BY PETER BOWES | LOS ANGELES | JANUARY 20, 2022 | 2034 PT

Muscle endurance can be improved, in older adults, without physical exercise, according to the results of a new clinical trial.  Scientists in the US and Switzerland say their research suggests supplementation with a gut metabolite, known as urolithin A, may counteract age-associated muscle decline.  This is significant as a potential intervention that could slow the onset of frailty in older people, and prolong healthspan.  

The study, sponsored by the Swiss life science company, Amazentis  (also sponsors of this podcast), was conduced at the University of Washington Medical Center and the Fred Hutchinson Cancer Research Center in Seattle.  It was designed to test the hypothesis that long-term supplementation with Mitopure, a highly pure, synthetic form of urolithin A, would improve mitochondrial function and muscle performance in older adults.  

In this LLAMA podcast interview, the study’s principal investigator, Prof. David Marcinek, explains the findings and why he believes they could be especially beneficial for older people who are unable to exercise.  We also delve into the importance of mitochondrial health and why the so-called powerhouses of our cells play such a pivotal role in our ability to thrive and enjoy a long life. 

Interview recorded: January 12, 2022 | Read a transcript

DISCLOSURE: This site includes affiliate links from which we derive a small commission. It helps support the podcast and allows us to continue sharing conversations about human longevity. LLAMA is available, free of charge, via multiple podcasting platforms. Our mission is to explore the science and lifestyle interventions that could help us live longer and better. Thank you for the support!

▸ Time-line is offering LLAMA podcast listeners a 10% discount on its Mitopure products – Mitopure Powder, Softgels, Mitopure + Protein and skin creams – which support improvements in mitochondrial function and muscle strength. Mitopure – which is generally regarded as safe by the US Food and Drug Administration – boosts the health of our mitochondria – the battery packs of our cells – and improves our muscle strength.  Use the code LLAMA at checkout

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Connect with Prof. Marcinek: Bio | LinkedIn | Twitter

Background: 

Read the paper at: JAMA Network Open: Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults

Listening options: Apple Podcasts, Audible, Stitcher, Tunein, Spotify, Pandora Podcasts, Google Podcasts

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“We actually improved muscle endurance in the absence of physical exercise. What we found in this study is that the endurance improved just by taking the supplement. That is exciting, that’s showing that there’s actually a positive benefit going on.”

David Marcinek

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TRANSCRIPT

Transcribed using Sonix AI. Please check against audio recording for absolute accuracy.

Peter Bowes: [00:00:22] Hello again, and welcome to the Live Long and Master Aging podcast. I’m Peter Bowes. This is where we explore the science and stories behind human longevity. This episode is brought to you in association with Amazentis, a Swiss life science company that’s pioneering cutting edge, clinically validated cellular nutrition under its timeline brand. Now, scientific validation of new lifestyle interventions is all important whether they be diet, supplementation or exercise regimes. Today we’re going to focus on the science of our evolving understanding of the role mitochondria play in the aging process and the many degenerative diseases that could impact us as we grow older. Mitochondria are often described as the powerhouses of our cells, their role being to generate energy in the form of ATP adenosine triphosphate, a little school biology here, energy our cells can use to make our bodies function. We cannot live without them. Our guest today specializes in the science of mitochondrial health in humans. Professor David Marcinek is a researcher in the Department of Radiology at the University of Washington here in the United States. David, welcome to the Live Long and Master Aging podcast.

David Marcinek: [00:01:41] Thank you, Peter. I’m looking forward to talking today. This should be fun.

Peter Bowes: [00:01:44] Yeah, really good to talk to you. My one line description there of what mitochondria are for and how they work probably didn’t do them 100 percent justice. So maybe right at the top, you could give us a fuller definition of of what mitochondria are, how they function and why we need them.

David Marcinek: [00:02:00] Sure. No. So actually, I think there was a perfect start. You know, that’s what everybody knows. That’s what everybody remembers from their undergraduate biochemistry right there, a little kidney being shaped, things that are the powerhouse of the cell. You know, if you ask your family doctor, you know, tell them you work with mitochondria, you’ll see them scratch their head and say, Oh yeah, powerhouse of the cell, right? Yeah, and that’s really for years that was thought of there to be their primary. And you know, really main process is to supply the energy for your cell, to do all the things it needs to do right? You know, you make proteins make new DNA, you know, pump ions – contract – allows your muscles to contract. But over the last couple of decades, it’s really becoming increasingly clear that these these little powerhouses actually sit kind of at the at the nexus or the intersection of both the energy that your cell needs, but also become really important for cell signaling and that they’re taking all of the all this information that the cell, and then, ultimately your body is receiving from the environment, from nutrient levels to stress levels, and they’re integrating that and then and playing a really important role in cell signaling, which then ultimately becomes, you know, really your stress response, how your body, how your cells and then ultimately your body then are able to adapt to these changing conditions

Peter Bowes: [00:03:25] And extrapolating that even further in terms of how we operate as as human beings, we rely on energy. We are energetic beings. We expel or we utilize energy to to get around to physically function. And that’s why ultimately, at a cellular level, they are important.

