Have you ever heard of Senolytics? It’s the latest breakthrough in aging and longevity science that I honestly had not heard about until learning about Qualia Senolytics. That’s what I’m SO excited to welcome todays guest, naturopathic physician Dr. Gregory Kelly, the VP of product development at Qualia Life, and author of the book Shape Shift. He was the editor of the journal Alternative Medicine Review and has been an instructor at the University of Bridgeport in the College of Naturopathic Medicine, where he taught classes in Advanced Clinical Nutrition, Counseling Skills, and Doctor-Patient Relationships. Dr. Kelly has published hundreds of articles on natural medicine and nutrition, contributed three chapters to the Textbook of Natural Medicine, and has more than 30 journal articles indexed on Pubmed. His areas of expertise include nootropics, anti-aging and regenerative medicine, weight management, sleep and the chronobiology of performance and health. In this episode, Dr. Kelly and I discuss why you should care about cellular senescence and how its different from autophagy, the hallmarks of aging, the, and how you can age better at a cellular level by helping your body naturally eliminate senescent cells.
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Episode Sponsor:
This episode is proudly sponsored by Qualia Life. As you approach 30, there’s a subtle form of aging that starts before you even notice it, and you should know about it BEFORE it picks up momentum: senescent cell accumulation. These “zombie” cells start accumulating in us over time, draining our energy and accelerating aging, contributing to typical aging symptoms like reduced energy, slower recovery, and joint discomfort.
Qualia Senolytic combines 9 vegan, plant-derived compounds to help your body naturally eliminate zombie (or senescent) cells, that help us age better at the cellular level so we can feel YEARS younger! Just visit www.qualialife.com/wellnstrong and use the code WELLNSTRONG for 15% off!
*Unedited Transcript*
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Jacqueline: So just to kick things off, Dr.
Kelly, I’m incredibly interested in this whole concept of senescent or zombie cells. Mitochondria and cellular rejuvenation have always been areas of interest of mine, but just to start off with the basics, Dr. Kelly, let’s, let’s go kindergarten level here. for listeners who, who never heard of the term cellular senescence before, what is it and why should we care about it?
Dr. Kelly: Yeah. So, the way I think of cellular senescence is um, first and foremost, it would be a cellular stress response. So, when cells are stressed, and this oversimplifies it, but it’s Pretty like, um, a useful way to think about it. If they have the resources available, then they’ll toughen themselves up. So they get a little bit of stress, they become fitter, smarter, more resilient, however you want to term it.
And they do that by upregulating things like antioxidant defenses. And other molecules but now imagine [00:01:00] stress is even more than that And so when that happens, maybe they’ll take on some damage, right? So that’s where Usually things like, you know proteins get a little bit misfolded Or dna may be damaged and what cells then try to do is repair the damage So you I know you would know of autophagy or the mitochondrial equipment, mitophagy, or DNA repair process.
That’s when those things come in, right? The cells took on some damage, but they’re fundamentally still repairable. And what a senescent cell is, is one that’s been so stressed, for some reason, that it’s not, no longer repairable. And when that happens, there’s certain things that can get enacted so that the cell won’t copy itself because we don’t want really damaged cells making copy after copy after copy.
That wouldn’t be good. So what would happen in a young person when a cell becomes that stressed and senescent is that shortly after either the cell automatically goes through what’s called apoptosis, but that’s a [00:02:00] Greek word that Translate something like falling off. So for listeners, think of like a fruit or a leaf falling off a plant like that.
The end stage for really stressed cells should be that apoptosis process and what apoptosis would look like under a microscope is a cell would just break apart into little pieces and then the immune system would gobble up that and recycle it. So what happens and why we care about cellular senescence and what we’ll talk more about is zombie cells as we get older is these cells Have figured out a way to resist going through that falling off process So they linger so like imagine now you’re looking at a plant and instead of the yellow leaf or fruit falling off They just stay stuck there and over time as that accumulates You know that tree or bush or plant is going to really struggle to do its job And that’s what fundamentally happens with us as we get older more and more of these senescent cells linger in our tissues and they can cause all kinds of You of [00:03:00] issues for us.
Many of the things we think of, of, you know, older age, like our skin, um, our muscles, our, um, you know, bone health, joint health, you name it. All of those things have some correlation to the accumulation of these senescent cells. Um, so because of that, this, you know, area called cellular senescence is now thought of as one of the core, what are described as hallmarks of aging.
Jacqueline: Interesting. And you, you keep mentioning aging, Dr. Kelly, but I mean, is that the primary factor that determines whether a cell goes through apoptosis or becomes a senescent cell? Like, what determines that?
Dr. Kelly: Yeah, so, um, just like our whole body, our cells, you know, are born, live their healthy life, and die, and you’ll, if you googled it, you’d see something like cells have an average lifespan of about seven years. And that’s true, but misleading. In a sense, what’s more accurate is that the length of the lifespan of a cell varies [00:04:00] tremendously depending on what tissue that cell happens to be in, right?
So, um, neurons are brain cells. Those are meant to last a lifetime. We don’t make new ones, whatever you and I have today. Those ones hopefully will carry through to the rest of our our days. Um, cells in the heart. I think it’s about four decades. is their lifespan in muscle tissue. It’s about 15 years. Um, but some cells like those in our liver are really short lifespans, like one to two years.
And so it’s, yeah, skins also cause we slough off skin right on a constant basis. So things that interact with the environment, like, you know, the cells that line our digestive tract also have really fast lifespans. So it’s completely normal that we would give birth to, and then cells would fundamentally get old
and then die off and be replaced.
