We're just gonna give it our all. And surely it only stands to reason that a patient who doesn't smoke, doesn't drink, and isn't sleep deprived has got to do better than one that is. So on that basis, good old common sense, I'm going to try and tackle this and just become the patient who is 1% better. And if I'm 1% better than I was yesterday, then I'll be 1% closer to being the ideal patient. And maybe my doctor can cure me then. And I'm a big believer in collaborating with our practitioners, not just saying, "Doctor, fix me." Yeah. Because I think that is expecting too much of them, especially given time constraints. And, you know, we have to work together in partnership with each other, which I know is something that you do with your own clients.

Yeah. And I think that's a really key thing. We were actually talking earlier today about clients that join us. And one of the things that we love about the clients that choose to work with us is that they all want to jump in. They want to do the work. They're looking for direction. They're looking for understanding. They're looking for empowerment. And that's something we can provide them., but you know, we can't hold their fork. We can't turn the lights off. We can't, you know, do all the things that they need to do. And yet when you have people that want to collaborate with you, we want to collaborate with them if they want to collaborate with us. That is the perfect thing. So if you're listening to this, you have to understand that nobody can fix you. It's a question of how do you become empowered to fix yourself by working with people that can actually empower you. I think that's a better way to think of it, which is kind of what you're alluding to there.

Exactly. So my own doctor had said that there was nothing more that she could do for me. But having been an IVF patient and been on a lot of patient bulletin boards where a lot of us women were actually matching our embryo transfers with each other, doing this as a group for community support, I knew that I could go to those community bulletin boards and speak to other lupus and RA patients. And it was —there on a lupus board that I discovered from other patients that there had been a study, a small trial of 13 patients done in Germany in 2000, using a novel therapeutic called intravenous immunoglobulin, or IVIG. And this is something that normally is given to patients who are unable to create their own antibodies. So it's basically a pooled donation from 3,000 to 10,000 donors giving their antibodies.. And when they did this, they realized that actually patients with overactive immune systems were calming the immune systems down. So it had this wonderful immune modulatory effect. And as soon as I saw this, because every single one of those 13 patients got better, I was so excited. I immediately went to my doctor and said, look at this. This is exciting. I need this. She said, 13 patients does not make evidence. That would be, it would be wrong for me to prescribe this for you. So back to the patient bulletin boards I went, where other patients told me about a doctor in San Francisco who would do this. He prescribed me 2 transfusions of this and, uh, basically with the purpose of resetting my immune system. And I did this all the while I had been injecting myself with immune suppressing drugs, such as Enbrel and Humira. And these are— anyone who, who's ever taken these drugs, the lifestyle change you need to make there is you have to avoid large crowds, parties, social events, and small children in particular. Yeah. Because your ability to fight infection is greatly reduced. And so I'm on these immune suppressing drugs and I'm thinking I'm resetting my immune system. What if I simply remove all of the triggers to my immune system so that by the time the IVIG treatment is done, if I remove those triggers, I'll be back in harmony and maybe I'll be okay. So I did this. And at that time there was a book by a fellow named Dr. Barry Sears called The Anti-Aging Zone. He did another one called The Anti-Inflammatory Zone. And he speculated that autoimmune patients like me were prematurely aging, that we we were inflammaging and that if we could remove these inflammatory triggers, whether they were dietary, uh, or lifestyle factors, we could actually restore our bodies to balance. So I immediately took, you know, a dietary allergy test, dairy, gluten, eggs were all a problem. So got rid of all of those. I improved my sleep. I got rid of stress because that could be a big driver of inflammation. Quit my work and started moving, walking every day in the Rocky Mountains, which were just down the street from me and did trauma therapy. I essentially looked under every stone. If it resonated with me, then I did it. I know that in your own system, you look at things like spirituality. And I think that we are human. We have always responded to things like this. And, you know, we shouldn't, we shouldn't poo-poo them because the quote unquote the evidence isn't there. We do respond to these things.

