Dysfunctional Mitochondria Are Fueling Cardiovascular Aging — Here’s The Fix

This is a really exciting conversation with Dr. Davide D’Amico from Timeline, where we’re taking a closer look at Urolithin A and heart health. It should come as no surprise that this mitochondrial wonderkin of a nutrient is showing promise here—especially when you consider that 40% of the heart’s weight is mitochondria. That’s an extraordinary factoid, and one that really shifts how we think about aging in the cardiovascular system.

What’s particularly compelling in this new preclinical research is that restoring mitochondrial function may do more than just improve ejection fraction. It may also have ripple effects on other hallmarks of aging—like chronic inflammation, cellular stress signaling, and impaired autophagy. I’m thrilled Timeline is continuing to invest in both preclinical and clinical research on this front—and yes, I’m totally nerding out over what they’re up to.

~DrKF

Mitochondrial dysfunction is a hallmark of aging—but have we fully explored its role in cardiovascular decline? In this episode of New Frontiers, Dr. Kara Fitzgerald sits down with Dr. Davide D’Amico, Director of Discovery and Translational Science at Timeline, to discuss the emerging science behind Urolithin A and its potential impact on heart health.

With mitochondria making up 40% of the heart’s mass, targeting mitochondrial function could represent a paradigm shift in managing ejection fraction, inflammation, autophagy, and other key mechanisms of cardiovascular aging. Dr. D’Amico walks us through compelling preclinical data that may inform future therapeutic strategies.

If you’re a clinician interested in applying mitochondrial support in the context of cardiovascular care, or want to understand what’s next in longevity science, this episode  offers timely insights you won’t want to miss.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And of course, today is no exception. Let me introduce you to my guest and we will jump right into it. Dr. Davide D’Amico, PhD, is the Director of Discovery and Translational Research at Timeline. With 15 years experience in mitochondrial and aging biology, he contributed to developing urolithin A as a science-backed, clinically validated nutritional product to enhance mitochondrial and muscular health. I think you’re going to love our conversation.

Dr. Kara Fitzgerald: Dr. Davide D’Amico, welcome to New Frontiers. It’s great to have you here.

Davide D’Amico, PhD: It’s a pleasure to be on your podcast, Kara. Thanks for having me.

Dr. Kara Fitzgerald: So listen, let’s dive in and talk about heart disease and heart health. This is something that is a international killer. It’s a top killer globally. Can you give me a little epidemiological background on heart disease around the world?

Davide D’Amico, PhD: Sure, as you pointed out, heart disease is the first killer worldwide and the statistics are quite impressive. 30% of all global deaths are actually because of heart diseases. Just to give another stat, there is one person that dies every 33 seconds of heart disease. And this makes it very important to intervene and support heart health as early as we can because that’s a very heavy burden for our health and also heavy cost for our health care system.

Dr. Kara Fitzgerald: Yeah, of course. I’m sure somebody out there has calculated the cost of heart disease as a killer. It’s just got to be massive, you know, just many economies.

Davide D’Amico, PhD: Yeah, just in the US it’s more than 200 billion per year. That’s massive.

Dr. Kara Fitzgerald: Yeah, it’s difficult to fathom. It’s such a ubiquitous issue. And I think as you point out, we’re not talking about it enough. It’s underappreciated. It’s underappreciated, I think, especially in women. Why do you think that is, actually?

Davide D’Amico, PhD: This is very good question. I don’t have an answer. I could think that you start thinking about your heart health only too late when you actually get into the disease state and then it’s too late. But it’s actually very easy to take care of your heart health. There’s very clear and simple recommendations that we can follow to reduce the risk of heart health.

Dr. Kara Fitzgerald: And what are those, actually? What does the American Heart Association recommend that we do?

