Disrupting Anti-Aging Skincare by Targeting Senescent Cells

Imagine accurately determining the status of your skin’s age to tell whether it is younger or older than your chronological age, and then use this technology to determine whether expensive anti-aging serums and creams are effective, or actually causing more harm than good. Amazing, right? This is precisely the technology today’s guest, Dr. Carolina Reis Oliveira and her fellow stem cell biologists at OneSkin created. I think you will find this interview fascinating on so many levels – I know I sure did! After creating their skin clock, the OneSkin team discovered peptide OS1, which targets senescent cells, one of the root mechanisms of aging, and is being shown in current studies to have a positive effect on hydration, firmness, elasticity, and the skin barrier. Listen as Dr. Reis Oliveira explains the science and ongoing studies exploring the possible benefits of OS1 for the skin microbiome, hair loss, inflammation, and overall health. ~DrKF

In 2021, over 62 billion US dollars were spent globally on anti-aging products, despite a lack of accurate tests to quantitatively show their efficacy. Today Dr. Carolina Reis Oliveira PhD, joins us on NFFM to share exciting new science that will likely disrupt the industry. After developing the skin biological age clock, Dr. Reis and her team of scientists at OneSkin have been able to test products and peptides to accurately determine both their positive and negative impact on skin aging.

Using data from these tests, they have developed a way to target senescent cells to improve the appearance and reverse the biological age of skin, and research is currently underway to determine how it may apply to the skin microbiome, barrier function, and overall health as well.

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. Of course, today is no exception. I am thrilled to be here with an amazing scientist doing cool disruptive work. We’re going to dive into who she is and what she’s about.

Let me just give you her bio right now. Her name is Dr. Carolina Ries Oliveira, and she is a PhD co-founder and CEO of OneSkin. Her PhD is in immunology from the Federal University of Minas Gerais in collaboration with Rutgers University, and is an alumnus of IndieBio, the world’s leading biotech accelerator. In 2016, Carolina relocated to Silicon Valley from Latin America to co-found OneSkin and to lead the development of the company’s disruptive longevity technologies. Carolina, welcome, welcome, welcome to New Frontiers.

Dr. Carolina Reis Oliveira: Thank you so much, Dr. Kara. Such a pleasure to be here today.

Dr. Kara Fitzgerald: I’ve been a fan of you guys when I stumbled across the fact that you developed a skin biological age clock. I was so excited about it. Now, I mean, you bought this because you were just really doing some cool, cool work around anti-aging topicals, and I want that. I want to know that, and I just want to know your whole journey. So give me your origin story, and let’s just talk about some of the fabulous background work to begin with.

Dr. Carolina Reis Oliveira: Yes. Yeah, so a little bit of my background, I have a PhD in stem cell biology and tissue engineering. Back in 2016, I joined with three other colleagues from my lab, and we want to make that translation from academia to the market and really use our science to help move humanity forward. One of the main opportunities that we saw is that based on our ability to grow human tissues in the lab so we could replicate skin, and we thought that we could use that skin that we grow in the lab to test anti-aging products that are out there in the market to really measure if they are promoting any rejuvenation or age reversal effect. So since we could grow these tissues, we thought, okay, if we can measure the age of that skin in the lab, then we can apply a product and then we can measure if the product’s changing what we call the biological age of the skin.

So that’s when we decided to build a specific skin clock, a clock that would measure skin biological age in a very accurate way. Because as you know, nowadays, how companies measure their products’ efficacy, it’s mainly through customers subjective perception, which is not accurate at all. So if there is a way that we can quantify this age reversal effect, and in this case of measuring biological age is through the DNA of the skin. So we know that our skin and all of our tissues we accumulate change in our DNA as we grow older, mostly on the epigenetic level. What this clock does is basically measuring those chains that accumulate over time. So once-

Dr. Kara Fitzgerald: How big is it? Just out of curiosity. How many CpGs in your clock?

Dr. Carolina Reis Oliveira: We use the Epic Chip from Illumina, so it’s more than 850,000 probes. Then the clock itself, it’s nailed down to fewer, 2000 and something probes. But we are trying as much as possible to reduce, to make it more accessible to commercialize it. So right now it’s still very expensive. We use it mainly for research. But to build the clock, we actually analyzed all the 850,000 probes.

Dr. Kara Fitzgerald: That’s so cool. Okay, so now it’s down to around 1000. I mean, I’m so sorry. I want you to continue with your study, but let me start with your story, but I just have to ask you one question around that. If you consider commercializing the skin clock, how would you do that? Would you be offering it to other industry folks working on products for skin? Would you be offering it to the consumer? Would I be able to test my skin age?