So actually the evidence is there over and over again. I mean that, you know, people that have a faith or believe in something, and we're not religious in the sense that we're espousing some form of religion, but we are very spiritual that people that believe or have faith or people that have people praying for them or, you know, sending good intentions or whatever, it all makes a difference. Every study ever done has shown that it makes a difference.

So it makes a difference, except that some, some practitioners are reluctant to discuss this.

Yeah, it's a little bit, I'll tell you, it's a sad thing because it's really kind of like the separation of church and state. I was, I learned recently that it was back in the, I think it was the 1600s that there was a division between medicine. I forget who the, who the person was and the Catholic church. And they basically said, look, 'You guys take care of the spirituality over there. We're going to focus on the biology over here.' And that basically became sort of the schism where, you know, the psychospiritual space really got segregated over towards the church. And you develop this kind of atheistic, science-based, 'we only believe in science' kind of mentality. If it's not a double-blind placebo-controlled trial, it doesn't count. And it's kind of been perpetuated You know, even your, your physician's comment about, well, it's only 13 patients, even though they all got better, that's not evidence. It's, it's such a, it's such an inbred thought process about how to evaluate what's potentially helpful, right? Exactly.

Whatever works for the patient works.

That's right. Whatever works, works. It's a cage that people put themselves in, right? And they build this cage around, well, we're doing the right thing, we're being ethical, we're, we're following the standard of care, that all the different constructs of this cage that go into it. And it's not that we're cavalier here, but what we're saying is that there are many things at work that don't come inside that cage, right?

And they work for thousands of years. Yeah, precisely. So I was open to all of these things. However, this idea of suppressing the immune system simply did not sit right with me. And it's perhaps because two of my grandparents went to medical medical school in Japan at the University of Kyoto. And they had always, I have always had this drilled into me that once you put the body back into balance, once it is in harmony, it knows how to take care of itself. It has an innate wisdom. And so once the second IVIG treatment was done, I actually stopped with the immune suppressing drugs and going back to, to my physician for a routine check-in. I'll never forget this. I went in, she had the folder. She was obviously very rushed. She opened the folder and she said to me, well, look at that. You don't have lupus or RA. And I just said, excuse me? And she said, all your labs have returned to normal. She's not looking up at me at this point. And I said, that's amazing. Do you want to know what I did? And without looking up, she just said, no, that's okay.

Isn't that just the most dramatic thing? Yes, that's when the penny drops, right?

The system has no time. Doctors are not going to be curious, right? But we have to be curious.

We see this all the time, right? We heal people in half the time routinely here, right, with things that we do. And they go to see their doctor and they're like, oh, well, you're a fast healer. But they never asked. They never asked, what are you doing? How's it working?

Because they, you know, the problem is the system does not reward them for getting curious because probably the answer to what healed each person will be a little bit different because we're each bio-individual. But they don't have time in their day to write this down or ask the questions or allow the patient to get started on the conversation because it's going to bleed into their next patient's time and they are on a conveyor belt of patients.

So if you're listening to this, I think this is one of the litmus tests you can use when you're talking to any physician, right? Any practitioner, it could be across any spectrum, right? Physical therapists or whomever. If they're not curious, you probably don't want to work with them. If they're not curious, because I will tell you, there is a world of solutions and a world of answers out there. We're finding them every single day for our clients, new solutions that we didn't know about. There are so many things that exist out there. If you are not working with somebody that's curious and wants to actually look at your situation from a place of curiosity instead of a place of prescriptive, you know, then you're working with the wrong person. You're really working with the wrong person. And I don't care if they're a functional doctor. I don't care who's been trained with functional medicine solutions for sick care problems. If they're not curious, you don't want to work with them. You really want curiosity because this is actually how progress comes forward. So exactly.

And this is historically how the best physicians and the physician scientists of the past actually leapfrogged and made progress. They were 1,000%. This is how all progress was made. Yes, exactly. So the fact that so many doctors are, well, I don't have time. I mean, I don't, I don't blame them, but it's the system within which they operate, which prevents them to do this.