And so that word I used apoptosis is a normal process. I don’t remember the exact number but tens and tens of millions of cells are going through that every [00:05:00] day. And what the issue is with the senescent cells is they’ve just resisting that natural process that um that fun I guess like a way to think about it is there’s lots of things that can cause cells to become stressed, right?
toxicity, um, you know, nutritional issues, environmental things like the sun as an example with our skin. And so it’s again, natural that cells should be stressed and then they should respond in one of those ways that I mentioned, right? Toughen up, repair the damage, or if they get too stressed, then you know, go away and be replaced by new, um, vital, young, healthy cells that can now do their job better.
And. It used, it’s always been thought of that senescent cells had some connection to aging since you mentioned aging and that’s in their name. So just like the word senile, the root for senescence is the same, right? It has to do with this idea of aging, [00:06:00] but it’s only really been say about the last 15 to 20 years that scientists started discovering how big a role and what they’ve found is one of the reasons is And the way we think of it at qualia is that there’s transient senescent cells and lingering ones so Imagine, you know If one of the listeners on the show is 20 25 years old or you know Has friends family that are young if they went out and ran a marathon they’d make some senescent cells You completely normal, right?
They just stressed out their body, even if they were in shape for that. But what you would see in a young person or a young animal is within days to a week after, those senescent cells would have been removed. They would have been transient. They’d come in as a wave, you know, kind of did some repair things that senescent cells tend to call the immune system.
into the tissue. And then, you know, once they’ve done their job, they’re cleaned up by the immune system. And what happens if you were to say, now look at [00:07:00] an old animal that did an intense amount of exercise, there’d be an explosion of senescent cells. So they would make way, way more. And then if you looked a week, two weeks, a month later, they would still be lingering.
In the tissue. And so that’s the key idea with aging isn’t that senescent cells, you know, writ large or are bad. It’s that they linger and that lingering process occurs because they resist falling off the plant, so to speak, quite the
resisting.
Jacqueline: What’s the, what’s considered the age cutoff for that? So I’m 29.
Dr. Kelly: Yeah. Um, so there’s no wrong with. Uh, like the field of senescent cells and cellular senescence is fairly old, but senescent cells are really hard to measure. So to do them adequately, it’s not like you could look at a marker in the blood, like, you know, cholesterol for risk for heart disease, as an example.
For senescent cells, some first, a scientist really needs to know what they’re [00:08:00] looking at, and then they’ll take tissue biopsies and there’s several different markers they’ll check. to verify that it’s a senescent cell. So because that studying senescent cells is one, it’s hard and two, it used to be thought that there was nothing that could be done about senescent cells.
And so we’ll get a little bit more into what you can do a little bit later. But because of that, there wasn’t a lot of research until I would say about 2015, the field’s really taken off in terms of the amount of research. So, um, getting back to your, your answer, like what age, the main thing we would know is that over time, whether they’re, you know, Animals being researched to advance the field or humans.
We accumulate more, but we do it unevenly, meaning that some people will accumulate more maybe in their muscle tissue. Other people may be more in their fat tissue. Other people may be more in their joints. Um, and [00:09:00] that, like many things, With our body, it tends to be a tipping point of sorts, right? So allergies is a good example.
Most of us, even if we don’t have allergies, if we were exposed to a whopping dose of, you know, some tree pollen, we would probably experience allergic symptoms, right? On a normal basis, we’re just below our threshold. Where things an issue and senescent cells are thought to be that so, you know 29 year old You probably have relatively few like, you know I’m assuming you would have like an age appropriate amount which would likely be below the threshold to notice them symptom wise in any of your tissues Someone that’s 40 may you know in one tissue We’ll just say joints as an example may now be past the tipping point there, but in every other tissue, maybe they’re they’re below it So they’re starting to have, you know, some joint discomfort, you know, maybe that’s showing up mostly if they exercise a bit more than they’re useful.
Someone that’s my age in their early [00:10:00] 60s likely has, um, you know, like a much bigger burden in multiple tissues, some of which may or may not be.
Beyond that tipping and so the key idea that we use at qualia is to think of a gardener So we’ll go back to our you know, yellowing plant analogy So what would normally happen ideally on a plant is you get a yellow leaf and then it falls off, right?
Like it it’s not getting good nutrition for whatever reason and the the Just naturally get shed, but sometimes that doesn’t happen and so good gardeners, you know, watch their plants and then periodically prune off leaves that aren’t, you know, as healthy as the other ones. And so one of the things that I believe is that.
And we’ll just step back to, like, give, like, the frame of reference. So we all, all would be familiar with the idea of an average person, maybe a man right now lives to 76, a woman to 78, it usually skews a few years higher for women. [00:11:00] So that, that’s, that average is again, a little misleading. I think a more useful thing is how long would someone live on average?
If they make it to age 60 so that would be what’s thought of as life expectancy at 60 And that’s of course higher right because we’re we’ve lost all the younger people that died in you know car crashes and for other reasons And in north america, that’s about 83 years. So, you know some more right? and um And then how much of that time is healthy and what in the newest study, which was about 2019, I think when it was published, it was about one third of that was experienced in really poor health, you know, so disabled and assisted living something along those lines, right?
So the goal is You know first and foremost in medicine, I think is closing that that gap right so that we experience more of Though that life expectancy after 60 is healthy life expectancy and the [00:12:00] way I think about okay Well, how do you do that? And you know having been a practicing naturopath at one point I can assure you It’s a lot harder to to deal with issues after they occur with our health than to prevent them from occurring in the first place.
