Episode 280: The Science of Aging & Cellular Senescence with Gregory Kelly, ND
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In today’s episode, Erin invites Gregory Kelly, the Director of Product Development at Neurohacker Collective, onto the podcast to deep dive into the science behind aging. Throughout their conversation, Gregory simplifies the complex process of cellular senescence, and offers his expert insight on what we can do to support our healthiest selves as we get older. After listening to the discussion, you’ll understand how aging occurs, certain compounds to support our body’s natural elimination of senescent cells, and what you can do now to support your mind and body as you age.
Gregory Kelly is Director of Product Development at Neurohacker Collective, naturopathic physician (N.D.), and author of the book Shape Shift. His areas of expertise include cellular senescence, nootropics, anti-aging and regenerative medicine, weight management, sleep and the chronobiology of performance and health.
In this episode:
The 12 Hallmarks of Aging [5:04]
Autophagy: what it is & why aging cells aren’t inherently good or bad [11:04]
How the dosage of senolytics impacts the immune system [21:11]
Signals that show your body is affected by senescent cells [27:45]
Research-backed compounds to support our body’s natural elimination of senescent or "zombie" cells [35:06]
Actions to take for a healthy life as you age [41:27]
Resources mentioned:
Qualia Senolytic (get up to 50% off and an extra 15% off your first purchase with link + code FUNKS)
LMNT Electrolyte Replenishing powder (Use code FUNK get a free sample pack with any purchase)
Ned Natural Remedies (get 15% off your order with code FUNK)
Kion Aminos (Get 20% off monthly orders and 10% off one time orders)
Learn more about Immune Support and Metabolic Health
Related episodes:
265: Muscle Mass, Nutrition, & Training for Longevity with Liz Wolfe
266: Protein Intake & Building Muscle Mass
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Erin Holt [00:00:02]:
I'm Erin Holt, and this is the Functional Nutrition Podcast, where we lean into intuitive functional medicine. We look at how diet, our environment, our emotions, and our beliefs all affect our physical health. This podcast is your full bodied, well rounded resource. I've got over a decade of clinical experience, and because of that, I've got a major bone to pick. With diet, culture, and the conventional healthcare model, they're both failing so many of us. But functional medicine isn't the panacea that it's made out to be either. We've got some work to do, and that's why creating a new model is my life's work. I believe in the ripple effect, so I founded the Functional Nutrition Academy, a school in mentorship for practitioners who want to do the same. This show is for you. If you're looking for new ways of thinking about your health and you're ready to be an active participant in your own healing, you'll get things here that you won't get other places. Please keep in mind this podcast is created for educational purposes only and should never be used as a replacement for medical diagnosis or treatment. I would love for you to follow the show rate review and share, because you never know whose life you might change and, of course, keep coming back for more. Now give me the mic so I can take it away. Hello, friends. We're back with kind of a deep dive episode today. Pardon my stuffy nose. I am on the tail end of COVID which, by the way, you want to piss people off, say the C word on Instagram, then stay out of your DMs for the next 48 hours. Anyway, I digress so many of you know, if you listen to the show or follow me on Instagram, do that, by the way, that I've been taking Neurohacker Qualia Mind for a while, and I love it. It really gives my brain, like, the boosty boost that I need to run this whole company. When I partnered with the company, they also sent me Senolytic, which is their product for optimized aging. And at first, I was a little bit nervous to take the product as I'll explain why in the show, and I wanted to learn a lot more, so I'll kind of try anything once or twice, so I started taking it. But I really wanted to understand the whys behind it. I always like to kind of self experiment, and before I bring anything to the show or talk about it on a larger platform, I want to make sure that this is something that I really enjoy and like myself. And we had been planning a meeting with the team over at Neurohacker Collective so that I could ask more questions and learn more about the whys behind this product. And then I thought, well, it's kind of silly to do that behind closed doors, because you guys, my audience, love to learn about health as well, and so that's exactly what today's show is. I have Gregory Kelly on. He is the director of product development at Neurohacker. He does a lot of education. He's super smart guy, as you'll hear. He's a naturopathic physician, and he's the author of the book Shapeshift. His areas of expertise include cellular senescence, which you're going to learn all about today, neurotropics, antiaging and regenerative medicine. And that's exactly what we're getting into today. I will say it's a more dense episode, but that's just because that's the nature of the topic. So I hope you learn a lot and enjoy. And after listening to the show, if you're interested in trying Senolytic, especially if you're in your late 20s or older, you can try it out by going to neurohacker.com Funks to save up to 50% off Qualias analytic. And as a listener of the Funk'tional Nutrition podcast, you can use Senolytic Code FUNKS at checkout for an extra 15% off of your first purchase. So that's neurohacker.com/funks to try Qualias Senolytic with Code FUNKS F-U-N-K-S. I've been taking it and trying it out, and I think you'll understand why after today's episode. Okay, welcome to the show, Greg. I'm very excited to have you here.
