[00:00:00] Luke: So tell me why I've become more of an introvert in terms of the signal to noise ratio.

[00:00:07] Gregory: Yeah. So one of the ways I tend to think about our nervous system, but all our senses are designed off what's thought of as proportional change. So the story I would usually tell is think of the darkest closet in your home. You go in. It's completely dark. You light one candle. It's like, wow. You notice a big difference. Now imagine you had that same closet. There's 99 candles lit. You light one more, and nothing. You don't notice much change at all.

[00:00:34] So that highlights how all of our nervous system and senses are designed to interact with the world. It's about not only the change, but the proportion of change. So a quantity of one is meaningless. Quantity of one against a background of nothing, crazy big response. Against a big background that's filled with light, one candle makes no difference. So with our nervous system, it's the same.

[00:00:56] If we're used to a really loud environment-- we go to concerts all the time or live in a big city and hear traffic. Our nervous system gets used to that. The background level, what I would think of, is the noise is ratcheted way up. So to get that proportional response, we need a big change, which when we're young, a lot of us enjoy, going out late at night, listening to loud music, things like that.

[00:01:19] But we need that to create the contrast. When we're living in a much more peaceful environment, listening to light with beautiful music or the sound of a chime maybe is enough for our nervous system really to lock in on it.  Maybe nature, all those things, the background noise level is so low. We don't need much of a change or contrast to really notice a big response.

[00:01:42] So tradeoff. Once our nervous system is used to that, it's usually not going to like the loud concert and the club thing because we're now much more sensitive. But general sensitivity is healthy. We want to strive for that.

[00:01:56] Luke: Yeah, that's really interesting. I remember the many years I lived in Los Angeles, my dad would very infrequently come visit, and he just hated the city. I'd pick him up from the airport and get on the freeway. He'd be slow down, slow down.

[00:02:11] But he's lived his whole life in the country, in Colorado, just outdoors all the time, hunting and fishing, and very rarely in a city, let alone a city as chaotic as Los Angeles. And I was so acclimated to it. I thought, what's wrong with him? Then I would go to the country, and I would feel so bored and restless. It was just too quiet.

[00:02:28] So it's interesting how you adapt to your environment. It's taken me a minute to figure out that I have had that adaptation since I moved to a much more remote area here in Texas. I have a very difficult time in crowds and cities. There's no way I would go to a concert or something like that. It's just too overwhelming.

[00:02:50] Gregory: Yeah. I think when you were in that, you needed that big change to really notice a difference, for your nervous system, your senses, to really pick it up. But that same degree of change when you're used to calm and peaceful, tranquil environments sounds almost like a thunderbolt. It's crazy big. It's overwhelming for a sensitive nervous system, so yeah.

[00:03:11] Luke: Yeah. Well, thank you for eliminating that. Give me a little bit of your background, Greg. You mentioned that you studied engineering. What else do you have under your belt? What's your paradigm of origin?

[00:03:23] Gregory: I grew up in a little fishing, lobstering town near Cape Cod, south of Boston. My first degree was engineering, and I was on a Navy scholarship, so did Navy stuff in the summers for a month, and then spent five and a half years in the Navy when I graduated my engineering degree, which got me to Coronado, the San Diego area, and then onto Pearl Harbor, Hawaii, and then Long Beach, and eventually back to San Diego.

[00:03:48] So that was my first career. I did that through my late 20s, and then around 28, because of a variety of circumstances, I'd gotten into becoming a vegetarian, yoga, some spiritual things. And it's like, well, the Navy's not a great fit for that. So abandoned that career. Got rid of everything except a backpack and left. I was in San Diego at the time.

[00:04:19] Got to Hawaii. Thought, oh, I'll spend a little time studying a couple of Asian languages. And then I'll move on to Asia once I've got a little bit of a base there. And during that, I was taking Thai as one of the languages, and the professor said, oh, there's a scholarship. There's six grants the US government gives out every year. You should apply for it. So I did, and I got it.

[00:04:38] So at the time, I just shifted and stayed and did a master's degree in what was considered Southeast Asian studies. But as long as I studied Thai language, I could do anything I want. So I took transpersonal psychology, and I would write a paper on how that connects to Buddhism as an example in Thailand.

[00:04:57] So it ended up my degree, my focus was on where food and plants meet traditional medicine in Thailand, which Thai medicine largely evolved from Ayurveda when Buddhism came. And so during that time period, I was taking yoga, looking for a meditation class. And turned out one of the people there was a naturopathic doctor.

[00:05:19] And at the time, I was like, wow, I've never heard of any of this thing. And I'd been studying on my own a bit about herbs. I was health conscious, obviously having become vegetarian at that time. And that profession just encompassed so many of my interests. I got rid of the idea of just slipping around the world and being a bag of bond.

[00:05:39] I think we'd have different words for it now, but at the time, it was fairly unusual and just went to naturopathic school from there. And that was '93 and was at a school called-- it's now Sonoran Institute, but it was Southwest College of Naturopathic Medicine. I was in the first class. At the time, it was pros and cons to be the first one through something, but more pros than cons.

[00:06:02] We got some amazing instructors. And it was almost like we got to be there during the birthing process of this new school. And then graduated in '96 and have been either in practice, working in supplements, doing corporate wellness, something, ever since.

[00:06:19] Luke: Wow. That's a long time. Damn. '96, I was 26 years old. You're already a grown ass adult.

[00:06:27] Gregory: In some ways, not in others.

[00:06:30] Luke: Yeah. You're out there helping people, doing your thing. And how did you connect with our friends over at Neurohacker Collective? Some of our listeners will know that company from an interview I did with Daniel Schmachtenberger and also from this stuff, Qualia that I've talked about a lot over the years.

[00:06:49] I think that was maybe the first product they made. And by the way, guys, we'll put the show notes today at lukestorey.com/qualia. So anything we talk about will be linked there in the show description. How did you connect with those guys? Fascinating group of people that seems to have evolved over the years. There's different partners. I've had Dan Stickler on show as well. We'll link to that in the show notes. Incredibly bright guy, both of them. So you're in good company. How did you meet them?

[00:07:18] Gregory: Yeah. At the time, I'd been working for a company that was in the corporate wellness space, supervising database analysts and techie kind of people. And that company didn't quite make it, and I was looking for a new gig, and Neurohacker was just up the road, so to speak, San Diego.

[00:07:34] So they had an had offer, I think it was for lead formulator, might've been what it was called at the time. But basically, the person that would help make these products. And so I sent a cover letter in resume, say, noon on a Tuesday, whatever day it was. And about 8:30 that night, I got a text message from Daniel Schmachtenberger just saying, you look like a perfect fit. When can we speak? I'm like, when do you want? He goes, I'm in a meeting. I'll call you in a half hour. And I was hired on the spot.

[00:08:04] Luke: Really.

[00:08:04] Gregory: Yeah.

[00:08:05] Luke: Faith.

[00:08:05] Gregory: Yeah. Very much.

[00:08:06] Luke: That's cool.

[00:08:07] Gregory: So Daniel Schmachtenberger's brother James is the CEO, and James would've just said, Neurohacker hunts for unicorns, and you were the unicorn for this position. And we'd looked at a bunch of other resumes, and yours just fit what we needed.

[00:08:20] Luke: Oh, that's awesome. Well, you're in good company. I love those guys. Yeah. I remember when Qualia first hit the scene and going on their website, and I was just like, these guys are on another level. The ingredient deck and the research behind every single ingredient, there was nothing like that at the time.

[00:08:38] And I think in the beginning, there were two bottles, and you had to take quite a few capsules of each one. And as I was telling you before, that was the first non-synthetic nootropic, brain enhancement formula that I'd ever taken. And probably fueled my first couple of years of podcast. I had had modafinil and piracetam on a somewhat regular basis. But as far as the nutraceutical side of things, it was very novel.

[00:09:08] Gregory: We usually refer to that either as OG Qualia or Qualia 2-step because of the two bottles. Because one it was like, oh, take these couple of pills away from food. Take these bigger ones and a whole bunch of them with food.

[00:09:20] Luke: Yeah, yeah.

[00:09:21] Gregory: It was a great stack and a really excellent product, but at the end of the day, we wanted to simplify it a little bit, reduced capsule count, and that ended with the Qualia Mind product.

[00:09:32] Luke: Yeah. The breakthrough for me with the Qualia Mind was the decaf version. Because I would find if I drank coffee and then took the regular one and I took the recommended dose, it would be a little too stimulating. So then I'd be like, okay. On days where I'm not going to drink coffee, I'd have the regular Qualia Mind, days where I'm having coffee, the decaf, and that's been like the sweet spot.

[00:09:56] So yeah, it's very cool. But anyway, today I want to talk about aging. And I'm glad that you're the guy that showed up to talk about this. I found the Senolytic product from Qualia recently and was very intrigued by that. I'm familiar with a few of the ingredients, and I thought, I haven't really done a show on senescence specifically.

[00:10:18] It's been mentioned here or there, but I'm not someone who is necessarily that interested in how long I live because I just believe in fate. And when it's time to leave this body, I'd be happy to go. But while I'm here, I would like to be vital, mobile, sharp, and be able to make a contribution to the world for as long as I'm here.

[00:10:41] So my perspective on anti-aging is, for as long as you're in your body, how good can you feel so that you can have fulfilling relationships and accomplish what you're here to do and not end up with a degenerative disease, or dementia, or any of these things that are unfortunately so common now? So maybe we could start off with just laying out the fundamental theories of aging as you understand them.

[00:11:06] Gregory: Sure. Before we get to that, I just wanted to play off what you just said because I think that's what I would want as well. Whenever my time comes to have lived, be able to do what's important to me up until the end. And it was really recent I saw a study on it, but basically, for an average 60-year-old in North America, they would be expected to live another 23 years, but about six to seven of those would be disabled either because of chronic health things or physically being unable to take care of ourselves.

[00:11:37] So that's not quite one third of that, but a good chunk of the end of most people's lives is spent in ways that isn't fulfilling. And so my goal is to make investments now but also have investments that I've made in the past hopefully pay off so that when I get towards that tail end, I'll still be able to live my life my way.

[00:11:59] Luke: 100%. I guess it depends how you live your life mentally and emotionally and where your interests lie. But with as much humility as I can muster I have much more wisdom than I did even five years ago. Going back, I mentioned when I was 26, wow, I was so unconscious and such a train wreck.

[00:12:18] So if you're someone who's invested in your consciousness and understanding of the world and reality and you really have something to offer the coming generations as you age but your mental capacity and physical capacity is so limiting that you can't pass that wisdom on, it's such a waste of life.

[00:12:44] And in our culture, we don't tend to revere elders unfortunately, and perhaps some of that's probably just social contagion, but a lot of it probably has to do with our elders becoming so physically disabled by the end of their life as they age that there's not a lot of energy for them to share.

[00:13:06] Gregory: Mm-hmm.

[00:13:07] Luke: Their energy is just hanging on in the assisted living and on a bunch of pharmaceuticals. And not to be cold, but who wants to hang out with them. As much as you love them, I can see why we shove our elders off into these homes. And it's very rare in our culture here that elders live with the family as they're getting older.

[00:13:29] And you look at some other cultures-- I was just watching this show. I think it's called Live to 120 on Netflix. And in some of these cultures, the elders all live in the family home, and the people idolize them and go to them for advice and wisdom because they've acquired that wisdom. But I think a lot of it is they have the physical vitality to pass that wisdom on. So I'm with you on that.

[00:13:51] Gregory: Yeah, that's my goal. Like you, I don't have any number in mind. If anything, loosely based off whenever I would've seen Finding Nemo way back, there's a scene with the sea turtles, and Nemo meets them, and they're surfer dude personalities in the Pixar movie. And I think Nemo says, oh, how old are you? And he says, oh, I'm 120 and still young.

[00:14:16] So I've loosely had in my mind, like, oh, I want to get to the still young at any age. Whatever that number is is less relevant, but still feel mentally flexible, physically as flexible as I can be, still able to travel, love life, things like that.

[00:14:36] Luke: Yeah, absolutely. All right. So what are some of the theories of aging?