Davide D’Amico, PhD: Yes, I would stick to the leading association in the field, the American Heart Association. They come out with guidelines pretty often. They update them regularly and they have a set of very straightforward, clear recommendations. The two main pillars are a healthy diet and risk assessment. A healthy diet is what is also called the heart healthy diet, which is very similar to the classic Mediterranean diet. So they recommend to have a diet that is rich in fresh fruit, in vegetables, in whole grains, lean protein, healthy fat, like olive oil and fish, and to reduce sugar, salt and the bad fats.

Davide D’Amico, PhD: So healthy diet is one and the second one that’s important is exercise. They recommend two sessions a week of moderate exercise for 150 minutes. This is like brisk walking or gardening, so very easy things that we can do. Or 75 minutes of more moderate activity, like a short run twice a week.

Dr. Kara Fitzgerald: Actually, I just want to point out for my listeners, who by the way are clinicians primarily, so they’re certainly familiar with American Heart Association guidelines. So we’re talking about exercise and diet and we’re certainly initiating medication management to lower lipids. And so I’d like your thoughts on that, on how we’re actually addressing heart disease directly, as well as heart disease prevention, you know, when we check our biomarkers and get in there and really primarily work aggressively on lipids. So I want your thoughts there. And then I also want to talk a little bit about functional interventions in our space, so antioxidants, omega-3s. Let’s talk about medical management. Thoughts there for heart health? And recognizing that you’re not a clinician, recognizing you’re a PhD, so you’ve got your scientist hat on, and then let’s move over and talk about antioxidants, omega-3s, and some of the standard tools we use as clinicians.

Davide D’Amico, PhD: So, the medical recommendation for heart health, one of the key aspects that we need to be careful about, is our plasma lipid levels. There is a clear association between an increase in what we call the bad lipids, HDL [correction: LDL] and triglycerides and the risk of heart disease. Now, I’m not a clinician, so I’m more here with my science and PhD hat and I can tell you that these lipids are bad and why they are bad. They’re basically accumulating in our blood vessels and creating what we call atherosclerotic plaques, which makes our vessels stiffer so the blood cannot flow properly. This creates stress and dramatically increases the risk of inflammation or oxidative stress, fibrosis and then heart diseases. So reducing the lipids that are bad for the heart is very important. How can we do it? The healthy diet and the exercise, these are proven to do it.

Davide D’Amico, PhD: The other classical supplement, or least nutritional molecule that is associated with lipid management, is Omega-3. Omega-3 is a healthy fat. It is recommended to have a regular intake of Omega-3, say 3 to 4 grams per day. The basic suggestion is to have fish or fish oil twice a week and the American Heart Association is giving a clear recommendation, which is food first. So if you can, get it from your healthy diet and then if this is not possible because you cannot eat or don’t want to eat fish, then it’s okay to supplement it.

Dr. Kara Fitzgerald: Yeah, but with these, as we were talking offline, we’re not addressing the heart per se. We’re addressing some of the problems that can drive heart disease forward. So with that, I know some of us, again in functional medicine, think about antioxidants and creatine, carnitine, et cetera, to kind of help there. And what are your thoughts on the data with regard to antioxidant use or some of our more classic tools?

Davide D’Amico, PhD: Yeah. There is not much scientific evidence on antioxidants, especially in healthy people. And again, the recommendation is to eat healthy and you will get enough of your antioxidants with fresh fruit and vegetables. But you’re pointing out a very interesting thing, which is direct versus indirect effect on the heart.

Dr. Kara Fitzgerald: Yeah.

Davide D’Amico, PhD: The indirect effect through the lipid is working, is important, but we are not really getting into the core problems that you can have in your heart cells when you age or when you have a disease. And here what we have been studying and we are interested in is to see what is actually declining in the heart cells and how can we intervene there precisely and directly.

Dr. Kara Fitzgerald: Can you talk about that? What’s happening? What are the physiological changes as we age to the cardiomyocytes? Cardiocytes more broadly?