So long story short, the way I think about it is if I want to have a different result than my dad or my mom or their parents, I have to do more things earlier than they had done. Um, and often quite different things, right? They didn’t know many of the things that you and I would know and that your audience and our listeners today would know So the the goal would be for someone say your age 29 is maybe oh like senescent cells aren’t a problem But long before they start to become a problem Maybe I want to start to be a good gardener and prune them away if that makes sense.
Jacqueline: Yeah. No, absolutely. I want to get into how we actually prune them away. But before that, one thing that came to mind that I’m really curious of your thoughts on, I’m sure you’ve heard of true diagnostic,
Dr. Kelly: Yeah. Yeah.
Jacqueline: right? So [00:13:00] what are your thoughts on that? They’re one of their, their test. It’s like, it basically tells you the rate at which your internal organs are aging.
I’m curious, does that take into account? Like senescent cells. I know you said there’s no way to actually measure them aside from doing a tissue biopsy, but from that one small, you know, drop of blood that we give for that test, are you, I mean, I’m just curious, are there any like mechanisms that, you know, in which like senescent cells play a role into determining that?
Quote unquote true biological age.
Dr. Kelly: Yeah. So, um, so the person that my contact at true diagnostics is Ryan Smith. He was one of the founders of it. And so I’ve known him since, you know, um, 2019, probably like a good chunk of time. And, um, so early on when qualia was developing our analytic product, I wanted a way that we could maybe. to see like, all right, is this making people healthier?
So I got him on the phone. I’m like, Oh, like do any of your tests, would these work? And [00:14:00] he’s like, no, they don’t. And, um, and, and at the time what they were doing is some of the, their team and some of the people, they know some like some functional medicine MDs were taking some of the, um, Cnalytics and measuring before and after, and they just weren’t seeing a pattern and they eventually did a bigger study and wrote it up.
I think it was published around August of 2023, but there’s there’s a variety of reasons they don’t. But one is think of what those tests are measuring is DNA methylation. Fundamentally, that’s what it’s called unhealthy cells and senescent cells are just their own category of cells. So what’s happening on them isn’t necessarily translatable.
To what those tests are measured. So, um, so, so far those tests aren’t, um, particularly useful for assessing senescent load now they’re picking up something
clearly, and, you know, my guess would be given enough [00:15:00] time, maybe you’d start to see something showing up on the DNA methylation patterns in healthier cells, but over like a six month period.
Um, which I think was their initial trial period. There was, there was nothing. And the origin, originator of those, um, they’re called aging clocks, but, and the, the pace of aging would be a third generation clock compared to one that would have given, you You or prediction of your biological age would be a first or second generation And horvath was the the founder of the original algorithms and idea and I want to say around 2020 he had even written that they these things just aren’t the same that senescent cells and dna methylation wouldn’t be expected to You know be a useful measure so that’s Still an issue in the field of cellular senescence is figuring out a way to measure them less directly than a biopsy because most of us don’t want to sign up for that.[00:16:00]
Jacqueline: right, yeah, it’s, it’s fascinating all of the, the testing that’s coming out. I had Dr. Matthew Dawson on the show not too long ago, uh, founder of Wild Health. I’m sure you’re familiar with him as well. And he’s doing some really cool things with AI. Um, so it’s, it’s really exciting to even just see what the next 10 or 20 years will hold, uh, in terms of, of testing.
Dr. Kelly: Yeah, I, I, um, spoke to him recently as well, really, and he’s, I think he’s currently acting as a chief medical officer
for true diagnostics.
Jacqueline: Yep. Yep. Very cool. Awesome. Well, going back to, to the main, uh, meat of the conversation, Dr. Kelly, so what can we do to quote unquote prune our garden and, and get rid of these, uh, senescent cells?
Dr. Kelly: Yeah, so the, um. Like one of the huge advances in cellular senescence in that field was around 2009 or 2010 where they did what’s called a transgene, but just, I’m oversimplifying it, but just think of they genetically modified these animals so that their system would get rid of senescent cells instead [00:17:00] of them lingering and dying.
Accumulating over time and what they saw in these animals was that they lived longer and they were way healthier So, you know glowing fur leaner bodies less joint issues, you name it And you know, so again, we can’t do that experiment on humans, right? We can’t genetically modify us, but at the time that really Caught some scientists.
I because all of a sudden it was like, Oh, these might be even more important than we thought, because if we manage them better as we age, good things seem to happen. And so in 2015, some scientists from Mayo Clinic And Scripps Institute of Aging, which, um, there’s a Scripps here in San Diego where I live, but the that Institute of Aging one is on the east coast in Florida.
Um, they got together and thought okay. Well What are these zombie cells these senescent cells doing? To resist apoptosis just from a mechanism perspective like what what pathways and other things [00:18:00] are they using? And they started figuring that out. They call those um scap networks. So s c a p for listeners Which stands for senescent cell anti apoptotic pathways, but just think simply like the Scientist figured out.
Okay. This is how the There’s staying glued to the plant and not falling off. And then they scanned their long list of compounds that had had some science on them about that mechanism. So things that were active on those pathways. And at the end of that result, then they just, this was only a test tube.
They then took some of the compounds that look like they should overcome those mechanisms and apply them to senescent cells and two of them at the time would then cause the senescent cells to finally What I would say recapitulate that journey to apoptosis, right? Like get out of this stuck place and finally go through this falling off [00:19:00] process.
They should have gone through and Those compounds were the satinib which is an immunomodulator Often used in some very specific types of cancer. That’s it’s out there Um, and quercetin, which is a bioflavonoid or flavonoid compound polyphenol that’s, um, concentrates in the skin of onions as one example, right?