I do hold them accountable. I do hold them accountable. And I will tell you why, because I think it's unconscionable not to actually rise above the system in which you're working to think about what's in the best interest of this individual. I do hold them accountable. I think that's quite honestly almost unconscionable because everybody that went to medical school when I started, you know, everybody was gung-ho about helping people. We all were. It's like, well, this is our opportunity to really help people. And it's unfortunate that the system crushes that into conforming with a, you know, a predetermined way of thinking and practice. We're brainwashed essentially. But I still hold them responsible because you really need to rise above that. I mean, when you see things like you coming in the door saying, look, everything is fixed. Aren't you curious what just happened? And they say, no, it's like, oh my gosh, you have really pushed your way.

I hold them accountable. Well, this is, this is exactly when the penny dropped for me. And I suddenly realized that I held an awful lot more power than I realized. Good for you. Fast forward several years later, the Hashimoto's thyroiditis was discovered and the fact that I really don't have much of a thyroid anymore was corrected, immediately I got pregnant. The, uh, the doctor who diagnosed that said, now just be careful, you're going to be very fertile now if you don't want to have any children. And I just thought, you must be kidding, you have no idea. I've spent over $100,000 trying to get pregnant. I've done donor eggs, I've done 5 IVFs, 3 IUIs. This doesn't work on And, lo and behold, within 3 weeks of doing adrenal support, just adrenal glandulars and Armor Thyroid, I was pregnant and delivered at age 43. So, now, we have to fast forward. Thank you so much.

Just stop there for one second because think about this if you're listening to this. This is somebody who really wanted to have a child who basically was starting from less than ground zero. She was in the negative, I mean, way in the negative. This was almost impossible.. And then she was told that, number one, she might not survive more than 5 years if she delivered the baby. I mean, think about, think about the courage that it takes to persist in that set of circumstances. I mean, this is— I just want, as you're listening to this, just understand this is like climbing Mount Everest 16 times, right? And then, and then to be able to actually conceive and carry a pregnancy. Oh my gosh, that's unbelievable. That's incredible.

Yeah. It was incredible to me. And I am, I'm so grateful really to my grandmother's indomitable Midwestern pioneering can-do spirit, you know? And thank goodness she, she passed those values on to me. But, you know, fast forward a number of years and I find myself in Oxford, England, and I have children. I have an adopted daughter and I have a biological daughter and I'm on the school grounds waiting to collect my daughters. And I began to speak to other parents. Now, of course, if you're in Cambridge, Massachusetts, Cambridge, England, or Oxford, England, the parents around you are more likely going to be scientists. And I was amazed by the things that they were working on, whether it was transcranial electrostimulation to treat resistant depression, or if it was using stem cells to regenerate tissue. Uh, it was absolutely fascinating. And I began through those conversations to fundraise for these, for companies in the regenerative medicine space in Oxford, England. And it was through this process that an individual who ran a venture capital fund, who was in charge of the biotech portfolio here, he said, hey, Leslie, you're a rheumatoid arthritis, you know, patient. There's something interesting happening over in rheumatology at the Kennedy Institute for Rheumatology here at Oxford. You need to see what these people are doing. And I went to meet the scientist, Professor Dr. Katja Simon and Gata Alsaleh. And they were using this compound called spermidine to essentially reverse immune senescence in elderly mice. And when I heard that, I realized the parallels with my own elderly, likely senescent immune cells at age 39 and the work I had done with IVIG and thought, Okay, so this is an immune modulating compound actually, and yet they're telling me that this comes in food. So does this mean I can actually eat more of the foods with this compound? Yes, exactly. Among other things, mushrooms. Yeah, mushrooms, soy, legumes, in order to actually bring my immune system back into balance. And the immune system, for those who, who are less familiar with it, it's not just whether or not you have an autoimmune attack where the immune system is overactive. If you have an underactive immune system, then you're more prone to things like pneumonia, COVID, flu, uh, colds, but also cancer. And if your immune system cannot properly surveil for cancer, that is also problematic. And of course, the RA patients, rheumatoid arthritis patients, had been, been given immune suppressing drugs to deal with, you know, to, to mitigate against the damage from their immune system destroying their joints, uh, and tissues. And actually, we know that these patients who are on immune suppressing drugs for a long period actually are more prone to getting cancer. That's right. So isn't it a better idea to modulate the immune system and restore it to homeostasis or balance? Yeah.