[00:14:40] Gregory: There's tons of them, absolutely, a whole bunch. but mostly, they fall into two broad categories. One would be the damage theory of aging, so that would posit that. The reason that we at least experience aging the way that we do is an accumulation of damage over time. And once that accumulates to a certain degree, then tissues become dysfunctional, and eventually our health declines.

[00:14:59] The other camp is really often thought of as more programmed aging or evolutionary aging. So the general idea would be that largely, for evolutionary reasons, we're programmed to age, almost like software, that certain things get expressed in different ways after we've reproduced. And the key thing is reproducing after that where no longer as important for the gene pool.

[00:15:32] Luke: Nature recycles us.

[00:15:34] Gregory: Yeah. And so you have those two camps. There's probably an element of not either-or, but yes to both. That there's aspects of both. And I think what we're going to end up talking about, senescent cells and senolytic, would fit more squarely in the damage control camp.

[00:15:52] Luke: Got it. Okay. And then in terms of defining age, we've got chronological, biological, functional, and perceived age.

[00:16:00] Gregory: Yeah, so we all know our birth age, our chronological age. ,My goal is for these other ages that you just mentioned, and we'll talk about what those are, to have my chronological age be greater than those. We didn't have it on that list, but felt age. So if I said, Luke, how old do you feel? That would be your felt age. And most people feel younger than their birth age.

[00:16:25] Then we have perceived age is how other people perceive. So if we were to show my picture and your picture to a 100 random people on the internet and ask them, how old is this person? That would be the perceived age, what they're thinking we are based off that picture. And perceived age actually tracks really closely with how healthy we are, believe it or not.

[00:16:46] Just that crowdsourcing how healthy someone looks is, in many ways, super accurate, much more accurate than our birth age at predicting when our health's going to fall apart or if it already has to a degree. And then what's called functional age would be more things like grip strength or ability to go from sitting to standing comfortably, things like that.

[00:17:08] How are we functioning? You start to see some biomarkers. VO2 max would be an example, a fitness biomarker. Those are like, are we functioning at a younger level? So exercise would play a big role in having a better functional age usually. And then the biological age is now we're looking at things like a TruAge test from, you had mentioned Dr. Dan Stickler.

[00:17:33] He's the CMO for both Neurohacker and a company called True Diagnostics that does an age-related task, where they're looking at methylation on cells and saying, okay, how old does this cell look? And so that's biologic age.

[00:17:48] Luke: Is that test something that one could order online and do at home, or do you have to go see a clinician?

[00:17:54] Gregory: No, no, that one you can do online. And they're not the only one. It's based off of Steve Horvath and Morgan Levine's work, were the ones that did these. They're thought of as clock. Grenage, I think was the original name of that. So the Clock Foundation offers them, and then True Diagnostics is another. I'm sure there's other ones, but those are--

[00:18:13] Luke: That'd be fun. I've heard about those and always wanted to do it. I think it would be, for those of us that are really committed to wellness, affirming to find-- I just turned 53. If I took that test and it was remotely accurate and said, you're 43, I'd be pretty, pretty excited. Make me, all right, I'm going to work out today. Or I'll take as sauna today. It'd give me a, a bit more impetus to keep doing the things that I'm doing.

[00:18:39] Gregory: There will be first, second, third generation of these clocks. And I think it's the third generation one, but don't quote me on that. But one of them is more the pace of aging. In one calendar year, we're aging one year. You want your pace of aging to be less than one.

[00:18:57] Luke: Oh, interesting.

[00:18:58] Gregory: Yeah. And one doc that consults with Neurohacker, once in a while, he-- I think his first time he did pace of aging, it was good. It was like 0.89 or 0.9. So less than a year for calendar year. And then he did a couple of cyclings of Walt Valter Longo ProLon, the Fasting Mimicking Diet, and then some of our Senolytic over a year and remeasured, and his was 0.68 or 0.7.

[00:19:26] What was interesting, he said it was a crazy stressful year from a work perspective because he was launching a website and transitioning from physically seeing patients to doing more consulting and other things. So yeah, there's some cool things out there. I think we're still so early in the anti-aging or longevity, however you want to describe this space, that I think 10 years from now, things like what we'll talk about today, senescent cells, senolytics, it's relatively almost unknown even in the medical world.

[00:19:59] Luke: Oh really?

[00:20:00] Gregory: Yeah, there was just a paper review, but by a bunch of cardiologists, and that was one of their laments, that this is just still so unknown.

[00:20:10] Luke: And what about the aging of our tissues?

[00:20:14] Gregory: Yeah. In a sense, some of those clocks are trying to get at that. So they've developed clocks now that would be specialized at saying, okay, this methylation pattern for the brain and try to predict a brain age. So yeah, it's being worked on. I know True Diagnostics is definitely going down that pathway.

[00:20:36] Luke: And what's your take on the latest in NAD testing? Do you think those are accurate?

[00:20:44] Gregory: So NAD testing, you'd have to go to a university. Special reagents. They need to do the test in a specific way. But with the popularity of the NAD boosters, the NRs and the NMN, so nicotinamide, etc. Niagen is the brand name of it.

[00:21:02] There's been, I guess, an impetus to develop before and after testing. That's easy to do because before, it was unavailable. And so there's a lab I know I've worked with called Jinfiniti out of Georgia that have home finger stick tests that you can do before-- well, you can do NAD by doing a blood spot.

[00:21:19] Just poke yourself. Get a few drops of blood. There's four little spots on it that you fill. And you just send it in. And about a week later, they'll tell you blood NAD levels, which doesn't necessarily mean in your muscle tissues or brain would be the same. But it's still a really useful biomarker. And those are legit.

[00:21:39] Luke: Oh, cool. Have you done one?

[00:21:41] Gregory: Yeah.

[00:21:42] Luke: How did you turn out?

[00:21:43] Gregory: So we actually have a relatively new product called Qualia NAD that just came out a few weeks ago. And one of the things I love about Neurohacker Collective and that caused me to say yes when Daniel and James offered me the job was their commitment to testing their products before just slapping a label on them and putting them for sale. So in the development of Qualia NAD, we made up a batch of it to take ourselves. I did before and after NAD testing, and my levels went up 156% over a month.

[00:22:17] Luke: Really?

[00:22:18] Gregory: Yeah.

[00:22:18] Luke: Wow.

[00:22:19] Gregory: So yeah, rocked for me. The other doc that was on it, his went up about 50%. We tend to think of responders and super responders. I was more of the super responder.

[00:22:30] Luke: How much of that type of testing do you guys do over there at Neurohacker?

[00:22:35] Gregory: Depending on the product, certain things, like this product, the Qualia symbiotic. So this is a gut health and gut-brain product. And the best way to measure gut health is really, how is your digestion doing? Using standardized questionnaires that are been used in research forever for that.

[00:22:53] And so that's what we did. We made up enough to do a small study, measured stress, mood, and then gut performance. Then in general, there's upper GI, lower GI symptoms like soft stools, hard stools, indigestion. But what we saw was about a 60, 65% improvement across the board in stress and all the GI performance things. And so we need to see that before we would say yes to bring a product to market.

[00:23:25] Luke: I wish more companies followed that protocol.

[00:23:29] Gregory: Yeah.

[00:23:29] Luke: I don't know. I buy stuff. I'm pretty good at reading websites and trying to find reference studies. And I look at the ingredient decks very carefully to make sure there's not any shady stuff in there. But sometimes you don't know if it's placebo when you feel like, oh, this thing's helping me or working. It's cool. Even if it's subjective and not based on biomarkers, it is nice to see that data before you spend your money.

[00:23:56] Gregory: Yeah. And I agree. I think it's a shame that more companies don't. And this is unfair, so take that for a grain of salt. But I tend to slice even people that would do my job and to-- are these people mostly marketers, or are they people that are more-- as an engineer, a doctor, I'm more that scientific archetype.

[00:24:15] I read studies. I'm a hard grader. Very rarely do I see studies that I'm impressed. And our commitment to study, I think, is exceptional in the industry. So matter of fact, we're going to talk about senolytic today as a thing. I, literally, about two hours ago got the results of our placebo-controlled study on senolytic. So maybe we can get into that a little bit.

[00:24:38] Luke: Yeah. We definitely will.

[00:24:40] Luke: Before we move on from studies in general, what's your sense of the relevance or lack thereof of animal studies? A lot of these things, it's not practical, feasible, possible to do at least large-scale human studies for various reasons. And so sometimes the best we can do is rats or rabbits, whatever lab animals.

[00:25:09] And I think there's some validity to that, but sometimes that's all there is, and you can't really equate that. I know a friend of mine, Dr. John Lieurance is a huge proponent of high dose melatonin, for example. And I love taking his stuff. I take 2, 3, 400 milligrams of melatonin. No problem. Feel great. At night.

[00:25:28] Gregory: He's in Florida, right?

[00:25:29] Luke: Yeah, yeah, yeah. His company's called MitoZen. He is in Sarasota. And lately, Huberman-- it's Huberman or Huberman, Andrew-- great guy, bright guy. He did a podcast shitting on exogenous melatonin, and I sent it to John. He's like, no, that's a rat study, and yada yada. He is like, juvenile rats have a different hormonal profile, yada, yada, and totally debunked it.

[00:25:54] And it's been debunked by other scientists, but there's things I think that are encouraging people to take certain supplements, for example, based on animal studies, and then other ones that are discouraging people from doing it and leading people to believe that they're maybe not advantageous or even unsafe in some cases.

[00:26:12] But then when you dig in further to the studies, the correlations aren't necessarily relevant because you're dealing with a tiny little mammal that has a totally different, in this case, circadian rhythm and nocturnal patterns than even infant humans. So it doesn't really anything. I don't know. What's your take on human studies versus animal studies in the realm of supplementation and--

[00:26:39] Gregory: Tend to think of the hierarchy of evidence. So the gold standard, the top of the totem pole would be having multiple randomized control placebo studies where the results replicate over and over again. That's the gold standard. But that's just so super rare.

[00:26:55] It's very common, even for a cognitive ingredient that has multiple studies, that maybe in one study it improved working memory. In another one, it was focus. So it improved something both times, but something slightly different. That's not uncommon. And then animals would be fairly down on the totem pole for predicting how humans would respond to something. But it's the best way to understand how something may work.

[00:27:20] So senescent cells is an example. Senescent cells aren't something that there's an easy way to measure. Senescent cells should be really thought of as a category instead of as single thing. And within that category, the senescent cells in your muscle tissue, or my fat tissue, or our brains may be slightly different than each other. So when researchers look to say, oh, is this a senescent cell on these tissues? They have to do biopsies. And not many humans are going to sign up for that.

[00:27:50] Luke: How do you get volunteers for that? Yeah. Cut a piece of my thigh out.

[00:27:54] Gregory: And it has to be a lab that knows what they're doing, like a Buck Institute, or Mayo Clinic, or Scripps Institute of Aging, to even know what to look for because senescent cells, it's not that there's one thing that would say it's something's senescent. It's a combination of markers they would look for.

[00:28:10] So most of the work on senescent cells and senolytics is in animals because it has to be. But then what you do is you hope, okay, well, based off what things look, they may help the body remove these unwanted cells. And from there, then you would move to humans and see, okay, the goal of removing senescent cells would be that we're healthier at whatever age.

[00:28:33] So the study we just did, we recruited people with joint issues because joints are one of the things as we get older. That's an area that just shows up in the real world that people struggle with.

[00:28:43] Luke: I've noticed.

[00:28:44] Gregory: Right. Walking up and downstairs, getting in and out of cars, flexibility, just bending.

[00:28:50] Luke: Or eating inflammatory foods. I swear to God, and I'm sorry for the people listening to the show, me and my redundant gluten stories. I have scaled it back a lot over the years, but every once in a while, I'll be feeling so good, and I'm like, you know what?

[00:29:05] I don't want to be orthorexic and such a control freak. My wife's having some pizza. It looks good. Doesn't bother her. I'll eat some pizza. Invariably, two, three days later, why does my back hurt so bad? Actually, you know what? My knee hurts too. My big toe hurts. It's crazy. It's a recent thing.

