487: Zombie Cells: How Cellular Senescence Is Secretly Aging You From Within with Dan Pardi

There are interesting, distinct differences, of course, between senescent cells and cancer cells. Cancer cells essentially will have mechanisms to continue to proliferate. It's like they are immortal. And that ends up becoming really problematic as they duplicate. And now they're not contributing to the function of tissues, but they're also now degrading the tissues around them.

Welcome to Midlife Conversations. I'm your host, Natalie Jill, and I'm passionate about having conversations that matter to us midlife women. On this podcast, I do what I do best, taking complicated health topics and breaking them down simply so that we can optimize aging together. I share actionable steps to help you thrive in what I believe are our best years to come. Join me as I interview the most inspiring people living their best midlife years and dive into essential topics like hormone changes, health optimization, weight management, blood sugar, emotional well being, relationships, beauty, and so much more. Detoxing. Is it necessary? And what the heck are zombie cells and why are we hearing so much about them and do we actually need to get rid of them? Is it important? You know me, if you've been listening to my show for a while where I am always on a search for how can we up level our midlife health. I myself have been through my own personal toxin journeys, quite a few of them, and I'm always looking for how can I get my body working the most efficiently. There is a company who I came across their product a while ago, it's qual senolytic. And I had seen their ads and this is not a company I was working with at the time. I just saw their ads and I was very intrigued by it and I thought, well, this is making a lot of sense if we can clean out old cells that are not doing our body any favors. That made sense for me that it would have to let our bodies be more efficient at healing then. But I didn't fully understand it. I tried their product. I had incredible results, like pretty instant. And I reached out to the company to learn more and to talk with them. And I'm very happy to be interviewing Dan Pardee right now, who is a chief health officer at Qualia Life. I have a lot of questions because if we're all anyone on social media, senior ads, we've seen the ads for it. We've heard the word zombie sell, but a lot of people don't understand what that means. Is it gimmicky? Do we really need this? Is this something for midlife women and how can it actually help us? So, Dan, thanks for being Here and answering all my gazillion questions around this.

You got it. I'm delighted to be here. Thank you for having me. These topics are so fascinating, and all of us are just trying to figure out how to navigate this sea of information to figure out what's worth actually investing effort, resources into and what's not. And then how do we tie it all together so that we take good care of ourselves as we get older? And so I applaud your audience for tuning in, showing up, learning, and for you for conducting these conversations to help people. So thank you for having me.

It can get super confusing, and I'm guilty of this because my audience will say, well, you're changing and talking about different supplements or different tactics. And I just evolve as I learn. I share. There's more and more information, and I share and I replace things. But I want to dive right into a lot of questions here, and I want. I want to share a quick little story. I have a friend who I was telling you before we started recording, she's had endometriosis her whole life. Like, she's navigated this her whole life and really suffers with it. And she's done a lot of conventional things. And she had reached out to me and she said, you know, I've been seeing these ads for a quality analytic. Do you think it would help with endometriosis? Which is not something that it says that it would help with. Right. It's not, like, listed as, hey, take this for endometriosis. And I said, well, you know, it couldn't hurt you because I understand what you've been doing, and you've been struggling, and this could make your body work more efficiently. And, Dan, I gotta tell you, she called me literally in tears, like, that this has changed, or she wanted to know if she could take it more than once a month because it made such a difference for her body. She said she felt like just it had cleared out all of this stuff that was weighing her down. And I had to share that story with you at the beginning because that is not even something that's really talked about with this.

That is why we do what we do, plain and simple. We're in this business to help people.

On their health journey. And when I hear a story like that, you just don't know how much of an impact it makes on us, who are working really hard every day, making all sorts of decisions. What kind of new products should we be working on? What are the areas that we think we can really impact in a. In a Significant way. What are the areas that are unaddressed. And so when you hear people benefit from a lot of hard work that's taken years, frankly, that we're a part of. Right. I mean we're building on top of research that has been going on now for three decades or more. You know, it's been, there's been more of a focus over the last three, three decades and it's built quite a bit. It's almost like this exponential interest in that timeframe and it's, I'm personally excited, you know, for myself and my family and the, and then in addition to the people that we get whose lives we get to touch. So when I hear that, it really makes my day.

It feels good. I can imagine. Because I, and I know just as being a business owner, you know, you'll get that like one negative review and you'll hyper focus on it. But then you hear about the life changing results or the impact and it's just such a, it reminds us why we do what we do. So I can appreciate what you're saying. Okay, I'm gonna jump right into it. So first of all, what the heck is cellular senescence? What does that mean? And why should we care?

Okay, so basically these are cells that have accumulated enough damage in the course of doing their work where. And that can be because they have replicated a certain number of times that they're at the end of their cellular lifespan or there's been environmental stress that's essentially caused them to age quicker, or there has even been some internal forces that might have caused the same thing as the external ones. But for the cell to age quicker, senescence is a process. It's a built in process to cells that reads when there's that certain amount of damage that's there, you do not want to keep those cells alive because that can lead to things like cancer. Right. If you're, if these cells are not undergoing a form of quality control essentially, then bad things can happen.

What does that mean? Because like when I, when you hear about something not in your body, like you would think your regular body clears that out. Like does your liver and your kidneys clear that out? Does sweat clear that out? Like what's happening with those? Typically if we don't do something about them.

So these cells, they have their own internal cleanup processes and quality control processes. And so when a cell goes into senescence, that is actually a protective mechanism. We do not want to stop senescence from happening. But once senescence does happen, it can do a couple of Good things. Right. It starts to release signals into the environment that can help with wound healing, for example. So it actually helps t. If. Let's see how to cut. It becomes a part of that process that helps with wound healing. So it's even doing some useful things.

So give me. Can you give me, like, I mean, I'm going to break this down real simple, but can you give me, like, a real life example? Because I would think as you're aging, you know, this is. This is important, but, like, if you could give me, like, a real example of something that would be happening as we're aging, that would. Would be this.

Well, so. Yes. So if we go to the. What's considered like, the canonical or like the. The example that we think of most is that back in 1960s, Leonard Hayflick created what we consider the Hayflick limit. He identified that. So when you took human cells and put them into a culture or petri dish, prior to that, we thought that cells were immortal, they would live forever. And he discovered, and it was a really monumental time in science. That's not true. Cells can replicate, basically turn over, produce new, younger cells that about 40 to 60 times now, different cells in our body have live for different amounts of time. Right. Neurons can live a lifetime where a liver cell might live one year. And so, you know, but let's say by the time you're 60 and you've gotten to the end of that cycle where they've turned over enough times, they will go and enter something called replicative senescence.