It's the silliness of it is can only be understood in the context of an economic model, right? Because if you, if you have a problem and something's elevated and you develop a drug to push it down, you know, that's something that somebody's going to need for a long time. On the other hand, if something's elevated and you go below the surface to the root cause of why it's elevated and you bring it back into homeostasis, that's a fix, that's a cure, right? And there is no economic model to that, right? So, as you're listening to this, it's really important to understand that when you think about the drugs you might be taking or the things you're doing, is it actually getting to the root cause of the problem? Or in the longevity space, what we think of as the root cause of the root cause. If you're getting to the root cause of the root cause, in other words, if you're focusing on these hallmarks of aging we described earlier, now you're actually making real progress in your own journey towards living young for a lifetime. Time. Apart from that, you're just quite honestly putting Band-Aids on top of stuff and probably 100% consequences from, right? 100%. Agreed. Yeah.

And I think that there is no patient that wants to just have a Band-Aid there. Nobody wants a chronic Band-Aid. It's not that we want our illnesses managed. We want them gone. And so this was when I began to get quite excited about spermidine's potential. But then I began to look into the research. Now spermidine belongs to, as you know, a class of compounds called polyamines. And they have been studied for years. There's something like 13,000 papers in the literature about polyamines. They include things including the delightfully named spermine and putrescine. Yeah, putrescine. They're just terrible names, but they're very safe. Nobody really understood their magic mojo until we learned that spermidine activated autophagy, the cell renewal process that was the subject of the 2016 Nobel Prize in Physiology or Medicine that was awarded to Professor Yoshinori Ohsumi of Tokyo Tech. And all of a sudden, we began to realize, actually, spermidine can do some amazing things. So as a cardiologist, you know that it helps with mitochondrial function inside cardiac cells, things like cardiomyocytes, which have— we have a very limited pool of these cardiomyocytes, which govern the rhythm of the heart. And, as I was saying to you earlier, I like to think of mine as 1965 Mustangs that I need to keep maintained and polish the chrome and get the oil topped up and new tires on there because I need them for life. When I'm 26, only 1% of them replace themselves every year. At my age, I'm about to turn 61 in a couple of weeks. Weeks, only half a percent of those cardiomyocytes replace. So I actually need them to undergo autophagy. And here's where the part about senescence is interesting. I don't want dysfunctional cardiomyocytes to necessarily undergo cell apoptosis or cell death, you know, just like that Mission: Impossible tape— this tape will self-destruct in 3 seconds. I don't want that to necessarily happen. If spermidine can actually rescue that senescent cell or pre-senescent cell, I want it because I'm going to need it because that pool of cardiomyocytes is so small. So, you know, there's cardiology. Then there was promising work in things around misfolded proteins, Parkinson's, ALS. Then there was promising research around the brain and autophagy in the brain for cognition. And I saw interesting research around, you know, kidneys, liver, for fatty liver disease, also for alcoholic liver disease, which amazed me that there were preclinical studies on how it benefited this. So all of these studies essentially persuaded me that this was a cause in need of a champion. And I decided to hold up my hand and say, Okay, I'd like to bring this to market. So it wasn't in the, the UK at the time. It wasn't in the US at the time. I wanted to get it to my mother who lives in California, in Southern California, and I couldn't get it to her. So I sourced it in Japan. We actually work with the Japan Autophagy Consortium. A senior advisor is Professor Ohsumi, the 2016 Nobel laureate. For his work on autophagy. And we sourced both a wheat germ-derived product there. We were first to market with that wheat germ-derived product in the United States, although we were very small. So perhaps lesser well-known. And that is really how I came to, to this awkwardly named compound and, uh, sort of became known as the queen of spermidine. Yeah.