[00:29:25] Past few years, it seems to be the joints are, for me at least, the most reactive in terms of, I don't know, inflammation or just veering off of my somewhat narrow path of what makes me feel good and what doesn't.

[00:29:38] Gregory: You're definitely not alone. I think it's one of the things that most limit people as they get older. And it can start at young age for some people. I'm 61, 62 now. I'll be 62 in February. So compared to even 15 years ago, I would have to take more breaks from heavy lifting and squats. I could feel that inflammation build quicker than when I was younger.

[00:30:03] Luke: Yeah. I played pickleball. I'm not a big sports guy, but group of friends were playing, and I was beholden to join them, and I had a great time. Actually, I've only done it once before. I didn't suck at it terribly, which made it a lot more fun. But I came home, and the next day I was sore in places that I didn't even know I had. And I played pickleball for three hours or something. I'm like, oh my God, dude, you're getting older. I never would've even noticed that a few years ago.

[00:30:31] Gregory: Yeah. One of the things with aging is that resilience that just slowly goes. And so it's called anabolic resistance, is the way researchers would term it, but think of like, it's the equivalent of insulin resistance but just with anabolic stimuli. So more protein, lifting weights. As we get older, our muscles just are less good at being responsive to these anabolic signals.

[00:30:57] So makes it not only more challenging to grow muscle but even to hang on to what we have, and especially for it to stay strong and supple. But the other downside of that is that the same trauma we inflict on a 20-year-old and a 60-year-old, say, pickleball for three hours, the young person, they'll make a few senescent cells. A couple of days later, a week later, they're gone.

[00:31:20] They've just all went on their journey, or the immune system gobbled up the rest. But in that 60-year-old, that same amount of acute trauma, it's almost like an explosion of senescent cells in their muscle and joints. And weeks later, they're still hanging out in the body causing problems.

[00:31:38] So as we get older, the landscape just changes in these ways that scientists are learning more and more. But the cool thing is now there's some things they're also saying, hey, maybe we could do this. Maybe the landscape's not going to change, but if we can clean it up and get rid of some of those things, then we'll be able to do pickleball and bounce back quicker.

[00:31:59] Luke: All right. Cool. So let's talk about senescence and senescent cells and start to just really drill down into this topic because I find it so interesting. So why, I guess we could start, is this particular natural process of the body such a key part of how quickly we age?

[00:32:20] Gregory: Yeah. So there's, I guess, a model called the hallmarks of aging. But what they propose is there's 12 areas that, no matter what organism, could be a fly, could be a mouse, could be a monkey, could be humans, could be an elephant, aging affects these different physiological areas. So telomere is the one. They tend to get shorter as we get older.

[00:32:42] DNA tends to get damaged. So when we replicate it, there's errors in that. Another one would be the gut tends to have dysbiosis. So our gut isn't the same as we get older. The species change. The performance changes. And one of those 12 hallmarks is called cellular senescence.

[00:33:01] And it's thought to be, again, into that damaged area. So to understand senescence, I think it's best just to start at a higher level. And that higher level would be stress. So when cells are stressed, they'll try to respond to that. And the initial response with a low level of stress will be, oh, let me upregulate my antioxidant defenses and other things to make me more resilient so that I can buffer that stress.

[00:33:27] So a low level of stress, that hormetic dose that biohackers would talk about, that would be what cells do. They'll get a bit tougher. But if there's more stress than that, the cell will take you on some damage. So I was in the Navy, I mentioned earlier, and on ships most of that time, and one of the rates of-- you would have people whose specialty was maybe fire control technicians working on the computers.

[00:33:56] Someone else were the deck hands. But one of the specialties was damage control. So their whole job was making sure that any damage that the ship might take or did take gets repaired. And then most of the engineering, which was my specialty initially, one of your side jobs was to be on damage control parties.

[00:34:15] So one of those specialists would run it, but you'd help. And a Navy ship could take damage, obviously, if there was a war, like Pearl Harbor, with ships being torpedoed, you taking damage, even maybe sinking. So that's external damage. Maybe someone doesn't do their job right and starts a fire. So there could be internal damage that now has to be repaired.

[00:34:35] And our cells are exactly like that. They can take damage because of normal things going on inside, and they can also caused to be damaged by what we might cause stress, external things-- EMF, radiation, nutrient stress, too much sunlight on our skin, if we get to that point of burning.

[00:34:59] So all these things we think of as stressors, on a whole-body level, can also be stressors on the cellular level. And when a cell takes damage, it doesn't have those damage control specialists in the Navy. There's its own damage control thing.

[00:35:14] So autophagy would be one of the big ones. So if a cell gets stressed enough that some of the proteins and other things inside it get gunked up or damaged, that's when autophagy comes in. It's like, oh, well let's just let fix that, repair the damage. But what senescence is, it's taken more damage than can be repaired.

[00:35:35] So fundamentally, it's an unrepairable cell that now it's just hanging out. And ideally, and this is what would typically happen in a 20-year-old, is that senescent cell is transient. It'll be made, but a couple days later, it'll self-destruct. Or if that process doesn't unfold, the immune system will find it because the immune system, one of its jobs is to find stress cells and gobble them up.

[00:35:59] So what happens in aging is what we would refer to at Neurohacker as lingering senescent cells. Those two things didn't happen. It didn't self-destruct. And in fact, lingering senescent cells are actually exploiting mechanisms to intentionally not go through that.

[00:36:16] And as we get older, it's called immunosenescence. But our immune system, as we get older, is less good at finding all kinds of stress cells. So that combination causes just this explosive growth in this special type of senescent cells in our tissues as the decades pass.

[00:36:33] Luke: And how does autophagy relate to senescent cells? Or does it?

[00:36:39] Gregory: It does. Think of autophagy as an anti-senescence program. By repairing a cell, it will prevent it from becoming senescent. But once a cell is senescent, the ship cell, so to speak, it's too late for that cell, but would still be helpful for other cells that are repairable.

[00:36:56] Luke: And what about mitophagy?

[00:36:59] Gregory: So mitophagy is the autophagy from mitochondria, so similar. One of the reasons cells become senescent, or a reason, is mitochondrial dysfunction. So mitophagy would, again, help prevent that. So it's a stress response that's preventing cell from being so damaged that it can't be repaired.

[00:37:19] Luke: Does having adequate NAD levels help one be more resilient to any part of that process?

[00:37:27] Gregory: Yeah. I think Charles Brenner would be one of the lab research experts. He's the original patent holder on nicotinamide riboside. But what his lab specializes in is where NAD meets metabolic stress and all kinds of things that would cause stress on cells, stress the NAD pool.

[00:37:46] It's one of the things that gets stressed first and foremost, and it's why I think the early animal experiments were so encouraging, because often, metabolic stress in an animal, you may just create that with a high-fat diet, as an example, in a mouse or rat model. And in those contexts is where boosting NAD seems to play a huge healthy thing.

[00:38:09] But the same if there's some exterior insult to the system as well beyond just diet. It doesn't really matter what the stress is. At a cellular level, a lot of the responses are the same.

[00:38:21] Luke: In terms of the buildup of senescent cells in the body due to an excess of stress, has anyone looked at how emotional stress factors into that?

[00:38:33] Gregory: I've not seen that.

[00:38:34] Luke: Experiencing chronic trauma, or is holding PTSD, or anything of that nature.

[00:38:40] Gregory: The area I've seen most looked at is with the telomeres and the length of those, and they tend to be a lot shorter in people that have had more trauma or stress. Short telomeres are known to be one of the things that can cause a cell to become senescent. I think it's probably not the main player.

[00:38:57] I mentioned think of senescent cells as a category. So telomeres getting too short would be one of the things that could cause a cell to become senescent. But I think the most common thing that happens over our lifetime, and it's mostly because of our environment, is stress-induced senescence. So I think anything that causes stress is very likely to be able to cause cells to become senescent. That particular thing I haven't seen studied yet, though.

[00:39:27] Luke: Okay. Got it. So obviously, it makes sense that if we're having this buildup of senescent cells as we age, in the example you gave of a young pickleball player versus an older one, we want to do things that can assist our body in getting rid of them, supporting it so that as you age, you can keep up with it and not get overloaded with these cells.

[00:39:47] And I could be mistaken here, but it seems to be senolytics, which we're going to talk about it could take different compounds that your body responds to positively in terms of dumping these excess cells. But then I've also heard that fasting can be a great way to support that process too. So let's maybe start with fasting and then get into some of the exogenous stuff that you can do also to help yourself.

[00:40:16] Gregory: Yeah, I think for fasting, I tend to be specific. So you've got your intermittent fasting, which, most people, that's a time-restricted window, eight hours, 10 hours, 12 hours, whatever. And there's definitely, towards the end of that window before refeeding again or eating, you're starting to see some ramp up in autophagy.

[00:40:36] Most things aren't binary. It's not like a switch. It's coming up. And for sure, a more prolonged fast, so a couple of days to three days, you're going to start to see autophagy now ramped up even more and get a bigger effect on autophagy.

[00:40:51] There's been very little to no research on when a water fast or something like the ProLon, the Valter Longo Fasting Mimicking Diet might start to get to some senescent cells. And in part is because they're so hard to measure. But my intuition is maybe that three- to five-day window is when Longo's research would show that you're really drastically changing.

[00:41:16] Some of the cells that would be most stressed would become maybe more visible to the immune system in that window. So I think the immune system, if nothing else, on a prolonged fast, even if the fast itself wasn't senolytic per se, it's now going to rejuvenate some of the immune system and maybe unmask some of the senescent cells that were doing a good job hiding from it.

[00:41:41] But a shorter fast, I would say, probably wouldn't do much. And a longer one, it's probably not worth being hungry for any more than just to get that initial unmasking and to make these stress cells stick out a little bit more.

[00:41:55] Luke: Do you think there's any difference in the response between say, a water fast and a dry fast for an extended period of time in relation to senescence?

[00:42:06] Gregory: So I think a huge amount of the response has to do with nutrient sensing. So our cells have elaborate gene networks, protein networks inside them that sense the environment. mTOR would be one that I think a lot of the, at least the biohacker space is really familiar with. But there's a whole bunch--

[00:42:25] Luke: [Inaudible] talks about mTOR all the time.

[00:42:26] Gregory: There's a bunch of other ones. So mTOR more specific for sensing amino acids and proteins, but other things sense sugar, you name it. As an example, have you ever heard of methionine restriction?

[00:42:39] Luke: Mm-hmm.

[00:42:40] Gregory: So methionine restrictions somewhat mimics what calorie restriction does, but you can eat all the calories you want. As a matter of fact, in a mouse, if you fed them perpetually a methionine restriction diet, they would eat more than normal. It's almost like they're sensing they're not getting enough of something, and they're trying to make dew. But just having inadequate amount of that changes the nutrient sensing.

[00:43:04] And a general rule of thumb, and this is crazy general, so, audience, beware, when something is missing in the environment or sends that famine, or fundamentally, the message might be the environment looks like it's going to be a little bit less good than it is right now. We better prepare for that.

[00:43:24] And preparation usually means, let me get rid of the things that are least necessary for survival. So the autophagy recycles things inside the cells, damage their stress cells, get recycled, because they're almost like leaves falling into a soil. If those get recycled, now available for new growth when the environment's better.

[00:43:44] So I think the key thing is always doing things that cause our cells to sense the environment's not as great. And there's all different ways to restrict that, but even what I would think of as the plant-based senolytic compounds, that's largely what they do. They're working on these elaborate nutrient-sensing pathways and just causing the cell to then toggle and say, okay.

[00:44:08] So senescent cells, almost, think of as stuck in this, should I stay? Should I go? The old-class song. And so it's not a binary thing. It's trying to make up its mind. But currently, the not-go has one out. And so what you're trying to do always, whether it's through fasting or these other tools, is to get it to change its mind and toggle back to, like, should I stay? Should I go? Yeah, I'll go. And then you go, finally, through that process of just disintegrating, it can now be reused and recycled.

[00:44:40] Luke: I wonder if that process you just described is a partial explanation as to why people that go on a restrictive diet like the carnivore diet or, conversely, a vegan diet have such great results at first. Do you think that that plays into it? It seems that people do really well for a while on a radical approach, and then, I don't know.

