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

Talking with Dr. Julie Faitg was a powerful reminder of just how much we’re discovering about mitochondria and aging. When you pair an elite mitochondrial scientist with a breakthrough nutrient like Urolithin A, the insights go beyond what you’d expect. Julie gives us this incredible look into how we can actually change the course of aging at the cellular level. This conversation made me rethink what we know about supporting long-term health and resilience, and I think it will do the same for you. It’s one of those big-picture, eye-opening conversations that I can’t wait for you to hear. ~DrKF

Dr. Julie Faitg, a leader in mitochondrial science, joins New Frontiers to reveal how mitochondrial health shapes skin resilience and influences aging. She explores the science behind intrinsic and extrinsic aging, how mitochondrial function impacts age-related conditions, and why Urolithin A is emerging as a breakthrough nutrient for both skin and cellular vitality.

The conversation covers Urolithin A’s potential to support skin health, speed up athletic recovery, and reduce inflammation, with highlights from clinical trials demonstrating reductions in photo damage and wrinkles. Tune in to discover how cutting-edge mitochondrial research is paving the way for transformative interventions in skincare, longevity, and functional medicine.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And of course, today is no exception. I am thrilled to be sitting next to Dr. Julie Faitg. She is a leading expert in mitochondrial research, with over nine years of experience focusing on muscle and brain biology and recently expanding her expertise to include skin health. She’s got a PhD in translational and clinical research from the Wellcome Trust Centre for Mitochondrial Research. She collaborates with renowned scientists worldwide, including Nobel laureate Eric Kandel and other mitochondrial experts. Currently, Dr. Faitg serves as Senior Translational Scientist and Regulatory Affairs Lead at Timeline, where she makes significant contributions to research and development across various organ systems in the field of mitochondrial biology. Julie, welcome to New Frontiers.

Dr. Julie Faitg, PhD: Thank you very much.

Dr. Kara Fitzgerald: Yeah, absolutely. I have just had the best time talking with you off-record. And I just want to say to you that, you guys, she is a real mitochondrial scientist—like, an in-the-trenches, hardcore, dyed-in-the-wool expert in this arena.

Dr. Kara Fitzgerald: We were having an interesting conversation about her backstory and finding Timeline and I was asking her if she was excited about the Urolithin A molecule. And, you know, anybody who’s been with me for a while has heard me talk to Dr. Anurag Singh, and we’ve unpacked a lot of the science. And so she gave me this really cool story – Julie, I have to share it— about how you heard Anurag present at a conference, and you guys immediately started dialoguing and you began to ping him with different ways to look at the data, and do appropriate muscle biopsies, and so on. You were immediately excited about this molecule. Anything to add to that? It’s just really fun to hear that.

Dr. Julie Faitg, PhD: You know, this conference is a tiny world and I was looking at everything and what a Dr. Singh presenting and I was pinging Timeline president, Chris Rinsch, and I was sending emails to people in the company. I mean, when it’s the theme of your thesis and you love everything about this tiny mitochondria, it’s quite a nice story to talk about all the time. And, that’s the mitochondria world.

Dr. Kara Fitzgerald: Right. And the fact that they actually listen to you. I find that Anurag is really open to new ideas and he has a curious mind. You guys are all a bunch of scientists wanting to ask the questions and wanting to answer the questions, and I’m a huge fan. I love working working with you. I love learning from you guys. But it’s amazing what this molecule is and where it came from and so we’re going to talk about all of that. But before we do, you know, let’s just get into some background on aging. Like what is aging? Give us a little breakdown of the hallmarks of aging and then we’ll move into where Urolithin A sits in that world.

Dr. Julie Faitg, PhD: Yeah. For sure. Everyone here knows the hallmark of aging and aging is so complex. I mean, it’s all the multifaceted processes influenced by so many various biological mechanisms. Definitely. And there’s several theories that have been proposed around that, including the 9 hallmarks of aging that was published by Lopez-Otin in 2013. And then they published another paper in 2023 where they have 12 hallmarks of aging. And the one that I like to focus on, for sure as a mitochondrial biologist, is mitochondrial dysfunction. And, some people know that mitochondria are kind of the powerhouse of the cells. I like to call them our little batteries, and the they play such a crucial role in energy production and metabolism.

Dr. Julie Faitg, PhD: As we age, dysfunction. This mitochondrial function, because there’s plenty of function and when we say function, it seems so simple, but it’s not. There’s many of them, like energy production ROS production, calcium uptake. But when you have mitochondrial dysfunction, you have reduced energy for sure, and an increase of reactive oxygen species. Mitochondrial dysfunction has been linked also to so many various age-related disorders. This can cause so much damage to cellular components contributing to aging and age related disease. So yeah, for me, that’s one of the key hallmarks for sure. For sure you have the gut microbiome as well. When the gut microbiome is disrupted, you also have chronic inflammation that has been added because the 9 Hallmarks of aging that have been cited before were maybe too vast and now they’re trying to specify them. And it’s exactly what’s happening with mitochondrial function. They try to really get specific with them because it’s too large.

Dr. Julie Faitg, PhD: When you say dysfunction, mitochondria could work for respiration, for example, producing energy, but not for working on the calcium retention. So there’s so many different things that you need to be more specific. So that’s why this is really important. And also, one of the key hallmarks that I think we need to talk about is microautophagy and also the mitophagy. Autophagy is really like eating the cells that are not working well, and mitophagy is essentially deleting the mitochondria that are not working. With age, autophagy really becomes less efficient, exactly like mitophagy, which leads to accumulation of damaged protein or organelles, so that’s definitely one of the big hallmarks of aging.