Okay.

And they'll become. You'll generate senescent cells. Now, like I said, there are some things that senescent cells do that are helpful to the body, including, like, it's not like you want to prevent senescence, but once it occurs, one of the characteristics of senescent cells is they start to leech all sorts of inflammatory and tissue degrading compounds into their surrounding space.

And that actually has a function. What is it doing? It's telling your immune system, hey, there's damage here. Come clean me out. So the immune system, typically when you're young, comes to the site where the cell has gone into senescence, and it clears out that cell, and it clears up all that damage, and that then creates a better environment for tissue renewal. But the problem is the reason why we care about this, and this has become a hallmark of aging, which is a new term since 2023, from a paper that published nine hallmarks of aging, which look at basically different ways that reliable, different areas of the body or functions or damage that reliably occurs in the aging process. And cellular senescence is one of those. And really the best way to understand this is that your immune system becomes less as we age. So now what happens when you have these cells that have undergone a natural process but are death resistant? So they also have this upregulation, which means that they become resistant to undergoing normal cell death. Internal processes, which we call apoptosis, which is programmed cell death. Cells have these built in mechanisms as a form of quality control to keep the good cells alive and the damaged or aged. A life cycle. So they die, then they're cleared out. And so anyhow, they become resistant to apoptosis. So they're partially alive and partially dead. Partially alive because they do continue to survive. It's not like they become necrotic. They're there, they're maintaining cellular activity and they're releasing all these inflammatory compounds into the surrounding.

Is this why it's called zombie cells?

Exactly. It's a really good analogy.

Okay, yeah. I've heard that term so many times. And I don't think I fully understand because if you think of a zombie, it's not dead, it's not alive. It's just kind of. It's a zombie. So that makes sense.

Yeah, there's one other. So it's. It's a great analogy. And what makes it even better is that senescent cells themselves can induce what's called bystander senescence. So they. You know what happens when you get bit by a zombie?

I don't know. I've never been bit by a zombie. I don't want to be. But what happens?

I hope that never happens. You turn into a zombie. Oh. Oh.

Okay.

So not only do these cells are problematic when they stick around, but they'll also cause their neighboring cells to become senescent as well.

Okay, I'm making a huge leap here. But I. And tell me if I'm completely off track here. And I don't. I'm just thinking of like a cancer cell. It's alive, but it's not doing any good in your body, but it's multiplying. Is that. And I know that's a completely different thing, but is it kind of like that same idea? It's like a cell that is thriving in your body, maybe, but it's just not supposed to be there. It's not doing anything to help you.

So, yeah, there are, there. There are interesting distinct differences, of course, between senescent cells and cancer cells. Cancer cells essentially will have.

Mechanisms to continue to proliferate. It's like they are immortal.

Okay.

And that ends up becoming really problematic as they duplicate. And now they're not contributing to the function of tissues, but they're also now degrading the tissues around them. And that's why we do want these internal mechanisms. When you see a cell start to be unhealthy, when the cell itself starts to essentially perceive a rising level of internal biomarkers that are signaling damage and problems, it will then switch over into senescence. So like I said before, you don't want to stop the senescence process from happening. But because the immune system, as we age, gets less good at clearing out senescent cells, we have a rising burden of them in the body. And the net negative result of that is a rising level of, of chronic low grade inflammation that then creates an internal environment in your body that makes all of your tissues increasingly less functional. It's kind of like disrupting the messaging system that all of your cells, tissues, and systems use to communicate. Right. It becomes a. There's like a lot more static in the air and it's harder for the body to do its job, to maintain that.

So this makes sense then why my friend and her fibroids, my, like while why her endometriosis? That would make sense then, right? Because. And you're having an overgrowth there. Is that. Am I jumping too far in? Does that, Am I jumping to a conclusion there? But it would, it would kind of make sense that she's got this overgrowth of tissue and fibroids and endometriosis happening, so her body needs to clear these senescent cells from that area. Or is that that accurate or why that would have helped her?

Yeah, so one of the reasons I. So we've not studied this directly, so I want to be clear that I'm, I'm speculating on, on this.

Because like I said, we, not only have we not studied this directly, but I'm not aware of any research that's looked at it directly.

Yeah, this was just my friend's experience. So I want to be clear to the audience. I just pointed it out to you like she was her own unsolicited experience.

Yeah. Is it biologically plausible? That is a question that scientists ask whenever confronted with a new area of could this, does it make sense that this could work? And unequivocally, the answer is yes. So one of the factors that all these inflammatory markers will drive, because they're both tissue degrading inflammatory factors, is fibrosis which is like scar tissue in the body.

Okay.

And so when more tissue becomes like scar tissue, that itself, it's not really functional. Think of an external scar on your skin. It has a function, but it's not like your regular skin. And really what it's done is it's helped to just kind of bind the tissue so that you stop bleeding.

Sure.

And. But it doesn't look like perfectly functional, healthy skin. And it's not. And that's happening internally as well. And so fibrosis is a. Is an issue that can be driven by a variety of different diseases that we want to try to avoid. And senescent cells can also cause that. So not only are they driving an increase in inflammation, but they're also driving an increase in local, you know, immediate area tissue fibrosis. And so you have a loss of. There's multiple mechanisms by which these accumulation of senescent cells are problematic. And now I want you to imagine this. So when you're young, right. You're making senescent cells as a normal part of your tissue homeostasis, or the ability of the body to try to maintain this internal balance.

Okay.

Okay. And so the first decade of life, the second decade, and the third decade, it's basically like net zero. You're not accumulating senescent cells. Then in that third decade of life, you actually start to see there's a rise.

The net equation has changed. The rate at which we make senescent cells increases and the clearance decreases. So now, before, where you would make senescent cells and clear them out, now you're making more and clearing less. And so the amount that you have in your body is actually going up.

Decades when you're younger. And it's clearing out. How is it clearing out the immune system?

Yeah, the immune system is listening, if you will, to those signals, those inflammatory signals which serve as a beacon, like, hey, come clear me out. Come, come out. I'm damaged. Come get rid of me. That's it.

