Stem Cells and the Science of Longevity - Episode 318

And so, as a company, we thought, is there a way that we can support the health of your own stem cells? So, not doing the medical procedure, but can we actually make your stem cell system function better? Because, as you know, one of the original hallmarks of aging is stem cell exhaustion, which means that stem cells will, as we get older, will reliably undergo certain transformations in their efficacy. So they just don't do as good of a job in helping our body repair tissues. So not only are stem cell. Is stem cell exhaustion one of the hallmarks of aging, but they are subject to the other hallmarks of aging as well. So genomic instability, telomere shortening, excessive DNA damage, loss of proteostasis, which is protein balance. And in fact, that is one of the really unique characteristics of stem cells in general is that stem cells maintain their proteins way, way better than every other cell in the body. So, you know, as. As you know, you know, the immune system is temporarily separated, so you do not want an immune system that is activated 24 hours a day. And in fact, there's plenty of good evidence that shows that stimulating your immune system too often is actually going to make it turn against you. So we know that with autoimmunity, but we do have different types of molecules that are working at different rates and intensities at different times of day.

Welcome to the Gladden longevity podcast with Dr. Jeffrey Gladden, where our passion is helping you to become an AJ Hacker. On this show, we want to help you optimize your life energy, longevity, health, and human performance with impactful and actionable information by answering four questions. How good can we be? How do we make 100 the new 30? How do we live well beyond 120? And how do we live young for a lifetime? Now, here's today's episode of the Gladden Longevity Podcast.

Welcome, everybody, to this edition of the Gladden Longevity Podcast. I'm your host, Dr. Jeffrey Glatton. And as always, we're here answering life's biggest questions, like how good can we be? How do we make 100 to new 30? How do we live well beyond 120? How do we live young for a lifetime? And then how do we develop that 300-year-old mind? Today, we're gonna have a really interesting conversation with a physician. His name is Dan Pardee, and he works for a company called Qualia Life Sciences, which I've known about for probably a decade, since they first came on the market with their first product in 2015. But he's been doing some supporting stem cells, not necessarily stem cell procedures, but the stem cells themselves to enable procedures to be better than they would be otherwise. And we have a really fascinating conversation where we go down the rabbit hole on sleep, we go down the rabbit hole on stem cells, we go down the rabbit hole on the impact of the psychospiritual space on all this as well. And numerous other technologies get brought up. But I think you're really going to love this podcast. It was a really interesting conversation wise individual. So I hope you love it. Welcome, everybody, to this edition of the Gladden Longevity Podcast. I'm your host, Dr. Jeffrey Gladden, and today I'm here with Dr. Dan Pardee. And Dr. Pardee is a representative Qualia. He does a lot of medical directorship there. And Dan, welcome to the show.

Jeff, thanks so much for having me on. It's really nice to be here.

Yeah, great. So tell us a little bit about Qualia and about you and Qualia, how you guys got together, what Qualia's mission is, kind of. What, what, what's the story there? What's this about?

Yeah, that's a good question. So I'll start with. With Qualia. This company started in earnest around 2015. Founders James and Daniel Schmachtenberger were working on a nootropic product which they first called Qualia. That was originally the product name.

Yeah, I remember when that came out. So nootropic is, you know, basically a brain enhancing product, cognitive enhancement product.

Yeah. And the distinction between a regular cognitive enhancer and a nootropic is a nootropic also is good for the brain. So juxtapose Adderall, which. Yeah, and so that was the goal. And the way that they addressed formulation was with the idea of complementing the entire system. That is doing thinking that instead of just let's say, adding one or two ingredients that have evidence behind them to support some part of the process, how could we address it in a way that enabled the entire system to perform better? So this could include things like precursors to neurotransmitters, phytochemicals, and botanicals that affect enzymatic systems that will maybe keep a neurotransmitter in the synapse longer, handling inflammation and oxidative stress. So that approach to formulation was the foundation principles that the company started with. The product was very successful and then. And I met them pretty early on. So I joined the company less than six months ago. And I'll get into that story in a moment.

But.

But I was a early user of Qualia. Now it's called qualia mind. And, you know, whether or not you use a product says a lot about what you, you know, do you. Would you want to be a part of the company? And if I didn't use the product or didn't like it, I probably wouldn't. But I benefited from that product for a long time. And I was working on a startup and I was also working on my PhD simultaneously. And I felt that.

How did you benefit? What was the benefit that you saw from the product?

Yeah, it was, it was clear. Imagine caffeine, the most ubiquitous nootropic on the planet. You do see, you, you do experience a cognitive boost through alertness, but there is also a crash. And the simplest formulation of a nootropic would maybe be the addition of a theanine, which is found in tea, which then can take away some of the anxiety of the stimulation that is caused by the caffeine. So that's like the, you know, the foundation idea there. And what I noticed is that I experienced very clear thinking across the day. No crash. I slept well at night, which I thought was a real benefit. And the way that they instruct usage of the product is to take it five days a week and then don't take it on the weekends. So when I first started to take it, I did notice a consistent persistent effect on my thinking ability. And I wondered if then when the weekend came after the first couple days of taking it, if I would feel like a crash then. And not only did I not feel that crash, I actually felt even more uplifted on days where I was not taking it. And that made me think that this was truly having a nootropic like effect. It was making the brain smarter or healthier.