Dr. Kara Fitzgerald: Yeah. It’s fascinating. So just being a mitochondrial scientist, it’s such a fundamental hallmark that you were working in aging.

Dr. Julie Faitg, PhD: Yeah, exactly. Exactly. Looking first of all on mice and after that in humans. And this damage is a consequence, but it could be also be the cause. You will hear a lot of scientists saying, no, the mitochondria is involved. When they’re dysfunctional, they will do that. And some people say, yeah, but aging is linked to a sedentary lifestyle, so mitochondria will be influenced by a sedentary lifestyle or lack of activity so there will be damage. They will not be pushed to do something because I like to call the mitochondria the good friends. They’re everywhere, so basically it’s really important to look at them.

Dr. Kara Fitzgerald: Yeah. We’ve had an okay toolkit in functional medicine to really support good mitochondrial function, but I know this is really next generation, you know, the ability to actually make Urolithin A. And toxins. You know, one of the things we always think about in functional medicine is the toxic burden. Acquired mitochondriopathy is something that we see ubiquitously, be it environmental toxins, or maybe it’s an infection or we see this mitochondrial dysfunction in Covid, etc.. It’s just a huge fundamental player, not only in the changes that happen with the aging phenomena, but the weight of all of the diseases and toxic exposures and so forth.

Dr. Julie Faitg, PhD: Yeah, exactly. You find mitochondria everywhere, except in blood cells. Their main function, people would say, is to produce energy, but that’s not their only role. That’s why I call them the “good friend,” because they do a bit of everything. It’s kind of my mantra, you know? I like to refer to them that way. They really are something special. And that’s why people need to be really specific when looking at mitochondria—because they have so many functions. When they become dysfunctional, you need to figure out exactly what isn’t working. That will help guide your research and what you need to look at.

Dr. Kara Fitzgerald: Good for you. No doubt you nudged Timeline and Anurag in that direction. I have no doubt you did. Good for you. Good for you, Julie. I just want to throw this out too, and then we’re going to talk about your newest research looking at the skin. But I just want to shout out on epigenetics as one of the hallmarks. And Urolithin A has been shown to favorably influence epigenetics and we’ll link to this in the show notes. And that was the reason why I originally fell in love with your company is I knew that Urolithin A had to be an epinutrient, just by design of its sort of origin story. And so it’s really cool that that has come to pass and you’ve demonstrated that and you’re publishing on that and its reversal of the bio age. So there’s just so much it does. But let’s talk about skin. Skin is always fun. Everybody’s always into talking about skin. And it’s more than just how we look. Hello. Obviously everybody wants to look great. It’s like aging kicks in there first. So why are you guys investing in skin?

Dr. Julie Faitg, PhD: As a translational scientist , I like to remind people that skin isn’t simply about appearance, like you said. It’s the body’s largest organ, so it plays a vital role in maintaining overall health. It’s kind of the first warrior to fight for you against all the environmental problems like pollution. I mean, skin is really the critical barrier that protects you from different environmental issues such as UV radiation, toxins, and pathogens.

Dr. Julie Faitg, PhD: But this protection becomes compromised with age. The skin loses some of its ability to regenerate and repair, so it’s something you need to take care of. I like to call it the three key pillars to support healthy skin: You need to nourish the skin to keep it resilient and really take care of it. You need to prevent damage to protect it. And third, regenerate, rejuvenate and repair the skin. So these are the three angles I focus on when learning more about skin. Every organ is really specific, but in the end, everyone wants the same thing and that’s to age gracefully. Because you don’t want take this old and make it look 18 again. You need to age gracefully and and live with it.

Dr. Julie Faitg, PhD: It’s not just about appearance because you can use Botox or whatever you want, but those won’t fix what’s happening inside. That’s why people need to realize the importance of using SPF. As an example, I was not putting on SPF—I swam all my life since I was young and I was not using SPF at all. And now we realize the problem is that even in the deep of winter or when it’s raining, you need to put on SPF every day to protect your skin. You take care of your other organs, like your muscles, liver, and spleen, whatever—you need to do the same for your skin. It’s your first, kind of, “nice friend” to protect you from environmental insults.

Dr. Kara Fitzgerald: Yeah, 100%. Yeah. It protects us from UV. It protects us from allergens, from toxicants, all sorts of stuff. And what’s interesting to me, when you were just talking, there was a cool study that came out, I think, in 2015, identifying that we can look at somebody and we can identify people who are aging faster and who are aging slower just by looking at their skin.

Dr. Kara Fitzgerald: That accelerated aging phenomena that might be happening on the skin is reflected inside as well, as measured by biological aging. It’s an extraordinary window into what’s going on inside. And so to your point, we want to take care of it. But yeah. Go ahead.

Dr. Julie Faitg, PhD: No, no. Exactly. And, you know, I think I’ll jump into intrinsic aging and what we call extrinsic, or photoaging. Intrinsic is what’s known as chronological aging and it’s really the natural process of your skin aging that occurs all the time. Things like gene mutations, as we said, epigenetic instability, immune system deregulation, hereditary DNA damage, and telomere shortening, these are kind of new things today. And, importantly, like I said, mitochondrial dysfunction because of energy decline. There’s also reactive oxygen species production, there’s mutations, and there’s a decline in mitochondrial turnover, which I like to call it quality control.