Gregory Kelly [00:03:58]:
Well, thanks for having me today. This should be a fun episode. I'm looking forward to it.
Erin Holt [00:04:03]:
It will be fun. It will be very informative. I always get super excited when I have somebody come on, and I feel like I'm in class a little bit, like I get to learn as much as the audience is learning. So I always love these, and I just want to preframe everything because I was taking or I have been taking Qualia Mind and really loved the product and reached out to the company to talk about a partnership because I just was so impressed and was seeing such great results myself. And you guys sent me Qualia's Senolytic as well, and I was like, well, what the heck is this? And I tried to do some of my own research, and I was like, I still don't have a firm grasp of what we're doing here. And so I wanted to speak with somebody on your team to learn more about it. But then I thought that's a little bit silly to have a private backdoor conversation when everybody who's listening could learn so much as well. So that's kind of my hope, and my intention is to learn about aging. Hopefully we can talk about some of the gray hairs that are coming in on my head right now, why that is, what I could do about it, and also just learn a little bit more about this particular product, because there really isn't much from my understanding, there's not much on the market like it. And I want to know the whys behind that.
Gregory Kelly [00:05:26]:
Sure. So I think I always like to start kind of at the helicopter level for a topic like aging and the helicopter level that we usually tap into is called the hallmarks of aging. So it's not something we created, but scientists got together in 2013 and proposed that all organisms, whether it's flies, worms, mice, primates, all the way up to humans, all share certain characteristics as we age. And originally they said, okay, there's these nine things that are shared in common, and one of those is something called senescent cells, or cellular senescence. And this past January, so 2023, they updated that list and added three more. So they added gut dysbiosis, they added chronic inflammation, and they added autophagy to it. So now there's these twelve hallmarks of aging. But the cellular senescence is the one that Qualia Senolytic was designed specifically to support. And what cellular senescence means, and I think maybe one way to think about it is we're us, right? I'm 61 now, and I would say, oh, I have this continuum. But my cells have been turning over all the time, or at least most of them. Cells are born, live their life, and then pass away, but they do it at different speeds. So in our blood cells, it's every couple of months. As an example, our liver, they live for about one to three years. Muscle tissues are pretty long lived cells, like seven years, heart's crazy long lived, like 40 years. And our neurons in our brain, they're designed to last a lifetime. So cells are constantly living their lives. And just like us, cells are exposed to stress. So when cells are exposed to stress, they really depending on the nature and the amount of stress. They do a couple of different things. A low level of stress are like, oh, I got this, I'm going to adapt to this, right? So maybe they increase their antioxidant defenses or do other things to kind of toughen themselves up. If stress is more than that, then they'll probably take some damage. So that's where something like autophagy comes in. An autophagy is a cellular program meant to clean up. It's a maintenance program. So it cleans up, it finds these kind of gunked up proteins and then recycles them so those individual parts can be put back to better use. And if stress is even more than that so now like, all right, there's damage, but there's too much damage probably to fix this cell. Then they put this programming called cellular senescence. And what that does is the cell is still alive, but it prevents the cell from making new copies of itself. So the metaphor you'll often hear in a news article, if they mention it, they'll often say zombie cells, because they're these midway between, they're not fully alive, right? They don't make new copies, but they haven't died off. They're just kind of stuck in this in between zone. And so senescent cells have been known about for decades and decades. And at one point in the 70s, it was thought, oh, these probably have something to do with aging. Right. And what really happened is the knowledge starting around 2010 exploded. And since then there's just a huge amount of research, but pretty much every issue that we think of with aging, right. Like you had mentioned, gray hair, but our skin becoming less youthful looking, right? Our joints not being comfortable, our muscles being more difficult to get, like a good anabolic response, and to maintain muscle tissue. And then metabolic, cognitive, all those issues, senescent cells have been linked to them.
Erin Holt [00:09:25]:
Would all of those be the hallmarks of aging? You said there was twelve. Well, now there's twelve of them.
Gregory Kelly [00:09:30]:
Yeah, the hallmarks would be more the characteristics rather than the issues. So they'd be things like DNA becoming unstable, telomeres becoming too short. I mentioned the gut dysbiosis and inflammation. But there are also things like cells not responding appropriately to the world around them, especially nutrient signaling like insulin, things like that. Internal communication of cells. One of them is called proteostasis, but that's the idea that the proteins inside cells just start to become dysfunctional over age. So they're more like the mechanisms of aging. And all of those happen on a cellular level because fundamentally, our health is built off the health of our cells. So if they're performing at a youthful level, then our function tends to be a lot healthier.