So the fact that you felt more uplifted on days you weren't taking, does that make you think about modifying the dosing schedule for yourself? Like maybe take it every other day or something like that?

You know, the way I didn't feel stimulated, but I didn't feel depleted. So that I thought was.

And that's on the days you were taking it.

Those are on days where I was not taking it.

So Saturday and Sunday didn't feel stimulated, but you didn't feel depleted. So what did, what did you mean by you felt more uplifted? What does that mean on the days you weren't taking it?

Yeah. So even compared to my own recollection of what my, let's say, weekends were like, after a hard week of steady mental work, I felt an Elevation even beyond what my regular baseline was.

Okay, so I. I get it now. So really, what you're saying is that if you had a baseline and you took the quality of five days a week, you went from, let's call it one to six, and then on the weekend, you still felt like you were at three. Is that kind of what you're saying? Something like that? Yeah.

Yeah.

Okay. Yeah. All right, cool.

So that was. That was my first experience with it, with the compound. Excuse me. And we stayed in contact. So I had Daniel Schmachtenberger on my podcast, Humanoise Radio. He talked about the science of nootropics. They had me on talking about the neuroscience of sleep. So I was doing my PhD in neuroscience at the time, and we just stayed in touch. I liked what they were doing, and vice versa. And so then In December of 2024, James Schmachtenberger, the CEO, was in Austin, where I live now, and he said, hey, let's grab coffee. So we did. And he said, we're. We're looking for somebody who can help lead the education on the therapeutic areas that we work in and also on the formulations that we're creating. And that started the conversation, which eventually led to me joining the company as the chief health officer.

Okay, nice, nice. That's good. And we won't go through all of your past history, but you've been involved with a number of other companies previously in sort of similar roles. Tell me a little bit more about the. The PhD. What were you really focused on in the PhD?

So, yeah, so I had worked for a pharmaceutical company that had a product for narcolepsy, which is a neurological condition where individuals who are afflicted with it are missing certain neurons in the brain called hypocretin neurons, probably due to an autoimmune attack on those sensitive cells. And if you think of hypocretin cells as, let's say, a symphony conductor that is telling other parts of your wake network when to be on, like, during the day. That's why narcoleptics manifest a very unique sleep wake pattern. They can get enough sleep in and be awake to the same amount of hours as a normal person, but it's more like a cat. So they're up for a few hours, and then they have to sleep. Then they sleep for a few hours, and then they can be up again. And so as a result, narcoleptics do endure a lot of sleep loss because they're trying to live in modern society that doesn't comply sure.

It doesn't accommodate that pattern.

Yeah. So I worked there in medical affairs. I started the medical affairs department at the company, ran research grants, scientific publications, helped grow that. That department to about 25 people overall. And then I had some questions of my own. I did publishing on the product sodium oxybate. And so I threw some prodding from Jed Black, who is somebody that I had collaborated with on several papers. He was the second director of the Stanford Sleep Clinic ever. And he, he was subtly encouraging me to do my PhD. And so I ended up having this relationship where I had two mentors at Stanford, Jamie Zeitzer and Jed Black. Jamie Zeitzer as a circadian biologist, and then two mentors out of the Netherlands at Leiden University. So the head of diabetes and then also a neurologist named Hartjean Lammers. And interestingly, when I started my PhD, I had specific questions to ask to address. But I knew that I didn't want to become a sleep researcher. I had previously worked with Dr. Dean Ornish looking at multifactorial lifestyle programs to affect different disease outcomes. I knew I wanted to get back to that. How do we harness all these different factors that matter in health to then help have a better pattern of living?

So just to complete the narcolepsy conversation. So you basically helped prove the efficacy of a particular drug to counteract the. Well, narcolepsy, just so people know, is basically this sort of uncontrollable urge to fall asleep that can happen, you know, almost at any time. Yeah, right. Because the symphony conductor to keep you awake is kind of taking a nap. No pun intended. So. Yeah, yeah. So how did, how did the drug work?

Yeah, so the drug is fascinating. It's known as GHB gamma hydroxybutyrate, very similar to BHB beta hydroxybutyrate, but this has a very storied history. So it had been used to be sold in GNCs. Bodybuilders would take it to stimulate both sleep and growth hormone. It had been used as a drug of abuse because it will promote feelings, hedonic feelings, so people like how it feels even had been associated with date rape because people would. Because it makes you sleep. So people would use it nefariously all the while. There was this other group of people that were advocating for its judicious use in narco, in narcolepsy, and there wasn't any good medicines for that particular condition. And so I stayed at the company for almost a decade because it was just such an interesting place to be. And I love the work that I was doing. But while sodium oxybate does not seemingly address hypocretin directly, it does make the symptoms of narcolepsy a lot better for, and quality of life better for people. So they sleep better at night and they feel more alert during the day.

So is it like a GHB sort of analog of some sort or, you.

Know, it's called sodium oxybate, which is a version of gamma hydroxybutyrate. So that is just a way that it is delivered as the sodium salt of, of ghb. Yeah. And the way that you take it is you. It only lasts for a few hours, but it robustly promotes slow wave sleep. And so all other hypnotics, at least at that time, not only they might help a person go to sleep, but they, they reduce the amount of, of deep sleep that a person get into. And in narcoleptics in particular, that you would see a five fold increase in the amount of slow wave sleep that they were getting. And so they would feel a lot more restored.