And what they found in that study, um, was then, okay, well, these look promising in a cell culture, but let’s now give these an example. to animals and see what happens in the older animals. And what they found was that the satinib as an example was um, active in some tissues. So fat tissue was one to help prune away senescent cells, but not as active in others.
And quercetin was active like in endothelial, which is the cells that line our arteries. As an example, um, but not active in fat tissue. So then they thought, Oh, cool. Okay, cool. Maybe we should just give these together, stack them and see what happens. And lo and behold, [00:20:00] the two together work better than either on their own.
And at that point, they’re like, okay, we need to come up with a name. For these things that, you know, helps in essence cells finally, um, normalize and, and complete their journey. And we’ll just call these senolytics. And so in that paper, they launched that term senolytic. And so a senolytic would be something in a strict definition that would be, um, used to get us an essence cell unstuck and to finally complete that journey.
And, um, and since then, the field has extensively looked at that combination of dasatinib and quercetin. There’s more papers on that than probably, you know, all the rest of the senolytic compounds put together. But other scientists have also looked to see, well, okay, if quercetin did it, maybe there’s other things in plants that are also senolytic.
Um, and so that’s, that, The the what do you do a part of that? What do you do would be doing things that are called senolytics?[00:21:00]
Jacqueline: Very cool. So what is, what is qualia? What, what are the, the main compounds in the qualia senolytic? Okay.
Dr. Kelly: Yeah, so um qualia is our brand. Um, and qualia senolytic is our our stack of compounds and and the reason stacking Becomes important I think is that original mayo concept or mayo finding that something could be senolytic But that doesn’t mean it’s it’s not Going to get rid of senescent cells in all tissues that um, and stepping back.
I mentioned that senescent cells, you know Um can be thought of as something that are caused by stress of all types So what it looks like is different stressors can cause Slightly different varieties of a senescent cell. So for listeners think of senescent cells as a category Within that of things that I’ll share the same, um, basic, um, you know, like you’d be able to find [00:22:00] them if you know what you’re looking for.
But if, um, if say UV light cause senescent cells in your skin and something else cause senescent cells in your fat tissue, the same signal, you know, that a compound may not equally work. on both of them. Um, senescent cells and joints may be a little different than the ones in fat tissue. So what qualia senolytic is, is we put together nine different senolytic compounds, some of which have been studied.
And again, for listeners, almost all of this research is still in animals. The, the human studies are just starting to be published or are in there like, um, to execution phase, but, um, for mechanisms, you know, what science invariably has to use is starting in, you know, in vitro, in cell cultures and then in animals.
And so, um, as an example, Fisetin was the next big senolytic compound that those same Mayo and Scripps, [00:23:00] researchers um published about and what they did was this was a couple years, you know after the 2015 paper they said okay. Well, of course it didn’t work Let’s you know gather some other polyphenol compounds from plants and see again in test tube Applying them to senescent cells if any of those work as well And what they found is one that sometimes you’ll hear called thysitin sometimes fisetin but um That one was even stronger than the quercetin They also found one called luteolin, which was more active than quercetin and curcumin which was about the same And curcumin i’m sure a lot of listeners would you know know of or use turmeric or turmeric extracts with curcumin and so um Then with Fisetin, all right, this was the strongest in the test tube.
So step two, let’s give these to animals and, and see what happens. And that [00:24:00] one was actually, again, really active in animals and it was more globally active than quercetin. So like in the, in that study, it, one of the places that was active was in fat tissue where I had mentioned in their original research, quercetin wasn’t.
So, you know, from my perspective, that original insight, right? That stacking. Things together might be useful is, um, my bias, especially with the plant compounds of how we want to approach it. So like Fisetin is good and, you know, maybe more globally, um, as seen a little than quercetin, but quercetin, you know, we know has activity in certain things.
So why not do the two together? And then the kind of the next big advance was, um, and this actually was published before. The study, there’s um, uh, are you beta plant called long pepper? So there’s a really famous it’s called tricot to um, but like it’s a blend tree like tricycle for [00:25:00] three of three. What are called the three?
Um, Spices of the three punching compounds, I guess, would be the more literal translation and it’s black pepper, long pepper and ginger that are used in a lot of our you beta preparations and, um, we don’t use long pepper here, but it would be very similar to black pepper like it’s a pungent thing that’s a spice.
It’s very close relative. Long pepper has something called Piper longamine in it that black pepper doesn’t. And so what it is. This other group of researchers, not Mayo anymore, found was that piperlongamine was also senolytic. And, but it was in a completely different way. So the, the things I mentioned, the quercitins, the fisitins, the luriolin, all work at least in part on a nutrient sensing pathway.
So cells, so our senses for listeners are things like our vision, our hearing, like we’re constantly sampling the environment and deciding how to behave. And so cells are doing the same thing. [00:26:00] They sample the environment through receptors and nutrient sensing pathways, and then determine how to behave. So that’s where, when we say something like calorie restriction or.
Um, MTOR would be something that you, yeah, so MTOR is a, a specific nutrient sensing pathway of protein, right? It’s what it’s, it’s listening for. And so what cells do is they listen to the environment around them. And when it changes, then they change their behavior. And sometimes that behavior will change in ways that will say, Oh, well, you know, the environment’s not looking so great, so I better make sure I prioritize repairing myself so that I’ll make it through this, um, you know, tougher period of time.
And so. the quercitins, the fisitins, they all work on a specific nutrient sensing pathway in part. And piperlongamine works in a completely different part of the cell. And so like one of the ways I think about it and at QALY we think about it is we want to be redundant in how we approach an issue and support it [00:27:00] from multiple angles.
