Longevity Breakthroughs with Chris Mirabile: Rational Wellness Podcast 313
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Chris Mirabile discusses Longevity Breakthroughs with Dr. Ben Weitz.
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Podcast Highlights
1:09 Chris noted that his interest in health started when he was 12 years old when he saw a Men’s Health magazine and got interested in building his body up. Then he started to feel faint and dizzy and had a seizure and discovered that he had a brain tumor. He had surgery that saved his life and this fueled his desire to take control of his life and become an entrepreneur and this also planted the seed for his interest in longevity that has blossomed into his current company, NOVOS.
4:19 Chris was in the technology business, but in his personal life he was focused on health and he was into biohacking. He experimented with nutritional supplements and various sleep, diet, and exercise routines. He was experimenting with measuring various methods of measuring biological outputs. About 10 years ago he came across a seminal paper in the journal Cell from 2013: The Hallmarks of Aging (López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. doi: 10.1016/j.cell.2013.05.039). This paper was updated in 2023 with 3 additional Hallmarks of Aging: An Expanding Universe. (López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278).
8:18 Chris’s personal diet and lifestyle choices for healthy living include what he calls the longevity diet, which is a modified Mediterranean diet that reduces the intake of wheat and grains and increases the intake of vegetables, mushrooms, and legumes. He is on the lower end of the carb scale of this longevity diet, though not close to ketogenic. He minimizes his saturate fat intake because he notices when his saturated fat intake goes up, his LDL cholesterol levels go up significantly. He does intermittent fasting, following a 16:8 or even a 19:5. His eating window is typically between 2 pm and 8 pm. He admits it would be better if this window were 9 am to 5 pm, since you tend to be more insulin sensitive in the morning, but he has trouble maintaining that, since he is not that hungry when he wakes up. Every so often he does a 24 hour fast. He starts and ends each day with a 2 mile walk. Six days a week he will work out for 45 minutes to an hour. Three days he will doing weightlifting and the other 3 days he will do a more intense form of cardio. Sundays he will rest, though he still might walk or go on an easy bike ride. He notices that after not working out on Sundays, his HRV will pick back up, which he monitors with his Oura ring or his Apple watch. He takes a high quality multivitamin/mineral and uses a salt that is half sodium and half potassium, since most of us do not get enough potassium and this keeps Chris’s blood pressure in a healthy range.
17:58 The Hallmarks of Aging. The first Hallmark of Aging is mitochondrial dysfunction. As we age, we have fewer mitochondria per cell, and the mitochondria that we have in each cell are less efficient, which means that we’re able to less efficiently produce the energy, and as a result, our tissues and our organs are not functioning as well as they otherwise would. A number of ingredients in the NOVOS core product that Chris developed support mitochondrial health, including magnesium malate, glycine, calcium-alpha-ketoglutarate, fisetin, glucosamine, vitamin C and pterostilbene.
20:58 Cellular senescence. There are cells in the body that are no longer functioning normally, which are referred to as zombie cells and they secrete something called a SASP (senescence-associated secretory phenotype), which are inflammatory molecules that impact nearby cells and cause them to become senescent as well. This is one of the reasons why our skin wrinkles as we age. NOVOS core includes fisetin, which is from strawberries, and has been shown to reduce cellular senescence. NOVOS has conducted an in vitro human cell study that shows that they were able to reduce the footprint of senescent cells by an order of magnitude nearly equal to Rapamycin, which is the gold standard longevity drug.
23:30 Genomic instability. Another way to understand this is DNA damage and we used to think that simply taking antioxidants would prevent this and some antioxidants can accelerate aging or increase the risk of diseases of aging. NOVOS core contains pterostilbene, glucosamine, and magnesium malate, which are all good for genomic instability. Pterostilbene is more effective than resveratrol. NOVOS is also funding another study that is ongoing that is looking at whether NOVOS core can protect cells from DNA damage from chemo drugs administered to the cells and preliminary results look very promising.
28:10 Proteostasis. Proteins accumulate inside and outside our cells and they impair the proper functioning of those cells. One of the ingredients in NOVOS core that favorably impacts proteostasis is micro-dose lithium. This is completely different than prescription lithium, which is 100 times this dose. This is equivalent to the amount of lithium that is found naturally in some water and fish, which is what we have gotten evolutionarily. People who live in regions that have higher levels of lithium in the natural water supply have been found to have lower levels of murder, rape, depression, and suicide, and lower rates of neurological disease like Alzheimer’s, dementia, and Parkinson’s. Glycine, glucosamine and fisetin also impact proteostasis. Glycation could be considered part of proteostasis, though perhaps glycation should be a separate category.
31:34 Altered intracellular communication. As cells age, communication starts to fall apart and if cells can’t communicate, they’re not going to be able control inflammation and this can also lead to additional senescent cells and dysfunctional stem cells. Ingredients in NOVOS Core that address this are ginger, fisetin and glucosamine.
33:58 Epigenetic alterations. Epigenetics refers to turning genes on or off and we want our epigenome to reflect the youngest possible state. Specific ingredients in NOVOS Core that have been found to have favorable impacts on the epigenome include micro-dose lithium, glycine, calcium-alpha-ketoglutarate, vitamin C (which combines with alpha-ketoglutarate), ginger, and pterostilbene.
39:45 Telomere shortening. Telomeres are the protective end caps of chromosomes, which contain our DNA. Various things can lengthen telomeres including physical exercise and weightlifting. NOVOS Core contains lithium, magnesium malate, and pterostilbene. each of which have been found to protect the telomeres or possibly even extend telomeres.
41:12 Deregulated nutrient sensing. As we age, our bodies and cells become less tuned in to nutrient signals. Fiseten and pterostilbene that are in NOVOS Core can improve deregulated nutrient sensing.
