Science Behind Improving Mitochondria Function - with Dr. Singh | The Empowering Neurologist EP. 144

You know, today for people who have IBD or Crohn's disease, they don't have many options other than steroids and maybe anti-TNF alpha therapy, which of course has its own— so I personally see this as something that can evolve for good gut health and be as important as the probiotics that, you know, people take to improve their gut health.

Hello everyone, I'm Dr. David Perlmutter. Welcome again to The Empowering Neurologist. So often on this program, we have talked about the importance of mitochondrial health and function. Mitochondria are the little organelles within our cells that are involved in creating energy, and so much of our health and functionality depends on these little organelles doing their job. We know that when mitochondria are not functioning at their best, that, that underlies things like brain degenerative conditions including Alzheimer's and Parkinson's. It underlies cardiovascular disease, diabetes, some of the consequences of obesity as well. Metabolic problems in general threaten mitochondrial function and then the downstream manifestations of mitochondrial issues are so many of the diseases and issues that we so want to avoid. So we want to do everything we can to nurture our mitochondria, that's for sure. We know that eating right and exercising, of course, are important for mitochondrial health. But we also know that there are a whole variety of plant-based entities that seem to be salubrious as they relate to the functionality, survivability, and activity of mitochondria. And to explore that further, I've invited Dr. Anurag Singh to join us on the program today. Let me tell you a little bit about him. Dr. Singh is currently Chief Medical Officer at Amazentis, an advanced nutrition biotech company based in Switzerland that discovers and develops next-generation natural compounds targeting improvements in mitochondrial health. And in particular, Dr. Singh has designed and led for the past 7 years the clinical development for the natural mitophagy activator— we'll talk about what that means— called urolithin A in a product called Mitopure. And this work has led to the commercial launch of several branded consumer health products including Timeline and Celltrient, which target specifically improvements in cellular health by targeting mitochondrial function. Dr. Singh received his medical training in internal medicine from the Armed Forces Medical College in India, and then went on to get a PhD in immunology from the University of Connecticut here in the United States. He has authored over 30 articles in top peer-reviewed journals, holds 10 patents, and has designed and led over 40 clinical trials over the last 15 years. So I'm very excited to spend some time with Dr. Singh today. I think we're going to learn an awful lot. Let's get right to it. Well, hello, Dr. Singh. Good morning, my time anyway. How are you?

Yeah, doing great. How are you, Dr. Perlmutter?

I'm wonderful. Where are you from right now? Where are you writing?

We're based out of Lausanne, Switzerland, by Lake Geneva.

Okay, well, thanks for joining us. The reason I reached out, as you know, I've been interested in this whole notion of urolithin A for quite some time, but you just had a new article that came out in JAMA Network And it was, the results were interesting, that's for sure. And, you know, in the intro, I talked to our followers about, you know, how we really do a lot to emphasize the importance of maintaining and even improving mitochondrial health, mitochondrial functionality. And now it looks like based upon this research and a lot of your other research that we'll go through in just a bit, that you're really onto something here that really insinuates itself in a very key position. As it relates to our health and, dare I say, possibly even our longevity. So let's first unpack this study on the 66 adults who were pretty much not exactly very active type of people. How were they studied and what was the intervention and then what were the findings?