Davide D’Amico, PhD: There are a lot. What we did some years ago as part of a broader study was to interrogate some publicly available data sets. These are studies done from other researchers where they took heart biopsies from people coming from a broad age range, from young to very old, and they did a transcriptomic analysis, which is basically looking at all the gene changes with aging. And we looked into which biological pathways were the most impacted with aging. And the top pathway, the one most significantly declined with aging was related to mitochondria. So the mitochondria are really the key components in the heart that declined the most with aging.

Dr. Kara Fitzgerald: Wow. Is that in lockstep with the diseases? With the various forms of heart disease that manifest on the aging journey, in younger and younger individuals?

Davide D’Amico, PhD: The change started pretty early, at least in these studies. You see a decline of the gene expression related to mitochondrial function every decade, already since you’re 30. And then what we did was also to overlap the changes with aging with the changes with heart disease. And heart and mitochondrial dysfunctions were really the common hallmarks of aging and disease in the heart.

Dr. Kara Fitzgerald: Interesting.

Davide D’Amico, PhD: And this was known, but it was not known that this was so important and really on top of the list. But at the same time, it’s not so surprising because the heart beat beats 100,000 times per day. And so this requires a lot of energy and 90% of this energy comes actually from mitochondria.So it’s not a surprise that with aging and with this heavy use of our heart muscle, the mitochondria might decline and contribute to unhealthy heart and heart diseases.

Dr. Kara Fitzgerald: Yeah, it makes complete sense. It’s interesting because it’s such a ubiquitous problem. And those of us in functional medicine, we’re certainly working with patients who’ve got abnormal lipids, who’ve got risk factors. We’re looking at various images and seeing evidence of atherosclerotic changes and mitochondria needs to be front and center. You know, when we’re thinking about the pathophysiology, mitochondria fitness just needs to be right there, of course. It makes total sense. I mean, we’re apt to think about it in cardiomyopathies and specific diagnosed conditions, but probably when we begin to see the lipids change, which we measure all the time, we’re paying very careful attention, in our brains needs to be mitochondrial fitness. I want to hear your thoughts on that, but I also just want to jump back to the mitochondria being so essential for all of the constant energy output that’s happening with the heart tissue, with the cardiomyocytes. I think it’s one of the most mitochondrial dense cell types. Is that correct? Is it the top or is it up? Yeah.

Davide D’Amico, PhD: It’s the top, totally right. It’s the organ, the most abundant, the most rich in mitochondria. Actually, 40% of the heart weight is made of mitochondria. It’s quite impressive. Yeah.

Dr. Kara Fitzgerald: 40% of the heart weight is mitochondria. Wow.

Davide D’Amico, PhD: And look, this is an organelle that is key for energy, but that’s a bit of a paradigm that we need to change. We know that mitochondria have a lot of functions, not just the simple powerhouses like we know them. They are extremely important to regulate cell oxidative stress, cell inflammation. And so if we know that mitochondrial functions decline with aging, this then has secondary effect on all the other hallmarks of aging.

Dr. Kara Fitzgerald: Yes. And as you already demonstrated in preclinical work, the changes that are happening with age with regard to the mitochondria really kind of map out with all of the hallmarks of aging. So if we get in there and we think about mitochondrial fitness as essential and foundational for cardiovascular fitness, we’re going to be addressing not only heart disease, but just the aging phenomena itself, I think more broadly.

Davide D’Amico, PhD: The interesting signature that we saw in the studies was actually not related only and mostly to the energy production role of the mitochondria, but was more related to the quality control processes of the mitochondria. There were a lot of genes that were declined and associated with the recycling of the mitochondria. So what it means is that when we age, the heart cell loses the ability to… So first of all, when we age, the mitochondria gets older, like the cell itself, which means they start being less efficient in producing energy, but they’re also creating these toxic byproducts like reactive oxygen species and this leads to also inflammation, fibrosis and so on. And the cells are not able to recognize and remove these mitochondria properly. And so what we were trying to do was to, well, first see what was changing in the heart aging. And that’s the first part of the study. And then asking ourselves, how can we restore this more youthful state of the mitochondria in the heart and does this have an impact for the heart function?