Well, it's a, it's an interesting title for sure. Right. Uh, but Yeah, no, it's, uh, it's great. I think, you know, you also have some history with, I think, measuring your biological age or ages. You know, we're a big fan of understanding that we're a mosaic of many biological ages. That being said, you've been taking Spermidine, I assume, on a regular basis. I'm curious. 7 years. For 7 years. So share with the audience the time of day you take it, how much you take, when, and, uh, you know, things like that, whether you take it apart from food, whether you take it before you go to bed, at first thing in the morning, before exercise. Tell us how you, how you've kind of aligned in with all that.

Okay. Before I do that, I'll just mention the biological age test that I did. So every 6 months I work with a functional medicine practitioner who's also a board-certified French endocrinologist here in the UK. She's in London. And I have always measured my cytokines, my TNF-alpha, my IL- toxic because the one thing I don't want is for them to go haywire again. And I've been doing this for decades now. So when I met Professor Gordon Lauch, who runs— he's chief scientific officer for a company called GlycanAge. And he said, you know, I— why don't you take this biological age test? And I thought, well, tell me more about it. And he said, well, this— we're really looking at inflammatory markers. We're looking at immune markers. I thought, "Oh, I definitely want this because this is something that I anyway do every 6 months." And so, I took the test. And somewhat surprisingly, the biological age, and again, keeping in mind your mosaic framework, we're looking at the immune age here. Yeah. Came back at 21. 1, which was incredible to me. I think I did this at Dave Asprey's conference in Florida. I was quite jet-lagged. I'd flown in the night before on a red-eye from London, and I was, I was really quite astonished. But what it told me was that I was doing a good job of keeping inflammation down and removing those triggers to my immune system. And that is what has always been of great importance to me. So in terms of how I take it, so I have been I've been taking it for 7 years and I am privileged in that I am the person who's bringing you, who's literally importing this from Japan. And so I do take it at night like you do. I do find it helps with sleep, but I do want it to kickstart the autophagy, which I would enjoy by fasting overnight. I know you do this as well. You're finishing eating, I think, in the afternoon. Yeah, early evening. Early evening. So I'll take Primadene Original. So the name of my product is Primadene I like to think the new prime of life, and I'll be 61 soon. That's a prime number. So it is. Yes, it is a prime number. So in any event, I'll take Primadene Original mixed in with some magnesium powder, and that will be kind of my nighttime cocktail together with 2 Primadene GF tablets. Now these are sourced from a unique strain of Chlorella that happens to be extremely high in spermidine, 'cause I had to test over 100 different strains to find this. So it's a gluten-free version. It has Okinawan lime peel. Okinawan lime peel is a bit like bergamot. It has bergamot lemon. It has something in it called nobiletin. And nobiletin, like spermidine as a compound, positively influences 2 of the 8 clock genes that we know of, and that modulates circadian rhythm and sleep. Circadian rhythm disruption is one of the additional hallmarks of aging that is part of your list and my list. So I take that before I go to sleep. And personally, it seems to, it seems to help me sleep better. I consistently get between 70 and 90 minutes of deep sleep on my Oura Ring. And usually, you know, an hour to 70 minutes minutes of REM sleep. That has been pretty consistent since I started measuring with the Oura Ring and been on the Primidine at the same time. In terms of the dose, the dose for the Primidine original powder is 1 milligram, and it's just a powder. You could mix it in with a smoothie, or you spread it on an acai bowl, or, you know, mix it with some fizzy water and it dissolves pretty easily. Then with the gluten-free Tablets, the two of those are the equivalent of, uh, 1.2 to 1.6 milligrams of spermidine. The reason it varies is because it depends on the time of year that we harvest the chlorella. This is grown in freshwater ponds under Okinawan sunshine, and if we harvest it in winter, we get less spermidine. If we harvest it in summer, we get 1.6 milligrams or more. And so we are now only harvesting in summer. But, uh, you know, truth in advertising, I have some of the winter product still out there and that's 1.2 milligrams. We will always state it on the label. And that's the variance that happens with, uh, with a food-derived product. Yeah.