42:23 Stem cell exhaustion. As we age, our stem cells tend to become dysfunctional and die off. Glycine and alpha-ketoglutarate have been found to improve stem cell health.
Chris Mirabile is the founder and CEO of Novos, the first nutraceutical company that targets the 12 biological causes of aging to increase longevity. Chris has achieved a biological age that’s 13.6 years younger than his chronological age according to the epigenetic test DunedInPACE, and he continues to age at a rate that’s 31% slower than normal. His website is NovosLabs.com.
Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure. Dr. Weitz has also successfully helped many patients with managing their weight and improving their athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.
Podcast Transcript
Dr. Weitz: Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting-edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast.
Hello, Rational Wellness podcasters. Our topic for today is why we age and what we can do about it with Chris Mirabile. Chris Mirabile is the founder and CEO of NOVOS, the first nutraceutical company that targets the 12 biological causes of aging to increase longevity. Chris personally has achieved a biological age that’s 13.6 years younger than his chronological age according to the epigenetic test DunedinPACE, and he continues to age at a rate that’s 31% slower than normal. Chris, thank you so much for joining us today.
Chris: Thank you for having me, Ben.
Dr. Weitz: Great. So, can you tell us about your personal story and health challenge you had to deal with as a child?
Chris: Sure. Well, I started getting interested in health when I was 12 years old. I was at the bookstore and I saw a Men’s Health magazine, and I was inspired by-
Dr. Weitz: Like Muscle & Fitness or one of those?
Chris: Muscle & Fitness, Men’s Health, Muscle Media magazine, all of them. There was a whole bunch back then. And yeah, I picked them up and I was inspired by the guys in the magazine and I wanted to be in good shape. Admittedly, it was purely superficial. I wanted to be attractive to the girls in elementary school. I was only 12. But I set up a pull-up bar in my basement with my father, and every day after school, I’d come home and do my pushups, my pull-ups, and then eventually started weightlifting. But then, I was suddenly stopped in my tracks when I was 16 years old. I was in New York City for a school trip, and I suddenly started to feel faint and dizzy, and next thing I knew, I woke up with blood all over my shirt. I had severed my tongue from a seizure that was caused by a brain tumor that was growing in my left temporal lobe above my ear unexpectedly. It was more than a golf ball size, and they had to do emergency surgery within just a few days. That took me from being very physically active to laying in bed in a hospital bed, contemplating more mortality and the possibility that I wouldn’t wake up after my surgery and all of the things I had yet to experience in life. And so, I started to think if I make it through this, I want to take control of my life and there’s so many things I’d like to do. And that’s part of what motivated me to be an entrepreneur but also planted the seed for my interest in longevity that has blossomed into my company now NOVOS.
Dr. Weitz: Right. So, you went to college actually for business. How did you come around to being involved in a nutraceutical business?
Chris: Yeah, so I studied at NYU Stern. I majored in finance, economics and international business largely because I knew I wanted to be an entrepreneur, and I wanted to understand business and entrepreneurship and especially the financial side of a business. My first year out of college, I went into private equity, more on the banking side, worked on Park Avenue. Although the money was great, it didn’t speak to me. And so, within one year of starting that career, I quit and I started a social network that won NYU’s Business Plan Competition. And that was enough to get me to leave that job and to start that entrepreneurial journey, which was far more difficult and challenging than most would expect when they hear the stories of the massive successes in entrepreneurship. But nonetheless, I was in technology and in my personal life, I was really focused on health. I experimented with the biohacking side of health with different types of supplements and sleep routines and diet routines and exercise routines and so on, and did a lot of quantified self where I was measuring different biological outputs.
And based on that, making more informed decisions than I otherwise would have if I didn’t have those tools. And all the while I was asking myself the question, “Are the things that I’m doing for these short-term goals?” And those short-term goals may have been to run a faster mile or to do more pull-ups in 60 seconds or to lift a heavier deadlift. They may have also been to focus better at work or to be able to work longer, be in a better mood, things like that. My question was always, “Are the approaches I’m taking good, bad, or neutral for me in the long-term?” And oftentimes there was no obvious answer. If you follow a specific diet or you take a specific supplement, knowing what the repercussions of that will be in 10, 20, 40, 50 years, it’s not always clear. What I didn’t realize at the time was I was dealing with a concept at least on a genetic basis known as antagonistic pleiotropy, which is the overly simplified form of that would essentially be what’s good for you today can come back to harm you tomorrow. And so, I wanted to make sure that I wasn’t harming myself tomorrow because of the experience I had with the brain tumor, and the last thing I wanted was to be laying in a hospital bed again, possibly dying. So, that was something I started to look into.
And about almost 10 years ago now, I came across a seminal paper in a prestigious journal known as Cell called The Hallmarks of Aging. It’s a very popular paper, and that was the moment of epiphany for me. That was the aha moment when I realized, “Wow, we actually do understand the biological causes of aging, and if I look through that lens, I can start to answer that question of is this good for me in the short-term and in the long-term as well.” And that started my journey in the longevity space.
Dr. Weitz: Yeah, I read that paper. I noticed that it had nine factors of aging, and there’s a 2023 version that now has 12 causes.
Chris: Yes, that’s right. So, just a few months ago, the same authors of that original paper published the new one that identified three additional hallmarks. Though anyone in the longevity space could tell you, “We saw this coming.” There was enough evidence and studies and presentations in the biomedical field where everyone knew that, for example, inflammaging was going to come up as another hallmark of aging, this chronic low-grade inflammation that takes place as part of aging.
Dr. Weitz: And the microbiome, that’s one of the ones that was added as well.