Dr. Julie Faitg, PhD: I may go into more detail later, but it’s really important to look at the entire complex of the mitochondria. There was a paper published in 2020, I think it was by Oblong, et. al, and they looked at transcriptomics data regarding fibroblasts from young and old people. In this biopsy, they saw that oxidative phosphorylation, which is related to respiration, showed that all these genes were inhibited and damaged from older donors. So you can see that with age, and even in the skin, all the mitochondrial genes are inhibited and have decreased expression. So all the cellular energy declines because of the oxidative stress and all the key hallmarks of intrinsic aging. And then you have the photoaging.

Dr. Kara Fitzgerald: Before you go into photoaging, I just want to put a pin in that for a second and underscore what you’ve said. So here in our skin, which we look at and address or ignore, however it is that we’re choosing, maybe we’re obsessive about it. There’s certain pieces that I’m like… I have this spot of nummular dermatitis, that’s driving me… Anyway, our skin has all of these hallmarks that you just introduced. That phenomena is occurring right there locally in our skin, causing the intrinsic aging phenomena. So that’s a really important point I want to hit home for everybody to get. And now… Yeah go ahead.

Dr. Julie Faitg, PhD: No no no I completely agree with you. Hallmarks of aging appears for every organs in a similar way.

Dr. Kara Fitzgerald: It’s amazing.

Dr. Julie Faitg, PhD: Yeah. It’s not just… You know, we talk a lot about muscles and the whole body, but it’s specific to all the organs. Everything happens similarly, and all these hallmarks are interconnected. That’s why aging is a natural process. We can’t fight aging, but we can age gracefully by doing things that are more beneficial, like eating better, doing exercise, not sitting on the sofa all day, and having interactions with people for mental health. So many things that link together.

Dr. Kara Fitzgerald: Yeah. That was a little bit of an epiphany for me. Thank you for that. That’s just really cool. So let’s talk about photoaging.

Dr. Julie Faitg, PhD: Yeah, I mean, photoaging, which some people call extrinsic aging. It’s quite a tricky word. Like, intrinsic, extrinsic… It seems like a Hollywood film. For sure, UV light exposure, radiation, lifestyle choices, and cigarette smoking or living in a smoke-filled environment— It’s really caused by these external factors and you will see it in the skin structure, you lose elastin and you have the breakdown of collagen, which happens more on the inside. But overall, you have the result of premature skin aging. You’ll have deep wrinkles, you’ll have a decrease in really important enzymes. But in terms of what you see on the outside, you’ll see really deep wrinkles, uneven skin tone, and chronic inflammation, such as redness. So, photoaging, or extrinsic aging, is truly driven by outside influences and intrinsic is really from the inside. So that’s really the main difference between the two skin aging types.

Dr. Kara Fitzgerald: But if you’re going to do a skin intervention, you’re thinking about intrinsic and extrinsic together in making a difference. And with both. Okay. So then specifically, what would we think about? I guess maybe with an eye towards your expertise and the Urolithin A molecule, what are we thinking about as far as interventions that can actually effectively address these two phenomena?

Dr. Julie Faitg, PhD: Yeah, for sure. There’s a lot of promising and really current approaches to counteract all this skin aging. We can talk really quickly about retinol, which is the gold standard today, but I would say that it’s essentially affecting the wrinkles from the outside, because the ingredient is not optimally safe. We know that we have a lot of irritation so we need to use it carefully.

Dr. Julie Faitg, PhD: But with Urolithin A (Mitopure), which has this as a patented ingredient, we have this promising molecule to explore both inside and outside the body because it’s a postbiotic from the gut microbiome. We have shown that it improves mitochondrial health while reducing age-associated inflammation and inflammaging and it increases mitochondrial function and improves muscle health. So, when we looked at it, we said using that for the skin, that could be, that could be game-changing— I mean, we have a curiosity and passion for mitochondria at Timeline, so we didn’t stop at muscle. The story of mitochondria is really something to explore further because we just know a little bit at this point. For us, topical application of Urolithin A represents a compelling approach to supporting overall skin health, because when you think about skin health, you need to rejuvenate from the inside, you need to promote collagen production, you need to promote elastin, and you need to promote plumping… So many things.

Dr. Julie Faitg, PhD: And we know that from the inside of the muscle that mitochondria produce a lot of things due to the quality control of the mitochondria. When you look at the life cycle of mitochondria, you know that these really nice energy cells produce ATP. And so for your skin, you need energy. It’s like the brain. It’s like the muscle. So when we looked at the skin, the first thought we had was that we should do the same because longevity is not just about muscle. It’s about brain, it’s skin, it’s everything. And skin is the largest organ of the body. So why not do that? We know that Urolithin A in Mitopure is promoting the mitophagy of mitochondria, so recycling the mitochondria. I like to think of mitophagy as Pacman, you know, it’s eating all the bad mitochondria that are not working. And Urolithin A is like the teacher who said, “Hey, you need to do your work properly please”, and just give them a boost of motivation. I think this is a nice visual to have.

Dr. Julie Faitg, PhD: And so Urolithin A is really here to say to the Pacman “Do your work” And after that you will have all the quality controls working properly. You will even have new mitochondria working and it gets rid of the bad mitochondria, so overall you have a good energy production and you have efficient mitochondria for your skin. So that’s why we think beyond the muscle about using that for the skin.

Dr. Kara Fitzgerald: Fascinating. It’s really fascinating that you decided to jump into looking at skin. I just wanted to circle back a little bit to using Retinols. I was sharing with you and I’ve talked about this on my podcast before, I had my own burn experience with it and that was it. I was kind of one and done with it. It was sort of horrifying. And if I’m understanding correctly, it has the potential to perhaps make my skin look better. It could be pushing cell turnover, but in terms of what you’ve just outlined as this real correction or potential to reach both intrinsic and extrinsic pathways and correct the various facets of them that are disrupted during the aging journey, Retinol is not doing any of that. Is that correct? Yeah.