Dr. Carolina Reis Oliveira: Yeah, I think ideally would be able to offer to the consumer because the consumer first wants to know what is the status of your skin age, it’s your chronological age, it’s younger, it’s older… So that’s the first point, to know your baseline. And then after that, people are still unsure in terms of products efficacy. So that’s a clinical study that we are actually running right now, interestingly enough, that we are following the participants over a course of six months up to a year using our products topically. And then we are measuring the change in the biological age to validate that our product is actually reversing the skin age. One caveat of this process is still that we need a biopsy.

Dr. Kara Fitzgerald: Okay. Yeah.

Dr. Carolina Reis Oliveira: So it’s still invasive, is still a little tricky in terms of logistics, how you partner with a dermatologist or a clinic that you collect the biopsy to send to us. And then the other piece that is still a little prohibitive is the cost.  I would say that our cost to generate the data is about a thousand dollars. So even to commercialize is going to be still a little expensive. And that’s why we are looking to reduce the number of probes that we are analyzing so we can reduce the cost and make it more available to consumers.

Dr. Kara Fitzgerald: Yeah, I understand that. When we ran our study in 2018, 2019, the arrays were at least 1200. The price is coming down. Do you think that you’d be able to get a reliable measurement using a non-invasive specimen or is… I mean, biopsy just strikes me as obviously optimal?

Dr. Carolina Reis Oliveira: I know. Yeah. We are working collaboration with another company to test if tape strips could collect enough biological sample.

Dr. Kara Fitzgerald: Awesome.

Dr. Carolina Reis Oliveira: And if we have enough biological samples, if that measurement correlates with the data that we get from the biopsy. So in the clinical studies that we are running, we’re actually doing both and hopefully we’ll find a way to eliminate the biopsies.

Dr. Kara Fitzgerald: I’m just thrilled though with what you’re doing, the investment, the financial investment, the science investment, because I mean, research in this space has been dismal. It’s an embarrassment. And products are incredibly expensive. I mean, it’s just, it’s mind blowing that the industry’s gotten away with it for so long. So the fact that you’re getting in there with real science, with actual biopsies that you’ve developed a biological age clock specifically for the skin and you’re testing it. And I know you started in vitro and now you’re doing clinical trials and we’ll talk about all of that. But I want to say that I love what you’re doing and I’m so happy to support elevating your work. So thank you.

Dr. Carolina Reis Oliveira: Thank you. Yeah, no, I appreciate it. And it’s interesting because as I was sharing, we didn’t start out to create a product or a brand. Our goal was initially again, to measure the efficacy of these products that were out there in the market. And then when we realized that, okay, there are many anti-aging products out there, but none of them were developed with the rationale of targeting aging in the first place. And so most of the products that are out there, they’re treating the surface of your skin and sometimes they make your skin look better, but there is no focus of attacking or no, what’s the root cause of aging in the deeper layers of the skin. And then in the end, you can have temporary results, your skin can look better, but it’s not biologically younger. So on the other hand, what we saw is that this new area of longevity and age reversal was evolving so much in the past few years and we now understand what are the main drivers of aging.

And we saw a very clear opportunity for us to develop a product that was addressing the root mechanisms of aging and that was going to promote a more significant age reversal effect. And in the end we set ourselves to find a new molecule that was actually going to reverse aging. So that’s why we’re a longevity company and once we found a molecule, we decided to create a product out of that molecule. So it was kind of a consequence of our research and of this goal of actually studying aging first, understanding how aging works and then looking for interventions that were actually targeting the root cause of aging.

Dr. Kara Fitzgerald: So fascinating. Do you guys were as or you ladies, you women, I know you’re a woman scientist company, which of course I love. Just another reason to support you guys knocking it out of the park. So you were coming from… Being stem cell biologists, you were able to actually create an in vitro skin model that you could test and then you developed the clock, which is incredible. And then you started to test products and we know the dismal selection of products. And I just want to say that you actually found that plenty of these products accelerated aging. Maybe at best, perhaps there was no change. But a lot of these things that we’re slathering on our skin were actually accelerating aging. And I just want to point out from a functional medicine perspective where we’re all reading labels, we certainly see that many, many chemicals we’re putting in our bodies are toxic. And it’s interesting that you found it. So I want to just link back.

So you started all of this research and you’re like, oh my god, these things are horrible. And then you decided that you were going to go into investigating the way that you could actually disrupt the aging process happening, looking at the hallmarks of aging and figuring it out. Okay. So speak to that and then get us back in the story and how you found your peptide.