Chris: Exactly, right. And we all know about the gut-brain connection, but few people know that there’s many other axes for the gut, like the gut-liver axis and the gut-kidney axis.
Dr. Weitz: Gut-heart axis.
Chris: Yes.
Dr. Weitz: In the functional medicine world, which I thrive in, is we’re always looking at the gut as a major factor in almost every issue we’re dealing with.
Chris: Definitely. It all, or I shouldn’t say all, but much starts in the gut. It begins there for many people in many conditions.
Dr. Weitz: Maybe you can tell us about your personal diet, exercise, lifestyle program that’s enabled you to reverse your aging.
Chris: Sure, sure. Let’s see. I’ll think of this in terms of maybe diet first. When it comes to diet-
Dr. Weitz: I noticed on your website you talk about the longevity diet.
Chris: Yes, yes. At NOVOS, we’ve put together something known as the NOVOS Longevity Diet, which is based on the foundation of the Mediterranean diet. The Mediterranean diet has been found in study after study to be the best diet for longevity, the most conducive to long lifespan, a long health span, reduction in risk of heart disease and cancer and diabetes and so on. Also, the best neurological outcomes, lowest rates of depression and so on. But what we’ve done is we’ve taken some less than ideal aspects of that. For example, higher intakes of, say, wheat products and grains and modified it somewhat to increase, for example, the intake of vegetables, mushrooms, legumes, to reduce the amount of those starchy lower nutrient-rich foods for more nutrient-rich foods with less starch. So, to that point, I essentially follow that type of diet. I’m a little bit on the lower end of the carb scale than I would necessarily like to be, to be honest. I find myself constantly going on the lower end of the spectrum, but I do find myself being more energized and in a better mood when I add more carbs into my diet probably because of the increases in serotonin that come from it. By extension, it increases in melatonin and better sleep I experience when I have a little bit more carb. But generally speaking, for the general population, I am much lower on the carb spectrum, but definitely not close to ketogenic.
Generally speaking, I minimize my saturated fat intake. Now I’m not afraid of saturated fats but I choose them carefully, which ones I take in, because I do notice that the higher saturated fat intake I have, my cholesterol LDL levels go up significantly. So, I want to reduce those LDL levels as much as I can. I intermittent fast, so I typically follow 16/8 or 19/5, something in that range. So, basically, 2:00 p.m. to 7:00 or 8:00 p.m. is my eating window. Now, ideally, that would actually be earlier. It would be better if I did like 9:00 a.m. to 5:00 p.m. but I have trouble maintaining that. I’m not that hungry when I wake up. And I also find myself not sleeping as well when I go that long before waking up without food. So, it shifted a little bit later, but ideally, you’re more insulin sensitive in the morning. Some studies have found it’s better to actually start eating earlier in the day and ending earlier. Every so often I’ll do a 24-hour fast. So, once every couple of weeks, I’ll go maybe Thursday dinner to Friday dinner without eating.
My exercise routine is every day, I bookend my days with walking. So, I’ll start my day with about a two-mile walk. I’ll end my day with approximately a two-hour walk. In both cases, I’m typically still being productive. As an entrepreneur, I’m always doing something whether that be on the work call or responding to emails or something or listening to a podcast. And then, in the mornings, I’ll exercise six out of seven days of the week. So, three of those days are weightlifting, 45 minutes to an hour, and the other three days are a more intense form of cardio for, again, 45 minutes to an hour.
And then, Sundays are my rest days where I’m still walking a lot. I might go on an easy bike ride, so I’m still physically active, but I’m not pushing myself. I’m not pushing my body. And when I look at my biometrics through the Oura Ring or the Apple Watch, my HRV really picks back up again from that lighter load. I supplement with a high-quality multivitamins, multi-minerals. I make sure I get adequate potassium in my diet, not only through the foods I eat, but I also use a Lite Salt, which is half sodium, half potassium salt. Most people are deficient in potassium even when eating a healthy diet. And this is my way to increase those levels of potassium. My blood pressure is in a very healthy range I believe as a result of that.
Dr. Weitz: What product are you taking for the potassium salt?
Chris: There’s a few out there. There’s some that are 100% potassium salt. They don’t taste very good. Morton’s brand, very common brand. They make a 50/50 mix of potassium sodium, literally called Lite Salt, L-I-T-E. Another way you can do it is you can buy the pure potassium salt, and then if you wanted to stick with something like pink Himalayan salt, some natural salt with other minerals in it, you do 50/50 and you do your own mix basically.
Dr. Weitz: That’s a cool idea.
Chris: Yeah, it’s a great way to get up into the multiple grams of potassium. If you look at, historically speaking-
Dr. Weitz: People take 99 milligram potassium capsule and it’s insignificant. Yeah.
Chris: It does practically nothing. So, if you’re able to add two, three grams of potassium to your diet per day, of course, making sure you’re getting adequate sodium. It actually really offsets a lot of the negative sides of sodium. People are oftentimes afraid of sodium and they say, “I have a sodium-free diet.” What I would say to that is, if you’re physically active or you’re out sweating, that’s actually not a good idea. You need the sodium. There’s a reason why the ancient Romans were paid in salt, the Roman warriors. They’re paid in salt because when you’re sweating, you need it.
So, I would just say, get that salt in your diet but then offset it with potassium. We have our cells have the sodium-potassium pump. You don’t want to be deficient in either one of those. It affects us neurologically. It affects all of our organs. It affects our muscles as well. That’s on the diet side. What I do, I mentioned exercise. When it comes to weightlifting, I do a combination of a little bit of powerlifting, a lot of strength lifting, sometimes high rep. I like to have a nice balance.