David Marcinek: [00:03:43] Absolutely, without energy. I mean, basically, you know, you know, kind of life is the science is defined by having this energy flow, right. So in order for us to move around in order for our muscles to work, we have a huge energy turnover. Estimates for the ATP production, which you described very nicely in the beginning are, you know, several pounds of ATP a day are kind of turned over in your body because that’s what allows your your cells to do all the stuff they need to do. And then as you mentioned, your body to move around and you know, really, I think the most obvious way we interact with the energetics is our ability to exercise or just do our daily activities, walk up a flight of stairs, go get groceries. You know, that’s a huge energy demand and that puts a big tax on our mitochondria. So keeping those mitochondria healthy are really important for maintaining our quality of life kind of as we age or in the context of chronic diseases.

Peter Bowes: [00:04:41] So linking that further to aging then and the process of growing older. Clearly, one of the symptoms, if you can use that word of being older is perhaps less energy, less physical ability to get around and to do stuff perhaps inferior muscle strength to what you enjoyed as a younger person. That ultimately can be drawn back to how your mitochondria are functioning as an older person?

David Marcinek: [00:05:06] Absolutely. So the it’s becoming clear now that the the the health of your mitochondria plays a very important role in your ability to, like you said, you know, just move around, you know, conduct your daily life. And as I mentioned at the beginning, from an energetic perspective, they’re critical, right? So as they become less healthy, you’re less able to generate the energy that you need to do all these normal activities. But I think also critical is this whole whole stress response and ability to deal with, you know, changing conditions as well. And you know, when that kind of breaks down, that makes you less resilient or less able to adapt to new stresses, which is another factor associated with aging.

Peter Bowes: [00:05:51] So let’s delve into that further. But first, maybe we could just talk in some general terms about you and your career and what got you to this point. I detect already your enthusiasm for this subject. Where does that enthusiasm come from in terms of what did you study initially and how did you come to specialize in this area?

David Marcinek: [00:06:08] Yeah. So I’ve kind of it’s been a been a roundabout way to get here. So when I entered undergrad, I was set that I wanted to study biology, but I was going to be a geneticist, right? That was that was my goal. And then it was an animal physiology class as an undergrad that really focused on energy flow through living animals and just really highlighted the critical role that the energetics plays in your ability to. So you and I are just sitting here right now, we’re not really generating requiring that much energy from our muscles, right? You know, I’m gesticulating with my hands a little bit, you know, so a little bit. But we’re pretty, we’re pretty much at rest. But then suddenly, if I needed to jump up, had to run out of the room, there would be a huge, energetic need in this really short amount of time and I just became fascinated with how the body is able to respond quickly and meet those energy demands that kind of took me to an interest in the mitochondria and metabolism and then a really big turn I entered when I went into graduate school, I actually studied tuna fish. Hmm. And energy metabolism in tuna. Because if you’ve ever been tuna fishing, you know that these are they’re hugely energetic, hugely strong, you know, you know, really powerful muscles in these fish and they’re a little different in fish and they have different temperatures. And I was interested in how how the temperature of the muscle affects energy metabolism. And then through grad school, I became more and more interested in how this sort of stuff I was studying. This comparative evolutionary context fit into a more sort of health focus, sort of clinical environment. And then that ultimately took me to the University of Washington, where I, you know, I started working in a more biomedical context in the Department of Radiology and, you know, try to understand aging and chronic disease and how what role the mitochondria play in this process.

Peter Bowes: [00:08:12] It’s always interesting to me talking to people like you that the interest in aging kind of creeps up on you as you develop your studies and your understanding of your. You’re very niche specialty. And I think there’s often a realization that many scientists in different fields come across, and that is that aging is is at the center of everything. When we’re talking about the living being.