Yeah, sure, absolutely. So happy to share sort of a summary of these key findings. So this was a randomized double-blind placebo-controlled study. This was done in partnership with the University of Washington in Seattle and the Fred Hutchinson Cancer Research Center. And these are 2 very well-known institutes. And we started working with the aging professors there, Dr. Dave Marcinek and Dr. Kevin Connelly in the past. And so the idea was to bring in a very unique study design, which not a lot of, forget nutrition companies, but even biotech companies in the pharma space were not using, which is to get healthy adults, older adults who are not very active, So the way we did this assessment was with a test that has been around for a number of years called the 6-minute walk test. And so basically it measures in a, you know, in a lined marked hospital corridor, the distance you walk in 6 minutes. And this has for long been seen as a test that is related to muscle energetics. So the bioenergetics of your muscle and your sort of peak performance and older adults who are not doing well, their muscle and mitochondrial health is declined. tend not to walk too further in the 6-minute walk test. They walk around 400, 500 meters on an average. An active guy will walk around 600 meters plus in this kind of a test. And so that was one sort of key inclusion criteria in this study, and that has been used in the past. The second criteria we used is we actually screened these older adults for mitochondrial function at their baseline, right? So we use a very sophisticated imaging tool called magnetic resonance spectroscopy, Okay. which is basically like an MRI scanner, except that you're exercising within the sort of 7-tesla MRI scanner, and you're able to see the energy levels at baseline. So the ATP, which is the currency of energy, before you exercise and as you exercise, this energy currency ATP declines. And when you stop exercising, how fast it comes back in your muscle is an indicator of your mitochondrial function. And so we use that to really just not take those people who are not walking well, but also those people who who had not very good mitochondria in their muscles. And so that's what makes this study very unique. And then we looked around, we screened, I guess we screened over 200 older adults in the Seattle area. We found sort of the 128 out of those 120, we had folks who were, you know, taking a lot of medications. So in this population, that's another key criteria that you don't want too many polymedicated people. And then you can't take people with implants because you're using, you know, with, with hip replacements, et cetera. So we came down to 66 older adults and we randomized them to 2 arms. So one got a placebo intervention and one got about 1,000 milligrams of urolithin A, as you mentioned, on the molecule. And this was the longest study. This is really the first study that looks at the long-term effect of urolithin A in this older adult population. We had seen effects at the biological level, And what we see in key is we noticed that as these people exercised in this sort of muscle test in the scanner, they did it longer. Okay, so that meant they were not— their muscles were not getting fatigued. And we looked at 2 muscles. One is the hand muscle here called the first dorsal interossei, which is key for hand grip. And then we looked at tibialis anterior in the leg, which is key for moving around and walking. And so these are 2 anatomically different muscles. And what we saw was both these muscles had, with the, in the urolithin A arm, had more endurance by about 20% compared to placebo at 2 months already. And this, no exercise was given, no dietary recommendations were given. So that's what also makes this unique. We also look at the 6-minute walk, which was the key primary endpoint, and that improved in both groups. And so when we looked at the statistics, it wasn't that big a difference between the placebo and the urolithin A arm. And one of the reasons could be that the 6-minute walk is just not about your mobility. It's about also heart function and lung function. And so we think if we had gone even longer, we would have seen and had a bigger sort of more than 66 adults. If we had about 100 older adults, we would have seen it. So that's— So

let's just, Focus on the mitochondrial health part of the functionality part. Where do you derive the best bang for the buck here in terms of what you're doing to the mitochondria themselves?

Yeah. So these mitochondria have more energy, right? So the whole idea with urolithin A is to rev up mitophagy, which is this process through which you're getting rid of your dysfunctional mitochondria. And so what we think is basically in these older adults, mitophagy triggered a phase of mitochondrial biogenesis, which meant by 2 months, these older adults had more energy and more muscle endurance as a result. And we also looked at biomarkers. So we had— we took some blood and we looked at the different biomarkers of mitochondrial health, and they all stand out with the urolithin A supplementation. We saw not just an impact on mitochondrial biomarkers like acyl carnitines, which are known to go up if you're not, you know, using your fuel, what you're eating right. And then we also saw things like CRP, which is known to be linked to inflammaging, for example. So mitochondria are just not key, you know, to mobility. They're also very key to things like your immune health, for example, and inflammation. So we are seeing these, you know, more global systemic effects than just muscle in this study.

Well, we'll talk a little bit later about the role of urolithin in immunity. I mean, there's been some really interesting work on deconstructing the mechanisms whereby it helps with respect to gut inflammation. As a matter of fact, I think you may have been involved in some of that research. But let's get back to this whole notion of why should we care if as we age, our mitochondria are becoming less and less functional?