And so, you know, piperlongamine starts to make sense. So, so that’s when we approached making QALY senolytic, that’s how we approached it. Let’s find You know, a variety of these compounds that in at least the existing studies have been active in different tissues, ones that, you know, have redundancy in terms of, you know, a pathway, but also redundancy in terms
of, you know, non shared mechanisms.
Jacqueline: So fascinating. For someone with no medical background, I would have loved to sit in on those discussions in terms of figuring out what compounds to include, uh, in qualius analytics, but so, so fascinating. Um, my other question for you, Dr. Kelly, is what compound targets senescent cells in the brain?
And would you say that the brain tissue is perhaps like, I don’t know, of all the organs of all, of all the places in the body where senescent cells. accumulate, like, what would you consider to be the most dangerous, let’s say?
Dr. Kelly: Yeah. So those are good questions. So, um, [00:28:00] so in the brain, there’s different types of cells. So neurons would be, you know, like the archetype of what we think of as a brain cell. Um, but then there’s all kinds of supporting cells. So the brain has its own immune system. Those are called microglia. Um, it has structural cells, which are other types of glial cells.
And, um, Yeah. It was originally thought when, when the field of senescence cells was, was younger, that the only cells that could become senescence were cells that could create offspring cells, you know, so whether you call them like clones or daughter cells, like our cells can divide, right? And so the, the same genes would then be passed into the, that those.
Those lineages of cells and so, um, cells that can’t divide. So stepping back, one of the reasons early on that it was believed that we, we had this senescence software program was that we don’t want a [00:29:00] damaged cell to make copies of itself and then, you know, have that damage ripple. Through time and that cellular senescence was an anti cancer functioned fundamentally, right?
Because, um, and that if a cell wasn’t ever going to divide like a neuron, I mentioned earlier that the neurons that we have never make copies of themselves, right? We want to make sure we the goal with those is to keep them, um, repaired, right? Or low stressed in the first place. But now in the last say seven or eight years like scientists have found that even a neuron can become senescent which that that wasn’t even thought as possible at one point in science.
Um,
yeah,
Jacqueline: one of the primary leaders, uh, or contributors to dementia?
Dr. Kelly: it would be more, so I haven’t mentioned it, but we, you’ve touched on zombie cell a few times. So the reason that sometimes you’ll hear senescent cells [00:30:00] referred to as zombie cells is in part because this being stuck right there, they’re not quote, quote alive, right? They can’t make. You know, offspring cells anymore, but they haven’t gone through apoptosis.
So they’re not. They haven’t gone through cellular death that there’s somewhere in the middle like a zombie would be
Jacqueline: So could they be, could they be reactivated though? Like once they’re in that zombie state?
Dr. Kelly: you mean turned back into like a healthy cell
Jacqueline: No, no, like, like more of like an active, like,
Dr. Kelly: where they’re metabolically active, right? They’re still using resources and they’re actually using a lot of resources And the reason is the other part of the zombie story So senescent cells will secrete into the microenvironment surrounding them a variety of compounds and You These are things called chemokines and cytokines.
But just think of the word inflammation. That, that they’re things that in a, a young person would call the immune system in after say, you know, like a lot of [00:31:00] exercise to clean up, you know, and help repair. Um, but in the lingering ones, it’s, it’s contributes to what is called inflammation, right? That chronic low grade that happens.
So the Net result of them secreting these things to you know in around themselves and impacting other cells is That they can stress out other cells and cause them to become senescent, right? So that’s the other piece of the zombie analogy and that’s a big reason that they’re so significant as we age because they contribute to both inflammation locally and In their environment, but then systemically throughout our body.
So getting back to your question, it’s the other ones like, so neurons can become senescent, but unlikely to be the main issue, right? Just because they’re, they’re not designed to. Replicate, right? So there they would have to be a lot bigger stress for them to become senescent [00:32:00] But all the other things in the brain that are the supporting cells for neurons can’t right?
So the microglia and inflammation contributes to Bad things where wherever it is if it’s if it’s um a chronic inflammation so, you know, whether it’s like like a mood issue, um anxiety or depression as an example or a Uh You know, an issue with the brain and aging like a dementia that inflammation is always, um, at least a piece of that.
Jacqueline: Right. Very interesting. So beyond stacking compounds, uh, for qualius analytic, what are some lifestyle interventions that listeners can stack, uh, perhaps in conjunction with taking qualius analytic? So you mentioned caloric restriction before. Um, I actually had someone yesterday on the show to discuss intermittent fasting, but I mean, I’m assuming exercise and, and also to Dr.
Kelly, I mean, you know, you’ve mentioned stress a lot as [00:33:00] a, as a cause for senescence, but I’ve also heard of the term hormetic stress, right? And things like hormetic stressors, like saunas, for example, that, you know, might actually help like promote autophagy through, you know, heat shock proteins and, you know, how that could also like clear out damaged cellular components.
So what are your thoughts on those? Absolutely.
Dr. Kelly: Yeah. So, um, so exercise will start there if that’s okay. So, um, exercise has been studied to see what it does for senescent cells. And, you know, going back, I mentioned that, you know, in a young animal post, you know, some intense exercise, especially if they’re not used to it. Okay. Okay. They’ll make senescent cells.
They’re transient. They call the immune system and they help repair and then the senescent cells are, um, cleaned out and that older animals make a lot more and that they tend to linger, right? So that, that there’s that connection to exercise. Um, but what’s also true is that, you know, when they’ve looked at [00:34:00] what would be more exercise as a lifestyle habit.
That that actually would mitigate the buildup of senescent cells. So it won’t completely make it. So we don’t get any, but they’ll develop slow slower. So, you know, an older animal and older human doing, you know, appropriate exercise is going to have at least in their muscle tissues, fewer, because that’s where they’ve looked.