Yeah, that's fascinating. I mean, that's slow. Getting slow wave sleep is an issue for people as they go through the aging process. So it sounds like people without narcolepsy could potentially benefit from this. Is that, did you think about that or. I'm sure you thought about it, but did you kind of pursue any of that or.

So my role in medical affairs was to run a research grant program. And for that I set up a way for academics to submit a grant proposal to study this for all sorts of reasons. And we would review it with a committee, the proposals. And we were looking at things like fibromyalgia, essential tremor, aging, even at that time. So this is early in the 2000s. There was all. Because, you know, well, that sleep is going to affect everything, all sorts of outcomes in the body. The interest in a compound that could promote deep sleep was interesting for a lot of different reasons. We even did a paper on Parkinson's disease showing that it improved different symptoms of Parkinson's disease too. Now again, that was partially. None of those necessarily became what the drug was approved for. But to answer your question, you know, does this potentially have other therapeutic utility? I think the answer is pretty clearly yes. It just hasn't gone through the rigorous steps there for different. For approval by the fda.

Okay, interesting. So gamma hydroxybutyrate.

So the actual drug is called sodium sodium oxybate. Same exact compound. Yeah, that's another official name of the.

Of the drug, Sodium oxybate. Okay, well, that's Interesting, because, you know, when you think about slow wave sleep and you think about all the benefits that it has, interestingly enough, you know, there's so much repair. The whole glymphatic system works during slow wave sleep. Right. The ability to kind of take out the trash, so to speak. The ability to kind of consolidate, you know, neuronal function, rejuvenate. There's just so much that goes on in slow wave sleep. Yeah. That is really, really critical to ongoing brain function. I mean, I can imagine that it could be really a nice adjunct for anybody going through the aging process, but certainly anybody with a neurodegenerative disease where they kind of are robbed of that, Any kind of restorative activity. Right. And then you've got a pathology on top of it. Right. So if you had a. If you had a combination therapy where you're giving them the restorative piece they need, but then you're also working on, you know, whatever else you're working on, it seems like that could be a really great combination. I don't know. Correct me if I'm wrong, but it's even for a concussion. Right. I mean, getting somebody. Because I've had concussions, and I remember the last concussion I had was snowboarding. I went down a mogul field that I wasn't actually prepared to go down and got caught off balance and, you know, pitched on my head. I don't know how far I fell, but, you know, it was. It was a long fall before my head actually hit. And it was a pretty icy mogul. And my HRV the next day was one. Right. Normally I run. Normally I run an HRV of like 70, 80, you know, sometimes over 100, you know, that kind of thing. Right. But it was literally one. And I was, you know, I'd really. And I know I've had concuss in the past. All my athletic stuff. I won't go into that. But the point is, you know, your brain just has. Has such a hard time recovering and your sleep is disrupted. Right. Your slow wave sleep is trashed. And it just seems like a drug like this could be really a great adjunct to any other healing modalities for the brain.

I don't know.

That's kind of what I'm sensing.

Yeah. So, you know, sleep in general, I describe it as. As both a health behavior, but also a marker of health. And you just described that you were suffering from a. Impairment in your health due to the concussion and your sleep suffered because of it.

Right.

But not only is it interesting that the compound will robustly enhance low wave sleep. But also the chemical structure of it is very similar to bhb beta hydroxybutyrate. And we do know that BHB is something that has evidence for protecting the brain after concussion.

That's right. And it simulates BDNF production and other things, if I'm not mistaken. Right. So I mean if you're getting activation of healing elements in the brain from this, at the same time you're providing it with slow wave sleep and the benefits that come from slow wave sleep, glymphatic drainage and all the other stuff. Oh my gosh. I don't know why, I don't know why this isn't, you know. And what's fascinating is you're talking about some nefarious use of it which I suppose has given it a bad name. But, but you know, if people are responsible human beings. Right. Not taking advantage of other human beings. It seems to me like it, it could be like a super useful thing to do.

Yeah. I wrote one of the papers that I wrote was disambiguating the usage of drug GHB that is made on the street with what we know about. Because a lot of the effects of, let's say, you know, GHB that was made in some, you know, bathtub somewhere, those effects were then associated with GHB and because of the OxyContin crisis, the FDA was really concerned about this getting into the hands of people and them having another major issue on, on their hands to deal with, which I am sensitive to and I, I understand that, of course.

Yeah. Everybody's sensitive to that. Nobody wants. Yeah, right.

Yeah. To your point.

Yeah.

Could this actually be something that actually helps a lot of people age better? So it's, I think a good parallel is steroids and anabolic steroid usage.

Right. Yeah. So yeah.

Or have we even.

Testosterone replacement therapy versus anabolic steroid.

Exactly right.

So yeah, there's a place for it and it's, it's a dose dependent scenario and it's a many things that go into actually optimizing testosterone replacement therapy, managing metabolites, etc, and we know too much of a thing. Is weight really a bad thing? The body really likes an economy of balance for sure. But it seems like this could actually bring the body back, back into balance and actually give it an opportunity. I'm curious, have you ever taken it yourself? I mean, with all the work you've done?

Yeah, so funny enough, I had taken it when you could buy it at GNC legally and I remember reading about it and it promoting both deep sleep, so supporting recovery from hard workouts.

Yeah.