Erin Holt [00:10:24]:
And part of that is the communication between cells.
Gregory Kelly [00:10:28]:
Some of it's the communication, yeah, for sure. Cells are all networked together. So think of the world wide web, right? Our cells are very much like a network system, but even within cells, there is this huge network of mitochondria. As an example, there'll be hundreds to thousands of mitochondria in a cell that are all networked together and working together. So at every level you look, you start to see that what's thought of as complexity, right? Like compliant systems, communicating and communication is a huge part.
Erin Holt [00:11:04]:
That's a beautiful thing when you think about it. I want to go back to what you were talking about in terms of cell turnover in stress. So it sounds like a bit of stress is okay and even beneficial in some cases because it helps us adapt, it helps us become stronger, it helps us create some resilience. More than that, you kind of broke it down to like three different segments. So the first one is like a little bit of stress. Not so bad, pretty good. We can get stronger. But then if there's too much stress, that kicks off autophagy. Can you spend a little bit of time explaining, in case listeners aren't familiar with that term or what's going on there, what autophagy is and is it a good thing, is it a bad thing? Do we want a lot of autophagy? Is too much autophagy a bad thing? Talk to us about that.
Gregory Kelly [00:11:50]:
It's a good general rule of thumb is to think of Goldilocks principle, right? Like one bowl is too cold one bowl is too hot, and there's another that's just right. So almost everything is there's just the right amount. And autophagy would be one of those things, but really, everything in physiology tends to be like that. So what autophagy is it's thought of as a cellular maintenance program. So cells just in the course of doing their job. So what will happen is I mentioned mitochondria, right? Those are the workhorses of our cells. They make ATP, the energy currency that our cells rely on to do a lot of their work. So a lot of the proteins that mitochondria uses to do its job aren't made in the mitochondria. They're made outside of it in some other part of the cell. And then they have to be moved into the mitochondria. And mitochondria, like cells, have these lipid layers that the proteins have to move through. And so what science would say is they're folded and unfolded to make that journey, right? So their shape is changed so that they can squeeze through, so to speak. And so what ends up happening over time is proteins get misfolded. And you've heard the tau with dementia, like tau proteins. Tau proteins would be an example of a misfolded protein. So misfolded proteins just happen. And one of the main jobs of autophagy is to find when proteins are damaged. So misfolded or other organelles and organelles are like these bigger things inside cells like the mitochondria, but there's other organelles as well where they're damaged. And what autophagy's job is, is to find those and recycle them so they're damaged. Rather than trying to fix them, let's just recycle those components and put them back to good use so that nothing is wasted. And so autophagy would go on all the time. But what typically happens as we get older is we're like, in the bowl is too cold, right? There's not enough of it. So it's not too much isn't the problem. It's too little. So in general, that's why autophagy ends up one of those hallmarks. It's because it's one of the things that's misfiring as we age. And so many of the things you'll hear some biohackers do, like intermittent fasting, or like a periodic fasting mimicking diet for three to five days, those are designed to basically drop protein low. In a sense, that's like a unifying theme for all these fasting behaviors. And when cells sense that, they're like, oh, there's not enough protein. I better scavenge what I have inside. And the first place they look is the misfolded ones. And then autophagy kicks in to reuse those proteins. So autophagies would be an ongoing thing. And I just think on that continuum of how cells respond to stress, it's after the resilience phase because there's been some damage, but before panic, oh, let's not make new copies of our cell. There's too much damage.
Erin Holt [00:14:52]:
So with the zombie cells, is that like panic? Is that a bad thing? That's not good it doesn't sound like a great thing that we would want to have happening in our body.