Dr. Julie Faitg, PhD: I mean, today, retinol is really the gold standard. I will not go against that.

Dr. Kara Fitzgerald: Okay. I don’t want to insult Retinol.

Dr. Julie Faitg, PhD: No.

Dr. Kara Fitzgerald: What’s it doing mechanistically though? Below the appearance, what is it doing mechanistically?

Dr. Julie Faitg, PhD: Retinol definitely is effective for wrinkles and also sometimes linked to collagen production. Not all the studies have been published, and it’s also something that I found really lacking in this area. So knowing that I was coming from brain and muscle, you know, people obviously say on all their websites that these are clinical results, but they’re not publishing on that.

Dr. Julie Faitg, PhD: At Timeline, we really want to have total transparency so people can understand our compounds even better. And when we started with the compounds, unlike Retinol, we focused on safety first, looking to see if people will have reactions, sensitization, and things like that. And we found with the trials that the results were just incredible because we have similarities with retinol however they do use the same pathway. Retinol is a commonly used active known to increase cell turnover and results in collagen production and anti-aging properties like reducing fine lines, wrinkles and irritant. While Urolithin A (Mitopure) is helping the skin to repulp and be healthy by countering both intrinsic and extrinsic aging, by improving mitochondrial health and reduce age-associated inflammation. In addition Urolithin A (Mitopure) is safe and stable . I see retinol more as being able to correct and give a nice skin renewal, definitely, but in terms of what Retinol is doing on the inside, studies are lacking.

Dr. Julie Faitg, PhD: And that’s why you need to use it carefully. That’s also why the concentration of retinol in different countries decreases year after year. People are saying okay, now it’s 0.3% I think. I’m sure the concentration will decrease even more because of the sensitization. And I’m sure when you use retinol, your skin will also be more reactive, year after year. If you use other products it may be more sensitive after that. That’s my opinion with retinol. think using it the proper way could be good, but I’m not really sure it’s doing something deeper. It’s more on the surface, definitely.

Dr. Kara Fitzgerald: Well, I hope that they hear you— the companies that are producing it — and consider engaging in some deeper research. I know you’re bringing some credibility to the industry that has been woefully— I don’t know if regulated is the right word— but certainly there’s been a real lack of commitment to good science. It’s like “Six weeks later, my skin looked younger…” And that’s it. I mean, that’s a piece. That’s a piece that’s valuable, but you guys are doing so much more. And we’re going to talk about that in a second, Julie, but I want to first ask you, or make any comments on that that you want, but I want to ask you about Urolithin A discovery. Just kind of the backstory for anybody who’s listening, who doesn’t happen to know. It’s kind of a cool molecule, so tell us about all that.

Dr. Julie Faitg, PhD: It started about 15 years ago when they looked at the pomegranate and they thought about all the health benefits from the pomegranate. When they looked at the pomegranate, they found that this molecule is produced from the ellagitannin inside the pomegranate. So when you eat that, the ellagitannin is converted into Urolithhin A if you have the right microbiome. Interestingly, when we did a study, at least 30% in Europe, or something like that, have the right microbiome to convert Urolithin A. In the US, maybe it was 10 to 15%.

Dr. Kara Fitzgerald: Not so good.

Dr. Julie Faitg, PhD: For some food. That was quite interesting. Definitely. And so if you have the right microbiome, you produce the Urolithin A. It’s a post biotic as I mentioned, and we have shown in so many clinical trials and we have done some really deep research into that showing that it improves mitochondrial health and all the age-related associations, like inflammaging and we improved muscle strength. I mean, we looked at many things related to the muscle. We were quite happy at the end to see all the results with this molecule and also the feedback from people. That’s the main thing. Internally we share all these results and all the comments we get and it’s just amazing.

Dr. Julie Faitg, PhD: So, to talk more about Urolithin A and what it’s doing, as I said, it’s boosting the the little Pacman, the mitophagy, to say to them, do the work and clean the cell, please. Clean the cell and bring more new mitochondria afterwards. So that’s what Urolithin A is really doing: Helping the mitochondrial quality control to be on top of it. Definitely.

Dr. Kara Fitzgerald: I think we evolved making a whole lot more Urolithin A and that our guts have just been damaged. My little working hypothesis is that our cells were probably bathed in the information from Urolithin A. Our mitochondria probably evolved just sort of relying on it to help us. And then over time our microbiomes have profoundly changed, linking it back to gut dysbiosis as one of the recognized hallmarks now. And not just Urolithin A. We were making a whole plethora of postbiotic compounds that maybe you guys will tuck into later, but, you know, we’re not anymore. And and even when we are— like, I’m a proud, card-carrying, Urolithin A producer, and I know Anurag talks about how he doesn’t make it.

Dr. Julie Faitg, PhD: Yeah. I’m not I’m not a producer at all.

Dr. Kara Fitzgerald: Ah, you’re not either.

Dr. Julie Faitg, PhD: A tiny bit, but not that much. And so, it’s so interesting to do the test.

Dr. Kara Fitzgerald: But here’s the thing. We’re doing an NIH grant right now. It’s funny, I was just talking about this with my little group. Like, “Yeah, I produce Urolithin A!”, but I don’t produce a therapeutic amount. That’s the thing. I’m not making enough. So okay, it’s cool that I’ve got, like, six of the microbes that will make it, but I don’t have enough to actually make the difference that I see when I take the product that you guys have created. So this is a really interesting thing. It was probably an important player that we need an abundance of and we just don’t have it.