So that makes sense that people that have autoimmune, that have multiple autoimmunes or have an autoimmune, they probably stopped that body getting rid of senescent cells earlier, like before they even got diagnosed or earlier. So their body probably has an even harder time doing getting rid of them, I would imagine.

Well, sometimes autoimmunity can be from a hyperactive immune system. Right. That's what ends up happening. It's probably a bit different. In fact, the immune system under autoimmunity is. It's Seeing your tissue as some sort of foreign agent substance that is now attacking. So, like an example that I used talking on a podcast yesterday is of narcolepsy. So narcolepsy is a neurological disorder where people have a loss of a very small.

Area of brain tissue called hypocretin neurons, and the immune system attacks those neurons, thinking that it's foreign. And we don't know why, why it happens, but it somehow those that tissue, under certain circumstances are vulnerable. Like maybe it could have been, you know, from. We don't know. Actually. All of the researchers at Stanford and elsewhere have been trying to look at the, you know, the causal factors for decades now. And basically what they've been able to ascertain is that, yes, this is an autoimmune process. But the example that I'm. Why I'm using this is because the are your own immune system is attacking your own tissue. And so it can be due to a hyperactive immune system. Hyperactive immune systems, like when you force the body to work harder at a time of life, when that is also something that can accelerate aging of that particular system. Because the body doesn't age in a uniform way. In fact, a lot of the most recent areas that are looking at biological age are the neck, which is how many years you've aged in the years you've lived. So you might be 50 years old, but it's like you've aged 52 years or 48 years. It's like you're aging at a slightly faster pace than your chronological age.

But you also have the more recent ways to assess. This is not just looking at this global score, but also how every individual tissue system, like your heart, your cardiovascular system, or your brain, or your kidneys, your liver, how they are aging. And you can have a situation where you have some tissues in the body that are multiple years younger than your chronological age and others that are multiple years older. And so that's a really interesting advancement in science. And then hopefully it can lead to more pointed care. You feel good, but your cardiovascular system is actually aging faster. Can we address aspects of that makes sense more aggressively.

So the reason. Let me. I want to come back to the autoimmune for a second. I know that it makes sense what you just said. So, for example, I have. I have two autoimmunes. One of them is celiac. So what you said makes sense. My dog, my body thinks that the protein in gluten, so wheat, rye, and barley, it starts attacking. It thinks that something's wrong, and it attacks my stomach lining and I have a flare up my lymph nodes and everything. So it's an overreaction. So I understand what you mean there. But what also happens with celiac or any autoimmune, I would, if it's my understanding is like, while that's happening now, your immune system is not really able to function on other things. So the reason maybe I would get super sick and probably get flu like symptoms after having gluten is because now my body's so focused on attacking my lining because of this gluten that it now can't fight off other things. So in my head, in my mind right now, where I'm going is if you, you've got to reduce that overall toxic load and the burden. So if you've got other senescent cells, you have to address them even more importantly if you've got an autoimmune because your body's already being taxed. Am I, is that wrong thinking there?

So I, I actually have kind of pushed back on this a little bit. Not that environmental toxins are not a problem. They are. But there are some other factors that are discussed much, much less that we don't hear about. And some of them, you know, are shocking, like just our lighting environment. So if you like, we have the circadian system in our brain. It is basically like a clock for the body. And that's really important because we want to separate.

Functions or tasks that are in a way diametrically opposed, like breaking down and building up. Right. You don't want those two types of processes working simultaneously. They'll just ram into each other and you won't have any efficacy of either the cleanup process or the buildup process. Right. So they end up being temporarily separated. So within a day, for example, you know, your immune system has periods of time where it is very low in activity and other periods of the day where it should be working really hard. And what happens when you end up in a situation where your circadian rhythms are messed up? Right. Which is not uncommon given how we live in our modern society. We undergo like, you don't always have to be on a plane traveling back and forth to the UK from Austin, Texas, in order to have a messed up system? You can do it socially called social jet lag. And that's where you just decide to stay up really late or have a light on. Right. Because your body's always trying to.

Or using your phone late at night or a computer.

Yeah, exactly. Right. So the immune system is very active in our gut and this makes sense, right? The gut is a place where we're readily exposed to foreign pathogens when we consume food and beverages. Like, you're taking the external things and you're putting them inside your body. You want your immune system to be on high alert. Right. So that it is working to figure out is anything coming into the body that shouldn't be there because we can't see it necessarily. Right. They're microscopic. So our immune system is in our gut is highly active, but only at certain times of day, not all the time. And the master clock is controlling when the immune system is most active. And so there was a really interesting study that was done by Laura Hooper. She's an immunologist at the UT Texas Southwestern. And she gave mice jet lag. She basically put them on a cycle where they were in jet lag, which meant that they shifted their timing like six hours every other day. And that ensured that their body clock was basically out of sync. So I'll just translate that, that that's something that can actually happen. What she was doing was creating an animal research model that reflects something that modern humans undergo, not irregularly. Okay, all right, so what did she find? She found that under those conditions of this light cycle disruption, that the immune system was twice as active.

In the intestines and the spleen. And now consider how many people are dealing with inflammatory gut diseases. How many people do you think are considering a mistimed body clock as the potential source of their issue?

No, you're right, they're not. And it's making sense. I'm thinking about me literally just getting back from Bali recently and getting completely sick there and destroying my gut, like cleaning all that up right now. But think about that 15 hour time change and the 36 hours to get there, there and the. So it makes total sense.

Yeah. And so you now have this situation where, you know, you people are like, I'm experiencing gut issues, right? Legit gut issues. And they will endlessly try to tweak their diet, searching for foods that are causing the issue. But it's not. The, the ultimate cause of the issue is the mistimed lighting environment that is doubling the intensity of your immune system, turning it into a health promoting force in the, into something where it is attacking, causing inflammation, causing Crohn's, causing irritable bowel syndrome. And we would never think it's a really cool example. I mean, it's a tragic example, but because it's so common, it's a useful example because everybody can head nod and say, Yeah, I would have never thought of that. Right.

You know, it's so interesting, whenever we talk about lighting or circadian rhythm, blue light blockers, you'll always hear somebody say, well, what if I'm a shift worker or if I work at night? Well, you're, you're still damaging your health. I mean this, facts are the facts. Like it's, it's like I, that stinks. I, I, I feel for people that say that they have to work nights or, But I, I'd say you're, that's one of the biggest destroyers of our health.