[00:45:04] I've seen some people that go for a few months, if not a few years, on either one of those plans, but it tends to plateau for people based on my observation. But I wonder if part of the initial boost that one gets is from eliminating glucose, or protein, or different things that might not be present.

[00:45:23] Gregory: I'm sure, on a molecular level, there's some of that. But I think going back to where we started, sense is everything's designed off proportional change. Think of the receptors on our cell as the ears and eye of the cell. So that same principle that we talked about. It's not just quantity of something, but it's how that changes is what creates response.

[00:45:43] So that's the same on cell receptors. And fundamentally, if you were to take an average person-- so this would've been when I was in practice in Greenwich, Connecticut. A lot of my New Yorkers in that part of western Connecticut, New Jersey, were my main clients, and a lot of them ate fairly healthy.

[00:46:01] But if you've got them to eat even differently, that often created a big change, and then you get a good response. But we accommodate. Anything that we hold constant eventually disappears from our senses. So if we could hold an image unchanging in front of our eyes or have the same tone playing constantly, our nervous system would block it out.

[00:46:25] And I think diet works somewhat the same. And so one of my nutrition teachers when I was in naturopathic school-- and unfortunately, there's not a whole bunch I remember of the wisdom he shared-- but the one thing that I locked in and I'll never forget is that there can be a huge difference between a diet that takes an unhealthy person and moves them to health and one that keeps them at health.

[00:46:49] And his idea was that quite often, the diets people would tend to go on to move dramatically from unhealthy to health, you'll just cruise right through health if you're not careful. And so I think that's what we see, and that's what you've noticed in your friend network and other people you've worked with.

[00:47:06] So the more extreme the diet, probably the quicker it's going to move us, but also the more likelihood it'll cruise us through. So independent of what's going on to cell, I think that's just something I tend to lock in. And I did the more restrictive vegetarian diet for about six years at one point.

[00:47:26] And then at the time, it was Barry Sears' book, The Zone, was the big thing. And I heard him speak a few times, and I'm like, I should see what happens if I reintroduce salmon and some fish. And I felt way better. So wasn't hard.

[00:47:40] Luke: I had the same experience. I've heard you talk about eating for your blood type.

[00:47:46] Gregory: Mm-hmm.

[00:47:47] Luke: I think the author you mentioned earlier. And some years ago, whenever it came out, I remember reading that and got on board with that. How these trends come and go, and then I just, I don't know, forgot about it and then just started eating whatever. But some years have passed. Do you give any credence to that philosophy?

[00:48:09] Gregory: So it was him that I worked for when I was in practice in Greenwich, Connecticut.

[00:48:14] Luke: What's his name?

[00:48:15] Gregory: Peter D'Adamo.

[00:48:16] Luke: Ah, okay. Right.

[00:48:17] Gregory: Yeah. He's a second-generation naturopathic doctor. His dad, James D'Adamo, was the originator of the blood type diet. And his dad was more that mad scientist. He was over in Brooklyn in one of the boroughs in New York City. And he just had this idea, oh, blood carries nutrition. Maybe I'll just blood type everyone, ask them what they eat, have them change some of the things they're eating, and just get their feedback.

[00:48:45] Almost what we would think of n of one, like biohacking now. Are they improving, and do I see any pattern in that? And so he wrote a book, I think it was in the late '70s, called One Man's Food, that largely was the same blood type diets. The majority of them came from him and his trial and error.

[00:49:04] And then Peter went to naturopathic school and wanted to see if there was scientific explanations for why his dad's observations worked, which eventually led to his book. So the diets, I would say, are more sciencey than science. They're truthy. But they can be really useful.

[00:49:25] So what I saw in practice, and some of this could be placebo or other things, but I can't tell you how many people I saw that came in because they'd gone on the O diet and had corrected an autoimmune disease or something else big.  So I saw some pretty amazing things on it.

[00:49:41] So I try to be fair-minded, and I often do things, like, is this useful or not useful? And I think of the blood type diets as in the useful camp. So I don't think it's going to work for everyone, but it's worth a shot, especially the A and O. The B and AB, in part, just because there's so few of those blood types relative to how many A's and O's there are, I think the original observations weren't as robust. So I think the trial and error to nail those down wasn't quite as good.

[00:50:11] Luke: Cool. Thanks for your perspective. I get questions about that sometimes, and I'm not sure. I didn't try it long enough to come up to with my own conclusion.

[00:50:19] Gregory: If you think just archetypally, your O would be more your paleo. The blood type diet for them wouldn't a high-carb grain type of thing. A's, often they're labeled as more vegetarian, but think of an Okinawa diet or Japanese fishing diet. I'm Irish ancestry. My ancestors would've had seafood, oats, potatoes.

[00:50:46] It's easy to oversimplify them, but I know I tend, personally, to do better on those coastal type of indigenous diets and less great if I go really meat heavy, where I've, like I said, over the years, known lots of O's that thrive on something that's more that type of diet pattern.

[00:51:05] Luke: What about brain aging and senescent cells?

[00:51:10] Gregory: Oh yeah. So senescent cells can really impact every tissue in the body. So just in a big picture sense, I mentioned it's a relatively new area. So the connection between senescent cells and aging only goes back about 20 years. But then the really big leapfrog was around 2008. They genetically created some animals so that they wouldn't produce senescent cells. And lo and behold, they found like, oh, a lot of the things that happen in old age in mice aren't happening in these animals.

[00:51:38] That's super cool. So that really, I think, leapfrogged the industry. And then 2013, the work was done and published in 2015 by Mayo and Scripps Institute of Aging. But they were the ones that found that certain compounds, including a plant-based compound called quercetin, could act as a senolytic. So you didn't have to genetically program these animals not to have them. You could do something and get rid of them.

[00:52:00] If there was a big uptick after 2008, it's just been like this since. I don't think there's any tissue they haven't looked at. Brain, joints, muscle, fat, tissue, liver, heart. The most, I guess, simplest way to describe it is you could pretty much bank that each decade you're going to have more senescent cells in those tissues. And in the brain, they used to think-- so neurons. Have you ever heard that an average cell lives about seven years?

[00:52:33] Luke: Yeah, yeah.

[00:52:35] Gregory: It's true but crazy inaccurate.

[00:52:38] Luke: Really?

[00:52:39] Gregory: Yeah.

[00:52:39] Luke: That's such a commonly held belief. Your body today is a totally different body than it was seven years ago. You hear people say things like that all the time.

[00:52:47] Gregory: It's true, but it's going to be very different tissue to tissue. So blood cells last about 120 days. Skin cells, a couple of months. Neurons, a lifetime. We never turn neurons over.

[00:53:01] Luke: Really?

[00:53:01] Gregory: Yeah. Retinal cells in our eyes, the same. Muscles, about eight years. Heart tissue, 40. So it's crazy different tissue to tissue. But we are constantly. Every minute, while we've been talking, we've turned over millions and millions of cells. In a day, it would be in the billions of cells that would die off. But it's very different tissue to tissue. So the average is seven, but that's a meaningless average.

[00:53:30] Luke: That's super trippy. You just debunked a really commonly held belief.

[00:53:38] Gregory: And that type of cell turnover, that's all going through apoptosis, which would be-- I said a little bit of stress, cells get more resilient. They toughen up more. They take some damage, autophagy and repair mechanisms. More than that, they're unrepairable and ideally should go through this than apoptosis.

[00:53:57] So that's the planned cell death. And that just causes a cell to just break apart, and the immune system comes in and cobbles it up. So that's going on all the time, all the time. We want ultimately more of the senescent cells to complete that journey as well.

[00:54:12] Luke: So we talked a bit about fasting as it pertains to senescence. Before we get into some of the different compounds that have been proven to help with this, are there any other diet or lifestyle practices that have been shown to slow that down, or rather speed that up?

[00:54:30] Gregory: Yeah. That's a great question. So the two things I've seen the most studied would be exercise and things to do with calorie restriction. Scientists use the term senotherapeutic to be the category of things that might be therapy, so to speak, in terms of either preventing the accumulation or doing something about it. And they use the term senolytic for things that would remove current senescent cells.

[00:54:54] And senomorphic in a way would mean preventing new senescent cells to be made. And things like exercise, good diet, get enough sleep, I think are in that senomorphic. They help either slow or prevent that from happening. But once a cell is senescent, I'm not sure. There's definitely not science that shows, in a broad way, as an example, playing pickleball wouldn't have been expected.

[00:55:27] Luke: Saunas and--

[00:55:28] Gregory: To remove existing ones, it would've created new ones in someone my age, for sure.

[00:55:32] Luke: So saunas and green juices aren't going to get you out of this one, in other words.

[00:55:36] Gregory: Yeah. They're probably keeping the amount, instead of going like this, maybe it's going to go more like this. So I think of those things as crazy useful in my useful analogy. The way I think of it personally, I want do a portfolio of things to keep me healthy just like I want to do a portfolio of exercise. So I want to do a little bit of yoga or flexibility. I want to make sure I do something aerobic, and I want to lift weights.

[00:56:03] Luke: You know what I just got back into because I just rehabbed it? Rebounding. I have this Bellicon rebounder. I've had it for years. And I just always keep it outside, so it was quite weathered, and it didn't feel that safe, so I wasn't doing it that often. And then last couple of times I did it, a couple of the bands busted, and I could have busted my ass.

[00:56:24] So I ordered the parts to build a new one, and I've been on that thing every day. I think that is my favorite form of exercise because it doesn't require any preparation. There's no set duration, I guess, unless you had specific goals. But I just keep it out by the ice bath, and I find it to be the best way to get the energy moving in the body, especially when I'm very sedentary, which unfortunately a lot of my work is, recording the podcast, working on the computer.

[00:56:53] Being a type of guy that doesn't do a lot of manual labor, I love that thing. I'm obsessed now. Many times a day, I go out there maybe just five or 10 minutes, and it's a really great refresher. And I can feel, when I come sit down again to do more work, that I feel like a different person.

[00:57:14] Gregory: Just thinking, again, going back to that proportional change, the degree you created just in that short break compared to walking around the block would be some change, but the rebounder is going to step that up a couple of fold, right?

[00:57:26] Luke: Yeah, yeah. I'm a big fan, so I highly recommend, folks, rebounding. And also, unless you fall off it and bust your ass, seems to be pretty safe and low impact, much more so than jogging on a paved street or something like that. I never feel sore, per se, after it, but you can get winded pretty quick.

[00:57:46] You can get the heart pumping in about five minutes and feel like, wow, I just actually did something. I haven't tested with my Oura Ring. I've been meaning to see because whenever I look at the stats on the Oura Ring, it's always like, ah, you suck. You didn't move enough. The sleep scores are great, but I was like, move more. That's the message I get every day. So I'm going to see. All right, Oura. I'll show you. I'm going to get on that rebounder 10 times a day.

[00:58:09] So your folks over at Qualia, your cohorts there sent me this Senolytic. Comes in this little pack, and they were kind enough to send it to me for free, but I'm like, ah, man. I don't even know how much it is, but I'm like, if I like this thing-- I'm already spending so much money on supplements. I can't take this every day.

[00:58:28] And then I opened it up, and there was, I don't know, eight of them in there or something. No, six of them in there. I was like, what? And this is a full-sized box. I was like, if I like this or I feel it, the science backs up its efficacy, I'm not going to be able to take this all the time. And then when I read the instructions, it says, take-- or does it come with 12?

[00:58:48] Gregory: Yeah, 12.

[00:58:48] Luke: Yeah, 12. Okay. It says, takes six capsules per day on two consecutive days, and then wait about four weeks. Use monthly for best results. I was like, all right, I can get behind that. That's my kind of supplement, man, especially just because I'm taking so many freaking supplements every day.

[00:59:03] And I know so many of you people listening to this podcast are just like, oh my God, I'm already taking so many freaking supplements. So break down how the Qualia Senolytic works and specifically why it's not something that you would need to or want to take daily.

[00:59:20] Gregory: Dosing's a really interesting topic when you think about it. So I tend to be-- and Daniel Berger was the same. He's a complex system, science think tank kind of guy. But complexity science, I think, is the best explainer for how adaptive systems like humans respond.