Dr. Julie Faitg, PhD: Yeah. This is quite incredible. I’m also leading the trial, what we call the Mitopure Challenge, and I saw the results of the people taking it. I’ve seen someone have, like, a zero level of Urolithin A, and then with the Mitopure, I’m quite surprised this is bringing it up around 200 (ng/ml). And yeah, that’s really amazing. And people said, really? I produced that much Urolithin A? And, you know, that’s exactly what we did with this molecule and why we put it into a supplement. It’s really something that is naturally produced by your microbiome—- if you have the right one. And it’s something that’s doing a natural job, so I think there’s no bad things about this one. So that’s definitely quite amazing to see that.

Dr. Kara Fitzgerald: Yeah it’s super cool. I also want circle back for a second. You were alluding to not just doing all this research that you’re so committed to, from preclinical to a plethora of clinical studies, but also just the anecdotal evidence of people using it. And I want to talk about the skin, because there’s some pretty cool science on the skin with Urolithin A. But just anecdotally, you had told me off air that, you’ve seen it and your family has really noticed it. I thought it was kind of neat that your boyfriend, who’s an Olympic athlete, you know, he’s a medaling Olympic athlete, can can use it and actually see his recovery time improve.

Dr. Julie Faitg, PhD: Yeah, definitely. I think Dr. Singh talked a lot about that. When you exercise you have more mitochondria in your muscle because you need more. You also have more inflammation. That’s where the natural inflammation is coming in and so the recovery is really quite an important period. And for the athletes that’s where it’s really the more important thing. I mean the improvement of strength, endurance is amazing, but the main thing for the athlete is really the recovery. Because if you if you period of recovery is much better, you can definitely perform better, and your mental health is better also because you feel like, oh, I’m feeling good, I’m ready for tomorrow’s race. It’s so linked: The performance, and the mind, and the recovery, and the muscle, and everything. And when I was asking him if he felt something he said, yeah, I think I sleep even better and I don’t have any problems with my muscles after a huge training and I’m feeling good.

Dr. Julie Faitg, PhD: And I was like, okay, that’s really interesting. So I was starting to see that too. I think it was the first year when I arrived at Timeline. It’s been three years now, but yeah, the first year when they welcome you and they bring you so many nice packages of pills, and I was giving it to him and it was definitely worth it.

Dr. Kara Fitzgerald: That’s pretty cool. That’s pretty cool. Are you guys doing any studies with athletes? I feel like you might have something going on, right?

Dr. Julie Faitg, PhD: Yeah. We finished one in Australia, and the paper should be out soon. It’s a really interesting paper with Louise Burke, over in Australia. They presented the results already at an ACSM (American College of Sports Medicine) meeting in the United States and it was really well received. So the paper is nearly there. Just need to wait a bit. It’s quite nice, really.

Dr. Kara Fitzgerald: Okay, we’ll keep everybody posted when it comes out. We’ll tell you about the findings. I don’t know what they are and I’m excited to hear about them. Okay. So let’s talk about how you started the journey of researching Urolithin A in the skin and what you looked at, what changes, all the measurements that you made.

Dr. Julie Faitg, PhD: Yeah. So, with nerdy scientists, we need to look at something first, like primary keratinocytes from a healthy donor for 24 hours with Urolithin A in Mitopure and a placebo. And we basically assess the impact of the compound on the skin’s cellular health. We did the analysis of the gene expression changes into this in vitro skin cellular model and when we looked at them it was really interesting because we could separate it a little bit in terms of extrinsic and intrinsic. In terms of extrinsic, we have seen a reduced gene expression of some really bad proteins, like the MMPs (matrix metalloproteinases), which are really promoting collagen breakdown with skin aging.

Dr. Julie Faitg, PhD: With a different concentration of Urolithin A, compared to the old donor with the vehicle, we had a real decrease in those levels, so we were so happy to see that. In terms of inflammation, also in interleukin-1 which really causes skin inflammation, that was decreased with Urolithin A. So, that was really amazing. And when we also look at mitophagy gene expression of these primary keratinocytes, we saw an increase of this gene expression with Urolithin A. So that’s where our minds were, and I was like, okay, we’re also seeing markers of improved mitochondrial respiration, all this mitophagy, so it definitely clicks. We said okay, we have seen that in the muscle and it’s just the first study, so now we need to move on and do something. Before doing the clinical program, we also three more tests on what we call the RHE, (Reconstructed Human Epidermis), that’s a 3D model, and we apply Urolithin A (Mitopure) topically and we saw similar early activation of mitophagy and autophagy genes compared to—

Dr. Kara Fitzgerald: Can you say that again? What were you looking at?

Dr. Julie Faitg, PhD: It’s the 3D Reconstructed Human Epidermis and you look—

Dr. Kara Fitzgerald: Oh, the epidermis. Okay.

Dr. Julie Faitg, PhD: Yeah. The epidermis, and you apply 1% Urolithin A in a moisturizing cream topically on a daily basis. And after that we saw in gene expression, early activation of mitophagy and autophagy genes and that was observed compared to the placebo. So we thought okay, 3D Reconstructed Human Epidermis— Then we moved to another type of cells, human dermal fibroblasts, and similarly to the keratinocytes that we did at the beginning, we saw a reduction of these bad proteins that breakdown the collagen, the MMPs. So we reduced them with Urolithin A. And also similar, we have the same signatures like increase of mitophagy and autophagy gene expression that was observed with Urolithin A in these cells. And then finally we also took human dermal fibroblasts from young and old. So young I think was 23 years old and old was 69.