Gregory Kelly [00:15:02]:
Yeah, and like most things, senescent cells aren't all good or bad, they're contextual. So if we have any, say, 20, 23 year old people listening to this podcast, you go out and do a marathon, you're going to make some senescent cells, right? Because that was a big stress to your system, no matter how well prepared you were for it. But what will happen in a young person is those senescent cells will come in, they'll actually help with that reparative process initially from that intense exercise. But a week later, they'll have gone through what's called apoptosis. And apoptosis is just a Greek word that means falling off. So think of like leaves falling off a bush or fruit falling off a tree, that type of thing. And so that's the normal thing when I said that cells are born, live, die. Apoptosis is the dying stage that they basically break apart into small pieces. And just like leaves that would fall off a plant, then they're recycled. So some people will ask, oh, like a senescent cells detoxed, and the answer would be no. They'll eventually ideally go through this falling off process and then be reused. Just like leaves falling into soil, their nutrients would be reused for the plants. And so the key thing with senescent cells, as we get older and we'll usually refer to this idea of transient versus lingering senescent cells. So in young people, you see these transient ones, like some cells are made to be senescent and three, five, seven days later they're gone. They've either gone naturally through this falling off process or the immune system has found them and coupled them up. But what happens as we get older is they linger. So what's called in science is they resist apoptosis. So they resist this natural falling off process. And then most people, at least in my world, would know that the immune system tends to underperform as we get older. That's called immune aging or immune senescence. So that contributes as well. The immune system is just less good at finding the stragglers. And so those are two of the reasons that they slowly accumulate. And a visual that we use at Neurohacker. I originally created this because our head of marketing is big into home gardening. So think of like a plant with a yellowing leaf. Like in a young person, they'll make a yellow leaf and it'll quickly fall off the plant, right, and be replaced with a new, vibrant leaf. But in a less healthy plant, that yellow leaf will turn into more yellow leaves, more yellow leaves. And before you know it, you have a plant that's really struggling because 20% of its leaves are yellow. And what yellowing leaves do on a plant is they'll still be using resources. So they're kind of wasting resources that might be better used. They also attract pests, right? From the environment. So they're like a breeding ground for dysfunction, and then they then cause nearby healthy leaves to become yellow because of that. Right? And so senescent cells do that last part, too. And that's also part of that zombie metaphor, because one of the things senescent cells do is they secrete these compounds into the microenvironment surrounding them, and that can convince nearby cells that would otherwise be healthy to become senescent cells as well. So the equivalent of turning a green leaf into a yellow leaf. And so that's the other part of the zombie analogy, right? They haven't been killed off, and they resist that, and they can turn otherwise healthy cells into new zombies. And so that's the third reason that they accumulate with age, right? So those are the three reasons our immune system is not as good at finding them. These transient ones are resisting falling off, and then they tend to make nearby ones. So it just creates this almost like, upward sloping increase until they've mostly looked in animals to see the accumulation, because you need to do tissue biopsies, but by older ages, tissue could have 20% or more of its cell senescent, and at that point, it's just not going to function well. So senolytic, that idea, that term was coined in 2015 by some scientists at Mayo Clinic and Scripps Institute of Aging. And the idea was, are there compounds that can be taken that will be the equivalent of a gardener that will go in and prune away these senescent cells so that we can keep the plant healthy, so to speak? And so the whole idea of senolytic is new, right? The field is eight years old, and among the first two compounds well, the first three plant compounds that were identified were quercetin fisetin or fisetin. I've heard it both ways. And piperlongumine, which is in an, ayurvedic plant called long pepper. So those were among the and still are among the most studied senolytic, especially the fisetin and quercetin, which they're a backbone, all three in Qualia Senolytic.
Erin Holt [00:20:09]:
So let me just back up a click. So these senolytic cells to some degree are normal in the body, like we have a human body, you're going to have some. The problem becomes when they start to linger because then they can essentially, I'm going to use my own language here, you didn't say infect, but they can kind of infect the environment around them. And so part of that is just part of the natural aging process. If our immune system is kind of not firing on all cylinders as we age, the immune system is just going to have a hard time tracking these guys down and kind of getting rid of them. Is bolstering our immune system or supporting overall immunity part of an effective strategy to keeping these senolytic cells at bay as well?
Gregory Kelly [00:22:02]:
Yeah, often the term they'll use is xenotherapeutics as like the overriding category and under that there'll be xenolytics. So senolytic are specifically things that would help prune them away, to help eliminate them. Then there's also things that are called xenomorphics. So those would be almost like a shield on healthy cells that would prevent them from becoming zombified. And then the third leg of that is the immune system. So absolutely. And originally when I was doing the research in this whole space, immunity was and this was pre COVID that I was first looking at this, immunity was one of the big legs that you'd want to support and still is. But one of the things just to be like even if you do everything for your immune system, it's thought that some senescent cells that linger, the lingering ones that accumulate, have figured out ways to hide from the immune system. So even if we did everything to support our immune system, we'd probably still want to do something to help in that senolytic category to prune them away.
Erin Holt [00:23:13]:
Got it. Okay. And I'm curious and the answer might be just like a shoulder shrug. Where does autoimmunity come into all of this? Is there any research that showcases a link between senolytic cells and autoimmunity or not really.