[00:59:39] And so in a simple sense, we adapt to things over time. So we want to create some intermittent for many things. And the exception to that would be if someone's on insulin or thyroid to manage a medical issue, they need to take that every day. A lot of medicines are intended to either occupy a receptor or block an enzyme.

[01:00:03] So those are things you need to do all the time, all the time to have that response. But think of water-soluble vitamins, like your vitamin C or B vitamins. You need those fairly frequently to run out, but you're not going to run deficient if you miss a day on vitamin C as an example.

[01:00:20] And then other things like fat-soluble vitamins store up. So you need those less. So depending on the thing, how frequently you might need to take it, your use case can be different. And senolytics, their use case is just so disparate compared to any of those things I just mentioned that really-- I mentioned that should I stay? Should I go?

[01:00:39] So that's a network of proteins inside the senescent cell that's voting currently like, oh, we're going to hang around. So all you want to do is just change the vote a little bit. Maybe it's currently 52 to 48%, stay verse go. All you need to do is disrupt that voting a little bit to get now 52 to 48 the other direction.

[01:01:01] And once that happens, the senescent cell will now finally recapitulate, is the word sometimes you'll see science-- but basically, finish that journey it started but didn't get to. So all you have to do is just temporarily change the voting, and then that senescent cell will go through this normal physiological process and be gone.

[01:01:20] So our VP of marketing loves gardening, and the way I described it to her is like pruning a plant. You don't need to prune your plants every day. Matter of fact, it's probably detrimental. You just need to prune them periodically, once a month, once every couple weeks, and then you're going to get good results.

[01:01:39] And so senescent cells should be thought of like that. When you're doing a senolytic, it's much more like you're just pruning away some of these cells and then you're good until the next time to prune comes along.

[01:01:49] Luke: It's not great for marketing. If I started a supplement company, I definitely wouldn't have the one that you just take once a month, but that makes sense. Let's break down some of the ingredients in here. Now, a couple of them I'm somewhat familiar with, and some I'm not, or I've heard of them but don't know that much about them. So the first one is fisetin.

[01:02:13] Gregory: Yeah. So fisetin is a polyphenol. So it's really yellow. It's actually from a German word that means something like yellow because it was a dye way, way back. Quercetin is similar, another yellow polyphenol. So I mentioned the original Mayo, Scripps Institute publication in 2015 that coined the term senolytic.

[01:02:36] What they did before that is they looked, okay, these are all the network of things that are causing the cell to vote that I'll stay around. Well, what things has science found that affect that network and different places in it? And they created this library of compounds, and then tested them, and eventually came up with two that acted as senolytics, especially when combined together, and would cause cells to finally go through that breaking apart process.

[01:03:04] And quercetin was that. But what it needed to be combined with to get the best benefits was an immunomodulator medication called dasatinib. So not a dietary supplement. So the Mayo Clinic and Scripps continued to work and said, okay, well, are there other plant polyphenols that may be even better than quercetin and be able to do a job without having to stack them necessarily with something else?

[01:03:29] And that panel led to them finding that fisetin was the most robust of the different senolytic compounds way more so even than quercetin. It's a plant polyphenol dietary supplement. So at that time, that was 2018, in a WhatsApp group that I'm in with a lot of the heavy hitters in the longevity space, all of a sudden, it was like, oh, what's called the D&Q stack?

[01:03:54] The dasatinib and quercetin. Dasatinib has potential significant side effects. Let's just move away from D&Q and just play with fisetin. So it became the big thing since 2018. And what I would say is that longevity biohacker niche of people that said, oh cool, this is doing some amazing things in mice. I'm going to give it a shot myself.

[01:04:19] And so because of that, last time I looked on clinicaltrials.gov, which, beware, you register trials in advance of actually conducting them, there was nine or 10 fisetin senolytic studies that were anywhere between recruiting and ongoing. Most of them sponsored by Mayo Clinic.

[01:04:41] Luke: Badass. Between this combo of the fisetin and quercetin, is this what they're going for when people use metformin, the pharmaceutical? Or is that a different goal?

[01:04:53] Gregory: Yeah, different goal. Metformin would be more on that nutrient-sensing, preventing cell from becoming senescent.

[01:05:01] Luke: Oh, okay.

[01:05:02] Gregory: And it works on decoupling energy production in mitochondria. There's all kinds of mechanisms, but yeah, metformin, I would think of as a completely different category. And a rapamycin would be different as well. That's going to be working on mTOR and, ideally, preventing a cell from becoming senescent.

[01:05:20] Luke: Got it. Okay. And then with the quercetin, I interviewed a really bright guy the other day from a company called Mara Labs, David Roberts. And he was telling me about-- I don't know. He didn't frame it this way, but the way I interpreted it was a dirty secret of the supplement industry in terms of quercetin specifically, is that it has a really low bioavailability.

[01:05:45] It's very difficult to absorb. And so a lot of the quercetin products on the market might have so many milligrams, but if they're not, I don't know, processed or designed in a certain way, they're basically expensive pee. Have you run into that particular issue when you guys were formulating your senolytic? Did you have to be specific or very intentional about the type of quercetin or the--

[01:06:12] Gregory: Yeah. So the answer is yes. We use something called quercefit, but I'll get to the polyphenols first. So as a category, polyphenols are very poorly absorbed. So we have prebiotics in this product, Qualia Symbiotic. So prebiotics are usually fibers that survive digestion and get down to the gut microbiome where the bacteria there can use them as food.

[01:06:35] Luke: I love that stuff, by the way.

[01:06:36] Gregory: Oh.

[01:06:36] Luke: You could probably feel it's almost empty because I've been using it every day. Yeah. Gut is something that's a challenge for me, and that's been very helpful. So hopefully we can get to that too, but anyway.

[01:06:49] Gregory: And I brought that up because polyphenols are prebiotic-like. They're not classically prebiotics, but most polyphenols survive to get at least a large portion of them, down to the gut and then certain organisms there thrive on different polyphenols.

[01:07:06] So because of that, like a berberine as an example, or even metformin, since you mentioned that, some of the effects of those are for sure happening in the gut, and then systemically we benefit. So it's often pitched as a downside, but maybe a lot of the reasons some things work is because they're surviving digestion and interacting with the gut microbiome.

[01:07:27] Luke: So actually, mentioning berberine, that was one that he was talking about too, that the low absorption can be an issue. Yeah.

[01:07:34] Gregory: Yeah. So that would be true for anything that's in that polyphenol categories. So resveratrol would be another one. Many of the things in Qualia Senolytic are polyphenol, so it's true for all of them. With fisetin as an example, all of the research so far in animals and what's going on in humans with Mayo and other groups is using what I would think is a non-bioavailability-enhanced fisetin.

[01:07:59] And so they dialed in the dose they're using, and it's 20 milligrams per kilogram of body weight. So if you look at Qualia Senolytic, you'll see a really big dose of that. But that's why. To get that senolytic effect, it's not just enough to have fisetin. You have to have enough fisetin.

[01:08:16] So with quercetin, the reason we went with quercefit, which is bioavailability-enhanced, is because that's been used as a senolytic in animal studies, and it's being used in human studies. So at the end of the day, I think bioavailability is a great story, but I care much more or did not something work in the experiment, whether that's animals or humans.

[01:08:40] And if the only thing so far that's been used is non-bioavailability-enhanced, I'm a little bit leery to then say, oh, the bioavailability-enhanced version would be better. Maybe, but maybe it'll be worse because now you miss doing a bunch in the gut. And 70% of our immune system resides in the gut. And the immune system is maybe the thing that senolytics most impacts because of senescent immune cells, and T-cell exhaustion, and all those other things.

[01:09:10] Luke: That's interesting. Yeah, it's something like butyrate, where you can take butyrate, and I take it, but probably optimal if you're taking foods that are great for the gut biome, and then that bacteria is creating the right amount of butyrate that it wants and needs.

[01:09:29] Like I said, I still take it because I don't trust my gut to make it. But it reminds me of that. There's all kinds of mysterious things going on in the GI tract that we probably are barely scratching the surface of understanding, and perhaps the reaction of the polyphenols that you described is part of that.

[01:09:46] Gregory: Yeah.

[01:09:46] Luke: So it's not, to use your word from before, a binary process.

[01:09:52] Gregory: Right. It doesn't make them bad. At the end of the day, and I think this goes back to maybe my more engineering brain, but also working with patients, did my patient's performance improve? Bioavailability is just the story. That if that story plays out in the real world, then maybe they improve more.

[01:10:13] But what I see quite often by the companies that pitch me their ingredients is, oh, I've got this great bioavailability study on this ingredient, Dr. Greg. And it's like, yeah, well, how about doing a study to see if it improves brain performance or something that I actually care more about?

[01:10:31] Because it's just a theory that it would. Maybe it would. Maybe it's going to be worse. So at the end of the day, that's like Sherlock Holmes. It's a capital mistake to theorize in advance of evidence, and bioavailability is pretty low on my hierarchy.

[01:10:46] Luke:  That's a good one. Say that quote again.

[01:10:48] Gregory: It's a capital mistake to theorize in advance of evidence.

[01:10:52] Luke: Wow. A lot of people needed to hear that over the past three years.

[01:10:57] AD BREAK > 60%

[01:10:58] All right. Now I don't know if I can pronounce these other ones. Piperlongumine.

[01:11:05] Gregory: I would say piperlongumine.

[01:11:07] Luke: Piperlongumine.

[01:11:08] Gregory: That INE is usually an alkaloid, like piperine, anything like that. INE.

[01:11:12] Luke: I know that one.

[01:11:13] Gregory: Polyphenols usually have, like the fisetin, the IN at the end. And alkaloid, usually, it's the INE, so things like-- think of some of the classical psychedelics. They're an INE. They're alkaloid these things. Reserpine is another. Yeah. So piperlongumine is this really cool compound that's found in long pepper, which, there's black pepper and long pepper. They're closely related plants.

[01:11:38] In fact, 1,500 years ago, 2,000 years ago, long pepper was used how we use black pepper today. And it's still that way in Thailand, and India, and places like that. So it's a relative of that. And the difference is that both have something called piperine, which you'll see sometimes with turmeric to improve its bioavailability.

[01:11:59] But only long pepper has the piperlongumine. And the piperlongumine is a senolytic compound, and the piperine isn't. And so one of the things that I think makes Qualia Senolytic distinctive is we sourced this really potent extract, or Piper longum, standardized for high amounts of piperlongumine.

[01:12:19] Luke: Oh, that's cool. I've also heard-- and again, I don't know if this is true, but thought memes travel for wellness aficionados, or at least those of us that are trying to be-- to activate the curcumin in turmeric, a lot of brands in their marketing will say, we put pepper in there to make it more bioavailable, absorbable, etc.

[01:12:42] And then there's another school of thought that says, well, that irritates your gut lining, and that's why you're absorbing it more. So you just get lost in some of this stuff. You're like, who do you believe? But it sounds like with that particular ingredient, then that's a non-issue.

[01:12:56] Gregory: It's different.

[01:12:57] Luke: Okay.

[01:12:58] Gregory: They're both alkaloids. They're both found in some varieties of pepper plants, but yet it's just a really different compound. And one of the things I think that's-- and this came out of that original D&Q research. So what Mayo thought at the time is that, oh, maybe you need to affect several different things in that network of things that are causing the cell to vote, like, no, I'm hanging around.

[01:13:25] And different compounds act on different proteins in that network of things. So often, they'll use the idea of nodes. Think of airports as being a node. You want to dismantle different nodes. And quercetin works on slightly different nodes than the dasatinib, as an example.

[01:13:43] So that was one of their initial, I think, aha. This is a complex network of things we want to have more than one molecule to intervene in it. The other thing that came out of the original work that has now been shown over and over is, I've mentioned senescent cells are a category.

[01:14:01] So what they find, even in that original research is there was some tissues that dasatinib worked in where quercetin wasn't very effective, and vice versa. Quercetin was more effective than others. And when you put them together, they were complimentary. You got more tissue coverage, and now you were getting more senescent cells because you're now dismantling more nodes in the network, so to speak.