Dr. Kara Fitzgerald: Yeah, let’s talk about the solution and what you saw in this study.

Davide D’Amico, PhD: (The study is, first of all it’s important to mention that that’s a great collaboration that we did with the top academic lab in the field. That’s the group of Dave Marcinek at the University of Washington. This is a group that worked on heart aging and tried a number of drugs and natural molecules for several years. And so they did some of the studies for this publication and we did some others. We used two experimental models to test our hypothesis. And what we used to try to improve the mitochondria and heart health was Urolithin A. Now you have been talking about Urolithin A a few times in the past in your podcast. I don’t know how much you want me to introduce it. I can give a quick intro here as well.

Dr. Kara Fitzgerald: Give us an overview. Yeah, let’s remind everybody of the wonderment of what Urolithin A is.

Davide D’Amico, PhD: So, Urolithin A is a naturally derived postbiotic, which means there are certain molecules in the food that, when ingested, can be metabolized by the gut bacteria and generate Urolithin A. These precursor molecules are called ellagitannins, and foods rich in ellagitannins include pomegranates, berries and nuts. So, simply speaking, if I take a glass of pomegranate juice, the ellagitannins go in my gut, the bacteria convert ellagitannins into Urolithin A. Now this is the theory, then the practice is not exactly the same. Not everyone can actually do this conversion. Me, I cannot do it. I mean, actually, if I take a glass of pomegranate juice, I cannot produce any Urolithin A, because I unfortunately don’t have the right bacteria to do the conversion.

Dr. Kara Fitzgerald: Interesting.

Davide D’Amico, PhD: And even those who can do it, usually have very variable and low level of Urolithin A, which do not reach what we call the clinically meaningful level.

Dr. Kara Fitzgerald: What percent of the population, well in the folks that you have tested, can actually achieve what would be a therapeutic amount from their microbiome.

Davide D’Amico, PhD: 30 to 40% can get some Urolithin A, but most of them not at the clinically meaningful dose. And to get this you need to get something like six glasses of pomegranate juice.

Dr. Kara Fitzgerald: Interesting. Right, which is going to have a whole fallout of problems for just the glucose content of that. Well, I would love your assay, the ability for us to test for UA, to be available to test clinicians. And whenever I talk to somebody over there at Timeline, I bug you guys. I was able to do it, I had access to it, and I am a UA producer.

Davide D’Amico, PhD: Oh you are? Good.

Dr. Kara Fitzgerald: Yeah, I’m a UA producer. Not much, I know. I want a T-shirt that says it, but I’m not producing a therapeutic amount. So I’m happy to have the microbiome and would love to nurture that so I could produce more, but we’re really still kind of unpacking it. But in the meantime, you guys have figured out how to manufacture a bioidentical Urolithin A molecule, and you’re rigorously involved in preclinical and clinical research just around the world. So it makes a lot of sense to me that you would be turning your attention to the most mitochondrial dense tissue. Of course you need to be thinking about the heart. And likewise, I think as your research comes forward, and we’ll talk about it in a second, it will help to shape our thinking as clinicians and really putting mitochondria front and center when we’re engaging in heart health. Not that we don’t pay attention to lipids, because of course we’re paying attention to lipids. It’s incredibly important, but that’s indirectly addressing heart disease. And I think to your earlier point, we need to be thinking about both of them.

Dr. Kara Fitzgerald: Perhaps I’m saying this for myself as a clinician, mitochondria need to be just first on that list. And incidentally, this is a thought that I had earlier, that the dietary changes, just the Mediterranean diet for somebody who’s a UA producer is going to be beneficial. Although for most of us it won’t be enough. And the research on the Mediterranean diet as a beneficial dietary pattern continues to come out. And so I think the American Heart Association is by and large correct in that suggestion. So after that commentary, I want to talk about some of the science that you’re engaged in on looking at UA and heart health.