And you know, I, I played around with it a little bit, but I didn't notice that much. So one of the issues of the compound is that it wears off. So it only supports sleep for three hours. And so you have to wake up and a narcoleptic will wake up in the middle of the night and take a second dose to get a more sleep for the rest of the night. Now could that be solved? Could they make an extended formulation?

Sure.

Exactly.

The other problem.

Yeah, go ahead.

Well, the other thing is, you know, we typically go through a couple of sleep cycles a night and that's the first sleep cycle where, you know, a lot of the heavy hitting gets done in terms of either growth hormone release or the glymphatic system being activated. So even if it worked for the first three hours, you know, it seems like there still could be significant health benefit from that.

Yeah. So definitely sleep is such an intimate dance. So if you have something that let's say robustly increases slow wave sleep, you might as a result suffer from reduced REM sleep on the back end of the night because of it, and vice versa. And so those are very different neurochemical states. Unlike wakefulness, where you're trying to promote overall alertness during the day, sleep is these different, is these different states that you're trying to go in and out of across the night. Therefore, it's really difficult to try to intervene upon, let's say, one aspect of sleep architecture, like slow wave sleep or REM sleep without messing up the other, that delicate balance. So it's a challenge. It's definitely a challenge.

I get that. I get that there's a push and pull on all this.

Yeah.

Is this like a scheduled drug or is it something that.

Yeah, it has a bifurcated schedule. So at the time, and forgive me, because it's been over a decade since I've worked in this space, but at the time when it was approved, it was Schedule 3 for appropriate use. And of course, as you know, as a medical doctor, you're able to prescribe off label. But one way they have tried to control that is with exorbitantly high prices. So narcolepsy is considered a rare disorder and so insurance pays for sodium oxybate for those people that have that condition. But there were other people that were clamoring for it as well, and they'd have to pay out of pocket because they did not have the diagnosis of the diagnosis.

Right. So what's, what's the cost? $100 a pill or something.

So it's a liquid that you take because you actually take grams of this. Yeah, you're taking the. The titration is aiming to try to get you up to three and a half grams of GHB twice a night. So. So six to seven grams across the night. Much, much higher than what you see with, you know, almost every other drug. But, you know, imagine what, how much BHB or beta hydroxybutyrate that you take. So if somebody's trying to take that for therapeutic usage, for all the different things people are exploring that for, that's like 5 to 10 grams multiple times a day. That it's more of a food in some. In some senses, food level dosing. But. But yeah, that's. That's part of the. The challenge as well. But now I think it's close to thousands, like, you know, tens of thousands dollars per month.

Wow, that's crazy.

Yeah, it's crazy.

Yeah, that's really crazy. Okay, well, interesting conversation. So, yeah, this is. This would be considered a detour, but an interesting one, right?

Yeah.

Yeah. Okay, so I think one of the things that you wanted to speak to was some things that quality is working on in the stem cell space or helping to augment or do something in that space. You want to chat about that for a minute?

Yeah, yeah. So we've recently come out with a stem cell product, and it's. It's quite different than how people most, mostly think of stem cells. So most people think of stem cell therapy. And in the medical sense. So you, let's say, get some stem cells extracted from your own body. Those are considered autologous stem cells. They're concentrated and put back into an area where you have, let's say, pain or you're not healing. And that is a whole different field. But those can be extracted either from bone marrow. So you have a little surgical procedure where you extract it from the iliac crest, which is a common site in which the stem cells is what he's referring to.

They go in through the top of the hip.

Yeah, exactly.

That.

That bony prominence that you can feel right in the front of your body. Or mesenchymal stem cells, another type of stem cell that can be extracted from fat, typically. Yeah, exactly. Yeah. But, you know, even going beyond that, like, what are they in general? What's their purpose in the body? They're a major part of our repair system. And so as a company, we thought, is there a way that we can support the health of your own stem cells and not doing the medical procedure, but can we actually make your stem cell system function better? Because, as you know, one of the original hallmarks of aging is stem cell exhaustion, which means that stem cells will, as we get older, will reliably undergo certain transformations in their efficacy. So they just don't do as good of a job in helping our body repair tissues. And that's generally.

Typically there's an accumulation of damage. And I believe there can be some telomere shortening that occurs for them as well, too. So they lose some of their potency when the telomeres are shorter, then they. They can't divide as many times. And you can think of the stem cell really as a conductor in an orchestra, as well as playing several instruments, but it's actually conducting. And along with the immune system, I will say the immune system is part of that conducting process too. Right. In terms of dragging all the stuff there that needs to be there. But once the stem cells show up, they're kind of conducting the regenerative elements of it, whether you have exosomes or peptides or other things going on. Right. So that's one way to think about it.

Yeah, it's a great point, Jeff. So not only are stem cell. Is stem cell exhaustion one of the hallmarks of aging, but they are subject to the other hallmarks of aging as well. So genomic instability, telomere shortening, excessive DNA damage, loss of proteostasis, which is protein balance. And in fact, that is one of the really unique characteristics of stem cells in general is that stem cells maintain their proteins way, way better than every other cell in the body. It's one of the reasons that they're the. Some of the longest living cells in the body. In fact, some people call them forever cells. And the way that they. The reason why they last so long is because they are mostly in the body. They're mostly living in this quiescent state. Think of it like hibernation.

That's right. Yeah. They're in hibernation.

They're in hibernation.