That's a great question, Dr. Perlmutter. And this is often asked—

As I get older. Go ahead.

Yeah. No. So what it means is that you have more energy to go and complete your daily activities, right? So if you're in your 70s and 80s, I mean, just anecdotally, I had a participant in the study who after the study finished and she came to know she was on the product and she had felt the benefit, she called him and said, hey, I want your product because I've, you know, I was in the trial and I was getting it and I was able to sort of walk and complete the, you know, cross the zebra crossing in the 20 seconds I get to cross. And now, you know, I feel like I'm losing some of the potential benefits. So it struck me that's what mitochondrial health is about. You know, you feel more fatigued if your mitochondria are not functioning better. You feel you don't recover well from an exercise. That's another key aspect. So in the end, that's what we are seeing is in this older adult population, endurance is better, resistance to fatigue is better.

So we are talking about a natural product called urolithin A. We'll talk about where it comes from in nature, the important role of our gut bacteria in terms of, dare I say, activation of urolithin A. But you mentioned the term mitophagy, and I think our viewers are certainly familiar with the term autophagy, a process by which we activate mechanisms in our bodies to help rid our bodies of defective cellular components. And the specific part of autophagy is mitophagy that you're talking about today. And so we know that the whole notion of getting rid of defective mitochondria, then allowing this mitochondrial biogenesis to happen, growing new, better mitochondria, or at least we suppose that's what's happening, is a 2-step process whereby generally autophagy is initiated. And then specifically downstream from that general activation of mitophagy, which Well, we can talk about some of the techniques to activate that. Then there's this priming of the mitochondria that happens whereby then they are selectively targeted. And are we— you're talking about activating mechanisms to get rid of these defective mitochondria, replace them with better mitochondria, therefore energy goes up. And, you know, one thing that just occurs to me now, because we've been looking at this for many, many years, is One of the downstream issues from defective mitochondria, important as it relates to the brain, is the activation of what are called the caspase enzymes. And that initiates this whole notion of apoptosis or pre-programmed cell death. So that in a very real sense, the dropout of brain cells that we see in things like Alzheimer's and Parkinson's is an indication of this apoptosis or the— Pre-programmed cell death activated by dysfunctional mitochondria. It certainly explains these environmental factors that are now really well characterized as they relate to Parkinson's and how we can induce Parkinson's in laboratory animals by simply giving them a specific mitochondrial toxin, if you will. But that anything that ultimately compromises mitochondrial function, including age, I might add, has a tendency then to lead to cellular death. So, you know, getting these processes on board earlier on while we're— while we can replace those defective mitochondria, the cell hasn't died yet, and we can get energy back to where it needs to be through the lens of inhibiting, you know, this pre-programmed cell death or apoptosis, I think is really fundamentally important. You and I started today talking about strength and endurance and muscular mitochondria and muscle because they're so active. But my gosh, you know, 25%, 20 to 25% of our resting energy is upstairs in the brain. That only represents 3 to 5% of our body weight. So what's the play here as it relates to the brain? What's this crossover? I know you've written about it. Maybe we can unpack that a little bit.

Yeah. So, you know, this field is a very fast emerging field of mitophagy and natural compounds. urolithin A is one of the most researched now. In fact, I believe the National Institute of Health has awarded a few years back about $3 million to the Buck Institute to study the specific effects of urolithin A for Alzheimer's disease. And they've done a whole library of screening of thousands of natural compounds in sort of animal models and showed that this was one of the most promising compounds and the way it was revving up brain cells. better cognitive function was through mitophagy. So this is what we know. This hasn't been really tested in human interventional trials. Right now our focus is muscle and sort of mobility in that sense. Well, you're right. I mean, you hit it out of the park when you said, well, brain is one of the biggest consumers of ATP, which is the currency of energy. And we know this compound from our work that it gets into the brain. So we know that it's highly bioavailable and it can get to target organs like muscle and brain. And so this is an ongoing field of research, Dr. Perlmutter, and I think you'll see more and more work coming around this field in brain and urolithin A and mitophagy and urolithin A.