Gregory Kelly [00:23:31]:
Well, so I would say yes, in the sense that senescent cells, because they secrete these things in their microenvironment, a lot of those things are inflammatory in nature. They're like cytokines and other things and white blood cells. Right. So our immune cells can also become senescent. Right. That's part of that immune senescence. Right. This build up and they're much more likely to misfire. And in fact, Valter Longo, the founder of the Fasting Mimicking Diet, he's a longevity researcher, I believe he's at USC in California. One of the things that he's seen in his studies is just doing repeated cycles of that fasting mimicking diet helps clear away some senescent immune cells and that helps lower autoimmunity threshold. And then the way I tend to think of it is most things are about a threshold. So we want to stay below the threshold where we're causing a problem. That doesn't mean we have to get rid of everything, right? So allergies would be a classic threshold, right. As long as the allergens in our environment are below a threshold, most of us won't have a problem. It's when they go above that. So it's the same with senescent cells. So the goal is just to almost do routine pruning so that we keep them below a threshold in the tissue where it would cause a problem. And then the other connection to autoimmunity is much more theoretical. So early on, really, from the get go, the Mayo scientists came up with what they called hit and run dosing for senolytics. So, like something like vitamin C or B vitamins, you could do that every day. The idea behind senolytics was to do a couple of days and then a window where you don't do anything. So, like hit and run is how they describe that. And part of the reason for that is I mentioned at the beginning that Goldilocks rule of thumb, too much convincing cells to go through apoptosis. One of the concerns is now we're overtaxing the immune system and may provoke autoimmunity, right? So senolytics would be not, oh, like two days. I'll just do four days in a row or six days, right. It's not that type of thing. You want to do things like that safe, because we want to always challenge the immune system in ways that it can adapt and learn from, but not over tax it. Does that make sense?
Erin Holt [00:25:54]:
Oh, that's so interesting. It makes so much sense. And that's one of my biggest questions is why is the dosing of this so specific? So you're taking six caps on two consecutive days, and then you do that a month later. And I'm like, oh, that's interesting. You don't see that too often with supplementations, usually more like an everyday thing. So that makes a lot of sense. And it's because you're not trying to stimulate the immune system to such an extent that it can essentially overfire, which is what we see with autoimmunity in a lot of cases.
Gregory Kelly [00:26:26]:
Well, and the other thing is, and this goes back to that gardening metaphor, right? Like if you pruned a plant every day, you'd kill it. You just have to periodically prune it. Right. And so it's the same. There's a lot of ways you could describe it. Often I'll hear people think of it almost like as a cleanse or a detox, which is right, kind of in an analogy. But you don't really detox senescent cells. Like I said, you recycle them periodically. I know. I get asked questions like, well, what happens to senescent cells after you do a senolytic? How are they eliminated from the body? And when they're not right, they're just the individual parts are just recycled and eventually turned into new healthy cells. But I think of that idea of a cleanse is the right general idea, right? Like you're just doing this periodically.
Erin Holt [00:27:18]:
Well, to be honest with you, when I first it took me like two months to try them because I was like, is there going to be this big detox reaction or some Herxheimer reaction or some healing crisis because of and for listeners, I took it and no, there wasn't. But I was like a little apprehensive about that. So it's funny that you bring that up, but it certainly wasn't the case for me. So we understand that lingering, like an abundance of lingering senescent cells is not ideal. And you had said that's when it starts to impact tissues and the tissues can't function correctly or appropriately, what would be symptoms that we would see? How does this translate to our physical body in terms of how we present or how we feel?
Gregory Kelly [00:28:09]:
Well, a couple of areas that I know I was most interested in when I first read the studies, one was that so it would be called anabolic resistance in science terms. But older animals, whether it's like, think of exercise like lifting weights or higher protein diet, those would be anabolic signals in a 20-25 year old. But once we get older, they don't produce that same signals. We'd be resistant to that. So anabolic resistance is what they call it. That's a well known thing in science. And what they found in several animal studies is the buildup of senescent cells contributes to that and removing them then makes the muscles much more sensitive to these anabolic signals again. So it rejuvenates the muscles, right? So muscles is a big thing, right? So our muscles tend to get weaker and less resilient as we get older. Metabolic health is another. So fat cells can become senescent. And when they do, almost all the things you think of as unhealthy metabolic responses can be bucketed as something that senescent cells negatively impact. Two of the areas that senescent cells were originally thought to be the most impactful and is still probably the case, are what are called fibroblast cells and immune cells. So fibroblast thinks connective tissue. So skin, joints, like aging, less healthy skin that builds up over time. Now, there's no way to prevent that, but the goal is to just maintain more resilience in our skin. And then discomfort in the joints is obviously crazy big, right. You start to see that in some people even by their mid 30s. So one thing that Neurohacker Collective, the company that makes the Qualia products, does is before we sell a product, we do our own study on the recipe. So we'll make enough of it to do a small pilot study. And it was challenging to figure out how we would test this Qualia Senolytic product because it's not easy. People aren't going to line up and say, oh, yeah, sure, you can take biopsies of my tissues. So in looking at some of the studies that were on clinicaltrials.gov, which is the website where you would register like preliminary or ongoing clinical studies. Several looked at joint comfort and I'm like, oh, well, we'll just copy what they're doing. And so that was our original study. We just found people in our we call it the Beta community, but people that wanted to try out a new product and had some level of issues with their joints. And then what we had them do is three cycles. So two days, period vacation from it, two days, period of vacation and two days. So I would describe that as three dosing cycles. And we measured their subjective response from baseline to at the end. And what we saw for things like going up and downstairs, getting in and out of cars, feeling less stiff, things like that, there was about a 50% improvement across the board on average in that group. I've read a lot of studies on different ingredients for joints and that's a pretty robust change to happen so quickly.