Yeah. They're there to be called upon when needed, but they're not. They're not actively doing anything. They're just kind of hanging out, sleeping until they're called for. Right. So it's like sleeper cells.

Yeah.

Probably the wrong term, but kind of like that.

No sleeper cells doing it that are ready to do a good thing when they're activated.

That's right. That's right.

But yeah, so they. And they're they're pretty fascinating because they can. They undergo this huge range of protein making capabilities. So like on one end, for example, hematopoietic, this is one type. These are the types of stem cells that come from your, your bone marrow. They can make red blood cells which are basically these oxygen carrying bags, and they hardly have any proteins in them. And then on the other hand, you have plasma cells which are turning out immune cells constantly, which is, you know, very high protein production. So loss of proteostasis is one of the hallmarks of aging, which is this loss of protein balance. And they do a really good job with that. But it's also one of the reasons why they're vulnerable because they live so long, if they do undergo some types of protein damage, then they themselves become, you know, less good at their job.

Yeah, that's right, yeah. Less good at their job, for sure.

Yeah.

So it is interesting, if you're listening to this, to understand that we're talking now a little bit about the hallmarks of aging. And there were initially nine. I think some people are talking about 12. I actually think there's about 16 when you actually go through and add them all up. But the most important thing to understand is that they all play together. So they all play together. So if you have a problem with one hallmark, it affects other hallmarks, and then the effect there affects other ones, which comes back and affects the initial one that was affected. For me, this is a little bit like the aging process. And one of the reasons it's an exponential decline is this interplay between the hallmarks sort of spinning up like a tornado. Right. It spins up and gets faster and faster in terms of the disrepair, if you will. And that's why people age so much more between, you know, 80 and 90 than they do between 20 and 30. Right. And so there's this accumulated inertia around the interplay of the hallmarks. And I think one of the absolute keys to cracking the code on aging is to be able to interrupt that inertia and then recycle the different hallmarks back into a more youthful form. And there are some that are more prime movers than others, let's say, like genomic instability, mitochondrial dysfunction. Telomere shortening is another one. Inflammation is another big one. Oxidative stress is right there with inflammation. They're linked by the hip. So some of those are mitochondrial dysfunction, if I mention that, but. And stem cell exhaustion becomes in there. But they all play a role. Proteostasis, autophagy, all of them. Play a significant role. And I think it's. It's really one of the most fascinating things in our practice to actually deconstruct the individual, to understand which hallmarks are out of line, what ones are out of sync, and then seeing how they. If they are out of sync, how they interplay with each other, and how if we start to impact these three, we can move them back and a fourth one moves on its own and that sort of thing. Right. So this is part of the. What I call really interesting work that we do here in the age reversal world is focusing on those. So it's pretty fun.

It's a prescient comment, Jeff. And it's good to talk about them individually because it enables us to then encapsulate or carve off a part of a much bigger challenge and issue and then talk about that discreetly and think about how we might be able to address it discreetly. But you're exactly right that they're all inter. They're all interacting with each other. Like we were talking a moment ago, even stem cell exhaustion is. Stem cells themselves are subject to the other hallmarks of aging. So the DNA damage, et cetera. And so. And to add to your point about how aging itself is. This is an accelerating process. Right. We're doing. We're getting. If we talk about DNA damage, you know, every cell in the human body undergoes a million molecular lesions per day. That's a lot of DNA damage to clean up. And so as the DNA repair mechanisms undergo damage themselves, now the ability to clean up that damage is hindered. And so you can see how.

Why.

It's one example about why the aging process wouldn't be linear. It's not a linear decline, but is one that actually accelerates over the decades.

Yeah, that's right.

And so the excitement with the hallmarks. Oh, I'm sorry. Go ahead.

No, I was just going to say it's such an important thing for the audience to understand this because we have a tendency to relate to aging in a linear fashion because it's chronological. And the interesting thing is that even though we see it, we know people age faster in their 80s or whatever than they do in their 20s. We have such a hard time relating to it. Like, Dan, if you. Even if we ask ourselves what are we going to be like in 20 years, it's virtually impossible to imagine we're going to be any different than we are today. Right.

Yeah.

So we're in this exponential game, and most of the time, we're actually applying linear solutions to an exponential problem. Right. And so what we are really trying to get across to the audience is, hey, you're in an exponential game. You need an exponential strategy and a piece. You know, if we're talking about sleep or we're talking about stem cells, or we're talking about. Those are just pieces of a puzzle. And it's about linking all that together to actually address the hallmarks in a systematic way that gives you leverage on the system. That's kind of how we think about it.

So, yeah, yeah, you know, we. We're really excited about the stem cell product that we just came out with. But what I'm most excited about is we were mentioned at the beginning is a combination of different products that are addressing declining NAD levels.

Yeah.

The accumulating burden of senescent cells, which raises inflammation in the body. And then now supporting our regenerative process by supporting the health of stem cells. So that you can actually replace tissues. Because the visible signs of aging and the ones that are internal that might lead to altered functioning of your tissues is because we're just simply not replacing healthy tissue with tissue that had undergo. Undergone damage. And so when you're young, there is almost a net zero effect of damage replacement. And so the function stays perfect, but when the damage replacement is diminished, then you start to see a decline in function.