Same thing when it comes to cardio. I like to be very fast to sprint, but I also like to be able to run six, seven miles without a problem. So, I’ll mix things up. Maybe I’ll go out for a five-mile run, but for two of those miles I’ll do high-intensity sprints, and then I’ll jog the remainder. I’m always shocking my body and doing things a little bit different for each of the workouts. What else? Sleep is very important to me. I’m very regimented with my sleep. I make sure that I’m getting to bed typically within between 10:30 and 11:00 p.m. work nights.
And then, on weekends, I might extend that to midnight or something, but generally speaking, maybe 11:30. So, within an hour, I wake up, I get sunlight in my eyes right away. I go out for a walk, have some coffee, actually after my morning workout. So, it’s a couple of hours into the day. It’s a black coffee. What else? When I sleep, I wear earplugs. I wear sleep mask. So, this way when my girlfriend is waking up and she’s doing things, she’s not waking me up. And that really improves the quality of my sleep, which I’ve tracked and see that it’s significantly better that way.
Generally speaking, despite stressors that might enter my life whether personal, or as an entrepreneur as you can imagine almost every day there’s some stressor, just really being mindful. I practiced meditation for more than a decade now. I don’t need to do it as frequently as I have before because I think I’ve gotten myself to a different set point. But sometimes when there’s a lot of stress, I will just sit still and just focus on my breathing, and that goes a very long way for me. Those are the main things I think of. And, oh, I was talking about supplements before.
Dr. Weitz: Supplements. That’s right. Yeah.
Chris: So, the general health, multivitamins, multi-minerals, fish oil, and then of course longevity supplements, which my company produces. Fortunately, I’m able to take the equivalent of 13 different supplements by just having a sachet drink mix and two pills. So, really simplifying that more complex routine and making it into something that’s a daily habit as part of my lunch.
Dr. Weitz: Cool. Let’s talk about the causes of aging, these hallmarks of aging, and then maybe we can work in some of the supplements that can be beneficial in moving the needle on these.
Chris: Sure. Happy to. I’ll start with the original nine that we talked about before from the paper, The Hallmarks of Aging. The first is one that your audience is probably very familiar with is one of the most popular ones. It’s mitochondrial dysfunction. So, our mitochondria being the power plants of our cells, they enable us to move, to think, for our organs to function, and they’re taking the carbs, the fat, and sometimes even the protein that we’re ingesting, and then converting that into energy in the form of ATP. And as we age, we have fewer mitochondria per cell, and the mitochondria that we have in each cell is less efficient. So, we’re able to less efficiently produce the energy, and as a result, our tissues and our organs by extension are not functioning as well as they otherwise would. And there are ingredients in NOVOS’s foundational supplement, NOVOS Core, that positively impact mitochondrial health. That’s everything from malate, which is contained within the magnesium malate, glycine, calcium-alpha-ketoglutarate, fisetin, glucosamine, vitamin C and pterostilbene. The second hallmark is cellular senescence.
Dr. Weitz: Why did you choose malate? Because when we talk about mitochondria, some of the supplements that tend to come up the quickest are things like alpha-lipoic acid, NAC, CoQ10, L-carnitine.
Chris: Yeah. Well, so not only is malate part of the Krebs cycle and it’s found to increase or improve healthy energy levels in humans. There’s studies that find that improves energy levels in humans. It’s also a substance that’s been found to extend lifespan in multiple organisms. In fact, every single ingredient that we use, we run it through this filter of multiple different requirements, which you can find. If you go to novoslabs.com/approach, you can see what those requirements are. One of those requirements is that it’s been shown to extend lifespan in at least one species, ideally multiple species, because if it’s found to do so in multiple species, that hints at the biological mechanism being evolutionarily conserved. In other words, evolution has decided that this is important enough to conserve it, and therefore it’s most likely going to be in us humans as well who are harder to test for lifespan because of how long we live.
Dr. Weitz: Right. Okay.
Chris: Make sense?
Dr. Weitz: Yes.
Chris: Okay, great. So, the second one is cellular senescence. This is what a lot of people refer to as zombie cells. These are cells that are not living nor dead. Sometimes the body produces these, for example, to arrest a cancer. It’s not the only reason but that is one of the reasons. And they fly under the radar of our immune systems. The immune system should theoretically identify these and remove these cells or through autophagy, digest the components and then recycle these components. But for one reason or another, they aren’t. And the problem with them is they secrete something called a SASP. And the SASP is senescence-associated secretory phenotype. It’s essentially a fancy way of saying it secretes inflammatory molecules that then impact nearby cells and cause them to become senescent as well. So, it becomes an exponential process as we age, is one of the reasons why our skin wrinkles, for example. And to reduce cellular senescence, there’s one key ingredient in NOVOS core. It’s called fisetin. Fisetin is found in strawberries and it has been shown to have favorable effects on senescent cells, reducing cellular senescence.
Now with that said, we’ve done an in vitro human cell study at University of Newcastle in the United Kingdom where we were able to show that we reduced the footprint of senescent cells by an order of magnitude nearly equal to the prescription drug rapamycin. And rapamycin is the gold-standard longevity drug. It is what everything is compared to, and the fact that we were practically equal to this prescription drug was really exciting for us for this specific dimension of cellular senescence.
Dr. Weitz: Especially since there’s all these problems around potentially taking rapamycin because it suppresses the immune system and people are trying to figure out ways where you can just take it once or twice a week to try to decrease the negative effects while still getting the positive effects. Somebody like myself, I’ve decided so far not to consider taking rapamycin. So, the idea that we could take a nutritional supplement that doesn’t have any of those negative effects is very exciting and very impressive that your nutraceutical company is able to fund research.