Yeah, and we focused on this before here on the podcast, this notion of Alzheimer's, for example, being ultimately a bioenergetic issue, a failure of energetics of brain cells, failure of their ability to, for example, utilize glucose as a fuel source. Hence the new and exciting work of Dr. Matthew Phillips looking at utilizing ketogenic diet and bypassing this failure of glucose utilization and supplying various ketone derivatives to allow, or let the body make ketone derivatives through caloric restriction or being on a ketogenic diet, and allowing brain cells to come back online. And we're able to demonstrate that now through specific PET scanning demonstrating both in FDG glucose utilization studies decrease in the Alzheimer's patients, but how it can be basically normalized again when these individuals with mild to moderate Alzheimer's are placed on a ketogenic diet. So again, and this is a situation where we're targeting energy. So why can't we just consume this in its natural state? We know that The precursor for urolithin is abundant in pomegranates, for example. Maybe we can go through why we just wouldn't eat a bunch of pomegranates or drink pomegranate juice, which, you know, at least if you buy it on the street or at the grocery store, has a lot of sugar, fructose.

Sure. No, this is another great question and a question I get all the time. Can you eat 4 pomegranates and crush them and get a juice, 100% juice, and get it naturally? Yes, some people can and some cannot. So there are 2 biases here. One, you need to be eating a healthy diet. So you need to be eating a bowl of nuts and berries and drinking a glass of 100% juice. And the second key factor, which a lot of people don't have, is a rich and diverse gut microbiome. Okay? For example, I have tested myself and we actually are in the works to make a small finger prick test through which we can tell you if you're a producer, natural producer or not. But I can drink 6 glasses of juice, my body will not make this naturally because I just don't have the right gut microbiome. And we've published actually very recently another paper in the European Journal of Clinical Nutrition where we took 100 people and we gave them a glass of juice and we said, well, first, how many were actually coming in— this was a study done in the US in a downtown metropolitan area— only 12% had urolithin A detectable levels coming from real life. And when we gave them the pomegranate juice, the 100% juice, and they all drank this glass of juice, 24 hours after, what we see is basically about 40% can convert well. The rest still can't make it or make very little amounts to get any sort of therapeutic benefits out of it. So that's the reason for calibrated direct supplementation, because there are folks like me who need the supplementation.

So we've heard this story before. In this case, we want to eat foods rich in ellagitannins and hope that then our gut microbes— we have the right microbes, we may not— that can then ultimately convert that to giving us urolithin. We've heard the same story as it relates to, for example, sulforaphane, that, you know, if you don't activate the myrosinase enzyme by chewing the broccoli sprouts, you're hoping that you have gut bacteria that can supply myrosinase and then activate and giving— ultimately give you sulforaphane. So It's very exciting. Who knew that the gut bacteria are playing such an important role that in this situation, when we eat foods like pomegranate or other foods that are rich in ellagitannins, that, you know, they're targeting our mitochondrial health and functionality and cellular ability to survive, how dependent we are. I mean, the story just keeps unfolding year after year. And, you know, I will tell you, you're a young guy, but, you know, many years ago, I wrote a book about the gut bacteria, etc., and people were shaking their heads saying, are you kidding me? The gut bacteria? They don't have any role in human health. And I recall, you know, in general surgery that we would do our best, though we were unsuccessful, prior to bowel surgery, we would do everything we could to sterilize The entire gut, if we had to do a bowel resection, whatever it is, you know, because there's nothing good related to the gut bacteria. How far have we come now? So the beauty then of urolithin is that we bypass this dependence on those specific species or strains of bacteria that would otherwise have provided us the urolithin from its precursor. Now we have access to that. And so what else then can we be doing? And we'll get back to the urolithin story in just a moment, but just a couple of other tips for our audience in terms of focusing on augmenting healthy mitochondria.