That's right. Yeah. Yeah. No, that's right. It's like, I don't know. I don't know what a good analogy is, but it's kind of like whether you're repairing the roads or you're just partially repairing the roads, after a while they get pretty. Pretty potholed. Right. And that's kind of what happens with aging.

Yeah, that's using that analogy. If, let's say you only repair the roads 90% every time that there's damage, at first, it doesn't seem like a big deal because you're like, you know, it's imperfect, but I can deal with it 10 years later.

Yeah, it's undrivable, right? It's.

It's undrivable.

Yeah. Right. So that's. That's why it's such a big deal. And quite honestly, given our lifespan and given the number of, you know, insults that we experience every single day, even if you're at 99% that accumulated damage, then it drops to 98, 97, 96, 95, 90, 85. You know, it's just this accumulation of the damage plus the decreased repair mechanisms are massive. So as you're thinking about this, obviously from, from your perspective, and you have, you know, supplements can only do so much, so to speak. Right. They're not going to be the be all and end all of everything, but totally through the lens that you're looking, you're addressing several different things. You want to just talk us through your strategy with that?

Yeah, it's, it's really important to understand how stem cells work because we're talking, I'll talk a little bit more about ways in which stem cells age because it's informative to how you would design a product. So from a very high level, what's the, what's the stem cell cycle? So we talked about earlier that they're in hibernation most of the time. And we, we want that because we want to preserve our pool of regenerative tissues, but we also want to be able to activate those stem cells when needed. And so that process of activating these dormant stem cells is key. Once they're activated, they undergo proliferation. And this is the process where the stem cells will divide into daughter cells. And one of those cells is a clone. So you're basically reproducing your own regenerative pool. The other daughter cell becomes a progenitor cell. And that cell is destined to become some specific type of tissue in your body that reads replacement. And so in order to do that, the cells have to actually follow this chemotactic signal. So, meaning, like they have to imagine that they've got a little nose on them. They have to find where the cookies are being on the shelf. They have to find where they need to go, and then they need to listen to very specific signals in the new environment that they're in to then turn into the right tissue. So imagine a stem cell being like a moldable lump of clay. It can become anything. But once you start to then form it into a plate or a cup or a bowl and it hardens, then it is now become that thing. It's locked in what we call itself fate. And when you get older, lots of interesting changes occur. So we talked about some of the reasons why they do occur. But there is a change in the resting state, for example, and in some ways think of it like a Goldilocks principle. The some versions of aging stem cells is that they're too deeply asleep, so you can't wake them up. And because of that, then the repair process is hindered. But on the other hand, on the other side of the Goldilocks analogy here is that they, some of them are too shallow. They're too, they're not asleep enough. And so that they are woken up too easily. And what does that do to your stem cell pool? It exhausts.

Exhaust it, right?

Yeah, yeah, sure. Right. And so the goal of us is, you know, for us here is not to just stimulate as much stem cell release into the circulation as possible, but rather to promote the health of the stem cells so that they can still do a. Right, yeah.

What they're supposed to do when they're called upon to do it. Right?

Yeah, exactly. Yeah.

There are some companies out there that have products that are, you know, constantly pushing stem cells out of the bone marrow. And we will use those products in the context of when we're trying to heal somebody, but it's not something that we want to be doing all the time. I know the company wants to do it all the time because that's how they sell their product, but we think that's actually misguided because you do have a limited reserve of these things. There is, there is a reserve, reserve stem cell pool out there also that we won't go into on this podcast. But the point is you still can exhaust them. And so it's pretty, pretty interesting. So it sounds like what you're doing is actually not trying to stimulate the release of stem cells from the bone marrow or fat per se, but you're, you're looking to how do we augment the health of the stem cells that are in this dormant state? Is that kind of what I'm hearing?

Well, what I would say is there's 15 different ingredients in the formulation, but you, you nailed it as the most superior goal. Goal of the product formulation is to improve the health of the system, which means we're not trying to override it and just say we're going to cause a lot of release. Like in some cases the amount of stem cells that are released is nine times higher than what's normal. And so that's not always a good thing to just continue to pump them out like you just said.

Right.

Another problem, for example, is that the cells themselves, like now that they're in the circulation, but they're receiving the wrong instructions on what to become. And so they start to turn into the wrong tissue. And a good example is where the micro environment around in the muscle, a satellite cell, which is a type of stem cell that becomes new muscle tissues, those will now not turn into muscle tissue, but they'll become turn into scar tissue. So imagine a 90 year old person and how stiff they are. That is because the composition of their muscles has now become more populated by scar tissue.

Infiltrated with scar tissue. And to some extent, fat replacement also can happen as they age.

That's exactly right. Yep. You have, you start to. For mesenchymal stem cells, instead of producing all the different types of connective tissue that they make, you're making more fat. And that has to do with alterations in hormones and all. Again, signaling, like the signaling environment changes, you also have a decrease in resilience. So a stem cell is halfway into becoming a useful functional tissue for you and it dies along the way. It self destructs because it's not strong enough. So all of that, all of those.

Tell us a little bit about how you keep these dormant cells healthy. It's almost like you're sprinkling pixie dust in an incubator or something. Where these things are resting, is that kind of the idea? Or they're not metabolically all that active in the resting state. So how do you influence that?