David Marcinek: [00:08:33] Absolutely, you know, it’s clear now that aging is really the main risk factor for most chronic diseases, right? So there are multiple reviews and studies out there that show, you know, you can, you know, if you cure cancer, you improve lifespan, a life expectancy, a certain amount. You know, if you cure heart disease, you improve a life expectancy, a certain amount. But that improvement really is a fraction of what you get if you can really slow the aging process or make people more resistant to these stresses as you age. You know, so from an impact on quality of life and, human activity perspective, focusing on aging, is really kind of, from my perspective, the place to be.

Peter Bowes: [00:09:21] It’s interesting. You phrase it like that as aging being a risk factor. And it’s a phrase, actually, I hear more and more these days. I also hear from from some people aging described as a disease itself, which I personally don’t get and don’t really like to hear of aging described as a disease, I see aging simply as the passing of the years and the process of growing old and the the number doesn’t change. It still gets bigger as we get older, and it doesn’t, to me, feel like a disease. I think, as you described it, better describe it as perhaps symptomatic of a number of chronic conditions that can affect us as we get older.

David Marcinek: [00:09:57] Yeah, I think that’s that’s an ongoing sort of controversy or debate. And it’s, you know, from right and it’s kind of, you know, tends towards the more, you know, philosophic, really, you know how you really think about it. It really, if you think about aging as part of, you know, it’s part of your life history, right? Just like development, you know, just like adolescence, you know, you’ve got these stages. So, you know, I think the body functions differently throughout these different stages and during what we term aging, you know, which is a constantly moving target, right? Or an age state, your body is just functioning differently, and it puts it at a greater risk for these, other diseases, you know, so I tend to agree with you and I don’t in my personal thinking, I don’t think of necessarily aging as a disease in and of itself, right?

Peter Bowes: [00:10:44] So let’s talk about your work now and how you carry out that research. You do in vivo studies as opposed to in vitro, which perhaps more people are familiar with. So can you just maybe in as simple terms as possible, explain that certainly the difference between those two terms, but how you actually carry out your research?

David Marcinek: [00:11:03] Absolutely. And so to explain the difference in the terms, I think it’s a good to go back to my transition from what I was doing as a graduate student and then why I ultimately end up in a radiology department, right? So the way most people study mitochondria and energy and metabolism is, you know, they take the tissue out of the body and either isolate the mitochondria or look at, you know, take the cells out and look at the cells and how they function. And that’s in vitro or in situ separating it from the body, right? And you can learn a tremendous amount by this approach. Right. You have exquisite control over the system. You can do very controlled, very detailed experiments, but ultimately you’re kind of removing what you want to study from the physiological system, right? And kind of as I mentioned in the beginning, mitochondria really sit at this intersection of pulling in all these signals from, you know, from the cell, from the environment. So a lot of things affect your mitochondria function. And so as a grad student, I was doing the in vitro work. I was taking these tissues out. I was kind of grinding them up, you know, I was looking can get enzyme assays. And I started to think that, you know, becoming a little less satisfied with this approach, and I wanted to kind of take a more integrative picture. So that’s when I moved to a radiology department. And so the reason I’m in a radiology department is because one of the tools we use is magnetic resonance spectroscopy. And so I came here to do a postdoc with Kevin Conley and Martin Kushmerick, who had pioneered the studies of actually measuring energetics using magnetic resonance spectroscopy. And this, the approach is similar to many people have gotten an MRI, right? So with the you go ,in the magnet in this big magnet and it uses the and I’m not going to get into this one because this gets over my head pretty quickly. Yeah. And you know, I don’t want to put everyone to sleep, but basically uses some of the quantum properties of some of the atoms in the body to generate a signal. And so when you go in to an MRI machine, you’re focusing on protons in water. Right. And so you excite these protons and they they give off signals under different conditions and you can get a picture of what your muscles and your different organs and your tissues look like based on their environment. So what we do, though, is instead of looking at protons, we look at phosphorus and phosphorus also gives off a signal. And we use spectroscopy instead of taking an image, we we get a basically it’s like a waveform that. Tells us how much of a certain molecules is in the muscle and going back to what you mentioned earlier adenosine triphosphate, right? So there are three phosphates on in this molecule. So and there’s also another molecule called phosphate creatine in your muscle. And so these phosphates are critical to the energy state of your muscle. So what we can do with this, with this magnetic resonance or MRS, we can look at the concentration of these different molecules and do things to the muscle. I have people exercise, stimulate it, make it a ischemic and watch how they change over time. And that gives us the ability to actually measure the energy flux through the system. And then we can calculate how much ATP the mitochondria are making under different conditions, how efficient they are in that sort of stuff. And so that allows us to take what we used to be these in vitro experiments. And now then we can kind of do similar measurements in vivo in this intact muscle, in people and animals and things. So apologize if if I went off a little bit and you know, it’ll get less technical now so you can tune back in.