Chris: Yeah, thank you. That’s not the only thing. So, maybe I’ll skip ahead to another hallmark of aging that we have found that we’ve done research related to and found benefits for. So, that’s genomic instability. Another way to put that is DNA damage. And this used to be what many scientists thought was the reason we age, DNA damage. And therefore antioxidants would be the way that we slow down or stop aging. And research has been disappointing on that front in the sense that antioxidants don’t stop or slow down aging. In fact, many antioxidants can even accelerate aging or increase the risk of diseases of aging specifically. But with that said, DNA damage is a factor. It is a contributor to aging. It’s just that there’s 11 others, right? It’s not the ultimate answer. Now, when it comes to DNA damage, something we want to reduce as much as we possibly can, NOVOS, we’ve done multiple in vitro human studies, one in which we irradiated human cells and one set of cells had NOVOS administered. Another set of cells did not. It was the control. It was found that we reduced oxidative damage to the DNA by more than 70%, which the lab that ran the study had done more than $6 or $7 million worth of the same study with different natural and prescription drugs and found nothing compared to the results that we were getting.
They were shocked by the result. They even called their CEO to tell them the results that we got from our study. There’s another study that we have not yet published that’s currently ongoing, but what I can say about it is it’s being done at a university in Italy. And they are administering chemotherapeutics to human skin cells. And the chemo that they use, they’re using two different ones. One is moderately intense, the other is extremely intense. The extremely intense one, it doesn’t simply cause oxidative damage to the DNA. It actually causes single and double-strand breaks. The analogy I like to give is oxidative damage would be like a car rusting. Strand breaks are like a chopping the car in half at the axle like you’re completely demolishing that car, right? And what was found was that with this intense chemo, practically 100% of the DNA was either single or double-strand breaks. After administering the NOVOS formulation, there was, I can’t say specifically what number, but a significant number of DNA that did not have any strand breaks whatsoever. That again, is very promising, the effect that we can have to protect the DNA.
Dr. Weitz: Right. That’s very cool. Do we have reasonable ways to measure DNA damage in humans?
Chris: Within the human in vivo sense-
Dr. Weitz: I guess maybe we have telomere length, right? That’s probably the best.
Chris: Telomere length would be an offshoot of that in the sense that your telomeres are going to shorten more when there’s more DNA damage because you need to then replicate the cells that much more frequently and so on. But it’s not a direct measurement of the DNA damage per se. I would imagine just getting a biopsy of the cells and then looking specifically at the DNA before and after, you could probably do it, but I’m not aware of many studies that take that approach. It’s oftentimes in vitro and looking at the loci and seeing how many loci there are is typically the marker that they use for the DNA damage.
Dr. Weitz: Yeah, it’s interesting. It’s too bad we don’t have ways to measure a lot of these hallmarks of aging commercially available for people. Like measuring mitochondrial dysfunction is not an easy thing to do either, measuring senescent cells is… it’d be cool to have some lab tests that could measure these.
Chris: Yeah, that would be ideal. And I’m sure that they’re coming down the pipeline. I’m sure there are people out there thinking about offering these types of tests but not easily available.
Dr. Weitz: Sorry for running down a rabbit hole. In your product, do you reduce genomic damage? What are some of the ingredients that you have to do that?
Chris: Pterostilbene which is the much more effective and better studied equivalence to resveratrol. Resveratrol is a popularized ingredient that has been shown by many researchers to not really do what… it hasn’t lived up to the promise, I’ll put it that way. Whereas pterostilbene is a close relative to that molecule. It contains three methyl groups, which is very good for methylation and the epigenome and NAD production, which we may talk about as well in regards to this molecule called NMN, which is in our NOVOS Boost formula. It contains pterostilbene, glucosamine, and magnesium malate are all good for genomic instability.
The next hallmark is loss of proteostasis. Over time, more and more proteins, they accumulate inside of our cells and outside of our cells. And by this happening, it impairs the proper functioning of those cells. Imagine having a lot of garbage inside of your house and outside of your house, it’s going to be harder for you to get indoors. It’s going to be harder for you to access the kitchen and the bathroom. Your home becomes somewhat dysfunctional. The same thing happens with our cells. Our bodies should be removing that protein, but because of a loss of proteostasis as we age, it becomes more difficult. And ingredients in NOVOS Core that favorably impact loss of proteostasis are micro-dose lithium. Lithium is this ingredient that raises a lot of eyebrows. A lot of people think of their cell phones and lithium-ion batteries and so on. Or they think of psychiatric patients who take prescription doses of lithium, which is far higher dose. Prescription doses are 100x the dose of a micro-dose. A micro-dose is equivalent to what we have gotten evolutionarily. Lithium is found in natural water supply. It’s found in wild fish and so on. And we’ve had it throughout evolution.
In fact, New York Times did a story on this maybe probably almost a decade ago now, where they looked at people living in regions that had higher levels of lithium in the natural water supply, and they found lower levels of murder, of rape, of depression, of suicide, lower rates of Alzheimer’s, dementia, Parkinson’s. It’s basically something that has a very favorable impact on the brain, on human psychology and neurology. It also has a favorable impact on the epigenome. It’s one of the more powerful ingredients in the formulation.
There’s also glycine, which is an amino acid found in collagen we’re deficient in our diets nowadays, glucosamine and fisetin. Next is altered intracellular communication. Cells need to… Cells are part of this vast network. And as we age, the communication starts to fall apart. Part of the reason for it is because of that loss of proteostasis. Imagine if you have proteins blocking the receptor sites on a cell is going to be that much harder for cells to be able to secrete molecules that are then received properly.
So, if the cells can’t communicate with each other that well, they’re not going to be able to set in motion the processes that should be taking place. This comes as a result of hostile environments with inflammation and so on, and they could then lead to additional inflammation. They can lead to additional senescent cells, dysfunctional stem cells and so on. And ingredients in NOVOS Core that address this are ginger, fisetin and glucosamine. We went over genomic instability. So, next is epigenetic alterations.