Yeah, yeah. And I mean, I'll even give you a more specific example is that there, there was a research that followed on to this whole line. It was done at Rush University by Professor Garst Swanson and this is something that was published in a journal, Frontiers of medicine, like around 2022. And so basically he had 42 patients with proven inflammatory gut disease and showing that they had documented. So basically they started with the gut disease and then they looked into their circadian issues and they documented circadian misalignment that associated with more aggressive irritable bowel disease history, increased intestinal permeability, increased pro inflammatory cytokines, dysbiosis. Right. Which is basically an imbalance of the gut microflora that is of course extremely important to our health. Like it's so right now, not to go on another, like a tangent of a tangent, but our gut is so important. We know that now, but we don't know all the ways on how to intervene to make it necessarily healthier. But you can see when there is a complement of internal bacteria that become dysbiotic, you can look at those and say, okay, this person's microbiome does contain more of these types of gram negative bacteria or pathogens versus the healthy commensal bacteria that we want to help flourish. So you know, that is just an example of how connected the body is. And so going back to senescent cells, I wouldn't imagine it's possible actually. I mean we, you could think that if your immune system is hyperactive for a variety of reasons, including circadian misalignment, which is easy to do.

Yeah.

That the immune system might be less effective. It's like over, you know, it's overly pumped up on handling non issues while not addressing the real ones. That's one possibility. The other possibility is that it is, it is actually equally effective. But you're going to cause your immune system to become exhausted earlier in your life, which would mean that you Would later downstream experience a faster accumulation of senescent cells at an earlier age.

Makes total sense. And this is, and I'm again making a huge jump and jump to something here. But like if you look at the controversy around the sun, I mean there's a huge, there's a whole different topic here. But you have a, there's a controversy literally around the sun. If you look at, I'm going to go to one extreme is it's causes skin cancer. It's so bad for us, you're going to get cataracts, you're going to damage your skin. Like there's that side, right? And then there's this other side of we don't have enough sun and we need to get it in our eyes, we have to get it on our skin and it's going to create all these things. But one of the huge. And I think there's a place in the middle obviously for a lot of people, but, and I've come a long way here where we need the sun to help set the circadian rhythm. So if you think about it with, based on what you're saying, if you get up in the morning and you first thing in the morning get natural light in your eyes and then at the end of the day you're with the sunset, you're getting that in your eyes. And then when the sun actually goes down, if you mimic that and you're not letting blue light in, you're not letting fake light in, you start resetting and you basically start winding down with the sunset that wake up with the sunrise. That alone would make a big difference in your health like what you're saying here. So I think when people go to this huge like the sun's fixing everything, I think the, the, the, the real, real on all that is kind of what you're saying here is that we need to get reset with the natural flows of circadian rhythm there.

Yes, it's incredibly important and underappreciated in our health. And it is, you know, we, we evolve from single cell organisms on the planet that have undergone a daily light and dark cycle. So circadian rhythms, the importance of them has been built in to the 37 trillion cells that make you up right. When humans evolved on planet Earth, it's not like we reinvented the wheel by recreating the cells that made us. We just were another life form that had very unique capabilities that had never been seen before. But we were building on top of cells that had took the first three and a half billion years of life.

Was just evolution, working on cellular efficiency to make cells work really well. And they reached a place of maximal efficiency before they even started to come together and form multicellular organisms. And so you're right. Circadian rhythms are not. Not. It's a modern problem, but it's an ancient need. Yeah, for sure. And the signal that we got was from the daily exposure to sun. So I gave a talk on this for the Ancestral health symposium, which is looking. So I gave a ted talk in 2017 on how to optimize light for health. It's like 12 minutes long. You can take a look at it. It didn't go into all aspects of light. It was more about the effects of circadian rhythm. And, and I remember there was a statistic I shared there about how like, for example, children that have screens in their bedroom perform worse academically at every single grade level tested.

Makes sense. And you think about when I was little, at least in the 70s, we had a black. I had a black and white tv. You know, so we. So we didn't necessarily have. I mean, we had. TV was ruining us for other reasons, but things are black and white. And I don't know if you guys know, one of the things I recently did is on my actual cell phone, you can turn it to black and white mode. Mode, which makes. So it's definitely a lot healthier for you that way and it makes you less likely to get sucked into. So it's. It's a whole. A lot of things.

I saw a. A teenager of a friend of mine, and I just happened to be kind of staring there and near him and he turned on his phone and it was all in black and white.

Oh, I love that.

I was so happy. And I asked him, I said why? He's like, well, it makes it less rewarding. Like you're less. Yeah, less interesting. Right. We don't. We don't prefer it that way. He was doing it to make it. The phone less seductive so that he wasn't on it for six years.

Dan I turned my phone to black and white. On iPhones, you can do a setting to do that, but then there's a way you can do it where you can click it. You set it as an auto thing where you can click your phone to make it come back. And I kept going back to the color. So I had to remove that from my. I had to make it more challenging for me because we're. We get addicted. It's what happens.

Yeah, it becomes, you know, a personal interest machine. And what's so insidious about a phone is that so many good things happen on it that are valuable and important for your life and productivity and connecting with your friends and family and connecting with work and recording awesome shows like, you know, you and I chatting about these cool topics. And then there's all the other stuff. And so you just, it's all paired together. It's not like you can separate them physically. It's all in one device. And so in a moment of weakness where you're not like fully on top of of like, what should I be doing with the next five minutes of my time? It's easy just to pull up something that's kind of like fun and easy. And the net result of that is that we're on our phones from morning to night. And so, you know, we could change this whole topic into behavior change. Yeah. And, you know, maybe we'll chat again sometime about that.

But senescent cells, one more question on that. And I have a bunch of other things about senolytics specifically. And then I want to ask you about stem cells too.

Yeah.

When you say they take hold, that these happen, the senescent cells are going to happen regardless and we've got to do something to clean them out. But where do they typically show up? Like, where do they take hold in our bodies?

Yeah, fascinating question. Because they can happen in any tissue. It's not like it's just in one one tissue, but it's actually a not, it's not a lot of cells. Like, it is less than, you know, amount of cells that turn senescent are 0.01% of cells. It's a very tiny amount, but unfortunately, 1 in 10,000 senescent cells can have an outsized impact on your inflammation.

And the surrounding tissue. And as I mentioned before, they can also drive by standard senescence. It's like the zombie biting the person who becomes a zombie. So it also has this eroding effect on our tissue. And so let me do a quick summary.

Okay.