Davide D’Amico, PhD: Yeah, let’s get back to heart health. There is one other important piece of information about Urolithin A, which is that most of the clinical studies that we did so far were on skeletal muscle. Right? This is an important point and another good reason on why we ended up studying heart. We’ve now done more than 10 studies in different populations, middle-aged, overweight, healthy, older adults, all healthy people, but with somehow a lower than average mitochondrial function. In all the studies we were supplementing the subjects for two to four months with Urolithin A and we saw statistically significant improvement in skeletal muscle health and we’re talking about muscle strength and muscle endurance. So the skeletal muscles are basically our biceps and quadriceps and so on.

Davide D’Amico, PhD: But of course, as you were saying, after all this research and knowing the role of mitochondria in the heart, we were asking ourselves, well, we have a molecule, it’s very good in improving mitochondrial function, it’s very good in improving skeletal muscle function, so what’s the effect on the heart? That was an obvious question. And so, going back to the topic, we teamed up with this great group at the University of Washington and we actually saw that it works. Now to get into the data, we did echocardiography in two models. One was a model of heart aging and one a model of heart failure. We looked at the two classic functions of the heart which is the systolic function, so the ability to contract, and the diastolic function, so the ability to relax. This is what allows the heart to constantly pump the blood throughout our body.

Davide D’Amico, PhD: And of course in both of these models they had lower diastolic and systolic functions compared to the healthy models. Some functions were more dysfunctional in a certain model and some in the other. But what was important is that when we supplemented these models for two months with Urolithin A, both diastolic and systolic functions were partially rescued. Not completely, but there was a significant improvement. And this was exciting. And as I told you, the group has been testing several other molecules in the same model. And they told us, look, this is the molecule that has the broadest effect, hitting multiple features, multiple parameters of multiple functions of the heart.

Dr. Kara Fitzgerald: Can you talk about some of those parameters that it touched upon? Why they said that it was such a powerful molecule?

Davide D’Amico, PhD: Well, the first is called ejection fraction. This is a standard echocardiography parameter that is measuring how much blood is coming out from the heart and it’s a proxy of how efficiently the heart muscle fibers contract. This is declining, mostly with heart failure, to some extent with aging, but the clinical space here it’s a bit more complex. There are different forms of, let’s say, heart dysfunction with preserved or reduced ejection fraction, but in general what is important is there is a general decline in the ability to contract in the heart muscle. And this can be due to many reasons. One which we think is important and we have some data to support is that there is a decline in the mitochondrial function. So there is less energy and more stress that impairs the contractive capacity of the heart.

Dr. Kara Fitzgerald: I know this is a preclinical model in this early research, but can you extrapolate what the— Well, let me ask you this way. I’m assuming that you’ll be beginning clinical studies in heart health and I want to hear about that. What your thoughts are, what you might have in store, and what dose would you think about with Urolithin A? Would it be 1,000mg or 500mg? I’m assuming it would probably depend, but speak to that.

Davide D’Amico, PhD: This is a question for which we would need data. As a scientist, I would not be able to claim and tell you anything before being a clinical study. We started preclinically because that’s how research works and also because we wanted to look at the mitochondria in these models and make sure that Urolithin A was working in the heart mitochondria like it did for the other organs. And we didn’t do a clinical study that is properly designed to claim Urolithin A improves heart functions. For this we would need echocardiography and proper readouts.

Dr. Kara Fitzgerald: Of course.