Yeah. So the 2 interventions that are known to trigger autophagy and mitophagy specifically are, of course, exercise. And this we know, there are multiple studies done on different aerobic and combinations of aerobic and resistance training over months and showing that it impacts mitochondrial health and specifically through mitophagy and autophagy. And the second is caloric restriction. Intermittent fasting is very well— in fact, in some of our earlier studies, we benchmarked the performance of how the molecule was behaving compared as an autophagy inducer compared to caloric restriction in worms and mice. And that's how when we started seeing these autophagy and mitophagy effects. So these are the 2 very well-known, let's say, interventions that are out there that people can take, or take as in follow. And yeah, it's difficult to be compliant to these interventions. But yeah, these are the 2 well-known ones.

So for our viewers, I would say as a reference to go back and look at the interview I did with James Clement, who wrote the book The Switch. And it's there that we talk about what are the things that activate or suppress what's called the mTOR pathway, and that is intimately involved here in exactly what we're talking about today. Now, the discovery was made, I think, by you back in 2016 as you were exploring activators of autophagy, mitophagy in experimental animals. How did you come across urolithin as being such a player?

Yeah, so we actually— the roots of the company are basically from Swiss scientists out here at the Swiss Institute of Technology, where the whole idea was to deconstruct the pomegranate because the pomegranate was this fruit associated with so many health benefits, right? It's the fruit of gods, etc., kind of nomenclature. So we started looking inside the pomegranate and looking at all these polyphenols, ellagitannins, and the different punicalagins. And what we started seeing, and, you know, as you go, there's— we brought in the sort of the biotech approach to natural product screening. We started with worms, and when we started giving all these precursors to the worms, they weren't changing, they weren't living longer, they weren't more mobile, et cetera. But when we started working with this gut microbiome metabolite, urolithin A, we started seeing about 45% increase in healthspan. We started seeing about 60% more endurance in older animals. And that sort of led to this idea, gosh, it's It's this metabolite that we should be focusing on rather than the precursors. And that's how we sort of moved to the next steps of clinical translation.

So you identified it in animals, and then I think the first human trial was just 2019, pretty recent.

Indeed. Again, this was a trial in healthy older adults where we took muscle biopsies before and after. We looked at how this compound absorbs. We, of course, wanted to document its safety very thoroughly. with increasing doses of the, you know, as somebody took 500 milligrams to a gram. And it turns out it's a very safe molecule. It's evolutionarily been present, right, from diet and those lucky few people who can convert it. It's always been around. So it was very safe. We could see it increase bioavailability in a linear way as we increased the dosage. And then most strikingly, we compared the muscle biopsies of people who took for 4 weeks different doses of urolithin A to those who were either very sedentary and/or those who had been exercising for all their life, training for marathons. And what was very clear was that we were hitting this very clear signature of activating mitophagy and mitochondrial health in the muscle.

I'm smiling because this is just so— it's such cool work that you get to do. And I mean, it's right on the edge. The reason it's so applicable, I think, to our viewers is because, you know, we get that mitochondrial dysfunction is something that is cumulative over time, that is certainly worse when we have metabolic issues, that, you know, now we can measure blood lactate levels and have an indication that mitochondria are dysfunctional in correlation with type 2 diabetes and obesity. and other marker— other issues in which there is metabolic dysfunction. But that said, there is— we know there are a suite of issues of mitochondropathies that we all had to study in medical school, whether it's MELAS, mitochondrial encephalopathy with lactic acidosis and stroke, Kearns-Sayre, progressive external ophthalmoplegia, whatever the list was that you had to memorize for your boards. But that said, a far more pervasive issue that is probably mitochondrial-based are the various forms of inherited muscle issues, the muscular dystrophies. And I think you were involved in a study, or it's upcoming, or you've looked at this type of intervention for muscular dystrophy.