Yeah, so one thing that we tapped into a few years ago, which was for a different product, but I'll use it, I'm going to illustrate it because it draws a nice parallel with what we are doing here. It was our senolytic product. It's the most popular product that the company's ever had. And the 30 sec. I don't want to go on too much of a tangent, but the 30 second overview is that we do have an increasing burden of these zombie cells that. That's a nickname for them. And those cells will release a lot of inflammatory molecules into their surroundings.

Another prime mover in all this, prime mover.

And because your immune system has gotten older, typically when you're younger and those senescent cells are releasing these beacons, it's designed to say immune system, come clear me out. Well, what happens when your immune system is weaker and you now have all these beacons going off around the body that have a disproportionate effect on raising body immunity, inflammation. And so now your inflammatory burden is elevated. And so we do know through work from Jan van Dursen and James Kirkland and others in the mid 2010s that a combination of different flavonoids like quercetin and facetin and others will target specific upregulated pathways in these senescent cells and cause them to die and clear them out.

And so that's because senescent cells don't want to die. It's important for the audience to understand this. They've actually turned off the pathways, these autophagy pathways. They're not cancer cells, but they, in a sense, they're dividing, but they've turned off the ability to kill themselves. So you have to go in and actually flip the switch for them to actually get them to die.

Yeah, that's exactly right. What's interesting about that is that these upregulated survival pathways is allowing them to stay zombies, right? They, they're, they're not quite, they're not functional, but they're not dead. But that also allows us to use the ideas of synthetic lethality to target those upregulated pathways, which is not affecting your normal cells. So when you target those upregulated pathways, you can actually cause them to go to die and then you've cleared them out. So that protocol is to take a high dose of these compounds two days a month to, I do mine on a Saturday and Sunday, and then you wait a month. But it is that punctuated dosing versus every single day, which helped make us think about how do we intelligently construct a protocol where you're doing something some of the time, but not all the things all the time.

That's right.

And with our stem cell product, it's a four day in a row product. Where in my, you know, the way that I do it is I do my senolytic pulse, clearing out senescent cells, lowering inflammation. Because guess what? One of the major inhibitors of stem cell function is increased inflammation. Right now you do a regenerative pulse where you're not only releasing the stem cells, but you are, you know, for example, targeting inflammatory pathways. So a couple of our product, A couple of the ingredients in our products are, they're acting, they're phenolic and polyphenolic compounds which act on master regulators of inflammation. Nuclear cap, effective beta. Right. When they, they get into the cells, they bind that regulator, inflammation and prevent it from translocating into the nucleus, where it can now make things like TNF, Alpha, Interleukin 1, Beta IL 6, all these inflammatory markers that you, you can measure in the blood. And so that lowering that inflammatory burden is part of the goal of now creating a more, you know, a friendlier neighborhood for the stem cells to exist and to do their work. So that's one.

Yeah, no, that's a really, that's really important and it's important for the audience to understand this. One of the things that we've come, what we do in this clinic is we do use senolytics followed by plasmapheresis in order to really clear out all the trash, right? Then you drop in some IgG, which actually tends to settle down the immune system, Then you can drop in, you know, all the other things to tame inflammation and oxidative stress, including hydrogen and, you know, other molecules that have a salutary effect. Beautiful. Then. Then you actually put in your stem cells, peptides, exosomes, whatever else you want to put in. Because now what you've done is you've cleaned up the milieu to where those things can actually work. Right. Because if you take. Here's the easiest way to understand it, or the way that I understand it, you can correct me if I'm wrong, but if you have a petri dish full of old serum, full of all these inflammatory proteins, and you drop in stem cells, healthy young stem cells, they can't work. They can't really do much. Whereas if you give young plasma, this was the whole idea behind young plasma. If you put it into young, non inflamed plasma, all of a sudden those stem cells can really go to town. So the idea is, if you're going through the aging process and you need a regenerative procedure done, or a procedure, you know, something done, going through surgery, for that matter, being able to clean out the senescence, take out the trash, put in the stuff at the right time, and then support it with ongoing peptide therapies and things, this is what we do.

Yeah.

And there is one other piece to this that's really fascinating as you listen to this, and that is that there was a recent study that showed that people that are able to access a deep theta state in terms of their meditation, which is like a very slow. It's a. It's a slow wave just above sleep. It's called the hypnagogic state. It's just when you're almost like to fall asleep. But people that are able to go into that very calm, relaxed theta state have a much better rejuvenation impact than they do if they're highly stressed. Right. Because when you're highly stressed, a lot of sympathetic nervous system drives, so that parasympathetic nervous system development prior to going through the rejuvenation procedure and then activating as you go through it also has a massive impact, is what we found, which is interesting. There was a study on Buddhist monks that showed that when they meditate and go into a theta state, 10 or 15 minutes later, they're releasing their own autologous stem cells to heal themselves. Right. So the mind plays such a role here. I know we're talking about the biochemistry, but I want the audience to understand that you can you can do things at home to teach yourself how to go into these state estates with binaural beats. And if you're using these other products, they're going to have that much more of a benefit for you.