Erin Holt [00:31:36]:
No kidding. That's amazing. What about anecdotally? Has anybody commented on appearance? So you were mentioning like skin appearance in terms of skin or is it just kind of too new to really.
Gregory Kelly [00:31:52]:
You know, just because my role is more on the science end, I'm not as plugged into the different things people mention on Instagram or like, I know Instagram is a big community for us, so I'm sure there's all kinds of things that have been mentioned that I'm much more likely to get, like, oh, this weird thing happened. What do you think, Dr. Greg? Recently it was oh, someone said they noticed the couple of days after taking Qualia Senolytic that they seem more sensitive to alcohol, meaning they would feel a little bit more buzzed on less alcohol. Do you know why? And it's like, no. In the Navy we would have said a WAG like a wild ass guess. I would just be, you know, wagging, but please let us know if that continues.
Erin Holt [00:32:46]:
Okay, I'm going to see if it will make my budding gray hairs go away. So let's talk a little bit about the ingredients that are in it. So you mentioned quercetin, curcumin, olive leaf. I'm just reading the list, actually. Let me start from the top. Fisetin. How did you pronounce that again?
Gregory Kelly [00:35:20]:
I always used to say fisetan, but I've heard so many other people say fisetin, so I'm assuming I'm incorrect and fisetin is correct. It's a German word originally. And so then it would be FIS would be more FIS than phi.
Erin Holt [00:35:37]:
And that's a plant extract. Is that what that is?
Gregory Kelly [00:35:38]:
Yeah, it's found in a lot of barks and leaves. Like strawberries would be a food source as an example, but we just get such a small amount in even a healthy diet. So one of the way I think these compounds work is I mentioned earlier that cells are all about sensing their environment, and nutrient sensing is a big part. Right. So mTOR, you've probably have heard right with protein sensing. But what these plant compounds tend to do is they cause almost a chain reaction in some nutrient sensing pathways that say, oh, the environment looks like that it's not going to be particularly great for us, right. Like food might be scarce, whatever, let's recycle the cells that we can most live without. This is my way of thinking about it. The only time we would have ever had a lot, and it would still be much less than what's in Qualia Senolytic of quercetin and fisetin in our diet compared to normal is in a famine. Because in famines, what you've seen historically, like the Dutch Winter famine in World War II is that people made soup from tree bark and ate leaves, like whatever, to fill their stomach. So that would be the only time there'd be a big delta, right. A big change in the amount of these because they're generally thought of as plant secondary metabolites or defense compounds. They're all polyphenols would be another way to think of them. And so based on how they work right, they cause cells to sense around them, like, oh, the environment looks like it's not going to be great. So let's recycle what we can't live without that these plant compounds tend to be in things or more abundant in things like bark, leaves and roots, things that would be not the yummiest part of the plants to eat.
Erin Holt [00:37:33]:
I'm curious because I think of polyphenols in relation to microbiota specifically, almost as like pre, prebiotics because they can help our bacteria to create metabolites, like short chain fatty acids and things that are really important for overall health and metabolism. So I'm wondering if taking kind of larger doses once a month would impact the microbiome in any way.
Gregory Kelly [00:38:01]:
I am absolutely certain it does, at least temporarily. So we have another product called Qualia Synbiotic. It's a scoopable powder, but it's prebiotics probiotic, postbiotics, fermented foods and some polyphenols as well. And when I wrote that up, I always do a blog post on a new product, why we made it a bit about each ingredient and the prebiotics. The polyphenols I described as prebiotic like or prebiotics with a twist, they don't meet strictly the definition of prebiotics, but they are things that some living bacteria in our microbiome do use for their food supply and do modify. So they for sure have a big impact. And the capsules for Qualia Senolytic are really yellow in color because fisetin is a yellow plant pigment, and curcumin is obviously that mustardy yellow, dark yellow, and quercetin is yellow and luteolin is yellow. Right. So it has yellow. So I know for me, I'll see a different color of my stools in the day or two that I take Senolytic, and my guess would be, I don't know how many of these you've heard of, but there's now like a gut muscle axis and there's a gut sleep axis, and there's a gut skin axis. There's obviously the gut brain axis, there's a gut joint axis. So my intuition is that a lot of the benefit you get systemically in the body drives off of the gut and that some of these polyphenols will be having a positive impact in the gut on those two days a month that you take it.