Yeah. So this is work done with Professor Johann Aubryx, who's a professor here at the Swiss Institute of Federal Technology here in Lausanne. And his lab has deep expertise in studying these different mouse models or animal models of of muscle dystrophies. And what they, and this is work published in Science Translational Medicine. And so they started first by looking at the biopsies of DMD patients first. And what struck them was that when they looked at it, there was a very clear signature of mitophagy being compromised and autophagy being compromised. And so they went into sort of the translational animal models and they wanted to see if they gave this as a in the diet of these animals, if they would recover some of the function. And they saw that first, they saw a better mitochondrial function in muscle stem cells. So a lot of issue in muscle dystrophy is that the muscle gets damaged, and so your stemness goes away, and so you don't have good muscle cells to build on. And the second they saw was again, improvement in mitophagy and endurance in this. And so of course, this work has now to be, you know, translate it further down the road. But for now, we are very focused in the healthy aging population. We are even doing a study in elite athletes because years back when you would have said that, you know, in elite athletes, well, you probably would expect optimal mitochondrial function. But what happens is that they overtrain, and overtraining is known to be associated with declining mitochondrial function. So, you know, that's the work we're doing. Today.

And elevation of their serum lactate levels as a marker.

And creatinine kinase. Which is what they track.

They can actually track that. We touched upon this earlier, the mechanisms, the role, the research of urolithin as a gut-related anti-inflammatory. How might that work?

Yeah, I think there's— this is a very, you know, it's probably what you said 30 years back when you saw the gut microbiome as a key field. This field of what we call as immune metabolism is in its nascency, right? It's very emerging. And so mitochondria, just not in your brain and your muscle cells, you have about 200 mitochondria per immune cell, for example. And this energetic of how your immune cell, how your T cells and B cells make— B cells making antibodies and how T cells fight off infections or others. sort of conditions is dependent on how good their energetic health is. And so what we are starting to look at is how is this molecule, is urolithin A, improving the mitochondrial health of immune cells? And so what we are seeing in our translation now, we have published 2, and one is in the works in middle-aged adults that hopefully will come out next month. What we are seeing is a signature where we see, well, A lot of people who are overweight and aged, they have higher CRP. And even in athletes, athletes who are exercising and training uphill and downhill training before going to Olympics, for example, we are seeing high CRP levels. And what we see is that urolithin A, in addition to its impact on mitophagy and mitochondrial health, is a mild anti-inflammatory agent. And I think that's mostly because there's a connection between mitochondria and immune cells. Well,

I think that's very important because we're seeing, you know, in the time of COVID everybody, I think, is really kind of dialed into what these inflammatory markers are able to do. Not markers, but actually mediators, the so-called cytokines, and all of the ideas to rein in those cytokines during the so-called cytokine storm. But I think there's also a cytokine drizzle whereby just elevation chronically of these inflammatory mediators is detrimental, and this happens at a greater rate when our immune cells have compromised energetics. And, you know, when that happens, we call these white blood cells, they're senescent, or they're old, like senile, they're senescent. And, you know, there's certainly a push to identify so-called senolytic therapies that can identify or target those parts of our immune system that are not functional and help us through autophagy, get rid of them. There's certainly a lot of interest right now in something called Himalayan Tartary buckwheat that seems to work along that way. Moving forward, what happens next? I know there's a lot of, in the literature as it relates to gut inflammation, they're calling, still seemingly calling urolithin a gut bacterial metabolite. And as opposed to As opposed to really looking at this as a standalone. So what has to happen for people to understand that, you know, this is something they can add to their regimen and maybe get the literature a little bit more dialed into the fact that it's available?