So, Jeffrey, you're doing really great work. I loved how you articulate how you approach all of this, and I couldn't agree more. And just to add on to what you're saying about the. Essentially the internal milieu shaped by the sympathetic and parasympathetic state in the body, we know that the immune system, for example, is active in finding and killing pathogens at night. And one of the reasons why is that a variety of different types of immune molecules, like integrins, they require a low sympathetic tone. So parasympathetic dominance in order, like when those sympathetic neurochemicals are chemicals are circulating in the body, they don't allow the immune system do its job of finding and adhering to the pathogens and then killing them. And that's why at night, it's such a state of restorative, you know, restorative abundance, if you will. And the same is going for not only finding pathogens, but also healing tissues. They too, require the right physiological state in order for them to do their jobs. And so even though it seems like how is, you know, sometimes it can be amazing or shocking that the brain state is going to connect, but they're totally connected, and it's creating a different hormonal milieu. So I think your recommendation of practicing mindfulness and relaxation is absolutely a part of the healing journey. So kudos to you.

Yeah, we've been, we've been impressed with just how deep that runs. It's almost like the master switch of the master switch is if you can put yourself into that theta parasympathetic nervous system tone, then all the other stuff can really start to work. It's interesting about the immune system gobbling up pathogens at night. You know, I have a situation where if I feel myself coming down with something, it actually happened this last week. I was visiting my. My son and his wife and my four grandkids. And my oldest grandson, who was six, was getting sick while I was there. But, you know, I'm like, I'm fine. I, you know, I didn't catch anything. But a couple days later, I feel like, oh, you know what? Something's happening. And I, and I, I do meditate on a regular basis, and I use a brain tap, actually to put me in theta state all the time. You know, photobiomodulation. And binaural beats. And I've actually learned how to go through the day in a theta state, which is actually cool too. So you can teach yourself to do that. But the point is, I took a bunch of vitamin C, echinacea, some Zycam, and went to bed. Well, I took it at four in the afternoon when I started to feel this, took it again at bedtime, and I wake up the next day and I'm perfectly fine. Perfectly fine. And yet that doesn't work for everybody. I think one of the reasons it works for me is because I have such a strong parasympathetic nervous system. When we measure it, it's like, you know, on a scale of normal, between 2500 and 4500, I'm at like 12,000. Right. Because I've trained that parasympathetic nervous system tone. And I think you could speak to this maybe that when you have that and your immune system is dialed in, you're probably also not only pruning senescent cells better, as well as pathogens, but you may be killing off cancer cells better. I don't know. Is there data around that? That's as much of a question as anything else. If you know.

Yeah. So, you know, as you know, you know, the immune system is temporarily separated. So you do not want an immune system that is activated 24 hours a day. And in fact, there's plenty of good evidence that shows that stimulating your immune system too often is actually going to make a turn against you. So we know that with autoimmunity, but we do have different types of molecules that are working at different rates and intensities at different times of day. So, for example, your natural killer cells are being released in response to, for example, food products that you consume. And some types of foods, like beta glucans from mushrooms and oats, they're going to bind to what we, what are called payer patches in your gut. That makes complete sense. Your gut is a, is a site in the body that is getting exposure to the outside world food. And so it is aggressively sensing for whether or not there is types of things that are coming into the body that are then going to make you sick. And so when these pair patches are stimulated, it's going to increase the activity of. It basically puts natural killer cells on alert. And natural killer cells are going to go and find pathogens and also cancer cells and do a better job of getting rid of both. And so absolutely you want that. And if you just to make a kind of Parallel comment here, but the parasympathetic state is something that's almost missing in modern society because we sit at a desk doing our thing and we are on all the time, even though we don't feel stressed. We live in what we call like a task on environment. So we're always focusing. And in a way, I think a very banal but interesting explanation for meditation is just stepping away for a few minutes, breathing, allowing your body to go into a different state and all of the complimentary things that happen in that parasympathetic state. You've now interrupted 1612 hours, whatever it is, of sympathetic drive and giving it these more naturalistic bursts of parasympathetic dominance for periods in that wakefulness state. And that is good for your health long term.

Yeah, that's a. That's a great point. The way I characterize that to clients now. I had an insight about this just a few weeks ago actually. Actually is that we spend a lot of our time efforting. Right. And so if you're going to go into a meditative state, you switch from efforting into receiving.

Yeah.

And when you're just here to receive, all of a sudden you become very present. It's like, oh, my gosh, what a beautiful. What a beautiful planet this is. What an incredible thing to be able to have this lovely conversation. You know, all of a sudden you get so much gratitude and appreciation because you're just here to receive so that you take the effort out. And when you take the effort out, it allows the parasympathetic to come forward. And it's a much more beautiful way to live your life.

So, Jeff, I know you've got a hard stop pretty much now. That's a beautiful way to end it, but really enjoyed chatting with you about this. Yeah, we should. We should chat more sometime because.

Yeah, we should. Yeah, we definitely will. We definitely will then. I really enjoyed it. Super fun stuff.

Yeah, me too.

Thanks so much for your being on the show.

Yeah. Appreciate you having me. Take care now.

Thank you for listening to this week's episode of the Gladden Longevity Podcast. If you would like more information on what we've discussed or other topics, please reference the show notes or go to gladdenlongevitypodcast.com you can also find us on Instagram, Facebook and Twitter by searching Gladden Longevity. If you've enjoyed this podcast, please subscribe to get future episodes delivered to you and share our podcast or this episode with someone in your life that you may find benefit. Thank you for listening. We'll be back next week with another exciting episode. The Glide and Longevity Podcast is provided for informational purposes only. It does not constitute medical advice. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding your medical condition. The use of any information and materials linked to this podcast is at the listener's own risk.