Erin Holt [00:39:50]:
It's so fascinating. I see soybean seed extract here. What is the benefit of that?
Gregory Kelly [00:39:56]:
Yeah, so that extract is standardized for isoflavones. So soy is known to have genistein diadzein. And those isoflavones do a couple of things mechanistically on cells that really. Milk thistle, the isoflavone in that silimarin does a little bit overlap, but those things just impact some of these mechanistic pathways in cells to help kind of tilt cells over into apoptosis that other compounds don't. So that's why it's in there. And one of the things, and this goes back to the original 2015, the very first written study that coined the term senolytic is that's where quercetin was identified as senolytic was in that particular study by Mayo. But another compound they identified as senolytic is a medication used, it's an immune modulator called dissatinib. And disatinib is in a family called tyrosine kinase inhibitors, which I know this is just going over, but think of the compounds in soy and milk thistle as doing some of the similar restoring things to normal function that that medication would have done in the original dasatinib and quercetin stack. So they mimic some of the mechanisms, that's why they're in our product.
Erin Holt [00:41:21]:
That makes sense. You do a good job of explaining some really complex stuff. So it sounds like taking Senolytic or a senolytic can be really helpful here for all of the reasons that you described. Is there anything that we can do from a diet, nutrition, lifestyle perspective that would also help with this?
Gregory Kelly [00:41:42]:
Yeah, so exercise for sure is thought to be xenotherapeutic but more like protecting other cells, like being a shield for other cells. So it's not really senolytic per se because the field is so new, there just hasn't been as much studied like on what would be diet and lifestyle, but the Fasting Mimicking Diet. So that's again, Valter Longo's, which is usually it's a three to five day protocol and his isn't a water fast, I think it's cut calories, but to down 800 to 1100 over those five days, super low protein, like low protein is a unifying thing I mentioned for getting these cellular response. And his work so far has suggested that his fasting mimicking diet does help with immune senescence. So my guess would be a lot of the fasting related behaviors help in sinotherapeutic sense, maybe some because they help recycle senescent cells and others because they shield healthy cells from the damage. So those would be the two main things. But in terms of so it used to be thought that senescent cells were almost all made because telomeres got too short, telomere attrition, which is one of the hallmarks of aging. And there's also this thing called stress induced or premature stress induced senescence. So long before telomeres get too short you can cause a cell to be senescent by too much stress. So that's the other thing in animal studies, in cell culture studies, things that are too stressful for cells cause senescence. So these are things like intense, like too much sunlight as an example beyond what our systems adapted to be able to handle in that moment nutrient stress. So I would say everything that you would think of as like oh, this is too stressful, is probably going to contribute to more yellow leaves than we want.
Erin Holt [00:43:57]:
And psychological emotional stress would fall in that category too?
Gregory Kelly [00:44:02]:
I would think so just because of the gut brain connection that always has a systemic effect on ourselves. So it's all connected.
Erin Holt [00:44:11]:
Got it.
Gregory Kelly [00:44:12]:
So I think I always think of mental and emotional as the worst strategy.
Erin Holt [00:44:17]:
No kidding? Yeah, for sure. I myself have a history of eating disorders through my teens and early twenties. And I know that a lot of listeners have a similar struggle. And as much as the research supports fasting and it can be a wonderful tool where appropriate, it can also be pretty detrimental mentally for a lot of, like a big part of the population. And so I think it's so wonderful to be able to have more tools at our disposal like Senolytic, like Qualia Senolytic for those who it's like while we understand that fasting can be therapeutic, it can also be wildly inappropriate for a lot of people and kind of tripwire and trigger some old harmful and unhealthy patterns and behaviors. So it's nice to have multiple tools at our disposal so we can choose the one that feels the most appropriate for us given our background and context.
Gregory Kelly [00:45:17]:
Yeah, people that know me would be really familiar. I use the word relationship a lot. To me, it's the relationship we have with something. And what I've seen in the biohacker community is many people their relationship with fasting can be a little bit less healthy than what I would think is ideal. Right. Like, oh, if a little is good, more is better. I'm going to be like the fasting king and I'm going to have this super narrow window of eating. And I like Dave Asprey's fairly recent book Fast This Way because he does spend some time in the book mentioning these things are as you meant. They're like part of a toolkit that they can be used and misused and often they're misused. I use the word time restricted eating. I try not to eat much into the darkness, period. But if I'm hungry, I eat. Just like if I'm sleepy, I sleep right? At the end of the day, I trust my body knows way more what it needs than my conscious mind ever will know. So just learn to pay attention to it.