[01:14:24] And so the reason I bring that up is because piperlongumine works in such a completely different way than things like fisetin or quercetin. It's really doing something that no other senolytic compound to date has been shown to do in terms of getting the system to vote.

[01:14:39] Luke: That's really cool and true Neurohacker Collective form too. You guys are always next-level. Like I said, when Qualia Mind came out, I looked at the ingredients. Not only that, but I went on the site, and I was like, holy shit, these guys have all the data on every single weird obscure compound in this stuff. So that's really interesting.

[01:15:00] What about the Synactiv? And I'm so glad you know the answers to these questions because it would be embarrassing if you're like, yeah, I don't know about that one. You know your stuff.

[01:15:09] Gregory: Yeah. Synactiv's a branded ingredient that's been clinically studied, and it's a mix of notoginseng, which is-- you have regular ginseng, panax ginseng. Panax notoginseng is a slightly different plant, but some similar compounds anyway. It would have the ginseng aside.

[01:15:25] And then it also has a sweet rose extract in it. And that combination has been studied particularly for-- it's really an exercise ingredient. And what they did in one of their studies, they looked at senescent cells after exercise and found that that compound removed them.

[01:15:43] Luke: Oh, cool.

[01:15:44] Gregory: And again, one of the Neurohacker Collective's approaches to making Qualia Senolytic is we wanted to cover a lot of different tissues because just because something's senolytic doesn't mean it's senolytic in all tissues. It may be an export in adipose tissue, so fat tissue, and not do anything in muscle. So we were looking for compounds that specifically had research and different things, and that's our muscle compound, the Synactiv.

[01:16:09] Luke: Oh, that's amazing. And then what about, Longvida optimized curcumin?

[01:16:15] Gregory: Yeah. So in that work that Mayo did subsequently, where they identified fisetin has the most robust of the plant polyphenols, other things they identified that were also senolytic-- that was the first time at least that they were identified as senolytic-- were curcumin and luteolin. So both of those are in it. And the Longvida that was developed by neuroscientists. And that company that makes it, their tagline for it is the cognitive curcumin.

[01:16:45] Not all of their studies, but they've had a really brain focus on that particular curcumin. It is one of the bioavailability enhanced to get more in the blood so more can get to the brain. And that's part of the reason we picked that one, is because it's a cognitive curcumin. And you had mentioned earlier, like, oh, the brain and senescence, what's the connection?

[01:17:05] And it used to be thought, since we don't make more neurons, that they wouldn't become senescent. Because the idea of senescence, as originally thought of, is it's a mechanism to prevent cells from making new damaged versions of themselves. But a cell, like a neuron that's never going to make new ones, why would it become senescent?

[01:17:24] But neurons can become senescent. And then, in the brain, there's all kinds of structural cells, so microglia, or the brain's immune cells. And astrocytes are actually our structural support and provide nutrition. So long story short is there can be a lot of senescence, with the brain, and particularly with aging.

[01:17:46] And we wanted to have a compound that we felt good, could get to the brain, and have some activity there to help support the brain. And Longvida, in terms of just even an individual product, has some good cognitive studies.

[01:18:02] Luke: Wow, I'm sold, dude. I'm getting on this stuff every month. Goddamnit. My wife hears me say all the time, I'm done. I have a cupboard full of supplements I don't need anymore. I feel good, but then something really cool comes along, and I'm like, all right, I can do once a month.

[01:18:18] Gregory: It's funny. When we created Qualia Senolytic, I think I mentioned earlier that, pre-COVID, I used to go for vacation in Europe, typically most years for about two weeks because, going from California, I want to have a long enough stay. And I'd usually bring something I was really interested in to just nerd out over coffee in the mornings type of thing.

[01:18:38] And so back-to-back years, it was senescent cells and things that would play in. And long story short, I created something like a 100-page word document on mechanisms, possible things. And so maybe early 2020, I was super enthusiastic. I wanted to take something that put these things together and had to try to convince our team at Neurohacker that it would be worth making.

[01:19:05] And they're like, well, how's it going to sell? I'm like, oh, probably not well. Some longevity people, maybe some biohackers, but it's the right thing to do. And I would like to take it. So I got a couple of people on board, like, oh, all right, yeah, part of our mission is to stay on the leading edge and make the world better. So yeah, we'll make it. And we had no expectation this would sell at all, and it's currently our bestselling product.

[01:19:32] Luke: Is it really?

[01:19:33] Gregory: It outsells Qualia Mind now.

[01:19:35] Luke: Wow. Damn. And it's pretty new too. Isn't it?

[01:19:39] Gregory: It's been out a little over a year and a half. Yeah.

[01:19:43] Luke: I guess it's just more new to me. I thought I was on the cutting-edge in the first one that got in there.

[01:19:48] Gregory: But anyways, because of that, I wanted to take it, so I took it. We made some up in the lab way before we ever brought it to market. So I think I've probably taken our product-- oh, I don't think. I know I've taken it longer than anyone. And like you said, it's great to just have this one thing I only have to do two days a month. And for me, it's the first weekend of every month. I just have to remind myself on the calendar. I take it those two days. Usually don't do any other supplements those days and feel like, oh, I'm good for the next month.

[01:20:17] Luke: Do you have any other areas of interest that you're going to try to talk your team into developing?

[01:20:24] Gregory: I'm always trying. So my current one, but I haven't made much progress, is hydration. There's no shortage of hydration products, but almost everyone's doing suboptimal. I don't want to go too far off, but I would say-- have you ever heard of oral rehydration therapy?

[01:20:41] Luke: Uh-uh.

[01:20:42] Gregory: So other than antibiotics, it's probably the thing that saved the most lives, of anything. So in a lot of the world, cholera and diarrhea, that dehydrates people, is still a big issue. And going back many, many years ago, they figured out IVs could save a lot of lives. But in many of those places where cholera as an example would be a problem, getting IVs was just out of the menu.

[01:21:06] So for decades, scientists, public health tried to create an oral way to rehydrate people. And like most things in health, and medicine, and science, one step forward. Two steps back. Three steps forward. One step back. But eventually, what they found was it required a certain amount of sodium, certain amount of glucose, because the pump that allows that and pulls water in is a sodium glucose-dependent pump.

[01:21:35] So you need both. Everyone's so phobic of sugar. That there's just tons of rehydration products that use things Stevia, as an example. But I'm not anti-Stevia. But if you're trying to rehydrate, you need not a lot of sugar, but you do need a little bit of sugar.

[01:21:52] Luke: Oh, that's interesting. I didn't know that. Yeah, the powdered versions tend to have a sweet taste, but I've not seen any of them that actually have any kind of sugar.

[01:22:02] Gregory: Yeah. The World Health Organization makes their own rehydration, sachets, that are used all through the world for oral rehydration therapy. There's probably things you could do to improve on that, which I think if Neurohacker was going to do, we'd want to make a better version even than that. But that science is pretty established.

[01:22:23] Luke: Cool. That's good to know. I didn't know that. Yeah, there seems to be-- well, it doesn't seem to be. There are waves. Somebody comes out with a product, like a hydration powder LMNT, or something, for example. And I'm like, oh, this is great. Convenient. I have a drawer full of them. I keep them in the car.

[01:22:41] They're super handy, especially in Texas in the summer when you get dehydrated in about five minutes outdoors. It's so damn hot. But then you'll see 15 other companies basically come out with the same exact thing. There's a lot of bandwagon jumping. But nobody's jumped on that one, so that's interesting.

[01:22:57] Gregory: Yeah. And I use LMNT myself, but I add a little bit of sugar to it. But I'd rather not have to jury rig it myself.

[01:23:05] Luke: Yeah, yeah. Totally. I want to let people know that are listening, if you guys want to check out any of the Qualia stuff, go to neurohacker.com/lukestorey. And if you use the code, LUKESTOREY, you can save 15% off. So if you want to check out the Senolytic or any of the other stuff, definitely recommend that.

[01:23:23] And we'll also put a clickable note for you there at lukestorey.com/qualia, and that'll be in the show description, and so on. I think I've talked about the Qualia Mind product in my prior episodes because it's the OG of the Neurohacker Collective offerings. But there's one thing that I found, I don't know, a few months ago, a year ago or something, was a vision formula.

[01:23:48] I don't have one here because I went through it. I don't think I'm alone in this generation of myopic computer and phone viewers that the vision becomes a problem. And I see this for a lot of people, even younger people. And I personally think it's just from staring at screens. And we're designed to be looking over the horizon, hunting and gathering for vast distances, not staring at something in front of our face for hours a day.

[01:24:16] What can you tell us about that vision formula or any other vision tips that you might have even outside of that?

[01:24:23] Gregory: That Qualia Vision, my understanding is it's going to go away. It's not going to be--

[01:24:28] Luke: Ah, man. I hope you have a sale at the end. I'm going to stack up on it.

[01:24:33] Gregory: So that was another one of my things that I really fought hard to get us-- to me, because I'm on a screen a lot, and the common thing that happens when we're on screens is eye strain or eye stress would be that. And usually experience a range of things, anything from watery eyes.

[01:24:51] But if you use that up, that ability to adapt up, your eyes would be drier, dry eyes. You could feel stiffness in your shoulders, neck, things like that. Some people, headache. So there's a clustering of things people experience with eye strain. And no doubt, screens are the main cause of it in our current world.

[01:25:10] And a couple of tips for the audience. The closer our screen is to your eyes, the more eye strain it creates quicker. So if we have a big TV across the room, that's less eye strain than maybe the iPad that you're holding arms-length away. And then you get a phone, and you're this close, that's going to cause eye strain symptoms for most people really quickly.

[01:25:34] And then we want to do things to, ideally, make sure we don't get eye strain. This is going to oversimplify it, but think of the back of the eye. That's your retina. That's connected directly into the brain. So that's a big Andrew Huberman area. His neuroscientist specialty is on the visual system.

[01:25:56] But then the front of the eye is completely different. That's more like a lens on a camera, as an example. And between that, there's a lot of fluid, and there's all kinds of things that go on. But a big chunk of then why things are irritating from an eye strain is that the front of the eye, the stress, like the blue light, just the repetitive stress of the flickering even of a screen.

[01:26:21] And then the eye has a bunch of muscle, ones that rotate. If we look over here, up and down, those are external muscles. It's called the near triad reflex. There's pupilary muscles and accommodation muscles. And the best way to think about it is when we're steering at a screen, the closer it is, it's more like you are holding weight, maybe like in a biceps curl or just out with your shoulder.

[01:26:45] And at some point, you're going to just actually feel that muscle start to quiver. And if you hold it longer, you might actually see it physically quiver. So that's what happens with some of these poor muscles. When we're just staring at a screen, they're fundamentally quivering. They're exhausted.

[01:27:01] And so one of the things about the Neurohacker vision formula, Qualia Vision, is there's things for the back of the eye. So like your lutein and xanthins, things that are plant pigment. Then there's things for the front of the eye. So that would be like a bilberry or astaxanthin. And there's things for those stressed-out muscles to help them have better endurance. So that was how, when I created it, I thought about it.

[01:27:24] Luke: Well, maybe a little side project going.

[01:27:27] Gregory: I've been squirreling some away because I take that product Monday through Friday.

[01:27:33] Luke: Yeah. I burned through it in a month just because I feel that eye strain. And you're, I think, the first person, other than one guest that I had on named Jake Steiner. He's got an outfit called endmyopia.com, and he's-- I love contrarians. They just fly in the face of conventional wisdom, especially wisdom that's not necessarily true or completely true.

[01:27:57] And his premise is that optometrists have all been in-- I'm going to use very broad and general terms, but he would say the vast majority of them have been indoctrinated into the false belief that-- talking about myopia-- your eyes go bad. That there's nothing wrong with your eye, and they're not broken.

[01:28:20] I think our episode, which we'll put in the show notes, was called Your Eyes Aren't Broken, and Here's How to Fix Them or something. And he's the one that turned me onto the screens being the issue. And he said that basically what happens is it's like you have a cramp on the back of your eye or an atrophied muscle that just gets stuck because it's not getting the exercise of looking really far away the majority of the time, and it just gets locked there.