Yeah, that's a good point. So the way I see it personally is this is a postbiotic, right? So you have the prebiotics, things that you need to keep your gut bacteria happy, and then you have the probiotics that You need to keep your microbiome diverse and rich. But in the end, what these gut bacteria are producing that is beneficial to us as the host, the postbiotic, is really what we are interested in, and that's what urolithin A is basically. Now, there was a study published about a few years back actually from a different laboratory in the US that looks at inflammatory bowel disease, And they also gave, supplemented the diet of these mice with urolithin A. And they saw that this was a very potent anti-inflammatory in that model. It protected gut barrier integrity. It lowered, as you was mentioning, it decreased these cytokines, especially interleukin-6 and TNF-alpha. So it was, you know, today for people who have IBD or Crohn's disease, they don't have many options other than steroids and maybe anti-TNF-alpha therapy, which of course, has its own. So I personally see this as something that can evolve for, for good gut health and be as important as the probiotics that, you know, people take to, to, to improve their gut health.

It's really fascinating. You know, for me, the notion of inflammation in the brain being perhaps a consequence of dysfunctional mitochondria, that's been a leap. But then when we connect gut permeability to increased inflammation throughout the body, and that primarily, ultimately being related to dysfunctional mitochondria, both as a cause and an effect. So that targeting mitochondrial function, gosh, it just has such— throws such a very, very wide net. And, you know, again, what you're talking about, this urolithin A, really, I think, is something that We should be considering along with intermittent fasting, along with periods of caloric restriction, certainly AMP kinase activation type lifestyle activities, doing our best to understand this whole mTOR thing and keeping that pathway under control as well. So this is a really important piece of the puzzle that you really bring to the table.

Yeah. This always has been the aspiration. We are a science-first sort of company and it was started by doctors and scientists who put 10+ years into figuring out the different mechanism of action, how this molecule work. And people need to realize that science in a spectrum of time takes time, right? So you start with initial discovery, then you move to animals and then you move to humans and it's just not one or two trial. We have invested in almost 7 studies and we are now even doing 2 or 3 more. And once we know and we document these muscle-specific effects, our aspiration then is to move to immune metabolism. We are in the works to launch some studies there. And in the, you know, I think your idea about brain aging and this being a very important tool, not just for brain aging, but gut health, I think these are the next directions we are looking in. And this will be the studies we'll do in the future.

And overall, just, you know, focusing on inflammation as a downstream manifestation of mitochondrial dysfunction. I really want our viewers to get that, that, you know, it's not just triggering apoptosis and brain cells dying, but it's mitochondrial dysfunction through the immune system, through the immune cells. When these cells are not working appropriately, they're spitting out these— they, you know, they take on a phenotype SASP, senescence-associated secretory phenotype, where they're spitting out these damaging molecules. And we can target that with lifestyle choices. And I think the addition of urolithin A is, you know, it's a powerful tool. And that's certainly something as a nutritional supplement that people can get here in America.

Indeed. So our company has, of course, launched this about a year and a half back in the US. And we also have an active R&D collaboration and a partnership with Nestlé Health Science that has then also taken and licensed this technology into their Celltrion brand. And so it's available in 2 advanced nutrition supplement products. What we also try to provide is we just not provide supplements, but also good-tasting food products with the bioactive. And so that's where We think people, you know, need to think of good health with good taste as well.

Excellent. Well, listen, I want to thank you for sharing some time with us today. And I think without a doubt, in a year or two, we're going to have to reconnect and hear what you're up to because you're up to some really cool stuff and, and moving the needle very quickly. So let's, let's plan on that. And I wish you all the best. Thank you.

Thank you, Dr. Perlmutter, for having me. It was a great chat. Thanks.

So a plant-based chemical that is strictly designed to target mitochondrial function. That's really very, very exciting and certainly adds to all the other things that we do to improve energy production, mitochondrial function globally, to improve autophagy, and specifically how we want to target mitophagy The ability that we have to rid ourselves of dysfunctional mitochondria. Very interesting stuff, that's for sure, and certainly has widespread implications in terms of brain health, heart health, and metabolic health. Thanks for joining me today. I'm Dr. David Perlmutter, and I'll be back soon. Bye for now.