Peter Bowes: [00:14:50] All right. I appreciate your honesty, there. It is a very complex area. But one thing you just said that piqued my interest was you talked about human response to different conditions and you’ve got all of these extraordinary tools at your disposal now. But ultimately, what you also need are the human beings in a clinical trial setting to make sense of what you’re seeing, right?

David Marcinek: [00:15:11] Absolutely. And you know, for all of these studies, you know, they really rely on people being willing to come in and, you know, take part in these activities. So it’s really been fun for me to kind of, you know, interact with these people and, you know, see their enthusiasm and their willingness to to come in and, you know, go into the magnet and, you know, go through these various protocols with us.

Peter Bowes: [00:15:36] And that’s not to be underestimated. The amount of determination people need to cooperate with the needs of a scientist going into a clinical trial is quite a commitment, isn’t it? For a lot of people, it can last over a number of weeks or indeed months. It can involve visits and, as you say, various scans or whatever the protocols require for the particular experiment and you, as the scientists need to trust those individuals, don’t you?

David Marcinek: [00:16:03] Absolutely. So, you know, so in many of these cases, you know, you have like, like you mentioned, some of these studies can go on for a while, right? So you have – a common design is you’ll do a baseline measurement and then you’ll do some intervention or some exercise training protocol or some other studies are involved in. They do a a weight loss intervention or something like that. And so you have these, you know, people go off, sometimes totally on their own. You know, sometimes you know, with a with a monitored exercise training and then they come back for another baseline. And in that meantime, you kind of you’re trusting that they are their willingness to kind of follow the program right to not kind of go off and change something or change your activity? Yeah.

Peter Bowes: [00:16:44] That’s a great opening to talk about your latest or one of your latest clinical trials and studies, and this is being carried out sponsored by Amazentis. Who I mentioned sponsoring this podcast, also, looking at Urolithin A supplementation and its effect on muscle endurance and mitochondrial health in older adults. Now let’s first of all, we’ve talked a lot about Urolithin A on this podcast over many episodes, and if you are interested in that, just search for Urolithin A in the index of the podcast. You can go back, listen to our other interviews. But I think David, it would be worthwhile once again. Just kind of setting the stage for the premise for this particular study and why the interest for you in Urolithin A which is a metabolite and again is hugely important to us as we live our everyday lives and of course, relationship with mitochondrial health?

David Marcinek: [00:17:35] Sure. So as you know, as as people that follow this, this podcast probably already know, as you mentioned, Urolithin A is a metabolite produced by the microbiome in your gut, actually, you know, so it’s kind of it’s a product of these bacteria, and multiple other studies have demonstrated that it can actually has the ability to stimulate a process in the body known as mitophagy. And so mitophagy, you can think of mitophagy as a mitochondria quality control, right? So it will it will this this process goes in it. It’s able to identify mitochondria that aren’t functioning well, break those mitochondria down to the more basic components, then that the cell can use to do other things or to actually rebuild healthier mitochondria. So part of my interest in Urolithin A is because this process of mitophagy is something that declines as we age. And you know, if you think of it as a mitochondrial quality control process, you can see how it’s, you know, pretty important for maintaining healthy mitochondria. Without it, what would happen is you would just build up all of these poorly functioning mitochondria, and that would not only change your energetics, you know, make it more difficult to meet your energy demand, but it also changed how the whole cell functioning. So the ability to kind of keep this process churning along is critical not only for aging, but also multiple diseases as well. So that’s kind of the context that we came into this study.

Peter Bowes: [00:19:07] And this study specifically, as I mentioned, looking at older adults. So this is people over the age of 65.

David Marcinek: [00:19:13] Correct. With aging, you get this decline in mitophagy, and it’s pretty clear that also there’s a decline in mitochondrial function that is associated with poorer muscle function. Right. So one of the one of the real interest in our lab is on aging and maintaining mobility and maintaining a healthy lifestyle as you age. So your ability to improve your mitochondria in this age group could have huge effects on quality of life and susceptibility to disease, so that’s our motivation to, you know, look at this aging population.

Peter Bowes: [00:19:52] So how did you set out? And this study has has just been published as we publish this episode of the podcast. So I’ll put a link into the show notes where you can go and read in some detail the methodology, the results and the conclusions. But just talk us through David in terms of the methodology. How did you set about to measure the impact of Urolithin A supplementation on these people? What did you get them to do?