Davide D’Amico, PhD: But what we did, which is very preliminary but very promising, was to look back to a previous study which is called ENERGIZE. It’s a clinical trial, one of the studies where we supplemented older adults with Urolithin A for four months. So these adults had better muscle endurance after four months and we had some blood samples left from this clinical study. And we asked, can we look at some biomarkers in the plasma that can give us an indication if there is an impact on heart health. And so we did it and we looked into a kind of biomarker that is emerging now as the new, the best one in the prediction ability of getting heart disease. And these biomarkers are called ceramides. Ceramides are lipids and we know that they accumulate with aging, with diabetes, in obese people, and with a number of other diseases. And it’s clinically proven that an accumulation of ceramides in the blood means you have a higher risk of getting a heart disease. So these are now clinically used. People can go in certain clinics and they have a panel of ceramides and they come back with a score and they can tell you your ceramide are at this level so your risk is low, medium, high.

Davide D’Amico, PhD: And so we looked into the ceramides in the group that took the placebo and in the group that took Urolithin A and the first observation was that in these healthy elderly, some of the ceramides were a bit higher than the healthy threshold. Some were actually quite higher. So they were not diseased, they didn’t have any history of heart disease, but still, they were on the trajectory of higher risk of diseases. And the second most exciting was that Urolithin A was significantly decreasing this marker. And so the bottom line is we didn’t measure the heart contractility, but we measured this proxy of heart health. So this is promising data that suggests health benefit of Urolithin A for the heart.

Dr. Kara Fitzgerald: I’m just so excited to see what further clinical data you’ll have with time since you’ve got these two pieces of information. It’s very exciting. I think, just for our listeners— And by the way folks, the other podcasts and content that I’ve done with Timeline we’ll park on the show notes. We’ll park the papers that Davide is referencing so that you can access all of this. I think that the ceramide panel is available right now through Mayo Clinic, but if I’m not mistaken, I think we’ll have access through Quest and perhaps other labs will step up so that we can begin to look at ceramides.

Dr. Kara Fitzgerald: And to your point, heart health, diabetes, I mean, there’s a lot of reasons why we might want to be exploring these compounds and high levels. I mean, we need ceramides. They’re essential players. I think about them when I’m thinking about skin health and different skin conditions. There’s often a deficit of ceramides locally in the tissue, but imbalances, with regard to high levels of ceramide are associated with, again, heart disease and other conditions. So an elevation of them outside of the realm of skin will prove itself, to your point, to be a useful biomarker for us and one that we will consider adding to our toolkit. The other piece that I wanted to just say regarding that four-month intervention, those were sedentary older adults, I believe.

Dr. Kara Fitzgerald: And I believe that their VO2 max also improved considerably. Not just muscle, but there was just a plethora of markers and I think there was a drop in CRP. It might have been in that study, but if it’s not, you can correct me. This is something that you’ve seen just with Urolithin A. And so in my mind, all of these suggest that there must be some kind— The change in CRP, and I think that you’ve also seen TNFα, interleukin 6, increased muscle mass, improved VO2 max, like, considerably. We’ve seen epigenetic changes, actually, to go into another study with Urolithin A— Favorable bio-age clock changes. I mean, all of them are sort of dancing around the possibility of this molecule in heart health. Thoughts on that?

Davide D’Amico, PhD: Yeah, I agree. Now, just to comment on your ceramide point, not all the ceramides are the same. There is a difference between the healthy ceramide for the skin and the less healthy ceramides that are associated with heart health and heart diseases. When you do your panel, there are actually just four that you’re measuring. And regarding the heart health, yes, you’re totally right, CRP was actually declining in all our studies. Inflammatory cytokines are declining in all our clinical studies. So this means that even without a disease in healthy people, the molecule Urolithin A decreases what we call inflammaging, this low grade, constant inflammation that we have, and which contributes to our aging process and it’s associated, as you said, to heart health.

Davide D’Amico, PhD: And I think the key is really still the mitochondria though. We published recently with the National Institute of Aging a review where we were trying to understand the literature connecting the mitochondria to inflammation and oxidative stress. There is a lot of evidence that actually, the mitochondria really accumulate in this bad state with aging and what they do is to signal to the rest of the cell. It’s a dysfunctional signaling that goes and checks all the other hallmarks of aging. So we don’t have clear proof of it, but there is a good indication that because we are removing these bad mitochondria and regenerating new ones, then we avoid reactive oxygen species, we avoid inflammation, and that’s then reflected into the CRP biomarker and the ceramide biomarkers.