[01:28:47] And that you can undo it with active focus practices and things like that, which I haven't done with any dedication just because they require a lot of discipline and a lot of time. You have to look at an eye chart to where it's just barely out of focus, and you got to measure the distance, and it's a whole thing.

[01:29:06] People can listen to that episode. And one of these days I'll get around to it. There's just always some other issue I'm trying to fix. But to your point and the point that he elaborated on even further, one thing I do notice is, first thing in the morning, if I don't look at my phone, which is a great practice just for mental health in general anyway, and I go immediately outside and get sunlight my eyes and just look at far-away stuff, my vision is way better the entire day.

[01:29:35] If I wake up, and sometimes I have to look at my phone because I'm running late and I need to check a text or something, if I get stuck on my phone from that dopamine addiction first thing in the morning, my vision's shot for the whole day. And it's reliable, quantifiable, 100%, at least for me, subjectively true.

[01:29:53] I think there's really something to our behavior patterns around how we use our eyes. And then there's added support, like some of the nutrients you mentioned, and things like that, which is, of course, smart. But man, I think so many of us are going to end up having to wear glasses just from the devices. And the blue light, like you mentioned too.

[01:30:15] Gregory: Well, I think in parts of Asia, it's an epidemic there of people with nearsightedness, fundamentally right myopia. And it's interesting. So I was Navy, Navy scholarship, Air Force also, but I have fairly bad astigmatism with some nearsightedness.

[01:30:34] I think I was 20-40, 20-60 back at that time period. So I would never have qualified to be a pilot no matter what, which is fine. I didn't have a passion for flying. But from my original driver's license when I was 16, I've had a driver's license in Hawaii, Arizona, Connecticut.

[01:30:54] I never could pass the driver's test because one of the things with astigmatism is letters tend to-- like an E, the lines would tend to blur together a bit. And often the tests are like, which way is it pointing? And it's like, it's all blurry. But I moved to California in 2003, and I passed every year. But, in part, it was working some of those eye exercises.

[01:31:18] Luke: Did you do the Bates method or any particular protocol?

[01:31:21] Gregory: I didn't even know of it at the time. What I would do personally, I would almost rotate my eye in a full range of motion, almost like when you're stretching and feel like, oh, it's sore here. When I feel that, I feel like I'm clenching the muscle there to get it to relax.

[01:31:40] Luke: Wow. Cool.

[01:31:41] Gregory:  But since then, the base message would be a more reliable method than my backing into it way. But I've found the same, that especially if I do more of those things or I'm more attentive to how I use screens, my eyesight is much better.

[01:31:56] And if I'm inattentive or do things I know aren't great-- so another tip for the audience, we always think of vision just in that nearsightedness thing type of way. But we have dark vision. We also have visual receptors that are sensing the change in daylight.

[01:32:13] They're much more directly tied in with our body clock, but those are sensing the change in the lighting to the sides of us. So if the room's black, but we have a bright screen in front, now we're causing this huge conflict of information.

[01:32:27] Luke: Oh.

[01:32:28] Gregory: Right. So that's worse. You'd be better off if you're on your phone and it's night before bed. You're better off not using it. But if you are going to use it, it's probably worse to have the black in the back than a lit room.

[01:32:43] Luke: That's interesting.

[01:32:44] Gregory: I don't use it, but it's more stressful on the eye, having that conflicting information.

[01:32:50] Luke: That makes sense. Yeah. You just reminded me. There was a guy I had on the show, brilliant guy, Dr. Alexander Wunsch a couple of years ago, and he's just an absolute genius about all things light, just light guy. And he was explaining that overhead lighting is really bad for your eyes and your brain.

[01:33:11] And we went into all the different color spectrums of light and talked a lot about why blue light sucks, and all of that. But one thing I learned that I didn't know was overhead lighting is really bad because, again, going back to nature and evolution, it's very rare that the sun is directly above your head.

[01:33:29] And that's the only natural light source part from fire or moonlight-- starlight, I guess. I forget exactly how he broke it down scientifically. It was way over my head, no pun intended. But it's just one of those common sense things. You're like, oh, duh. Only at a certain time of year at solar noon is the sun pointing at the top of your head and your eyes are acclimating to that bright light being above.

[01:33:52] Most of the other time, throughout the day, it's off to the side, in the periphery. So it would make sense if you were lighting the interior of a home that you would want to use. And he recommended using sconces. If you're able to build a house, don't use overhead lights at all. Just have all sconces, and then adjust the color temperature according to what time of day it is.

[01:34:11] And I'm like, ah God, it's going to be a few years before humankind is like, oh. It's like asbestos, EMF, lead paint, DDT, all these stupid ass things we do. There will be a time, hopefully in my lifetime, when we look back and go, oh my God. I remember when we used to put all the lights in the ceiling, how stupid that was.

[01:34:29] And you can even tell when you walk in a room at night, say, with amber lights from lamps on tabletops versus walking in a room with bright blue light up above your head. It's a marked difference to your nervous system if you're attuned to that kind of thing.

[01:34:45] Gregory: Yeah. You would use the idea of naturalistic light. That would be something, I think, the more closely we can mimic nature, the better. And even if we were out full exposure middle of the day, our ancient ancestors would've been in trees, and the leaves were filtering out quite a bit of it. We're designed to freak out from things that are above us. Probably because our mammalian brain, once we were the prey, not the predators when we were little--

[01:35:14] Luke: You mentioned light flicker. I had this thought one day, or maybe I heard someone say it, even more likely, and I just don't remember who, but when we look at these LED bulbs, and fluorescent bulbs, and even some TVs and computers, if they're shittily designed have this 60 hertz flicker, where it's turning on and off 60 times per second, and it's imperceivable to the conscious mind, but it's really irritating to the nervous system.

[01:35:41] And if you think about evolutionarily, the only time we would experience a bright flickering light would be chasing prey through the woods or running from a predator through the woods, of that light flickering through the trees. It's like never in nature is there flickering light. It's always, always static unless we're moving. Quickly and there's only two reasons we're moving quickly, to get towards something or away from something. In both cases, your nervous system is going to be in a heightened state. It's really interesting. I love stuff like that.

[01:36:12] Gregory: Yeah, me too. I wrote a book around 2012 on, basically, how would Sherlock Holmes approach weight and issues? But one of the chapters is on light and lighting and how it impacts that, but all kinds of things. So it's crazy important. And again, in our world, we all know about it, but if I was to pull my cousins, and siblings, and nephews, and nieces, I don't think it's crossed out of our little niche.

[01:36:38] Luke: If you go to your average person and go, hey, do you know blue light exposure makes you obese? Like, what? How does that work? And you dig into the science, and it's there. It's true.

[01:36:48] Gregory: Yeah.

[01:36:50] Luke: All right. Before we jam here, I have a list here of some of the Neurohacker and Qualia stuff. And some of these I didn't even know about. There's a sleep. There's an NAD one, Resilience, Qualia Life, Skin. Oh yeah. I have had the energy shot actually before. Are there any of these that you're really excited about?

[01:37:11] Gregory: Yeah. I'll share what I use.  So this is relatively new, the gut-brain product, Qualia Symbiotic. So that's most days for me. So I would use one of our nootropics on a workday. Sometimes it's Qualia Mind, sometimes it's Qualia Focus, sometimes it's the energy shot. So today it was the energy shot just because, traveling, it was easy to throw one of those in my bag then take a bottle of Qualia Mind for this trip.

[01:37:40] The Qualia NAD is brand new, so that's only launched within the last month. So that's an exciting one that, so far, it's been great out of the gate. I think, for the audience, if you do things to boost NAD, it's really important just to do that first thing in the morning or as early as that.

[01:38:02] Not a lot of studies so far on what I think of as chronobiology, like circadian rhythms in the NAD system, but sometimes you have to live with what you have. And in one of the only studies I know of, when they gave NAD booster or infused NAD, like more as an IV, to animals at the end of their day, so the equivalent of our dinnertime, it actually made metabolic function worse, metabolic health work.

[01:38:28] When they did it at the beginning of their active cycle, it made it better. So until I know more, I would say take NAD boosters at the beginning of your day. And that's how I do it. So I usually take our Qualia NAD fairly shortly after I get up.

[01:38:43] Luke: That's good advice. I played around with some of the precursor products over the years, and now mostly just do straight NAD. There's a company called Ion Layer that has these transdermal stickers. Now, truthfully, not to shit on them because I still use them, but they irritate my skin quite a bit. But I just, ah.

[01:39:05] But one thing I noticed that's interesting about that NAD, and it's way cheaper and a lot less harsh than getting an IV, like an infusion, you don't even notice it. You just have a lot of energy. But I put one on later in the day, and then I'll be afraid it's going to interfere with my sleep because I have so much energy. But it doesn't seem to affect my sleep negatively, which is strange because most things that give you more energy and ramp you up will make sleep suck.

[01:39:34] But, to me, in terms of if one does get a crappy night of sleep or you're traveling-- traveling is the thing I find to be the most deleterious to my energy levels-- NAD precursors or NAD, nothing beats that. There's just something about it. I don't know. You probably know scientifically why that is the case, but I think there's a lot of value in NAD products for energy. But I'm going to take note of that and not use them at night.

[01:40:01] Gregory: Yeah.

[01:40:02] Luke: That makes sense.

[01:40:03] Gregory: And unfortunately, most of human studies today, similar to most studies and things, the easiest default is do some at breakfast, some at dinner. And I only can think of one or two studies that only bolus did all at breakfast. And they've tended to have the best results in the things that have been measured to date in humans.

[01:40:23] Luke: Cool. Noted.

[01:40:24] Gregory: So that's my default. I'm a big fan of Qualia Resilience, but it's another one of our products that it seems like it hasn't really found a big audience. and it's cool for a lot of reasons. But the simple story is a stress product. So we may eventually rename it Qualia Stress just to be clearer for people.

[01:40:45] Luke: Yeah. You'd probably sell more of them. People respond to that word because we all have it.

[01:40:50] Gregory: Yeah. And so that's part of the reason we made it. In part, some of the compounds that help the most with stress are also almost too calming. Ashwagandha would be an example. It's one of the better adaptogens. A subset of people, especially over time, if they take it, it's almost too calming. So what you'll sometimes see on subreddits, people will describe it almost like kryptonite for motivation.

[01:41:14] And being a Neurohacker Collective, the last thing we want for our stress product is to be an anti-nootropic. So when we created Qualia Resilience, we used a special form of ashwagandha in it that's been made to remove the more calming things and just leave the stress adaptation compounds in it. So periodically, instead of taking one of our nootropic stacks, like Qualia Mind, I'll just do Qualia Resilience for a month. And my productivity motivation is essentially unchanged on that product.

[01:41:43] Luke: I'm going to have to try that.

[01:41:45] Gregory: The people that have used it love it. There's certain things I think, we're more skilled at making people aware that we have it and how cool a product it is. And that one, I don't think we've done as much promoting it, but I was just on Thaddeus Owen's podcast recently, and like me, it's one of his favorite products. And we were joking like, we've got to do our best to keep this alive so it doesn't go the same as Qualia Vision.

[01:42:11] Luke: Yeah. No shit, dude. Yeah. I think putting the word stress in there-- marketing is marketing for a reason. But yeah, that raises a good point. I find sometimes I'll take so many things that are stimulating during the day for the nootropic factor and things like that. And then by the end of the day, I'm amped up, then I'll start taking all the calming, and then I'm toast, like a strong CBD.

[01:42:37] There's a CBD I really like called Element health. My buddy Adam makes it. I don't know what he puts in it. it must be super concentrated because when it comes to CBD, I'll see like, oh, take half a dropper. I'm like, eh. I do two or three droppers, and I'm on my ass, borderline stoned. Not like a THC high where you can't make sense of anything, but just the body high.

[01:43:06] And so I know to stay away from that during the day because I'll just want to lay on the couch and relax, and I won't get anything done because there is a slippery slope there with things that are meant to help with being resilient to stress but can knock back your energy or productivity.