David Marcinek: [00:20:18] Yeah, so so there was we kind of took a couple of different levels of approach. So the first thing was just this is a standard test that people do. It’s just called a six minute walk test or six minute walk distance. And the idea is you just have people walk for six minutes and at a sort of comfortable, steady pace and then you measure how far they get in that six minutes. So it kind of gives you a picture of kind of just sort of, you know, normal functioning. Then we also wanted to zero in a little bit more on just the muscle because obviously the six minute walk test integrates a lot of different functions of your body, right? So then we looked at the endurance capacity or the the resistance to fatigue in two muscles, one muscle in the hand and one muscle in the leg. And then we also use the the MRS measurement. I talked about this in vivo measurement of mitochondrial energetics to look at mitochondrial ATP production.

Peter Bowes: [00:21:17] And this is, as they describe it, a double blind study. There is a control group that is obviously not receiving any supplementation, but doing the same range of tests and exercises. 

David Marcinek: [00:21:30] Correct. Yeah. So I think that’s an important point because really, these double blind it’s called the randomized control, double blind clinical trial, and this is really the gold standard for a clinical trial. You know, if you’re testing an intervention, this is the gold standard. And what this the double blind means is that neither the subjects nor the researchers know whether the subject that any individual subject is taking the what’s called the placebo or the control group or the intervention. And so the way that the clinical trial works is you enroll your subjects, you do your baseline measurements, you as an independent party not involved in the actual measurements, assigns people to different groups. They take their supplements for this period of the study and then we measure them at the end. And then once all the data is collected, then and it’s locked, then that’s when the the unblinding happens. So that kind of removes the natural risk of personal bias, right? Even if you’re trying to do things as you know as much as possible on the up and up, you know, we can never completely eliminate our human bias. So this idea of this double blind study removes that ability for that bias.

Peter Bowes: [00:22:44] And for those who are following closely this area of research, let’s just you and I delve into a few more of of the details. So it’s a thousand milligrams of Urolithin A, which was the proprietary Mitopure, which is produced by Amazentis. This is the daily dose that was given in capsules, so presumably the control group were also given a capsule – a blank. In effect,

David Marcinek: [00:23:08] Yeah. Yes.

Peter Bowes: [00:23:09] Because they they would need to take something because they weren’t taking something. They would know that they weren’t taking any Mitopure.

David Marcinek: [00:23:15] Absolutely. And you know, and in this study and a true double blind study, the the pills that the control group takes look identical to the pills that the that the intervention group takes. So they take an identical looking pill, you know, in identical size, you know, identical time. And it’s really what’s also important to is that the control group is taking … Everything about that pill is exactly the same, except for the intervention that you’re testing, so any fillers or dyes or anything are exactly the same.

Peter Bowes: [00:23:47] And how did you settle on the dose of 1000 milligrams? Because I know this has been an ongoing debate for people who have been using in their health regimes Mitopure – Urolithin A for a couple of years now – as to what the optimum dose might be.

David Marcinek: [00:24:03] Well, I will say that. So that was based on previous studies that people have done with other randomized controlled studies that Amazentis has done.

Peter Bowes: [00:24:13] Got it. Ok.  So one of the interesting kind of moving into the findings here, but one thing that really piqued my interest was the placebo effect and my first thought when I read about groups of people over the age of 65 doing the the short six minute walk, wasn’t it, on a regular basis? Logic would tell you that even if you weren’t taking any supplementation in your diet or doing anything else to improve your performance, pure repetition of that would likely improve your performance. And that’s what you found in both groups.

David Marcinek: [00:24:46] Yeah. Yes. I think that’s an important point is that so in this study, we found both the placebo group and the intervention group significantly improved their six minute walk time from the baseline. And you know, one of the as you mentioned, one of that is just the repetition rate. You get more comfortable with the study. In this case, they did it once at the baseline, they did it four months later. But another thing that can happen in these studies is, you know, you have people that maybe are that actually are relatively sedentary, right? And then they’re part of a clinical study, right? Testing mobility, they’re testing their function. And suddenly, maybe this is an inspiration to say, OK, you know what? I’m going to get more active, right? I’m going to start walking more. You know, their instructions are, you shouldn’t really, you know, try not to change your activity much, but you know, you’re not going to tell people, you know, you can’t can’t walk for four months, right? So there’s always the risk that people become more active. So in addition to this placebo effect, just the idea of being involved in the clinical study has the potential to change behavior.