Dr. Kara Fitzgerald: So, this is an incredibly important point. Urolithin A is stimulating mitobiogenesis, but it’s also stimulating mitophagy. So it’s both allowing for stimulating the production of good, new, healthy mitochondria, as well as clearing out the old ones. And I think the old ones just end up breaking down and really turning on damage signals and really driving inflammation forward.

Davide D’Amico, PhD: Totally right. They literally burst inside the cell, they release molecules that are usually inside the mitochondria, and when they get into the cell, they are recognized as foreign bodies. And so they activate the same signaling that you have when you have an infection, which boosts inflammation and all the downstream signaling. And if we remove these damaged, dysfunctional mitochondria, we prevent this process and so we have less inflammation. And then just to be clear, the mitophagy and regeneration process are sequential. When you instruct the cell, hey, this is a bad mitochondria, remove it, then this signaling is tightly linked, coordinated to what we call biogenesis. It’s really a sequential process. You first remove them and in parallel you instruct the cell to activate the machinery to rebuild the new mitochondria.

Dr. Kara Fitzgerald: Exciting stuff. It’s really exciting stuff. Again, I’ve said it a few times already on the podcast, but I very much look forward to the further research that you’ll be doing in this arena. And it’s pretty remarkable. We usually think of this domain as, you know, most impacted by exercise. And so again, just thinking about your other studies where you’ve shown just with Urolithin A, without an exercise prescription, in fact, in sedentary individuals with no exercise prescription, no dietary changes, only the introduction of the molecule. And I believe the most impactful changes were noted in the 1000mg. You can correct me if I’m wrong, but just pretty remarkable turnarounds.

Davide D’Amico, PhD: Yeah, that’s correct. This doesn’t mean that we should not have a healthy diet and exercise. This should be on top of healthy lifestyle. But the effects are there independently of exercise and healthy diet. And yes, the most efficient dose is the one gram.

Dr. Kara Fitzgerald: Of course. Yes. And I think, to your point, of course we need to continue with healthy diet and exercise habits, et cetera. And I do think you’ve got some studies happening now looking at layering Urolithin A with athletes who are… So instead of just looking at sedentary older adults, you’re expanding the population, you’re investigating the efficacy of your Urolithin A. Am I correct?

Davide D’Amico, PhD: Yes. That’s correct. There is one study we are wrapping up with another amazing research group. This is led by Louise Burke at the Australian Catholic University. Here we have been looking into semi-professional and professional athletes, professional runners. There there was an exercise intervention that was actually pretty intense. These guys were in a training camp and training hard. They were doing downhill running, which is this eccentric exercise that really boosts muscle damage. And what we saw, the results will be published soon, is a mild effect on the performance. It was mild, but still, it’s not surprising it’s mild.

Dr. Kara Fitzgerald: They’re well trained. Yeah.

Davide D’Amico, PhD: These athletes have a very high baseline, but even a small change… And this small change that we saw is kind of what’s needed to go from second place to the gold medal. So it’s quite relevant. The other data that we got was on muscle recovery. There was a reduction in muscle damage markers and inflammation markers in the blood of the subjects, which means you do a strenuous exercise, but you can recover faster and so exercise more efficiently later on.

Dr. Kara Fitzgerald: Nice. Well, I will look forward to that publication and exploring more of these with you. Davide, one final question and then I’ll just ask for a couple of your wrap up thoughts. I’m curious. You did your postdoc research looking at interventions for improving mitochondrial function and ultimately that brought you to Timeline. You must be in your happy place being in the laboratory at Timeline, I would imagine, working with Urolithin A. But I’m curious what you did your postdoc work in. What molecules were you looking at specifically then?