We don't want to stop senescence from happening in cells because that actually has some favorable beneficial effects to bodies. But we don't want to let senescent cells accumulate because once the immune system becomes less strong with age at clearing them out, now an accumulating burden of senescent cells is raising the inflammatory burden of the whole body. And that is going to have a aging, age accelerating effect. So if we can't clear them out, if the immune system is not doing a great job, you know, what are some Ways that we can actually clear them out. And this line of research basically came into existence between the mid 2010s and 2020, where you had researchers like James Kirkland at the Mayo Clinic and Janssen Durson that were looking to create a new field called senotherapeutics, which is ways to manipulate.

Senescent cells in the body in a variety of ways. So, for example, you have this idea of a cenomorphic where you don't kill the cell, but you convert it into something that's less toxic. Right. Driving less toxicity, if you will, in the body. There's cenoantigens. Can you figure out a way to make these senescent cells express something that would make them amenable to a vaccine? Clearing them, like a targeted approach where, you know, the vaccine finds the exact target on only senescent cells and then goes and clears them out. That's another area. The most prominent area right now. The one that's generated the most excitement is sinolytic. So lytic means breaking down.

Okay.

And as I mentioned earlier, that senescent cells, they have a couple of distinct characteristics. They are upregulating their survival pathways. They're actually resisting. They've become more resistant to death and what ends. But that also provides us an opportunity. And we found that flavonoid like compounds. Flavonoid compounds and some others are. When you give them at a higher than dietary dose, it can harm senolytic cells and have no negative effects on healthy cells.

Right. It's basically taking care of a vulner. It's taking advantage of a vulnerability that senescent cells manifest, which is this heightened activity of prevention of cell death pathways. And so what these. Because those are amplified within. Within the cells, these flavonoid compounds can get in there and through a variety of different targeted mechanisms. Mechanism. So like receptor tyrosine kinases and bxl, you know, all these. All these names of like, you know, complicated pathways. These different compounds work there. And it causes the senescent cells to die.

So it's basically. Senolytics is basically a zombie slayer.

I love it.

Did I say that right? Okay, so it's. So if the zombie cells are the dead, they're not dead, but they're not beneficial. They're just kind of clogging us up. And they're sitting around. Senolix basically comes in and slays them, but is a good guy because it's not doing that to anything else.

That's exactly right.

Okay, okay.

In fact, when I take Senolytic, It's a bunch of flavonoids, which I have. I'm sort of enamored by the, the pharmacopoeia of nature and all of the different compounds that are not essential micronutrients like minerals and vitamins, which of course are really like.

Quercetin's a big ingredient in here.

For example, that's what you can call either like a phytonutrient or a phytochemical. Right. It is a plant compound. And these plant compounds are so interesting because they are typically a, they're a plant defense system. Plants make these so that bugs won't eat them or.

It develops resistance to stressors in their life. So if they're under harsh sun and they, interestingly enough, they don't get enough water, like all sorts of stressors to the plant, including.

Bugs trying to eat the plant. Those are all risks, existential risks for the plant. So they make these compounds like quercetin, facetin, these all sorts of flavonoids, there's a million of them and polyphenols and terpenes. Like there's a huge panoply of different types of phytochemicals all doing super interesting things in the body. I think one of the main reasons we have.

One driver of poor health in our society is the fact that we don't have enough diversity of plant derived phytonutrients in our life that completely change our physiology in a more healthful, resilient way. They can have an impact on how we metabolize plant compounds like, you know, carbohydrate containing compounds. Like. I don't think carbohydrates are necessarily problematic. I think they're really problematic when they are not delivered with the plant compounds that they typically come with that totally modify how they're absorbed, how they metabolized, how they're, you know, everything. And so it's kind of like a diabetic that just is not getting their insulin. It's like you're not getting the compound that is the, that is going to help you handle those processes better. And that's just an analogy of like.

Well, there's this whole theory about that with all types of food too, by the way, like eating an entire fruit, like eating parts of the seed too. Or like if you look at an egg eating the whole egg versus just the egg white, which can then create an allergy. So there's like, there's a lot of. It makes sense that if we ate foods the way they were complete versus Taking them apart and modifying and processing the way we do, we wouldn't have as many issues.

Do you, Are you familiar with the product Juicero?

No.

Okay. This is a really interesting product. And it was interesting for a lot of reasons, but this was a company that raised gobs of money, $120 million.

For a juicer.

And I mean, that sounds ridiculous, right? And in fact, because of that, it became a story. The story that happened was that this was a symbol of Silicon Valley largesse, like a total disconnected with modern, you know, real world people. They were selling this juicer for $800. And it was. You had like a subscription where they were getting, you know, like odd shaped vegetables that people don't want and then packaging and then sending them and then you would juice it. And so basically it had like the, the power of a industrial strength juicer.

But that there was a lot of good there. And I was partially involved with that company, like, not officially, but they were looking at me as an advisor because. And they didn't. It's sad because they didn't really use me. Like, I didn't get there with them. But then Business Insider did this report where they basically showed somebody hand squeezing the bag. Then they had one from the Juicero machine and one from the person who just did it with their hand. And it was like the same volume of juice. And they're like, look, you don't even. This whole thing is so ridiculous. Well, the truth is, and I'm bringing it up because you just mentioned this, a lot of the phytochemicals are concentrated in the seed, the pith, the rind, right? And so when we masticate, we chew and chomp, chomp, chomp, chomp, then that we release the phytochemicals, which are good for us. If you just hand squeeze the water out of the juice. You have a murky glass of water, but you don't have. You need the £12,000 of pressure that the machine generated to get the helpful phytochemicals that are fresh out of the important areas that we don't always eat and squeeze them into a juice that was absolutely. I remember they did one with pomegranates. It was like, like glowing bright. It was so rich, right? And it was really sad to me because they didn't have a scientist to defend the, the virtue. And so the response at the time was like, oh, yeah, we're sorry, we'll offer refunds. And I'm like, no, they totally mischaracterized the value of your work. And you don't have any, you don't even understand your product well enough to defend it.

They're not, they didn't understand that, that huge benefit there. That's so interesting.

Yeah, yeah.