Dr. Weitz: Let me just ask you one question.
Chris: Sure.
Dr. Weitz: On the proteostasis, is glycated proteins, proteins damaged from sugar, is that part of that proteostasis concept?
Chris: Yes, it is. In fact, before the 12 hallmarks of aging were introduced this year, we actually suggested that there was a 10th hallmark when there were only nine, that being glycation. So, technically, you could say it’s part of proteostasis, but just like autophagy was just added when it could also be considered somewhat related to proteostasis, we felt like glycation deserved almost a category of its own. And perhaps one day there will be, and it will be 13 hallmarks or 14 hallmarks. But glycation, they’re all interconnected. As I think people are realizing as I talk through them, they all cause each other in one way or another. And that’s why it becomes exponential because as one starts to pick up, it accelerates the other, which accelerates the first one again and so on. And they all are either working together or against each other. And unfortunately, as part of aging, they’re working against each other.
Dr. Weitz: Right. Okay.
Chris: Let’s see. So, next is epigenetic alterations. The epigenome is, epi being layer on top of your genome. It is essentially which genes are turned on or off. So, if you think of your genome as being the piano keys, this is something permanent. It’s something that’s set in place from your birth. Your epigenome are which of those keys are being played. And so, when you’re young, it might be playing a beautiful song. It might be Tchaikovsky. But as you age, certain keys are misplaced or not played when they should be. You don’t have the rhythm anymore. And these patterns start to emerge. And that’s how epigenetic clocks and biological age clocks function is by looking at specific genes, whether they’re turned on or off or to what degree, because it’s more like a dimmer switch. And then, they can find these patterns and then determine how old you are biologically by comparing you to everyone else out there. Now, certain genes are turning on that shouldn’t turn on. These might be genes that are inflammatory or cells might start to identify as the wrong cell. Your skin might think it’s a hair follicle or something, and then suddenly hair starts to appear where it shouldn’t and vice versa.
So, a gene that should be on like an anti-inflammatory gene might turn off. And so, we want our epigenome to reflect the youngest state possible. And there are specific ingredients in NOVOS Core that have been found to have favorable impacts on the epigenome. And that would be, again, micro-dose lithium, glycine, calcium-alpha-ketoglutarate, vitamin C, in particular the way that it combines with alpha-ketoglutarate, it basically enhances the effect of the alpha-ketoglutarate. Ginger and pterostilbene.
Dr. Weitz: I just want to stop you for a second, sorry.
Chris: Sure.
Dr. Weitz: I was reading on your website about the alpha-ketoglutarate and I’ve been using alpha-ketoglutarate. And you make a point out of the fact that calcium-alpha-ketoglutarate is more effective than just alpha-ketoglutarate, which is I don’t think the calcium-alpha-glutarate is readily available. And I also notice that in your product, you have 1100 milligrams of the calcium-alpha-ketoglutarate. And most of the alpha-ketoglutarate supplements that we’ve been carrying have 300 milligrams in a capsule.
Chris: Thanks for raising those points. So, a couple of things to point out. One is that the calcium form of alpha-ketoglutarate is most conducive to improving lifespan, partially mediated through the absorption time, the amount of time it takes for the body to break it down. So, it’s a little bit more of a continuous dose of the AKG. Calcium, also, a lot of people, especially health-minded people aren’t consuming as much dairy or milk. A lot of people are becoming deficient in calcium, so it’s good to have a little bit of added calcium. And then, in terms of the dosage, that brings up a more broad concept, which is the dosage across the NOVOS Core product.
We have nearly 7 grams of active longevity ingredients in our formulation. So, think about that 7000 milligrams of actives, whereas most supplements that are $50, $100 are only giving you 500 milligrams or a gram or 2 grams of actives. We’re well above that. And our price point is between $79 to $109 per month, depending on whether you subscribe or you do a one-time purchase. So, dollar per gram. We are amongst the most affordable products out there, and we’re definitely the most powerful out there as well.
Dr. Weitz: Is your product available for practitioners to set up a wholesale account?
Chris: It’s funny you asked that because yes, we just begun that process of bringing on wholesalers. So, we’re talking with a number of medical clinicians who are interested in offering NOVOS Core, NOVOS Boost, which is our NMN product, and NOVOS Age, which is our biological age test kit, which includes the DunedinPACE clock for your pace of aging, a biological age clock, which is not as accurate as DunedinPACE, but people want to scratch that itch so we include it. And then, telomere length, and we will tell you your percentile according to your chronological age for your telomere length. And we also then include in the results, the report you received a lot of advice and guidance for how to improve your scores.
Dr. Weitz: Okay, cool. And so, practitioners listening, where would they go to find out about that?
Chris: If they go to novoslabs.com and they scroll to the bottom of the website, they’ll see a Contact Us link. They’ll see a section specifically for either affiliate, or there’s no purchase required. They just get a hyperlink, and then they’ll get a commission for sales. Or they’ll find the wholesale form where they would be purchasing in bulk and getting a substantial discount.
Dr. Weitz: Okay, cool. Okay, go ahead.
Chris: All right. I think we’ve gone through seven or so of them so far. Telomere shortening is something that we’ve already begun to discuss. The idea of telomeres are, these are the protective end caps of chromosomes. And chromosomes are what contain our DNA. And so, they’re essentially protecting our DNA. Every time a cell divides and we’re producing replicas of the DNA, the telomeres get shorter. By extension, you would expect that someone who is older, who has had more cellular divisions, or someone who has had a lot of DNA damage, they’re going to have shorter telomeres.