Dr. Julie Faitg, PhD: And as expected— I mean from the old donor, we have a an impaired basal and maximal cellular respiration. We use an experiment that is a seahorse. And when you use that for muscle, like mouse or human, you use the ouroboros. And this is a kind of a technique that is quite interesting to measure the respiration of the mitochondria here. And so we have an impairment of maximal respiration in the old donor compared to the young and Urolithin A was really able to rescue both basal and maximal mitochondrial respiration of old fibroblast cells in a dose dependent manner. So that was really something. When we look at all this preclinical work that we can see on the cells, we were really sure about moving forward with our clinical program. Definitely.

Dr. Kara Fitzgerald: That is so cool. You used a seahorse?

Dr. Julie Faitg, PhD: Yeah.

Dr. Kara Fitzgerald: That’s fascinating. Let me just underscore before the train leaves the station, you were able to demonstrate in these cell studies that you changed intrinsic and extrinsic favorably. So both. Cool.

Dr. Julie Faitg, PhD: Exactly. That’s the main thing to do because you can’t just look at some proteins. We saw from this paper, like the one I mentioned before by Oblong in 2020. They looked at mitochondrial expression in young and old donors. They indeed, saw a decrease in mitochondrial gene expression with age. Then we looked at mitochondrial respiration to see if with Urolithin A at different concentrations, we have an improvement. And that was the case. So that was quite amazing.

Dr. Kara Fitzgerald: Incredible.

Dr. Julie Faitg, PhD: It’s science, you know, to look at that and not do a half job. You need to be sure of what you’re seeing. And also, reproducibility is really something we focus on. We’re not just doing one experiment and saying, “Okay, it’s working.” No, not so.

Dr. Kara Fitzgerald: Yeah, I know, I just so appreciate it. I appreciate your commitment to the science. I mean, you’re elevating the whole field. I think this is really revolutionizing our field. But I just want to go back to this basal and maximal cellular respiration increase in the 69 year old fibroblast and how extraordinary it is. And it just makes me link back to the paper of sedentary adults and their VO2 max increased, I think, on average by 10%. Sedentary adults, so they’re not exercising. The only intervention is Urolithin A and you’ve increased their ability to utilize oxygen. I mean, that is mechanistically linked right from the micro to macro.

Dr. Julie Faitg, PhD: Yeah, exactly. And it’s compared to their baseline.

Dr. Kara Fitzgerald: That’s right. Right.

Dr. Julie Faitg, PhD: That’s pretty important when you look at when they first started the trial and then after. That’s the best comparison to make. You can have the— But looking at the baseline I think that’s also what you’re looking for. If you go into a trial you want to know if you’re making things better.

Dr. Julie Faitg, PhD: And yeah, that was an increase and that was really nice to see that. Definitely. And seeing that in the skin cell, I mean you’re quite happy to see a similar signature in all the other organs. And you know, respiration is a little bit controversial because for some people who are doing exercise, their respiration is not changing that much. It’s not a parameter that is always increasing or decreasing— it depends. What does change a lot is calcium retention capacity.

Dr. Kara Fitzgerald: Oh, interesting.

Dr. Julie Faitg, PhD:  Which is changing a lot when you look at aging. And respiration could change sometimes or not. But when we looked at the cells here and also with the VO2 max there was a clear signature. So that’s quite, I mean, we trust these compounds now 100% and you see a similar signature across different types of cells, you know.

Dr. Kara Fitzgerald: But you’re looking at that calcium retention element as well.

Dr. Julie Faitg, PhD: So not in this study. In the future clinical trial that we have ongoing we will do it because, as I mentioned at the beginning, mitochondrial function, there’s so many things.

Dr. Kara Fitzgerald: Yes, yes, yes yes.

Dr. Julie Faitg, PhD: And calcium retention, done by my last PI who was was in Montreal, is really key. We’re doing the clinical trial with them and they’re looking at it. I’m sure it’s going to give us great results. They already started recruiting and they have like six patients at the moment. I’m really happy to see that moving forward. And yeah, that’s definitely one of the main functions of mitochondria.

Dr. Kara Fitzgerald: Oh my goodness. All right. I would love to connect with you when the data comes out. Yeah. Maybe we could have a mitochondrial 101 from you. I mean, I just really appreciate that I’m learning. Okay, so where are we? Do we want to talk about some of the clinical research? Do we want to move into that, or is there any more preclinical that you wanted to talk about?

Dr. Julie Faitg, PhD: Well, we stopped at the preclinical stage at this point. And, you know, I think what really adds value to our company in terms of research is when we started the clinical program. I like to call it the clinical program because I remember being at a conference and talking about our first clinical program—the first test was HRIPT. That’s Human Repeated Insult Patch Testing to assess the sensitization and reaction of the skin to the compounds. Not everyone mentions this, you know, and I think showing that a compound is safe and that it can be used at certain concentrations is key before moving forward.

Dr. Kara Fitzgerald: Yeah.

Dr. Julie Faitg, PhD: Yeah. Before moving forward on clinical trial you don’t know how people will react and you can have like at like 20 to 26 people reacting with erythema or something and we don’t want that. We don’t want like people to experience burning on their face or redness or other problems. I think that’s the key when we built this program, and Dr. Singh really pushed it forward, and we were so happy when we got the first results. We were like, okay, we’re moving forward, and we’re testing on both males and females. So, that’s also important.