Dr. Carolina Reis Oliveira: Yeah, this was… I mean, a surprise in some ways, but not a surprise in other ways. As you mentioned, we know that if there are toxic ingredients there, that definitely is damaging our skin. But sometimes it’s hard for us to see at a naked eye, right? Sometimes you’re going to get a rash or you’re going to get some kind of irritation. But when you grow these skins and then you apply a product that’s not clean or safe that has toxic ingredients, the skin will start to degenerate. The cells that were supposed to have a certain morphology, they start to become really weird and it’s so clear and reproducible the products that are actually bad. And it’s funny because initially we used some best-selling anti-aging as a positive control. Let’s see if how they perform so we can find something that performs better than them.

And then we realized that there were the negative control because they were consistently causing a lot of damage to the skin.  And other products that are really used in this market, for example, retinol and retinoid acid.

Dr. Kara Fitzgerald: Yes.

Dr. Carolina Reis Oliveira: We can also reproduce what they make our skin to do. This peeling effect that the upper layers are coming out. And retinol is interesting because for a certain period we will elevate markers of inflammation, aging, and we will also increase collagen – some other important markers for your skin. But the learning that we had with retinol is that if you overuse retinol and you cause too much of the cell renewal, you are exhausting your tissue and you are inducing so much inflammation that in the long term is also not good for your skin. So there is a very fine balance of how to use retinol in a way that you harness its best results.

But then what we realize is that, okay, right now most of these products that are considered effective, they are only promoting good results by harming your skin. That’s what retinol does. Is there a way that we can actually harness our biology, that we can promote this rejuvenation effect without causing the harm, without causing the inflammation? And when we started to understand about aging, and we saw that one of the main drivers of aging was the accumulation of those aged zombie cells, we thought, okay, if we can find a way to decrease the number of those aged cells in the skin, we may be able to selectively remove them and then allow the healthy and young cells to proliferate. And then we are rejuvenating the skin in a very safe way without disturbing the good cells. And then you end up with a very similar result that you get or better with retinol without the side effects.

Dr. Kara Fitzgerald: Without the… So let me ask you just a couple of questions before you move forward in what you have discovered to do this. I’m curious if any toxins were a standout to you in really disrupting this in vitro skin model that you were using. Were there any particular toxic players that come to mind?

Dr. Carolina Reis Oliveira: I need to go back and analyze the ingredients list.

Dr. Kara Fitzgerald: Okay.

Dr. Carolina Reis Oliveira: Yeah. And my team, I have a chemist that she is… She’s the one that knows exactly all the ingredients that are very bad. But for us, again, when we see that, and you can use some websites that help you to rank the ingredients, for example, EWG, right?

Dr. Kara Fitzgerald: Yes.

Dr. Carolina Reis Oliveira: And when you put the product name and depending on the score, it really matches with the results that we-

Dr. Kara Fitzgerald: Fascinating. Oh my God, that’s so interesting. Okay, well if your chemists can shoot us any, we’ll put them on the show notes, you guys. Yeah, we’ll follow through with it and see if we can get some of them. Also, I want to let everybody know too, that we’ll link to the website to th OneSkin website where they have a clearinghouse of all the studies that they’ve published for. So any super geeky people if you’re interested in that original skin clock that they developed, we’ll make sure that you have access to all of those. Let me just ask you one more question about retinol because it’s sort of like the anti-aging workhorse compound. I mean, you look to mimic retinol. I’m going to guess that you would probably say don’t use it because the therapeutic window is probably very narrow when you can hit damage if you go too far in either direction. I know some people put really, really concentrated amounts of retinol on their face and then instead you found that your product can mimic the benefits of retinol. Would you say that you should just avoid it? I mean, what are your thoughts there?

Dr. Carolina Reis Oliveira: I’m not a hundred percent against. I think there is a way that you can even use retinol in combination with other products that can counteract their side effects. So I think my main recommendation is not overuse or not induce too much inflammation for long periods. So I think if you give your skin time to… Because we’ll peel off your skin, even those that cell renew, we’ll build more collagen. If you give your skin time to recover and reduce those levels of irritation or inflammation, you can definitely get some benefits of it. So I need more research to actually say, don’t use it at all. There is something that’s… Because the mechanism of action is different. The way that our peptide works is completely different from… In the end, with aging, there is not only one way to target aging and there is definitely attack this process from multiple angles.

Dr. Kara Fitzgerald: Let me just say that, I mean personally I don’t know that there’s a place… I experimented a little bit with retinol in my life and I don’t know, listening to what you’re saying about it seems like the risk isn’t worth it. The risk-benefit, especially where we are. So let’s talk about you. Let’s talk about this amazing peptide and how you discovered it and thinking about the hallmarks of aging and what you’re addressing with it.