Peter Bowes: [00:25:50] So that improvement and especially the improvement that you saw in the Urolithin A group, you couldn’t necessarily or maybe you could to some extent. But could you correlate that with the supplementation with the Urolithin A?

David Marcinek: [00:26:03] The short answer to that question is no, because so, so part of doing a rigorous clinical study is, you. What you need to do is compare the improvement in Urolithin A to the improvement in the placebo. And since both groups improved so much, we didn’t see a significant effect of the treatment. The treatment, the improvement in the Urolithin A was, you know, just by numbers was a little bit bigger, but it wasn’t significantly bigger than the placebo.

Peter Bowes: [00:26:29] But you did have other findings which you describe in the paper as “maybe a promising approach to countering the age associated muscle decline” that clearly we’ve just talked about. And see in most people as they get older, you did see a difference there?

David Marcinek: [00:26:44] Yes. So what was for me, what was exciting about this? You know, even though we didn’t see the improvement in the six minute walk, this, you know, this real this integrative measure, what I mentioned before is where we looked at actual muscle fatigue, right? Or muscle muscle endurance. And in that case, in both the hand and the leg, we saw significant improvements in the Urolithin A treated group in their ability to repeatedly contract these muscles. So this is really just focusing in on skeletal muscle function. And so, you know, with this treatment, the muscles became more fatigue resistance.

Peter Bowes: [00:27:19] I don’t know whether it was actually part of the protocol of the study, but did you ask people, especially in that Urolithin A group, how they felt as opposed to pure clinical measurements? Was there something discernible about how they felt at the end of it?

David Marcinek: [00:27:35] You know, in some studies, there’s associated with sort of a fatigue questionnaire that wasn’t part of this study. So this is really focused on, you know, purely the quantitative, more objective physical measurements.

Peter Bowes: [00:27:50] So where do we go from here and what is your conclusion moving forward? And I notice the phrase “further studies are required” to to look into this. Would you have a different study? Would you want perhaps more people? Would you have different protocols looking at this?

David Marcinek: [00:28:05] Yeah. So you know, I think, you know, expanding on this study, you know, there are a couple, directions that I personally would like to see. One, you might do a little bit longer intervention. One thing I think that would be really interesting and I think important, as I mentioned, you never know how the just being enrolled in the study affects someone’s behavior, right? So you can actually monitor people’s behavior, you know, with little accelerometers or, you know, Fitbit type things right to see if there is a change in activity. And that would kind of be important, I think. Going forward, but we’re a lot of our research in the lab is going what I think is interesting is how does this … What I would like to see is maybe pair Urolithin with a prescribed exercise or prescribed walking program or something like that, because as I mentioned, I really I know I may be harped on a little bit earlier and that this role for mitochondria in controlling the signaling and ability to respond to stresses. And that’s one thing we’ve noticed with aging, too, is your ability to adapt to exercise goes down a little bit. So exercise is still the best thing you can do for aging. But the bang for the buck you get as you get older goes down a little bit. So can improving mitochondrial function with the mitochondria targeted intervention say like Urolithin -if we can improve those mitochondria before and during this exercise, can we increase the the ability of the body to improve with exercise? So that would be, I think something that would be interesting to do in the future is combine a supplementation study with an exercise training.

Peter Bowes: [00:29:39] But it’s fair to say that you still have a positive view of the potential based on what you know now your positive view of Urolithin A supplementation.

David Marcinek: [00:29:47] Absolutely. And I think one of the things that’s exciting for me is I, as I mentioned, is that we actually improved muscle endurance in the absence of physical exercise. What we found in this study is that the endurance improved just by taking the supplement. So I think to me that that is exciting. I mean, that’s showing that there’s actually a positive benefit going on. So now it’s, you know, it’s figuring out, you know, as you mentioned earlier, there’s a lot of things that go into trying to optimize conditions or figuring out what role this plays in a strategy for improving health. Right? You know, you know, you touched on dose, but what’s the context? As I said, exercise is the best thing we can do right. We all know that right. However, exercise isn’t really an option for some people or, you know, people become either so deconditioned or the recovering from a hospital stay or something, whereas the real barrier. So if you can do something to improve that muscle function that allows someone to get back into exercise, then I think that is a really important strategy for, you know, being able to enhance quality of life for people.