Davide D’Amico, PhD: The beginning of the postdoc was not really on molecules. It was really basic research to understand which checkpoints are altered with aging and disease, especially in the muscles. We were knocking down genes, removing proteins, and seeing which one was good and which one was bad.

Dr. Kara Fitzgerald: Interesting.

Davide D’Amico, PhD: And this was exciting basic research which was done in a group which is still a leading one in the field of mitochondria. It’s the group of Professor Johan Auwerx at the Swiss Federal Institute of Technology. Towards the end of the postdoc I started getting into more interventional studies. We started knowing what is changing, so how can we prevent these changes? I had the opportunity to collaborate already with Timeline towards the end of the postdoc with one project. And then I think there was a drive to bring all the beautiful, basic research into something that had a real impact. So it was a great opportunity to go from not only basic research, which we still do, also into clinical, I would say translational, in my case, and with the extended team into the clinical, research down at Timeline.

Dr. Kara Fitzgerald: Very exciting. Anything you wanted to add? I think we covered a lot of bases today, but did I miss anything?

Davide D’Amico, PhD: No, think that’s pretty much it. I think the mitochondria are one of my passions since the beginning. And yeah, I would encourage you to look at the picture of the mitochondria. We talk a lot about the importance of the mitochondria but I always say that mitochondria are also beautiful. I had the chance to spend many hours looking at them with the microscope. And in the latest study, we really have amazing pictures of these mitochondria in the heart and you can really see them. I think it’s very powerful when you see it. You don’t just have a graph, but you have real picture of this mitochondria and how they get dysfunctional. They get less complex and they lose all the beautiful dense internal structure where all the energy is made. And it’s beautiful to see how they get better when they have the right intervention, in this case, Urolithin A. So, yeah, just a note on the importance and the beauty of the mitochondria.

Dr. Kara Fitzgerald: Well, maybe I can bug you for a graphic that we could pop on our show notes to just kind of illustrate what you’re talking about. I know in past webinars that I’ve had with Anurag Singh he’s shown graphics and you’re absolutely correct. It is quite impactful to see the changes happening and the movement back to the improvement. You know, just kind of that journey. It’s really quite extraordinary. My team will bug you guys or we’ll find an image somewhere to illustrate that phenomena and we’ll pop it on our show notes, folks.

Davide D’Amico, PhD: Amazing.

Dr. Kara Fitzgerald: Well, thank you so much for joining me on New Frontiers today.

Davide D’Amico, PhD: Thank you, Kara. It was a pleasure.

Davide D’Amico, PhD, is the Director of Discovery and Translational Research at Timeline. With over 15 years of experience in mitochondrial and aging biology, he contributed to developing Urolithin A as a science-backed, clinically validated nutritional product to enhance mitochondrial and muscle health.

Timeline Studies

Scientific Articles – Summary Points

Research: Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers

Dave Marcinek, PhD

Research: Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults

Mayo Clinic Ceramides Panel

Research: Impact of the Natural Compound Urolithin A on Health, Disease, and Aging

Professor Louise Burke OAM

Professor Johan Auwerx

Dr. Anurag Singh, Chief Medical Officer Timeline

Ceramide Article: Straight From the Heart

Article: Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Blog: Urolithin A: Mitochondrial Support for Longevity, Strength & Heart Health

Podcast: Beyond Retinol: The Role of Urolithin A in Aging and Skin Health

Blog: Immune Health as You Age: How Urolithin A Is Revolutionizing Longevity

Podcast: ​​Beyond Mitochondrial Health: Can Urolithin A Slow Down Aging?

Podcast: Optimizing Mitochondrial Health with Urolithin A, with Dr. Anurag Singh

DrKF Clinic: Patient consults with DrKF physicians including Younger You Concierge

Bio Age Self Assessment Quiz

Younger You book

Better Broths and Healing Tonics book