[01:43:23] Gregory: Yeah. And Qualia Night, that would be our sleep product, but that's-- when we created that, I thought of it as more of a nighttime nootropic. So just like a nootropic stack, Qualia Mind be at the beginning of the day to get alertness, and focus, and all those neurotransmitters up and going, where our physiology is so different come the end of the day, in darkness.

[01:43:48] GABA is starting to take over, and melatonin starts to ramp up eventually. So Qualia Night was really, to me, like, oh, take this at dinner to really set the table to have a more calming and relaxed night. I guess the way I described it at the time, a lot of sleep products are designed to take right before bed, and it's almost slamming the brakes on to force you into sleep.

[01:44:12] But let's just gradually decelerate into sleep over a couple of hours and make your evening more calm and relaxed. That was Qualia Night. And the goal was that you'd wake up the next day feeling like more ready to get at it no matter how, subjectively, you felt asleep. So if I take Qualia Night on my Oura Ring, sometimes my first plunge into deep sleep seems so quick that I also pop up almost like you put a ball underwater.

[01:44:41] I pop up, and I'm aware that I woke up. All of us wake up multiple times a night that we're not aware of. But with Qualia Night, sometimes I'll go so deep so fast that I'll pop up and be aware.

[01:44:54] Luke: Yeah. I'm familiar with that. That happened to me last night. I've been going to bed much earlier lately, which is a great habit. But if I fall asleep at 9:30 or 10:00, it's pretty much inevitable I'm going to wake up at 1:00 or 2:00 with full energy like it's morning. Oh, what happened?

[01:45:10] Man, I think I got too much good sleep in that crucial window, and then I wake up energized. Yeah, it's weird. The sleep thing is just an endless mystery to me and how to really dial that in. There's so many contributing factors.

[01:45:23] Gregory: Yeah. People of all age, sleep is just a huge issue. You have sleep neglect, people not allowing enough time. But then a lot of people that even realize sleep's important. And for them, trying to get it dialed into sleep well can be challenging. If I was here one night, in a hotel, scientists would call that the first-night effect.

[01:45:45] Our first night in a new environment, it's almost like our brain's not sure it's safe, and a big part of what-- priority one, keep us safe. So it's not going to let us get quite as deep asleep because it wants to make sure that that environment's safe. So I always feel super lucky that I'm 61. I never get up to go to the bathroom at night. I go to bed. I wake up seven or eight hours later, pretty much like clockwork. And it's unusual when I would have a night like you just described.

[01:46:14] Luke: Yeah, it's weird too, tracking the sleep, because if you're playing around with sleep supplements, you find that some make you get great REM, but then your deep goes down. You do something that helps you-- it's like the sleep architecture gets to the point where, oh, okay, I'm sleeping great. Subjectively, you feel good, and you have energy, and you feel rested in the morning.

[01:46:39] But then when you look at those scores, it's a mind eff because where's the sweet spot of the architecture? I've been taking an Amanita mushroom extract, and my REM sleep is insane, especially if you do a decent dose of it. Crazy lucid dreams. And it's almost a bit of a journey in the night if you take enough of it. And I'm not recommending that people do that. I'm just experimenting. That's what I do.

[01:47:05] And then I'll look at my rem. I'm like, I got three and a half hours of REM sleep. This is amazing. I look at deep, and it's like 40 minutes. Like, Goddamnit. So then I'll take some DSIP peptide, get two and a half hours of deep sleep, and the REM goes down. It's like trying to find that perfect architecture is a real balancing act.

[01:47:27] Gregory: Yeah. There's such different physiological states in our brain. Sometimes what helps one hinders the other. Sleep's noisy. I think it's super important for people that are tracking not to get fixated on a day or even a couple of days. Look over the course of weeks to see how you're doing before you make any big decisions about a whether something worked or didn't work.

[01:47:49] Luke: That's a good point.

[01:47:50] Gregory: With Qualia Night, we've even seen that, that sometimes people will respond poorly maybe their first dose or two, and a month later, it's really helped their sleep a lot. So one thing I know we teased earlier, and I wanted to make sure we covered was we just did our placebo-controlled Qualia Senolytic study.

[01:48:07] Luke: Oh yeah, yeah, yeah. Thank you for remembering that.

[01:48:08] Gregory: The results came in--

[01:48:10] Luke: And could we put a link to it in the show notes?

[01:48:12] Gregory: Yeah, I'll be writing it up.

[01:48:14] Luke: Okay, cool.

[01:48:15] Gregory: We may not have the link for a couple weeks, but I'll be writing--

[01:48:18] Luke: Okay. I think it should come out in time.

[01:48:20] Gregory: Yeah. We had done two pilot studies. Science would call them open label, so not placebo-controlled, just to get a sense, like, oh, is the formula tallable? Is it doing some things that are showing up in measurable ways? And one of those had to do with joint function that I mentioned earlier, like discomfort, activities of daily living, things like that. And it did really well. And what we did in that study, we did two days, then break from it.

[01:48:48] So just to get people through three dosing cycles. So each dosing cycle is two days. We had dosing cycle, then 12 days off, then another one. So instead of doing two days once a month, we were doing two days basically every two weeks. And so we were able to get three dosing cycles into five weeks.

[01:49:07] And so we replicated that study, but with a lot more people and a placebo this time. And so the same three dosing cycles. So two days, 12 days off, two days, 12 days off, two days. And what we saw was about a 68% decrease in the issues with joints, which is crazy big. And it's statistically significant compared to placebo.

[01:49:31] There's usually a big placebo response in things that you use questionnaires, like with gut health or with joint health, as an example. But it was more than double the response that we had in the placebo. So we're super excited to-- it's always a little bit-- you do a study, and quite often, more often than not, things don't translate. Placebo response can be big. Study that separates from that is hard.

[01:49:57] I've probably read, just on cognitive ingredients, I bet, over the last two years, 300 studies. And so few of them show much compared to a placebo. So we could go into a whole episode of how you balance or how I would balance that out. But bottom line is Neurohacker Collective is super excited to now have a nice clinical study on Qualia Senolytic.

[01:50:25] Luke: Yeah. That's the thing with the studies, is you have to pay for them even if you don't get the results you're looking for. I can only imagine everyone waiting for the email, like, ah, God.

[01:50:34] Gregory: Yeah.

[01:50:35] Luke: Studies are expensive, from what I hear.

[01:50:38] Gregory: Yeah.

[01:50:39] Luke: Especially the higher levels of sophistication.

[01:50:43] Gregory: And time as well. Yeah.  So it was great timing because, like I said, I got the email with the results about an hour and a half before I Ubered over to your home.

[01:50:53] Luke: Amazing, dude. Perfect timing. Well, I think we'll be able to get it into the show notes and share it with people. Tell us about the Collective Insights podcast.

[01:51:02] Gregory: So the Collective Insights would be the Neurohacker Collective podcast. We have what I think of as a couple different hosts. So we don't have just a Luke Storey, and they've changed over time. So originally Daniel Schmactenberger was the sole host, and some of the archive shows, he's the host, and they're great.

[01:51:20] And then, for a while, Jamie Wheal had his own channel, and then a naturopathic, Dr. Heather Sanderson did the health people. She's incredible. And I think she was a brilliant host, but she's a practicing naturopathic doctor and doing the Bredesen protocol for Alzheimer's disease and has a medical home in the San Diego County area that does that.

[01:51:46] She has a recently published study on it. So she just got too busy. So because of that, Dan Stickler took that over. And more recently, I've taken over Dan. Dan and I rotate. My specialty, what I've been focusing on, is reading books that I love, getting that author on so that they can talk about a book that I think was brilliant and share it with our audience and share them.

[01:52:11] Luke: Awesome. I like that idea of rotating host that way. I should try that sometime. Cranking these things out five times a month is a lot of work. It's a lot of time.

[01:52:22] Gregory: I can imagine.

[01:52:22] Luke: No one realizes. Now you're in the podcast production game. But I think few people realize after a few years of doing at least this type of show, that's two or three hours sometimes per episode, it's a lot. I enjoy it. I'm not complaining by any means. I get to talk to brilliant people like you every freaking week. It's the greatest gift ever. But yeah, I like the idea of having a few hosts.

[01:52:50] Gregory: Yeah.

[01:52:50] Luke: You could take a week off here or there, or there might be someone, a guest whom you're less passionate, and you're rotating a host who is more passionate, and so on. I'm just a good cherry-picker. I just talk to people that I'm personally vested in speaking to. But yeah, that's a cool idea. I'm going to check the show out.

[01:53:10] Gregory: Well, and Dr. Stickler, there's areas that he's just-- he's a practicing doc in the longevity space. There's things he's just, in the real world sense, using and knows the people. He is just a better fit to interview them. And then some of the people that I get is because I love their book or I like them.

[01:53:30] We're planning to interview Jim Kwik coming up a couple of months from now because our schedule goes-- but I've been on his podcast, so I'm thrilled to get a chance to have him in the opposite seat and get to really share him with our audience and Collective Insights.

[01:53:46] Luke: Right on. Right on. Well, that's a perfect segue into my final question for you. Who have been three teachers or teachings that have influenced your life and your work that you'd like to share with us?

[01:53:57] Gregory: So I would say the first one was that person I mentioned. Ron Schmidt was his name. He was a naturopathic doctor. Passed away. But I think in terms of foundations of how I think about diet and nutrition, he was very much that native nutrition, evolutionary eating kind of thing, which has influenced me a lot. And unfortunately, he got called from us too early.

[01:54:23] I don't think he's known at all in the biohacker space, but Mark [Inaudible]. He's a dual ND DC. And when I was like, no joke, my first maybe month or so at naturopathic school, he was coming through using our big auditorium to talk to a bunch of local chiropractors. And since they were using that, we all got invited. I think I was the only one from my class that showed.

[01:54:46] And at the time, he was like, Tony Robbins meets natural health. He'd have been a biohacker type of person in advance. So he'd probably be the biggest influence by far. He's up in Canada doing some cool stuff, and actually, we're planning to have him on Collective Insights coming up, but I think of him almost like both a brother and, by far, the biggest mentor I've had.

[01:55:11] And then the third, I don't know if I would say that it would be a naturopath or things like that, but in terms of making an impact on my life, when I was in the Navy from '84 to '89 was when HIV/AIDS was really just coming into prominence. And on my ship, there's like a captain, the head person, and then the second charge and executive officer.

[01:55:41] And the executive officer on my first ship was one of the early Navy, at least as far as I know. HIV/AIDS cases back then, it was a death sentence really quickly. So my story is that I was his favorite officer on the ship of the young officers in a park, as I was more physically active, and he was as well. But I remember visiting him in the hospital.

[01:55:59] He was late 30s, so not particularly old. Relatively newly married, new baby. And he just said, Greg, I'm here. I know the end's near. There's no solutions back then for that. And he just said, promise me that when it comes your time and you're in this bed, you'll feel like you lived your life because I feel like I've done everything right.

[01:56:22] I went to Naval Academy, did everything right in my career to get to where I got. I feel like I missed living somehow. I was probably 24 at the time. I didn't really know how to execute that, but it was the most memorable thing ever in my life, was that sense of like, all right, there's a different game to play than the one my father would've played, like doing all the right things for that sake.

[01:56:50] Am I doing things to feel alive, contributing, things like this? So in a sense, he might've been my best mentor because that one challenge, more than anything, has colored my life ever since then.

[01:57:04] Luke: Beautiful. Thanks for sharing.

[01:57:06] Gregory: Sure.

[01:57:07] Luke: Yeah. Thanks for joining me, man. This has been fun.

[01:57:09] Gregory: Oh, my pleasure. I loved it.

[01:57:10] Luke: Yeah, I love deep diving and geeking out with really smart people. It's fun. I love to learn about all this stuff. I'm just a sponge for information, so thank you for educating me and inspiring me and the rest of the people watching and listening today.

[01:57:24] And I'll remind everyone the show notes for this bad boy can be found at lukestorey.com/qualia. I know we mentioned a lot of stuff and links, and the Neurohacker products and all that stuff, so you'll be able to find everything we talked about there. Until we meet again, Greg. Thanks for joining me.

[01:57:40] Gregory: Oh, can't be soon enough.

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