I, I mean this is, you could get into an argument with this on every food. I mean, I'm not, I don't even want to go down on the raw, the raw milk side of things. And I, and like there's this whole argument with raw milk those, like some people are like, oh, pasteurizing only takes a few seconds and it's going to kill all these gross pathogens. And then there's this whole other thought process. Well, but if you leave it in its whole form, then you're getting all the enzymes and everything that you need, so you don't have the lactose problem. So I don't know. I, it's just, it's just another example of when you look at food and how we're modifying it, we need to consider that if do we want food in its whole form or we're losing benefits when we tweak it and change it.

It. Yeah, yeah, exactly. Yeah, yeah.

With senolytics, do you. Okay, I have a couple questions there. One, should everybody use it? Like, is who should use it and, and why do you have to do intermittent dosing? Can you do it more frequently? Can you spread it out more? Talk to us about that.

Yeah. So we are following the protocol that was originally created by James Kirkland where he was testing a variety of different compounds. High dose facetin, which is a plant flavonoid.

That you, you see a high amount in strawberries and cucumber. But you, but you'd have to have a lot of it. And, and then the very, the combination that has been tested the most is quercetin and something called dasatinib, which is a repurposed cancer drug. But they are, it's targeting these same upregulated survival pathways to try to knock them down so that the, you, that the, the typical apoptosis, apoptosis pathway can actually take hold and those cells die off. Right. That's what we're basically trying to do. And so he gave this in a two days, once a month protocol. And you don't want to be taking high dose of these plant compounds all the time because that in itself could be toxic. Right. You're doing super high doses that are really like a pharmacological level. Right. You're not necessarily getting that amount in nature. And you do that just in two days, clear out the senescent cells, Then you wait, you do it again. Some studies have looked at doing it every two weeks. So there was one study that looked at joint pain and mobility and they gave it every two weeks and found that people did benefit that way as well. There haven't been comparative studies, however, looking at a once a month protocol versus a twice a month protocol. But there have been protocols looking at either once a month or twice a month, both showing positive, positive effects.

So any, there's no downside. If somebody wants you to do it twice in a month, then.

It doesn't seem to be. There does not seem to be. We just have not tested that ourselves.

And then what about if you have to skip a month? Like if somebody says they, they didn't take it one month, does that matter? Can you, does it have to be exactly every four weeks? Could you do four weeks? I mean, could you do six weeks if you forgot? Or like, does that matter?

Yeah. No, it doesn't. You can, I mean, think about doing versus not doing at all. You know, so I think the most, you know, the plan that we think makes a lot of sense, but we could discover that there are protocols that make even more sense, but we think doing it once a month in perpetuity. Right. So you do it 12 times a year is helping to clear out your senescent cells and keeping, you know, we talk, we talk about longevity and the new term is health span. And the easiest way to think of that is extending a higher level of health farther into the lifespan, even if you don't affect lifespan itself. And the whole conversation around lifespan is interesting because you might affect your lifespan if, I mean, theoretically, right. If you are now confronting premature mortality, like dying early because of poor health. But the things that actually manipulate how long we live, it's like a whole different scientific question, like, can we exceed the upper bounds of longevity by doing some of these techniques? So there's some groups of people that are looking at how to do that that would be like, so we have a theoretical maximum of 125 years that humans will not live beyond that. And there are those people who are saying, well, what could we actually help a person theoretically? Could we extend that theoretical max, what most people are interested in in the near term and maybe ever, like some people might only be interested in this is how do I preserve my youth longer for the time I do have to live?

Yeah. And I think it's not just preserving youth. It's, it's the how do I feel good, how do I like I, you know, I had a talk with my mom recently and she's, she's 80 and she's, and she made, she made some comment and I said, well, mom, you're gonna be here for a long time. She goes, well, I don't want to be here for a long time. And I'm like, what do you mean you don't want to be here for a long time? I said, and then when I really dug on that, it's like, well, I understand what she's saying. If, if you're declining, if you're, if you feel terrible, if you're in pain and you can't see and you can't hear and you're losing your memory, I get all that. But if you could have a healthier like, and you feel vibrant and you feel youthful, then there is no reason to want to not live longer, I would imagine. I mean, that's so. I think that's what. When I hear Hellspan, that's what I think of is like, well, I want to. You want to have the healthiest longevity that you can not just. Not just push through and in pain and miserable just to be here. Yeah, that's my thought.

That was something that we sort of clumsily discovered as a society is that we now had techniques that could keep somebody with very low level of health longer alive longer for decades, with very low quality of life, 24 hour care. You know, imagine like the sort of. The most obvious example is somebody that's on life support. Right? Yeah. They're not conscious and we can keep their body alive for a long time.

Right.

Should we. Is that any sort of. Yeah.

What quality? Yeah, yeah. What quality? So when you see all. If you're watching on video, you can see it, but I, So I basically take it. I take it once a month. I've been doing this for the last year. And it's, it comes with. There's 12 pills. So you take six one day and then you take six the next. I personally feel nothing negative, literally nothing negative. And I did it the first time thinking I would. I did nothing. It felt nothing negative. In fact, I felt way clearer, I felt better, I felt cleaner. I felt all of it the following week. And that's been my experience for most people. Now I do see on some ads that are run, I'll see some comments and they're rare, but you'll see somebody say I felt sick on it or this happened. And I have my theory on that. Dan, I want to hear your theory. My theory is if you're new to it and you have a lot of cleanup to do, and maybe you have a huge toxic load. There's. There's reasons that you could feel it. Almost like a Herxheimer response, I would imagine. I don't know though, Dan, why. Why would somebody have a negative reaction if they did?

Yeah. So just to my. Just I'll say this. My experience is exactly like yours. I look forward to taking it because I feel super clear on the days that I take it, you know, I wish I could take it more.

Yeah.

In fact, we know that. So flavonoids have a really powerful potent effect on the brain. They can. Like. I spoke on my podcast Humanoise Radio with Pamela Maher from the Salk Institute, and she's a really cool researcher who is as enamored with the natural world as I am, and she was talking about how, you know, she was working in these drug development systems where they were trying to basically get. Turn it, make some of these compounds into a drug for the ability to protect it. And, you know, don't get me wrong, like, there are good things that can happen. Like you can actually reduce side effects sometimes of like an effective dose. Good things can happen in the drug development process. But oftentimes you can also see they're just trying to create something that is equally effective, but they can protect. And that's the game that the pharmaceutical industry is, of course, playing. Which is why they can dedicate billions of dollars towards clinical development programs, because then they can develop monopoly profits on that going forward for a particular condition. And it's just how it is. Right? That's just how that system works. But the reason I'm mentioning it now is because. Because in that conversation she said, yeah, we had the hardest time figuring out how to create a drug that could do what these natural compounds could do, like getting into the brain, causing vasodilation, improved blood flow, binding toxic chemicals like heavy metals.