Right. Um, but that doesn’t mean maybe in their joints or somewhere else that exercise prevented or mitigated that buildup. That. May, but science hasn’t looked at that. And my guess is that it may a little bit, but it wouldn’t completely offset it. So if it did, then one of the things you would see classically is that people that, you know, use their joints a lot in their exercise, um, their joints have a degree of soreness and don’t bounce back as well, even by often their forties or fifties compared to when they were younger.
Right. So, so my guess is that, that exercise is really [00:35:00] useful for slowing the buildup in muscle, but maybe not as much for other tissues, but net like a huge positive. Um, I started the conversation saying something along the lines is, you know, there’s a range of doors that a stress cell can walk through, right?
So, you know, door number one is, and this gets into your idea of hermetic, right? Like, all right, well, the right amount of stress, which is going to be a low amount. And assuming a cell has the resources to respond appropriately, The cell will become more resilient, right? It’ll be a hormetic thing, right? So we want that, right?
We want ourselves to be more resilient, tougher, right? Because, um, just like us, they get stressed and they don’t always expect it. And so if they’re tougher, they’ll, you know, more of them will then stay healthy cells and that, you know, a bigger amount of stress or stress that a cell might be unprepared for.
then some damage will occur, right? So that’s, you know, the goal then is to do things to clean up that [00:36:00] damage. So that’s where autophagy comes in and it any, you know, any of the things that we know now help with autophagy. I would default to thinking of those things as things that would prevent a cell from becoming senescent.
You know, so that you’re, you know, maybe saunas, maybe your periodic, like a fasting mimicking diet or, you know, these other things, um, calorie restriction, you know, works maybe more on nutrient sensing pathways, but then, you know, what often happens when a cell senses the environment is going to be more challenging as they prioritize surviving and repair over, you know, growth and other things, right?
So they, they hunker down and, um, and make it. So, um, my Guess would be as science does more studies on some of these diet and lifestyle things that you know The biohacker community or functional medicine or the longevity community know how? Organisms live longer healthier lives [00:37:00] will find that there’s a connection to
senescent cells If that, I don’t know if that answers your question,
but,
Jacqueline: no. No, it does.
Dr. Kelly: and conversely, you know, we know, like when I said stress, you know, the original, if you were trying to stress cells in a cell culture, you would deprive them of nutrients or, you know, bombard them with radiation or expose them to UV or, you know, make the environment harsh in some way.
And we know that causes more cells to become senescent. And so, you know, when we, when I said, you know, Stress to certain amounts can cause that. Think of, you know, all of those types of physiological stressors to cells. But then, you know, my intuition would be that stress large, like the mental, emotional, financial, caregiver, like this
whole,
Jacqueline: chronic daily stress
Dr. Kelly: yeah, it’s Is going to likely be found just like that’s been linked to shortening of telomeres I think we’ll [00:38:00] eventually find that that’s linked to premature buildup and um, like as an example You know, you have a lot of passion and knowledge about cancer and so, you know cancer Cells aren’t senescent cells completely different thing, but they would have in common that they’re stressed cells, right?
Um, the senescent cells, you know, they’re, they’ve been, you know, like zombified so that they can’t make new copies and, you know, grow and multiply and multiply cancer is the opposite, right? Like the, it’s a very different outcome, but the thing they would have in common is they’re both not going through apoptosis, right?
And so, um, you know, what a lot of the medical, right? Approach to cancer has been over time is to do something that creates a lot of stress That finally gets them like so stressed that they have no other choice but to go through apoptosis So, you know, that’s your radiation or some [00:39:00] chemotherapeutic drugs So, you know what science is starting to look at is okay These these things were really big stressors what happens to previously healthy cells
and what would be your guess?
Jacqueline: Looking at like patients who go through chemotherapy radiation who perhaps might be older and again, like their immune defenses aren’t as strong. I’m assuming they’re going to go on to develop more senescent cells
from those therapies. Yeah. So, um, yeah. So that’s something that science is now, um, starting to pay attention to that. Um, because we did this thing, you know, to get a good result, something we needed. But one of the downsides is that previously healthy cells, more of them became senescent. Um, and so, you know, what’s starting to, uh, or what I’m starting to see on, you know, studies in PubMed, the medical databases, you know, thoughts of like, Oh, maybe we should do a two step approach.
Dr. Kelly: And, you know, at some period after chemo or radiation or whatever that therapy period has ceased, then we do [00:40:00] something to help get rid of the senescent cells we created as
part of that. Yeah, exactly. So, so interesting. Well, I mean, it’s encouraging to know that we can get rid of senescent cells, right? This is not something that, you know, someone has to be afraid of that, oh, they’re going to have this indefinitely. Um, and there certainly are, as we touched on lifestyle interventions as well.
Jacqueline: Um, going to nutrition and, and diet, Dr. Kelly’s, this is an area where I know many folks have very strong opinions. Has there been any research on the optimal diet? Um, from a, a standpoint of limiting senescent cells in the body.
Dr. Kelly: There’s nothing to do, the only things I’ve seen is connections to calorie restriction. That tends to, just because that has such a strong, um, history. Of being connected to, um, slowing aging, um, but my, you know, my guess would be that, you know, as the essence cells become easier to measure, cause I’m, I’m at least optimistic that at some point there’ll be [00:41:00] some non biopsy way figured out to get a better sense of their, um, the body burden or tissue burden of senescent cells, then those types of studies become more possible.