Dr. Kara Fitzgerald: You know, it helps that you’re working with a compound that originally came from pomegranates and some nuts. I mean, there’s a safety track record going back millennia. So you have that little piece of information, but the fact that you’re going through basically the same kinds of hoops that we go through for something that’s going to be regulated as a drug is awesome.

Dr. Julie Faitg, PhD: Yeah, exactly. And, you know, I think sometimes people do the safety at the beginning and say, okay, it’s all fine. But no. You don’t know how it’s going to affect different organs. You need to do some drug studies, you need to do some safety study assessments, and by doing the skin I was— I mean, in the beginning at Timeline we were not skin experts. We learned something every day and we are still learning a lot. It’s really amazing the way we learn about skin at Timeline because the science always comes first.

Dr. Julie Faitg, PhD: And by looking at this safety study, we included both males and females. We didn’t just focus on females in our skin trials; we had participants ranging in age from 18 to 64. We applied different concentrations over six weeks, not just 24 hours or something. It was great—we had no reactions at all, and it was safe and tolerable for people. That was definitely amazing for us.

Dr. Kara Fitzgerald: And what did you see? What did you see?

Dr. Julie Faitg, PhD: When we had no problems with reaction sensitization, we started the photodamage trial, which was quite interesting because, you know, you want to see how it reacts with exposure to UV radiation.

Dr. Julie Faitg, PhD: So, we did a trial targeting extrinsic aging, as I said, photodamage. The skin was irradiated with the minimal erythema dose and immediately after we applied our Mitopure cream for 24-hours. What was amazing is that Mitopure reduced skin redness significantly by 14%. We were completely impressed.

Dr. Julie Faitg, PhD: I can tell you that I’ve also seen this in real life being at the World Conference of Dermatology in Singapore and having someone come up to me with a really red face, and she said, “I have this redness on my face and head; it’s really not nice.” I reassured her that these things happen, and she asked if I had a cream she could apply because she assumed I had anti-inflammatory things. She had read about some of our research. I gave her some samples of our night serum and day cream the day after she came back with her little suitcase—the kind they all have at dermatology conferences to collect goodies—and she said, “It worked so well!”

Dr. Julie Faitg, PhD: “Look at my face. It’s beautiful.” And so she bought so many products after that. When you know the results of this study and you also see people react in a really nice way, you understand that it was right. I mean, the 14% that we have seen decreasing erythema and the redness, it’s also happening in real life, you know.

Dr. Kara Fitzgerald: Yeah, yeah. What was the duration of the study?

Dr. Julie Faitg, PhD: So after 24 hours. You do it for 24-hours immediately following the irradiation. You don’t need to wait too many days or weeks. It’s instant—you look at the redness right after. When you apply Mitopure at 1% for 24-hours just after irradiation, you see a 14% decrease in redness. That’s quite significant for us; it was a key. And it shows the effect on the muscles and some decline in CRP (C-Reactive Protein). That’s one of the best things about this compound, definitely.

Dr. Kara Fitzgerald: Nice. Nice. What else have you looked at clinically.

Dr. Julie Faitg, PhD: After that, we targeted intrinsic aging. We looked at Mitopure for different age groups, people aged 50 to 75 years old, I think. In this eight-week study, we examined crow’s feet, wrinkles, and fine lines—really visual signs of aging. It was really interesting because, from before to after on day 57, we saw a decrease in wrinkles by 4%.

Dr. Julie Faitg, PhD: The effect was also visible after just two weeks, which was quite amazing. It was a split-face study, so that was really interesting—not just using the product. It was also a placebo. We looked at both sides of the face, and we also took biopsies. With these biopsies, we really looked inside and looked at different pathways. Because when you just do the visual signs, you measure the wrinkles using all these tools which is really nice, but then you want to understand basically what’s going on inside the skin. From the biopsies, we looked at pathways related to collagen. What was interesting was that while collagen fiber organization was really decreasing with aging, this same pathway was increased with Mitopure. It was definitely the opposite.

Dr. Julie Faitg, PhD: When you saw the images, it was like, —those whose skin was declining with the placebos, and in the other they were using Mitopure. And the same gene that was suppressed with aging was activated with Mitopure. For example, there was collagen fiber organization and it creates firmer and smoother skin. This was amazing.

Dr. Kara Fitzgerald: Very exciting. What do you expect for longer term use?

Dr. Julie Faitg, PhD: Yeah. So for longer-term use, that’s why after that, when we made the finished product, we built a patented ingredient putting Mitopure with niacinamide and trehalose together to boost the finished product. And we did the same kind of study looking at wrinkles in an eight-week study, trying to replicate the results.

Dr. Julie Faitg, PhD: We looked at people actually using the cream and we got the same feedback from them saying the wrinkles improved using the day cream, the night cream, and the serum—and we saw similar results across all three. In the study on the finished product we also did HRIPT (Human Repeated Insult Patch Testing) on the safety to see if the formulation was well tolerated. And we used both men and women in this study, because, as I said, it’s not just females. It’s important to look at different ethnicities and genders. So we looked at participants aged between 40 and 65 years old and in the end, we saw that the Mitopure regimen showed a significant decrease in wrinkles and boosted skin hydration with all three products. This was really something we were looking at in terms of skin barrier, elasticity, hydration, all the things I already mentioned.

Dr. Kara Fitzgerald: 00:50:54 Across ethnicities.

Dr. Julie Faitg, PhD: Exactly. Yeah.

Dr. Kara Fitzgerald: Awesome. That’s a huge point. How do you have people apply it? How do you recommend applying it based on your research?