Driving down master regulators of the inflammatory process, like nuclear factor kappa beta. All these positive things that then would. Would lead to better cognition, better brain health over time. Plant compounds can do that, and we're feeling that acutely when you take the synolytic product. Going back to your question, why might a person not feel good? This is speculative. We don't know. It's always difficult to know what is happening in a particular person. So we can list out the possibilities. One possibility is that the negative effects corresponded with taking that, the supplement, but it were not attributed to it. That's one possibility.

Another possibility is that because the cinnolytic is effectively causing senescent cells to clear that you do have an increase in inflammation. Which. What happens when you typically have an increase in inflammation when you're sick, it is the immune system that is actually making you feel sick versus the pathogens. And so because of that increase in inflammation, you feel maybe a little bit nauseous, maybe feverish, like all. And it can. It can be all sorts of things, right? Yeah.

And so I think that's my estimate of likely what's happening is these people are having a very effective experience.

Yeah. So I. I'm gonna. Based on what you said, that kind of aligns with what I'm saying. For those of you who don't know, Herxheimer reaction is kind of like. Like when you've got something that's not supposed to be in your body, and. But it's. It's living, symbiotic in your body. So it's. It's making. It's negotiating with your body. It's. It's working. It's in there doing something. And. But when you then yank it out, you take it out. It's. It kind of throws your immune system off for a little bit. But that's not a bad thing. It's a good thing. We don't want it in there. So we have a response to that. And I. And I have this literally as I'm recording this right now, not from the. This product, but just in general, because I'm working on clearing out my gut stuff that I got in Bali. So what? And I wanted it out quick. I didn't want to, like, take months to. So I zapped it out pretty quickly. And I had a Herx response. I had hives. I had. And I know that that's what that's from, and that's just temporary. It's a few days. So sometimes a response is. It's like what you said. It's just your. Your body's reacting. It's responding to your immune system, not necessarily the product. So. So you also said before we started recording that the rare amount of people that have had that happen, it's usually the first time, but it's not again, and it is very rare. I will tell you. I've only seen that comment a couple times on ads for it. I've never had that comment from a friend or clients or myself or anyone. Like, most people have a really good response, and people that have good responses don't typically comment on ads or groups. I just know that in general, it's negative people that had the bad thing that will do it. So we just will tend to see that more, I think.

Yeah, there's, you know, there's just a lot to say there. Like, there, There are some people who have, you know, a form of. I mean, not to. Not to dismiss. True.

Oh, I'm sure some people do. Yeah, some people do.

But you also have people who.

Are neurotic, where it is like the reverse placebo effect right there.

Yeah.

They're taking something new and the anxiety of it all drives a negative experience. And you. And typically with those people that. These are people that have gone to see a thousand doctors, they're never satisfied. It's. There's something happening more internal to them and their. Their mind that is generating symptoms in the body. And I know that can seem really dismissive, but it is true. It can happen. It just doesn't mean that that's happening in any one instance. Right. The very. The opposite.

Effect there is that a person is having some of some real reaction and they're not, and the modern medical system is not able to identify it. And that's frustrating. Right. So you have two examples, and you're like, well, is this the kind of a reverse placebo, if you will, or is this, you know, like.

Right, because somebody could have a true allergy or something, too. I think it would be. I mean, most. If I'm just reading the ingredients, it's things like Corsicano, these are like variants, natural ingredients. Like when you look at polyphenols, things like that, these are all really good nutrients that we would get from food. So there's nothing. There's nothing funny. I will say I feel amazing and I'll probably be taking it for the rest of my life. And you do have clinically, clinical tests on this. There's some clinical data here.

So that's something I'm very proud of. I joined the company. I've known the company since their origin around 2015, but I joined the company just three months ago. I've been here for 90 days. So I've been, I guess we'll call it, friends of the company. I've been an advisor.

I've been a friend, you know, supporting the people behind it. And. But one thing that I'm really proud of, and now to be a part of the company, and one thing that attracted me here is I think Qualia is doing everything right for what a supplement company can do to get good products out into the world. That starts with having smart scientists that read a lot, identify, let's say a therapeutic area that's of interest. And then, you know, the, the documentation that our product team has on each one of these ingredients and each one of the formulas is hundreds of pages long. So not only are they assembling the research related to this, but they're analyzing it. So they, you know, you'll go through those product documentation and you'll look and it'll say, you know, we don't even believe in the conclusion that the author in peer review said, even if it was in our benefit, like, I don't think the data supports, like, we, we have not gone with products because we felt that the data was very, very weak, even though on the surface it looked positive if you just read the, the abstract. So we are really digging in to say, okay, how do these things truly work? Because it makes sense even from a business perspective for us to invest and promote things that generate a real effect. So that's totally. But then on the other side of that is once we've created a formula, I'm also really proud that we put all of our products through clinical testing. And so Qualius Analytic has been tested and the results are super encouraging. So in the study that we did, participants took the formula intermittently. So just like we talked about two days in a row, once a month, and then this. And in this case in this study, they did that for two months. Right. So it's sort of like this hit and run strategy, right? Get in, do it, get out. And by the way, that's contributed to fantastic compliance. People prefer that. It's like, oh, I can do that two days a month versus like always.

Having to do easy.

Yeah. So we were looking at various biomarkers of cellular senescence. So something called P16 Inc. 4A, which is, is those levels rise in senescent cells and it's not perfect. Unfortunately, there is no perfect biomarker of senescent cells because there are different types of senescent cells in the body and there are different markers. So it does give us an impression. We do know that certain cells do express this P16.4A biomarker. And we can look at that.

But then we don't just look to see if biomarkers change. We also look to see how do they feel and are they performing better. So we saw improvements in physical measures like walking speed went up, grip strength got stronger, and on the subjective side, people reported less fatigue, greater overall vitality. And that's exactly what you want to see, right? Is that even if you don't know how something's working. You want a way to test something so that people are like, I just feel different. Yeah. And it's good to test that objectively because there's a saying that I made up called the meaningful but invisible. So imagine let's say you had a 25% improvement in some, you know, some MA metric that mattered. We acclimate to that over time. And there are some people who are very attuned to their body and others are not. Right. You experience this pretty dramatic improvement in something, but you, it's just your new you and you forget how you felt before for sure. Right. And that can happen in both directions. It can happen in a positive and it can also happen in the negative.