Dr. Carolina Reis Oliveira: Yeah, so as I was saying, we were studying the aging process and what are the main hallmarks of aging that we could intervene, that could promote this rejuvenation effect. And we got really interested in senescent cells or the zombie cells. So for those who are not familiar senescent cells are cells that are already in the end of their life cycle, they have accumulated a lot of damage. So they stop dividing because if they continue to divide, they could become a tumor. But they also, on the flip side, they start secreting inflammatory signals that basically function like a bad apple in a basket. So one senescent cell spoils the good cells around to age faster. And back in 2016, we saw the community really interested in ways to eliminate specifically senescent cells. So there is a lot of research in the longevity space focusing on molecules on peptides that could eliminate them.

So we decided to search for new peptides and we chose peptides because it’s a biological molecule, it’s already used in skincare products and it tends to be safer. And we tested over a thousand different peptides in order to find the one that was able to decrease senescent cells to a very minimal level that was not causing that damage anymore and was also safe. And that was also able to penetrate the skin. So after a few years of research, we found this peptide called OS1, and we could show that when we treat aged skins with OS1, we can decrease the levels of those aged cells up to 30 to 50% depending on the model. And then in turn, what we see is that the healthy cells can proliferate again and they start producing more collagen again. And this results in a healthier, more functional and a younger-looking skin.

So it’s very interesting because again, when you understand, okay, if this is the cause, if we have fewer of those cells, your organism knows what to do. So you let your organism go back to that healthy functional state. And this hypothesis was proven when we did the studies in vitro and then later on in vivo with humans.

Dr. Kara Fitzgerald: What kind of bio age reversal did you see in the in vitro model using OS1?

Dr. Carolina Reis Oliveira: Yeah, great question. So in vitro, I mean the conditions are completely different. It’s a totally isolated system. When we applied the peptide in the condition media, so basically the media that is in contact with this skin, so there is I would say a higher delivery rate. We saw a reversal of around of 2.6 years during five days of treatment.

Dr. Kara Fitzgerald: Wow.

Dr. Carolina Reis Oliveira: So very short. I know, but that’s why now we are running these clinical studies and when we finally have the peptide in a cream, and obviously when you have the peptide in a cream, not all of the peptide that’s in that cream will penetrate the skin. So you need obviously many applications and longer periods to see this data or this result. And we have run this experiment from six months up to a year. At the end of 12 months, we saw a reversal of 3.3 years, but this was a smaller cohort was only eleven participants. So we are now increasing the cohort to see if we can show this significant reversal effect within six months. So we are just starting again a new study, but again, it’s super cool that we can already show in humans that we can reverse your skin biological age with a topical treatment.

Dr. Kara Fitzgerald: That’s very cool.

Dr. Carolina Reis Oliveira: Yeah. Measure it and again.

Dr. Kara Fitzgerald: And this is the product, this is the OneSkin product.

Dr. Carolina Reis Oliveira: Yeah.

Dr. Kara Fitzgerald: So it’s not some special research formulation that we don’t have access to.

Dr. Carolina Reis Oliveira: That’s the product that is actually available in the market. We did with our main products. That’s the OS1 face. And that’s the one that we have more studies because it was the first one that we brought to the market.

Dr. Kara Fitzgerald: You showed… Well actually I want to… In your clinical studies, you looked at more than biological agents. So I want to talk about some of the more classic measurements that you reversed. But before we do that, the OS1 peptide is able to sort of quench senescent cells. And maybe this is beyond the scope of our conversation, but I’m just curious mechanistically, what’s going on there?

Dr. Carolina Reis Oliveira: No, I love this question. Actually, I love our customers in our community because they always bring the same question: How it works and what this peptide does with the senescent cells? And we actually did a pretty, I would say, deep study to actually understand how it works because there is the classic way that the molecule can induce the senescent cells to die, to enter apoptosis. And there is another way that the peptide or senotherapeutic can act by suppressing the release of those inflammatory signals. And now our peptide works by this way so that the presence of the senescent cell itself, it’s not a problem, but it is their secretion that’s causing the damage in the surrounding cells. So what our peptide does, basically it suppresses the senescent cells to release those bad signals to the cells around. And with that we can recover again the homeostasis of the skin and some of the senescent cells that were already present will enter in autophagy. So in the end, you don’t induce formation of newer senescent cells and you also reduce the number of the senescent cells that were already present in the tissue.

Dr. Kara Fitzgerald: Incredible. It’s like a pleotropic anti-inflammatory compound.