Dr. Julie Faitg, PhD: We have different types of cream. We have a richer cream, we have a light cream that we called night and day creme. But we also believe at Timeline that the right cream can change depending on the season. Our night cream, which is the richer cream, can be also applied during the day if your skin is really dry. You need to think about how your skin reacts and what it needs, and your skin doesn’t need the same thing during the whole year. What works really well is applying the serum twice a day and using the cream in a way that’s best for you. But in this study we applied the night cream at night and the day cream during the day.

Dr. Kara Fitzgerald: Okay, okay. What about a body lotion? When is that going to be in my bathroom?

Dr. Julie Faitg, PhD: Definitely. We have a few ideas coming very soon. I think a body lotion is something we really need to look at, because, as I mentioned, the skin is the largest organ of your body so this is something you need to think about when you’re doing your skincare regimen. It’s not just about the face—it’s the entire body. That’s something that will come soon, I hope.

Dr. Kara Fitzgerald: Good, good. Anything else on the horizon for you guys for Urolithin A that you can mention?

Dr. Julie Faitg, PhD: At the moment, we have a few clinical studies that are going to start soon. One is going to start really soon. I’m so excited to do that because it’s a clinical trial that will use the richer cream to look at efficacy for anti-wrinkle, but also the effect on skin epigenetics.

Dr. Kara Fitzgerald: Oh cool. Yeah.

Dr. Julie Faitg, PhD: And we’ll also be bringing in my specialty, which is visualizing mitochondria. We’ll be taking biopsies and look at the morphology of the mitochondria both with and without Mitopure, which is something I really want to see. This will be a 12-week study with male and female participants aged 50 to 75. It’s going to be really interesting to be able to visualize how mitochondria look and how they might be linked to skin biological age. I think that’s going to be a really nice study. I think it’s really important that we’re increasing the duration of the previous study from 8 weeks to 12 weeks and we’ll be able to go even deeper. The biopsy will essentially be on the last subjects that we had because nobody wants to go through the biopsies. But we will have really nice visuals to share with the people because I think it’s important to know how your skin looks inside. It could be tricky, but they’re really nice to look at. They’re really nice.

Dr. Kara Fitzgerald: So, you’re excited. You’re in your happy space with that. Have you recruited yet? Have you started recruiting?

Dr. Julie Faitg, PhD: Yeah. It’s starting. We already have the first biopsies going to the lab in Newcastle to do the analysis of the electron microscopy with the electron microscopy in 2D. I’m going to do the analysis unblinded. I will be able to tell you really soon how it looks. The trial will end up in December because we didn’t want to do that in the summer due to UV radiation and etc. You don’t want to be like, yeah, people went on holiday and did the trial. No, that’s not going to be good for for this trial. So that was the right period to recruit them now and finish in the beginning of December.

Dr. Julie Faitg, PhD: So we hope to have a trial soon. And then, you know, there’s a whole area that Timeline has involving nutrition, so we want to combine some trials with that as well. I think it’s really a great and exciting journey for us in the skincare area. It’s quite new but we are moving forward step by step and I think it’s working well. We are completely transparent with everyone. We have published and preprints and one currently in review, including all the cell work— everything that I’ve talked about. I think it’s quite good that we’re moving forward in a similar way to muscle.

Dr. Kara Fitzgerald: Yeah yeah yeah. I can’t wait for the nutrition work. Hopefully we’ll be able to participate in some way. Folks, I want to let you know that Julie has referenced many, many, many papers and we’re going to corral them together. You will find all of them on the show notes page with the full transcription. This is also going to be on YouTube. And, really, this was a great, fun, tour de force conversation. You’re such a such a badass scientist. I just have to say it.

Dr. Kara Fitzgerald: Let me just mention everybody, Timeline is offering an amazing promotion. So if you go over to Timeline.com/Kara right now and use the use the code KaraSkin, you’ll get 10% off on your suite of products. And I’m really excited for you to try them. I love them and, of course, I want to hear from you what you think. All right. Thank you Julia, that was great.

Dr. Julie Faitg, PhD: Thank you.

Dr. Julie Faitg is a leading expert in mitochondrial research, with over nine years of experience focusing on muscle and brain biology, and recently expanding her expertise to include skin health.

Holding a PhD in Translational and Clinical Research from the Wellcome Trust Centre for Mitochondrial Research, she collaborates with renowned scientists worldwide, including Nobel laureate Eric Kandel and mitochondrial experts.

Currently, Dr. Faitg serves as the Senior Translational Scientist and Regulatory Affairs Lead at Timeline, where she makes significant contributions to research and development across various organ systems in the field of mitochondrial biology.

Email: jfaitg@timeline.com

Timeline

MitoPure

Eric Kandel Nobel Laureate

Study: The Hallmarks of Aging

Study: Hallmarks of aging: An expanding universe

Preprint: Topical application of Urolithin A slows intrinsic skin aging and protects from UVB-mediated photodamage: Findings from Randomized Clinical Trials

Study: The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans

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

Study: Quantification of biological aging in young adults

Study: Metabolic dysfunction in human skin: Restoration of mitochondrial integrity and metabolic output by nicotinamide (niacinamide) in primary dermal fibroblasts from older aged donors

Mitopure Challenge

Louise Burke

Timeline Blog: Cutting edge research at American Society of Sports Medicine

Study: The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans

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

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

Blog: Beyond Beauty: Targeting Skin Longevity with Urolithin A

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 Lab Test

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Younger You book

Better Broths and Healing Tonics book