Very true.

We're more likely to see the negative because it's a decline from the default state, which is not grabbing our attention.

Right.

Makes total sense.

We're less, it's almost like the more effective it is, the less likely you are to notice it. It because it's just you're back to not having any signal that there's a problem there and so your attention is driven elsewhere. So that's one of the interesting challenges that doesn't just apply to what we do, applies to everything in health, particularly as you get older. But anyhow.

So I'm happy when my midlife, women especially, I mean this is not just for women. Men can obviously can do this too. But I'm very happy when my, I loved like everything that will support them, having their longevity, their healthiness, they're having their weight loss loss in a healthy way, all the things. So I have definitely, I mean I've, I've shared this with my email list a few times. I've shared it on social media. I'm such a huge fan of, of qualia you all, if you go to Qualia Life Q U A l I a life.com forward slash Natalie Jill. So quality of life.com forward slash Natalie Jill. There's also a code Natalie Jill. If you're just going on their site on your own, if you use the code Natalie Jill, you're going to receive an additional 1515 off any Qualia order. Dan, I know we talked a lot about qualia Senolytic and I. We have, we'll have to do like a whole nother episode eventually on stem cell. But can you just, just in like a quick. I know that's a, it's a big conversation here, but I just happened to notice the last time I was ordering, ordering qualia analytic that you had another Product called Qualia Stem Cell. And I kind of disregarded it initially. Like, what? Huh? I was so confused. Like, stem cells to me is something new. And. But then I, when I saw you and your team recently at an event, they were like, no, no, this is so good. It's such a perfect thing to follow it up with. Can you give us just a little like Cliff Notes on that and why you all created that?

Yeah, I'd love to. And just to put it out there, I would love to do another full conversation, because what I think is most helpful is when you can get into the details a little bit for sure and, and, and see that. But to cue up some curiosity on that for sometime in the future when we do chat about this, this. So stem cells are a part of the body's way to regenerate ourselves. And a stem cell, we have these different pools of stem cells throughout the body and they have the ability to make a copy of themselves and a version where that cell is destined to travel to different tissues and become. And differentiate is the term differentiate from. Like, think of this mold of clay that could become anything into a very specific cell, like a muscle cell or a nerve cell. And that is one way that our bodies will regenerate themselves over the course of a lifespan. It's not like you're born with 37 trillion cells and they never change over. They turn over all the time. And similarly, kind of like with senescent cells, where the net balance is that we're making them and clearing them when we're younger, and as we get older, we're making more and clearing less, so they rise. Well, remember what was the consequence of increased number of senescent cells, increased inflammation. And it just so happens that our stem cells have a harder time doing their job replacing worn out tissue under a highly inflammatory environment. So another hallmark of aging is called stem cell exhaustion. And that term essentially means our stem cells are not as good at doing what they're natural. Healthy job is. We created a formula that I think is a perfect one, two punch, right? Clear out the inflammation, clear out the senescent cells, lower the inflammation, wait a couple of days, two days, and then for a four day period, you stimulate more stem cells and the whole product is 15 ingredients. And we're trying to then affect the whole life, the healthy life cycle of a stem cell. Make more, help them travel to the sites where they're needed and then differentiate into healthy, functioning tissue and then protect them.

Got it.

Okay.

So I have not tried this yet. At the time of recording this. But by the time it releases, hopefully I probably will have because I'm gonna now do. So if I'm understanding correctly, you do the senolytic once a month. You do that two days back to back. Then you wait a few days. So two days after. And then you start these, which basically is going to put the good stuff in. So I. Okay, I'm gonna. I'll report back back. I'm gonna try doing both, but it makes total sense to me.

That's great. Now I do them in the evening. So I take my. The stem cell product with dinner or after. Because when is the body naturally regenerate and repair tissue sleep. Exactly. So do you.

But senolytic, do you take during the day then or does it matter?

Yeah.

Okay. So I usually take it in the morning. Yeah.

Here's what I do. I do a low protein diet the night before. I do cinolytic. I have it in my calorie.

Low protein the night before. Okay.

Yep. The first Saturday and Sunday of every month. And I do a low protein diet the night before. And then in, you know, very low protein, no protein up until like the middle of the afternoon the next day for the, for those two days. Because protein helps to stimulate something called the MTOR pathway. It stands for the mechanistic target of rapamycin. That is a growth pathway. All right. It actually makes cells stronger. We do not want to make cells stronger when we're trying to kill the vulnerable senescent cells. Right.

So just the night before y', all, we're gonna go lower on protein. Makes sense.

Lower on protein that night before that morning. So we're now creating an internal environment for the senolytic product to actually have maximal efficacy. The other thing you can do, do like 20, 15, 20 minutes of high intensity training, like get on a bike and then do some intervals. Right. That's also going to then drive. We know that independently can drive the senolytic process too. It's a lifestyle factor that can do that. Then because the stem cells are dying, your inflammation might rise for a day or two as the natural process getting rid of those bad cells. And that's the youth. Then I wait till Wednesday and then from Wednesday to Saturday, I do the stem cell product. And in that period, I'm doing more steady state, you know, zone two type of exercise, facilitating blood flow, but not doing really heavy training because I'm trying not to drive more damage. I am trying to let my body regenerate in that period. I take it at night four days at dinner or right after.

And I'm eating normally, I'm having higher protein. This is where you want all of the forces that are going to help your tissues rebuild. And so it's just like senolytic stem cell is once a month, but it's four days, not two. So it's two days on the weekend for senolytic. Wait two days. Four days with stem cell.

Okay.

Go back to doing your own.

I will report back.

Yeah.

And then we'll have to be continued on the stem cell conversation. All right, you all, I know you have heard me talk a lot about zombie cells, but if you have not tried this yet, I highly Suggest go to qualityoflife.com nataliejill Use code nataliejill. You get an additional 15% off. And I wanna hear from you. How did you feel? Did you feel clearer? Did you have a response? Like my friend with her endometriosis, which was phenomenal. I can't wait to go tell her that she doesn't have to wait. She can do a second round if she wanted to because she said, can I only do it once a month? I didn't really realize there's an option to do it twice a month. Thank you so much, Dan, for being here today. Thank you.

Oh my gosh. Thank you for having me on and I look forward to our our next chat.

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