But, you know, like as an example, stepping back. If we just say, all right, like, um Like brain health like, you know, what diets are most strongly either correlated with or impact brain health As a you know cause and effect as we get older and then that menu starts to you know So Mediterranean diet will have been one of the more well studied ones from a brain aging perspective you know with people that Already have a um, you know, like have lost some cognitive function keto diets become more important, um, you know for What I would think of as you know a healthy Functioning brain so someone’s you know Irrespective of age You know, they’re not having memory issues.
They’re [00:42:00] able to have good focus. Keto is probably not going to matter. They’re, they’re the brain, a big part of, you know, when we think of, okay, what do we need for the brain to perform at its best? And this oversimplifies it, but you know, we need to protect our neurons and other things, right? So, you know, protective things, but then it’s about energy.
So the brain is, um, a voracious consumer of energy. Of energy. We have basically, you know, the, uh, hungry brain for energy and the main energy sources is glucose, right? Like a component of sugar. Um, and then, you know, as a backup ketones, you know, fat, things like that can be burned. But what often happens is that some people genetically aren’t as good.
At burning glucose, maybe at a young age, they start to have, you know, issues, more issues with, you know, mood issues or, um, other things. And often then keto will make a big difference in how [00:43:00] their brain performs. They just didn’t get the, you know, the software package, so to speak, that allowed them to, you know, Be as good burning glucose or sugar other people not so much.
And then, you know, diet like the Mediterranean diet is going to have good oils, lots of antioxidants and protective compounds. Um, so that’s a, you know, a good default one, but one that won’t work for everyone. So, you know, the, the. Key thing, um, you know, this goes back to when I was a naturopathic student, I had a few different, um, naturopathic professors that taught our nutrition classes at the time.
And, um, one of the things that I remember, like really sunk in at the time, because at the time I was vegetarian. So if you’d asked me this question then I said, Oh, everyone should be a vegetarian. But he said, you know, like I’ve done a whole bunch of diets. And when I do them, I do them hardcore. And I’ve worked with a lot of patients and diet is the main, you know, my main thing that I focus on.[00:44:00]
And the one thing I’ve learned over all these years, and this is him speaking and me paraphrasing, is that there can be a big difference between a diet that takes someone that’s unhealthy and moves them to healthy and then the diet that keeps them healthy. So, you know, don’t be as dogmatic, be more flexible and pay attention to, is this really working for you?
Right. So that would be the key thing for listeners is experiment, but don’t get attached to this way is the right way. It’s, it could be, it’s the right way for today, but maybe not going to be as useful come December of this
Jacqueline: Right. spring of next year.
Yeah. No, I couldn’t agree more. I mean, and that’s another reason, too, Dr. Kelly, why I really like, um, like, wild health testing, for example, is because it also gives you the DNA component where, like, I, for example, found out I’m sensitive to saturated fats. And I found that reducing my red meat intake has actually helped me feel better.
Um, but had I not known that little bit of information, I may not have been, you know, inclined to change my diet. [00:45:00] So I think there is certainly are, you know, helpful information bits about our, ourselves and our makeup that, you know, can inform some of the lifestyle choices we make.
Dr. Kelly: Yeah. And you know, so it’s always important to. Pay attention to us, right? We’re all biochemically somewhat unique. Um, you know, a good heuristic often is, you know, what did my ancestors thrive on? Because, you know, at least got them to reproduce, you know, to the point of me. So my, I, I, we were talking, I grew up in the Boston area.
Both of my parents have, you know, like all of our ancestors on both sides came from Ireland, right? So, um, You know, so I feel well and metabolize potatoes really well, but I had at least, you know, generations of my ancestors that were subsistence farmers that had, uh, figured out and live on potatoes and probably, you know, the genes of the people that most suited for that eventually made their way to me.
But, you know, someone [00:46:00] that’s, you know, ancestry maybe is Japan, maybe not, right? Um, someone, you know, and then like You know, I mentioned our health status can make a big difference. There’s, you know, um, you know, like I have a naturopathic Friend that does the breadness and protocol and is, you know worked Specifically with dementia patients and you know in her work.
She would say okay keto is almost Every single thing I can do, keto may be the most important to get their brains just back, you know, really thinking well
again. And so it’s just going to vary. Maybe, you know, one of those people was Irish and would have done great on potatoes 30 years ago and not on the menu anymore.
Jacqueline: we all change right now. I love that. I couldn’t agree more. Um, we’re coming up on time. But one other question I had for you, Dr Kelly. So aside from some of these compounds like chrysanthemum and whatnot, are there any drugs being studied right now when it comes to [00:47:00] looking at reducing senescent cells?
So, for example, I initially first heard of rapamycin as an anti cancer agent. In fact, my mom was on a protocol of that along with metformin. She was doing some repurposed drugs for cancer. And then I started to do more research on it and I heard that it actually has a lot of incredible anti aging benefits as well.
Um, again, when given in small doses. So what are your thoughts on, on rapamycin? Um, and
its correlation to senescent cells.
Dr. Kelly: so within like, think of there’s a category called seno therapeutics, right? Like things that would help manage senescent cells. One of them, the, the doors is senolytics. And senolytics are things specifically that then help the cells go through that, you know, apoptosis process. And senolytics are things that are typically given in a hit and run manner.
Meaning you would take them for a couple days and then you’d be at some window that you don’t take them. So it’s an intermittent process. strategy. Then there’s other things that are thought of as xenomorphics. So what those tend to do would be [00:48:00] they dampen down that inflammation that the senescent cells are sending out.