Peter Bowes: [00:30:56] And I think that’s a really important point because as many people age, the issue of frailty comes in, and it’s very difficult to reverse that that once an older person senses that frailty, experiences what it’s like to perhaps sit down on the floor and have real difficulty standing up again. It’s very difficult to reverse that without some significant interventions, and for many, it is the beginning of – I would hate to put it like this, but the beginning of the end, that kind of slippery slope towards a really slow lifestyle that ends up with a lot of sitting in the armchair and watching television, and that’s putting it in kind of brutal terms. But that’s what happens to a lot of people.

David Marcinek: [00:31:35] Absolutely, I think that’s a great point. And, we’re focusing here on on the older adults and this transition into frailty. But I mean, I know from my own experience that, you know, if I’m in an exercise program, then I take off for a while. It’s a little challenging to kind of get back into that. Now if you compound that with a recent hospital, stay the natural effects of aging on our muscles and our cardiovascular health. Getting back into that or becoming active is is going to be that much harder. So if there’s something a supplement or an intervention strategy that can improve your exercise capacity ahead of time, or that’s going to help you take that next step into becoming more active and, you know, just kind of doing your normal activities and then you can kind of slowly ramp that up. So yeah, and that’s that’s the real goal of a lot of our or the research in our lab is that that transition is, you know, what can we do to help people stay more active since we know being active is the key to is one of the keys to healthy aging?

Peter Bowes: [00:32:44] Just a little aside here, this study ended mid-2020, so mid the first year of the pandemic. And I’m just curious what the challenges were concluding a study. Clearly, a lot of the work was done before the pandemic, but concluding a study that involves people and a lot of physical contact. What were the challenges that that faced you and especially a study involving this cohort of very old people?

David Marcinek: [00:33:08] Yeah, this was definitely a major challenge in that sort of. The study was going along when the pandemic hit and then that paused all human research for a while. And so one of the consequences of that was we missed out on some of the endpoints for some of the subjects. So we can’t. So we lost some of those endpoints. We had to delay the study. So the study got extended significantly as we waited for the these initial waves of the COVID situation to pass. And then it was it was a little bit of a challenge getting people back in right because, you know, and I think rightly so. We’re dealing with an aged population, you know, so you know, as we all know, they are the people most affected by the serious effects of COVID. So setting up the the conditions in the lab to, you know, first make sure that everyone was as protected as possible. You know, the subjects and the researchers, but then also conveying that that care and that concern to the subject to get them back in, you know, was a was a bit of a challenge. So it was a, you know, we relied on, you know, as a fantastic team … that just really developed a great rapport with with a lot of these subjects, you know, to really convince them that we are taking their safety first.

Peter Bowes: [00:34:29] Yeah, exactly. I’d like to get your thoughts in more general terms about the the value of this kind of research. We live in a world where we are bombarded with advertising about this supplement or that supplement that’s going to help us stay young, reverse the aging process, a phrase I don’t particularly like because I don’t think it’s relevant to most people, but we are bombarded with advice, information and suggestions as to what we should do. But you are at the heart of making sure that these products are at least some of these products clinically stand up to what they are potentially promising.

David Marcinek: [00:35:04] Yes, and I think that’s a critical point to make. I think, you know, as you mentioned, you know, there’s there are a lot of people peddling anti-aging strategies or supplements. And as I mentioned earlier, this randomized, double blind controlled study is is the really the key. It’s the gold standard for assessing whether there’s actually an effect. And, you know, I think it really does a disservice. The just the overwhelming information out there, it’s hard for the non-expert to sort out what’s promising and then what has no evidence. So, you know, I think it’s it’s important for anybody making these claims to be able to back it up with, you know, a rigorously designed study. And that’s we’ve been able to be a part of multiple studies like this. And I think that’s exciting for us. That’s a really important, I think service we have, you know, that we can actually provide this test for these compounds.

Peter Bowes: [00:36:01] I’m just wondering, post-pandemic, or, maybe we’re not post-pandemic yet, but hopefully we’re going to get there at some point.

David Marcinek: [00:36:07] I hope we get to a post-pandemic at some point.

Peter Bowes: [00:36:09] Exactly that will be good. Do you detect any greater interest in people’s concern about their everyday health? And I think if there’s one thing we’ve learned is that our everyday health, our lack of underlying conditions hopefully is going to serve us positively in terms of this virus or any other future viruses. And I think hopefully made some people at least look at themselves in terms of how they live their daily lives.