No, that's awesome. That's really, really interesting. Yeah. The GlycanAge is an interesting test. We use it on all of our clients as well. We find that it's also impacted by thyroid as well as hormone levels.

Yes, HRT, very, very important, and I'm a big advocate for HRT.

HRT has an impact on it as well, and also bovine IgG and colostrum. Colostrum actually is the one I was thinking about, but colostrum also has an impact on it. So there are ways to improve it with some different things. But anyway, the spermidine, that's a really interesting product that you have with the combination and the way you're kind of orchestrating the circadian rhythm. So that's, that's interesting. Do you have studies on sleep in a larger group of people, or—

Well, that's one of the issues with being a food-derived company is that we don't have a patent on these compounds. And so getting the financing for a clinical trial is difficult and it's expensive. You know, you have to invest hundreds of thousands, if not more, in order to do a proper clinical trial. Even just to get ethics, at least in the United Kingdom, is a minimum of £5,000 to £10,000, which is anywhere from, let's say, $8,000 to, you know, $15,000 US dollars. So it's quite prohibitive. However, there are preclinical studies that have been done in other labs on some of these clock gene and because it's a food, there is no downside. So I don't know if you're familiar with the work of Dr. Terry Wahls, who basically came back from a really devastating case of MS, but her philosophy, which I have adopted as well, was, okay, I'm going to look through the literature. And even if there's not, even if the studies are preclinical, which means they are not yet in humans, but if the compound shows merit and it is not dangerous to humans, i.e., it's in food, then I will try it and I will see. I will be N of 1, and I will see if it proves to be a benefit to me. And in her case, she discovered turmeric was of benefit to her. In our case, we know we have so many thousands and thousands of clients who report back to us that their sleep dramatically improves with, with both the, the, the Primidine Original and Primidine GF. With GF, what's interesting is it's very good for jet lag, and it is— it actually is better than Primidine Original, the defatted wheat germ version of spermidine that we have. And I almost didn't want to believe it because I'm very partial to Primidine Original as my first product, product, but I was flying out to Dubai to give a lecture and went to bed ready to take my Primidine Original and then discovered, oops, I don't— I didn't bring it. And then took the Primidine GF, which I brought some samples of, and lo and behold, my aura scores were amazing, even though I'd gone to bed at what was, you know, sort of 3 AM and was waking up at 8, you know, the next morning. I still got my, you know, 70 minutes of deep sleep and 60 minutes of REM sleep. And we have had other clients and influencers who have actually done similar things. These are usually people who are, say, in Spain and doing courses virtually in, say, Los Angeles, and they show their Oura scores using Primadene GF as well to time shift and still get that deep sleep window I love that.

Yeah, that's great. I've not tried the Primadene. I've used Spermidine, of course, but I haven't tried the Primadene. So this is new for me. Yes. Well, I want to try it.

And we'll send you both the powder, the Primadene Original, where again, we remove the fragile omega-6 fatty acids that are often in wheat germ that cause it to go rancid. You don't want that incorporated in the outside membrane of the cells. Right. And you can just sprinkle it in. It into your food, which I think is great. We've got a powder as well coming out for Primidine GF, the gluten-free one, which people on the autoimmune paleo diet can take as well. And that tastes pretty good. That's in all the Erewhon stores in Los Angeles as well. And yep, we were invited to the Grammys to do longevity mocktails this year. And we had, uh, you know, our little theme was we had that song, that Cher song, Turn Back Time, which was perfect because she was just accepting her Lifetime Achievement Award this year and they were playing that. So, you know, we never thought that neurons were plastic. Neuroplasticity was not believed to be a thing. We now know it is. And I deeply believe that the body has a plasticity and that if we give it the right inputs and environment that it has the ability to respond. And I like to say I'm living proof that, you know, whether it's 60 is the new 20, or in your case, you know, 100 is the new 30, it is possible. It is. You should never be defined by your diagnosis. Again, your mindset philosophy is so important there, but But the body responds. And I hope I inspire others to take control of their healthy aging, work with practitioners like you to get the guidance they need. And then, you know, they, they of course are the ones who, as you say, are responsible for lifting the fork, you know, putting, putting the, the, the training shoes on, getting onto the bike. But I've just got to say that I've come back from 8 days of hill cycling in Tuscany. Nice. And it is hard. Yeah. It is hard. Chianti is full of mountains. I did not realize doing 73 kilometers and 1,800 meters of elevation in one day. This is hard. Yeah. That is. But, but, you know, I'm doing this. I know you do mountain biking too.