So they’re at least mitigating the zombie. Impact of creating new ones. Um, and then there’s the immune system. So things that support the immune system, if the immune system is, you know, rejuvenated in a sense, it will do a better job finding the lingering cells. So rapamycin fits somewhere between that immune and the seno morphic, that, that managing inflammation thing.
So, um, and it works like nutrient sensing mTOR specifically is thought to be its main mechanism. But, um, It’s one, if not the only compound that so when scientists study, um, lifespan extension, they’ll usually start in yeast. Then they’ll move to like, you know, flies and worms. And eventually they move to mice and maybe even then eventually to primates.
Um, you know, humans, we have, it’s just too long a study. [00:49:00] So rapamycin is, I think, If not the only, one of the only, that’s actually shown lifespan and extension in all of those organisms. So, presumably that means it’s doing it on something that’s a conserved pathway. Something that we would all share that evolutionarily, it’s ancient.
You know, so rapamycin because of that is maybe the most used, you know, compound in the longevity category by people that are doing their own self experiments and are
comfortable doing things in advance of science saying, yeah, this works in humans.
Jacqueline: Yeah. So, so interesting. Yeah. I’m definitely looking forward to keeping abreast on that research. Um, and one other thing too, Dr. Kelly, you mentioned intermittent dosing. So with qualia senolytic, how often does one take it? Is that something that’s supposed to be taken indefinitely? How does that work?
Dr. Kelly: Yeah. So the. The original work on senolytics by the Mayo and Scripps researchers gave the, it [00:50:00] was dasatinib and quercetin, that original study I mentioned, they gave it intermittently. So they would give it for a couple days and then take, um, you know, uh, say a week off or two weeks off. And so the reason they did that was twofold.
One, um, dasatinib is a really, Powerful immune potentially suppressor agents. So they thought, okay, well, Let’s give this instead of every day intermittently to maybe get Some of the upside and prevent some of the downside Um, and so that was just kind of baked in from the beginning was this idea of hidden or hit and run dosing Intermittent use and so even with the natural compounds like vicetin then this that’s been integrated in let’s do a really large amount of this compound and But just do it for a couple of days and then take a vacation from it and then we’ll repeat.
And so that vacation from it, that intermittent window varies in studies from, you know, maybe it’s seven days, maybe it’s a couple of weeks, maybe it’s a [00:51:00] month. And so that’s what we do with quality of scenolytic as well. So me personally, I take quality of scenolytic the first weekend every month. I take, you know, one dose on Saturday, one on Sunday, and then I don’t, Think about it again until the next beginning of the month rolls around in our studies today We’ve tended to bring people in that already have an issue often We we’ve recruited people with joint issues because those are something that we know senescent cells contribute to and that we can more directly study without having to do lab work.
And in those studies, what you’ve seen is the best response happens when instead of doing it once a month, we do it twice a month. So we take it for a weekend. Don’t take it until, um, not that next weekend, but the following weekend. And then we’ll do that for a few cycles and see if we can get someone’s, um, comfort levels with their joints way better, their flexibility improved.
And the way that I would approach it is once that’s those, [00:52:00] that comfort has improved, then you can maybe slow it down to once a month.
And then in a younger person, if say someone was 35 and having no issues,
but wanted to do senolytics, then it’s like, Oh, well, you know, it’s, you just need to be like a periodic gardener.
So maybe once a quarter, like you would do an
intermittent fast, do senolytics just to prune away the ones so that you make sure you’re, uh,
Staying comfortably below the threshold where they’re causing any issues.
Jacqueline: Right. Very interesting. Well, Dr. Kelly, this has been one of my favorite conversations to date. I just want you to know that, um, you’re such a wealth of information. I, I look forward to having you on again soon because there’s, there’s so much to talk about, but this is certainly an area that I’m, I’m really fascinated with, as you can probably tell.
but with that, where can listeners find you and also learn more about QALYOS analytics?
Dr. Kelly: Yeah, we’re um, qualia life. com It’s q u a l i a life l i f e dot com and instagram is where we’re really prominent, you know, [00:53:00] sharing education and And things so, um, I would say the the best start is, you know, either Following us on Instagram or going to our site. I wrote, um, when we launched qualia senolytic, I wrote a long blog talking about senescent cells and, you know, some of the senolytic compounds and why, as a company, we decided to make the product the way we did.
Um, we also have a studies part of our website. If you’re more inclined that way, you can look at our senolytic study and see what we’ve saw. Um, you know, in
Jacqueline: Wonderful. Awesome. Yeah. I follow qualia as a Instagram account. I absolutely love it. Some really great information on there. So I will be including the link for that, um, and everything you mentioned in the show notes. But my last question for you, and this is my favorite one to ask, and that is, what does being well and strong mean to you?
Dr. Kelly: um, getting to live my, my life, my way for as long as I’m alive. So, um, I, I have always liked the idea of [00:54:00] vagabonding being like a digital nomad of sorts. And, um, so for listeners, I’m 62 now. My, by the time my dad was this age, He’s a big guy, you know, he struggled even to, you know, navigate airports comfortably.
And, you know, I want to still be, you know, flexible to do yoga, able to travel, you know, many, several decades into my future from here. So, um, you know, that’s what it means. So like, I, um, I think, what’s important to you, to me, to other listeners is going to be somewhat different, but, you know, I want as many people to be able to Do what brings them joy and purpose for you know, as many of their years as as we can help them get to
Jacqueline: Love that. Amen. Couldn’t agree more. Well, Dr. Kelly, thank you so much for your time. Um, really looking forward to sharing this with listeners and, yeah, I hope to have you on again at some point soon.
Dr. Kelly: Yeah, I would love that. Maybe we could talk about the brain in the
future
Jacqueline: So many, so many, topics.