Now, with that said, there are different things you can do that can actually lengthen telomeres. For example, certain diets, certain supplements, even like physical exercise and weightlifting. I believe there’s a study that found weightlifting can extend telomere length. So, if you find you have shorter telomeres, for example, maybe you purchase the NOVOS Age test and you see that you’re in the 40th percentile, hope is not lost. You can improve that and actually raise your percentile.
And within NOVOS Core, we have lithium, magnesium malate, and pterostilbene each of which have been found to protect the telomeres or possibly even extend telomeres. I believe number eight or nine, I think eight at this point is deregulated nutrient sensing. So, as we age, our bodies and our cells become less tuned to nutrient signals. What are nutrient signals? It’s, for example, having sugar in our blood glucose, right? It is having insulin in our blood, the fatty acids in our blood.
Our bodies should be tuned to these to know that, for example, if your blood glucose is at 120 release insulin to lower that below 100. But as we age, our bodies are less tuned to this, and therefore our blood glucose might start to creep up. It might require more insulin to be able to shuttle that glucose to the cells because we’re becoming insulin-insensitive. And so, this is something that can then lead to metabolic disorders. We see it manifest in the form of additional body fat and so on. And so, ingredients like fisetin and pterostilbene can improve the deregulated nutrient sensing.
Number nine is something that your listeners are probably very aware of, which is stem cell exhaustion. Our stem cells are essentially making replicas of themselves to create new cells. And as we age, they either become dysfunctional or they die off. So, we have fewer stem cells and those that we have are not capable of reducing perfect replicas anymore. And so, we want to be able to keep them healthy, keep as many of them around as possible, even have copies of stem cells. Stem cells can copy themselves. So, have copies of stem cells produced and ingredients like glycine and alpha-ketoglutarate have been found to improve stem cell health.
The three new ones, we’re on the final stretch here. One is inflammaging, which we referenced earlier. So, this is the chronic low-grade inflammation that starts to pick up as we age. When we’re in our 30s, it’s this mild hum. You might not even hear it. And when you’re in your 40s, you start to hear it, becomes audible. And then, in your 50s and 60s and beyond, it starts to really be present. And so, the question is how can we reduce that chronic inflammation? Because as we all know, inflammation is the root cause of so many different illnesses. Sometimes it’s an acute inflammatory environment.
For example, a workout causes acute inflammation, but that’s a healthy inflammation that the body through the process known as hormesis comes back stronger from that workout. Or there might be inflammation from cutting your skin. There’s some inflammation localized to that area, that’s fine. The immune system takes care of that and repairs. But when you have this systemic body wide, low-grade inflammation that starts to wear on our bodies over time.
And many ingredients in NOVOS Core have been found to reduce the inflammatory environment. So, that’s everything from glycine to fisetin, pterostilbene, ginger, the micro-dose lithium, magnesium malate, alpha-ketoglutarate, Rhodiola. And then, in NOVOS Boost, the NMN has also been found to reduce inflammaging.
Dr. Weitz: I’m surprised you didn’t include curcumin in your product, which is one of my favorite herbs and very powerful anti-inflammatory.
Chris: Yeah. There are specific ingredients that show a lot of promise but that we intentionally didn’t include. And every ingredient has a different reason why we didn’t include it. If you go to novoslabs.com and you click on the little search button on the top-right corner, and you search for something to the effect of ingredients not included, you’ll find that article. And it’s got a couple of dozen different ingredients that we consider. Quercetin was another one for the senolytic activity. We decided not to, partly because of our consultation with one of our scientific advisory board members. We have six scientific advisory board members from Harvard, MIT, and the Salk Institute.
This one is from the Salk Institute, Dr. Pamela Maher. And she studies quercetin and fisetin and other similar molecules. And she was concerned about the possibility of damaging healthy cells from quercetin, from chronic intake of quercetin. Whereas fisetin seems to be more powerful for the senolytic activity while meanwhile also having a lower side effect profile essentially. So, next is disabled autophagy. We talked about autophagy or we referenced it earlier. That’s the idea of our bodies, our immune systems taking cells and their components and recycling them.
Imagine an old cell, it’s starting to break down. It’s not functioning properly. The immune system can identify this and basically digest it and then use the proteins and lipids from that and recycle it for new cells, for example. And ingredients in NOVOS that help in with this process are micro-dose lithium, glucosamine, acetyl glucosamine, which is a distinct ingredient from glucosamine. And acetyl glucosamine is contained within hyaluronic acid. We included hyaluronic acid in our formula specifically for the acetyl glucosamine. But a nice added bonus is that hyaluronic acid orally ingested actually improves skin health.
It improves skin moisture, joint health as well. It helps to lubricate the joints. So, there’s multiple benefits from that hyaluronic acid, but we really wanted it for the acetyl glucosamine. Finally, there’s dysbiosis. So, this is the microbiome that we mentioned earlier. And so, as we age, the composition of our microbiome, the different bacterial species that we have within it, even fungal species and so on, it changes. And there are certain types of bacteria that start to proliferate that can lead to, for example, inflammation and not the ideal environment.
And when we look at some of the longest-lived people, the centenarians and the supercentenarians, we find that they have a distinct microbiome compared to the average person who’s dying much earlier. For example, they have higher levels of a specific bacteria known as akkermansia. There are different ingredients that have been found to have a favorable impact on the microbiome. And within NOVOS Core, those include ginger, pterostilbene, fisetin, rhodiola, and the micro-dose lithium.
That was all 12 of the hallmarks of aging that scientists have identified to this point. And as I hope you can see, we have multiple ingredients that impact each of these hallmarks of aging. So, it’s a combinatorial synergistic approach that we’re taking, being mindful of also not having any dissynergies, which are essentially negative synergies that can also take place when you combine ingredients. These are things we were careful to avoid while formulating the product.