David Marcinek: [00:36:35] Yeah, you know, I could say I hope so, and I know that there’s been I’ve seen, you know, more and more workshops and symposia, at least within the aging research community. Putting this, you know, this idea of a healthy lifestyle or healthy aging in the context of susceptibility to these other things that people are maybe not associating with aging. Right. So I think that messaging is probably if it’s not already, it’s going to change in that it’s not just staving off frailty that allows you to, you know, live independently or go to the grocery store or just do your normal activities. It actually affects all aspects of your disease risk. And I think that messaging, like I said, I hope maybe permeates a little bit more and is able to penetrate people to think about how how they’re how they’re living their life to in a healthier way.

Peter Bowes: [00:37:30] Yeah, I hope so, too. In terms of David, how you live your life based on your lifetime of research and studies and detailed studies in this area. I’m curious what you have learned that perhaps influences how you live your life. And you’ve talked a lot about exercise, of course, being crucial. But in terms of a day in the life of yourself, what do you apply in terms of the science to yourself?

David Marcinek: [00:37:53] I think that’s a great question, right? You know, healer heal thyself, right? Right. So I think the main thing that I focus on that I have really gained from my last, you know, 15, 20 years studying aging muscle is I. It’s really critical for me to maintain a regular exercise program and some sort of activity. And that’s not necessarily the same thing, but just of, you know, maintain function. Stressing my muscles constantly is something that I, you know, I really think is important to maintain this healthy lifestyle. And then I, I really think about what I eat. And those are the main, the main effects it’s had. And I think the way I live in the way I try to look into the future. And then, of course, you know, managing stress, right, but that’s yeah, everyone’s trying to do that, right? You know, and I think those are those are the three things that that I sort of implement daily exercise eating and stress management and then looking at at the different supplements, I think, you know, and different interventions. I think, you know, the there’s a lot of promise out there for, you know, strategies for the future. I think we’re not quite there yet from where I’m not, you know, taking a supplement to say, you know, I’m that I know this is the right dose and the right context for me. But I think that there’s so much interest now in targeting mitochondria. I think in the next few years, I think where there’s really going to see some breakthroughs in this area.

Peter Bowes: [00:39:21] Yeah, it’s a fascinating area of research when you talk about stressing your muscles. Yes, in terms of your exercise, you’re talking about lifting weights and perhaps pushing yourself to an extreme level, what might feel like extreme at the time, but it is just pushing yourself gradually every day.

David Marcinek: [00:39:37] Yeah, yeah. Yeah, I have to chuckle at the extreme level

Peter Bowes: [00:39:42] I had to quantify that. Yeah, yeah.

David Marcinek: [00:39:45] So, so it is lifting weights and weight bearing type resistance type exercise is what I really focus on. And, you know, walking and, you know, staying active is great. You know, for me personally, I noticed the greatest benefits from a weight lifting or a resistance type exercise. And you know, you know, I just went at, you know, and I think also for me, I do a lot of other activities that I think finding something that you enjoy is as important or more important than hitting, you know, than lifting weights, right? You know, even if you just can’t stand sitting at a bench and, you know, doing bench presses or squats, you know, finding an activity that pushes you, I think, is what’s critical.

Peter Bowes: [00:40:26] I think there’s one thing that I’ve learned it is having a variety of activities as well, and this can this can apply to diet as well, not just focusing on one thing that you think is good for you and perhaps going to an extreme to use that word again. But to do a variety of whether it’s endurance, exercise, weight lifting and a colorful diet is probably the best way to describe it.

David Marcinek: [00:40:47] Absolutely colorful diet and colorful activities, right?

Peter Bowes: [00:40:50] David, your enthusiasm is quite infectious for this area. I really appreciate your time. Thank you very much indeed.

David Marcinek: [00:40:55] Oh, thank you. Now this is really fun,

Peter Bowes: [00:40:57] And I will. As I said, I’ll put some details of this particular study into the show notes for this episode. So if you are following the science of mitochondria and Urolithin A you can really delve into the details, you’ll find those details at the LLAMA podcast website Live Long and Master Aging. That’s LLAMApodcast.com. You can also navigate all of our previous interviews on this subject for a really deep dive into mitochondrial health.

Peter Bowes: [00:41:24] This episode of the LLAMA podcast was brought to you in association with Amazentis, a Swiss life science company which is pioneering cutting edge, clinically validated cellular nutrition under its timeline brand.

Peter Bowes: [00:41:37] The LLAMA podcast is a healthspan media production we’re available on all of the main podcasting platforms. You can follow us in social media @LLAMApodcast. You can direct message me @PeterBowes. Many thanks for listening and take care. 

The Live Long and Master Aging podcast shares ideas but does not offer medical advice.  If you have health concerns of any kind you should consult your own doctor or professional health adviser.