Erin Holt [00:46:32]:
Yeah. Our bodies are ancient and the mental stories we have are not as ancient as our bodies. I found the company because I was looking for brain support. It's important that my brain stays sharp given what I do. And so that's how I found Qualia Mind. So I'm curious if there's any connection between the brain, brain aging and these senescent cells that you're talking about.
Gregory Kelly [00:47:03]:
So it used to be thought. I mentioned at the beginning that neurons are meant to last a lifetime. So neurons are a type of cell that doesn't make new versions of themselves. Like, once the neuron is made, we'll prune them away and we can structurally change them. But neurons used to be thought since they didn't make copies, they couldn't become senescent, like what would be the point? Right? Because senescence was thought of as something to prevent cells from making unhealthy copies of themselves. But in the last handful of years it's been found that neurons even can become senescent. But even more important, what surrounds neurons in the brain are all these support cells. So glial cells is the general name, but microglia are the brain's immune cells and astrocytes in these and they can all become senescent and that becomes problematic. So, so far the only studies I've seen on senolytics that have looked at the brain have all been animal studies. But like as an example, in those fisetin was senolytic for some of those structural cells. And then the other thing in the brain, autophagy becomes really important, right? So we want to support periodic autophagy for the brain so that it can keep maintaining healthy neurons since we don't have an abundant supply and we don't want to damage what we have. So for sure, to my knowledge, there's been no tissue that's not impacted by senescent cells. I kind of keep folders for each clinical area and it's everything liver, kidneys, skin, muscles, fat, tissue, brain, you name it.
Erin Holt [00:48:42]:
So it's kind of a big deal is what you're saying.
Gregory Kelly [00:48:45]:
Yeah, there's a reason it's one of the twelve hallmarks, right? It's just a characteristic that has been well known about for a long time. But it wasn't until relatively recently there seemed to be a solution, which is why it's gotten so much research, because there's not too many things in those hallmarks that have solutions currently.
Erin Holt [00:49:08]:
And so to kind of like tie all of this up with a bow, would you say that supporting this, I don't know if supporting senescence is not what I'm trying to say, but supporting the clearance of lingering senescent cells maybe is what I want to say. Is that a way to sort of slow the aging process and promote longevity?
Gregory Kelly [00:49:36]:
Yeah. So I think probably it's not going to make us live longer, per se, but I know for me, the reason I take Qualia Senolytic and I do it the first weekend of every month. So just given when we're recording this, it's tomorrow for me, I'll be doing it for two days. And that's just easy, right, for me to remember the first weekend every month. But I think of it as an investment in making sure that when I'm 80, 90, I'll be able to still live a healthier life doing more of the things I want to be able to do. So that's how I think about it. You'll hear the term health span, but the way I think about it is you'll sometimes hear what, like 50 is the new 30, right? Like people just expect and want to be able to perform at a higher level longer than might have been the case with my grandparents as an example. And that to do that, I know I just have to do things differently than my grandparents because they probably had access to better food in general than we do. A cleaner environment. So I just think of things like Qualia Senolytic, but other things like exercise as well and stress reduction and getting enough sleep. All these things are investments that I make in my long term health portfolio and that I know when we first came out with Qualia Senolytic, marketing was like, well, what are people going to feel? It's like, well, if senescent cells aren't causing an issue, then maybe nothing, right. If they're below that threshold, they're just investing in keeping them below. If they're already struggling with their joint comfort, then they'll probably experience it there. Right. So it's variable, but I think the right mindset or the mindset that if I was working with someone, it's just like investing for our financial health when we're older, right. We want to make prudent investments, and I think of Qualia Senolytic, personally, as one of those investments that I make every month.
Erin Holt [00:51:36]:
That's a wonderful analogy to help folks kind of understand because we're so on the perpetual hunt for the quick fix and it's like, just tell me what to do, and then I want the immediate results. And it's healthy aging, probably we're not going to see the immediate results of that. Right. So investment in your long term health portfolios is a really great way to think about it. So thank you so much. I definitely have a much more clear understanding of the what and the whys behind this product and this whole thing that's going on in our bodies. So I really, really appreciate you coming on the show to teach us all about this.
Gregory Kelly [00:52:13]:
Oh, it's been my pleasure, Erin. Thanks for having me today.
Erin Holt [00:52:21]:
Thanks for joining me for this episode of the Funk'tional Nutrition podcast. If you got something from today's show, don't forget to subscribe, leave a review, share with friend and keep coming back for more. Take care of you.