Dr. Weitz: And then, you have your Boost product, which is NMN.
Chris: Correct. Yeah, NMN, nicotinamide mononucleotide, is a precursor, a direct precursor to the molecule NAD plus. NAD plus is involved in energy production. It’s involved in the production of sirtuins, which are enzymes or proteins that repair our DNA. They help to maintain the epigenome. So, there’s a lot of vital processes that come from NAD plus in the Krebs cycle. And as we age, we have less NAD plus, we have less NMN. And there are many studies finding in animals, as well as in humans that NMN can improve health span and energy production. Some people even report anecdotally online that it reduces gray hair. A lot of different benefits people are experiencing from it.
Dr. Weitz: Why did you decide to go with the NMN as opposed to NR?
Chris: A few reasons. One is if you think about NR, it’s actually a precursor to NMN. And so, you have to convert the NR to NMN and the NMN to the NAD. The question for a while was, is NMN actually absorbed through the gut? And we got the answer. Yes, it is absorbed through the gut, so you don’t need the NR. We wrote an article about this. This is actually one of the more popular articles on our website. If you search for NMN versus NR, we talk through that, and I think there’s close to two dozen different points that we raised for why we chose NMN over the NR. But essentially we feel that it’s more effective and NR is, it’s difficult to absorb through the gut. The liver converts a lot of it, and ultimately, we think that you get more bang for your buck with the NMN.
Dr. Weitz: Interesting. Yeah. It seems to be not that easily available as it-
Chris: NMN.
Dr. Weitz: Yeah, NMN. Yeah.
Chris: Yes. Well, there’s this ongoing issue where there’s a question of whether it is going to be restricted to prescription sell only or over the counter. And this is an FDA-level issue. It’s not yet determined. So, we’ve been advised to continue selling it. Ultimately, it’s a natural substance. It’s found in human biology. It’s also found in food like tomatoes and so on. And so, the question really comes down to whether there’s any reason to restrict consumers from being able to purchase something that is found in the foods we eat and in our bodies to prescription-only use. And it really comes down to a loophole that one company is trying to exploit to get exclusive rights to it but that is far from definitive at this point, and many companies in the industry are fighting that. In fact, I’ll be meeting with members of Congress next month to discuss the issue specifically.
Dr. Weitz: Interesting. One company is trying to make it a prescription drug, yeah?
Chris: Yes. And one very well-known scientist is on the board of that company. The company is called MetroBiotech, but I won’t throw any mud. I won’t name names, but there is someone well-known in the longevity space who’s on that board.
Dr. Weitz: Yeah, I think I know who you’re talking about. Well, that’s interesting. Okay. Awesome discussion. Final thoughts for our listeners and viewers?
Chris: Sure. Well, I would say that when it comes to longevity, there’s no magic pill. And NOVOS despite the fact that we create formulations, I would not try to sell you on the idea that there is a single magic pill that’s going to extend your lifespan, and you can neglect these other aspects of your life. There’s all of these components that come together, everything from diet to activity to stress reduction, rest and recovery, in particular sleep, making sure that you’re not deficient in any critical required nutrients. These are the vitamins and minerals that there are RDA is set for. And it’s nearly impossible to get an adequate dosage through diet alone.
And then, there’s longevity supplements as well, which are shown to improve health span and lifespan. So, it’s all part of this bigger picture. And NOVOS as a company, we’re public benefit corporation, so my intention is to improve human health whether people are customers of ours or not. Of course, we hope people will sign on to our platform and purchase our products because we really do truly believe in them and we’re proving them out with science. But if not, we still want to improve people’s health spans and lifespans. So, we provide a lot of free resources on our website.
We’ve got almost 150 articles on our website written by MDs and PhDs, scientifically referenced. We offer free tools. For example, we just launched last week this longevity assessment that you can fill out. It’s a questionnaire, and then we give you recommendations for what is most important for you to focus on. So, those are the red, recommendations, yellow for moderately important, and then green, these are the things you’re doing well. And we’ve got articles linked to each of these recommendations for you.
We’ve also got something called Face Age. Face Age is an AI power tool where you can take a selfie and it will, based on a data set of more than 12 million people, be able to tell you how old your face looks biologically, your eye age, your skin health markers like wrinkling and pore size and so on. But most importantly, we then give you advice for how to improve all of these scores. It’s another metric that you can keep track of over the months or years ahead to see how that’s evolving with time. So, we’re trying to get as much out there for free for public consumption as possible.
Dr. Weitz: That’s pretty cool content. Where is that available?
Chris: So, if you go to novoslabs.com/faceage, you’ll find that tool there.
Dr. Weitz: Wow. Very cool.
Chris: It was just featured last week in Daily Mail, and we had more than a million people hit that in just a couple of days.
Dr. Weitz: Really? Wow.
Chris: Yes.
Dr. Weitz: Very cool. So, you guys developed the algorithm point?
Chris: We partnered with a team of researchers to develop the algorithm.
Dr. Weitz: Wow. Very cool. All right, Chris, thank you very much and we’ll talk to you soon.
Chris: Thank you for having me, Ben.
Dr. Weitz: Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify, and give us a five-star ratings and review. That way, more people will discover the Rational Wellness Podcast. And I wanted to let everybody know that I do have some openings for new patients, so I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions, or for an executive health screen, and to help you promote longevity, and take a deeper dive into some of those factors that can lead to chronic diseases along the way. That usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing. And we’re going to look at a lot more details to get a better picture of your overall health from a preventative functional medicine perspective. So, if you’re interested, please call my Santa Monica Weitz Sports Chiropractic and Nutrition office at 310-395-3111, and we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.