Yeah. I went this morning.

Snowboarding. Well done. And the thing is, is that these are not things we saw our grandparents doing. Bless them. We have to redefine what it means to be our age. And the International Monetary Fund came out with a report last year where they said that 70-year-olds in 2022 across 45 different countries in the world, sorry, 41 countries around the world had the same grip strength as 54-year-olds in 2002 and the same cognition as 52-year-olds in 2002.

Oh, I love that. We're making progress.

We're making progress in spite of the obesity crisis in, you know, the US and the UK. Actually, progress is being made and we have to come up with a new mental image of what 50, 60, 70, 80, 90, and 100, what that looks like. Absolutely.

Yeah. No, I think it's wonderful. I think your story is really, really inspiring. I think if you're listening to this, you know, Primadene, Primadene Dr. Jeffrey Gladden, GF, you can check that out. So is there a website where people can go to look at this?

Or yes, you can go to Oxford Healthspan, like the span of a bridge, dot com. I believe you've got a special code as well that, uh, that people can use to try it to get a discount there. That'll be in the show notes. Yeah. And I also have co-founded a nonprofit here in Oxford with some of my colleagues, Sir Muir Gray, who has been writing textbooks on preventative medicine for the last 4 decades. Sir Christopher Ball, who's a 91-year-old former paratrooper, still out there running his marathons. Nice. Professor Dennis Noble, a cardiovascular physiologist of some, some repute, big systems biologist here, and Dr. Paul Chen. And if people want to get free information there, they can go to Oxford Longevity Project. Project.org and get information there. And then I have my own, my own little YouTube channel called Leslie's New Prime, L-E-S-L-I-E and then an S, New Prime. And there's some information there on some more sort of, it's, uh, they're topics that essentially my girlfriends have asked me to talk about. Okay, cool. Yeah, very cool.

Yeah, I love that. Well, beautiful. Yeah, I really appreciate you coming on the show. What time is it where you are?

It is now 9 o'clock. 9 9 o'clock in the evening.

Yeah, you'll be getting your, uh, your good rest here.

Yeah, I'll be, I'll be putting my, uh, blue light blocking glasses on in a second.

Yeah, exactly, your True Darks. Yeah, yeah, exactly.

Well, it's been such an honor, and I'm such a fan of the work that you do. And, you know, keep up the, keep up the amazing work. I, as a patient who's always looking for good doctors. You know, I think it's such a treat to be able to have this conversation with you today. Oh, I love that. I know all your patients are lucky to have you.

Oh, I appreciate you saying that. Yeah. I mean, one thing about us is we are eternally curious and we are married to the questions. Right. And so that's, I think that allows us to continue to innovate at a pace that sometimes is bedazzling to us. There's some things coming right now that we're super excited about. So that's for another conversation. But Leslie, thank you so much for joining us. Yes. You know, really, really appreciate it.

It was a pleasure. Likewise. Thank you so much, Dr. Gladden.

How do we live young for a lifetime? How do we make 100 the new 30? The answers are out there, and we're bringing them to you every episode. Make sure you're subscribed. Check out more episodes right here, and follow us on social media so you never miss a breakthrough. Thanks for listening.