Dr. Carolina Reis Oliveira: Yeah, yeah, exactly. And peptides are known to be more pleotropic. They basically combine the different receptors, but the end result was in terms of cytokines release, we can see that decreased a lot the levels of inflammatory cytokines. And with that you allow the healthy cells to proliferate and produce more collagen, hyaluronic acid, and improve the skin barrier function. So it’s very, very interesting.

Dr. Kara Fitzgerald: Very interesting. And it begs the question, I want to stay on the skin focus, but would we use this internally, this peptide? Is that something in your future?

Dr. Carolina Reis Oliveira: That’s another great question. People say, can I drink my cream? Yeah, we actually… We have some studies in C. elegans. So, C. elegans is a very common model to study aging. And basically what we saw when we fed these worms that live very shortly around 22-30 days with our peptide, we saw that we increased their lifespan around 16 to 20%. So it does have a potential of a really extend lifespan. Obviously, for humans, we needed to go to preclinical studies and eventually clinical studies. So we have several collaborations on the side going on to test this peptide in different conditions. And I think our ultimate goal to have… Can we use this peptide either orally or intravenously and basically help our bodies to clean up those bad cells so our bodies can perform well for longer? But this will take a few years still.

Dr. Kara Fitzgerald: Very interesting.

Dr. Carolina Reis Oliveira: To be validated.

Dr. Kara Fitzgerald: Wow. So it’s a topical senolytic therapeutic. That’s so cool. And maybe one day it’ll be an internal.

Dr. Carolina Reis Oliveira: Yeah, for sure.

Dr. Kara Fitzgerald: All right. Let’s talk a little bit about then what else the product does, or I’m sorry, in your clinical studies, you guys gathered a bunch of classical measurements on barrier and elasticity, et cetera, et cetera. So show us, tell me about those.

Dr. Carolina Reis Oliveira: Yeah, definitely. So obviously in the end, people want to know how targeting senescent cells will impact their skin health and appearance. So we ran the classical clinical study that participants use the product for six weeks and up to 12 weeks. And we could see measured significant improvements after six weeks on hydration, on firmness, elasticity and fine lines and wrinkles. We have almost like 90% of the use is showing improvement in fine lines and wrinkles. I would say that for fine lines and wrinkles, this can take up to 12 weeks because obviously the way that the peptide works is by penetrating the skin, basically working from the inside out, changing a little bit of the makeup of the skin on the dermal layer. And the dermal layer is the cell that is the layer that will produce more collagen that will lead to that firmness and better appearance.

But another great result that we saw was the improvement in the skin barrier. And our skin is designed to be a barrier for a reason. We want to protect our internal body against pathogens and several stressors. And when the barrier is compromised, we have several skin disorders. We have eczema, we have severe inflammatory diseases. And maintaining the skin barrier is a way to show that your skin is functioning properly and it’s also important to maintain your overall health. That’s another area that we are super interested in connecting your skin with your overall health.

Dr. Kara Fitzgerald: I just want to underline how important that is, improvement in the skin barrier. So I mean I’m on faculty at the Institute for Functional Medicine in the immune module, and I specifically talk about skin barrier as it relates to eczema. But in general, once the barrier is compromised, not just pathogens but allergens, I mean an infant can become sensitized to peanuts through the skin. I mean it’s that… Through a compromised barrier, but also UV, also environmental toxins. So a compromised barrier is going to promote the production of senescent cells and it’s going to drive the inflammation forward. So the fact that you’ve significantly corrected that is… I mean I think it’s essential to the success of the product.

Dr. Carolina Reis Oliveira: Yeah. And actually it was our primary goal. I think as a longevity company, we are mainly focused on improving the health of your skin. And we believe that a healthy skin is a better-looking skin. So the aesthetic benefits, they are consequence of really fixing the underlying cause of unhealthy skin or aging skin that there is not any problem with aging itself, but we know that with aging comes all of those impacts on our health and the function of our tissues and that’s what we are trying to counteract.

Dr. Kara Fitzgerald: It’s awesome that we’re moving beyond just the obsession with the aesthetics alone at any cost, even as they accelerate the aging journey. It’s like it’s just time to move well beyond that.

Dr. Carolina Reis Oliveira: Yeah. And I think it is very good to see that consumers are getting more and more educated and for all these alternatives that are both good for your health and also good for your aesthetics, but never, that’s what we are pro- , never compromise your health to get flawless skin because in the end, what is the point if internally you are not healthy and that won’t last long.

Dr. Kara Fitzgerald: Yeah. Absolutely. So moisture was improved and you conducted the study in winter, which is really cool because that’s something that doesn’t happen…

Dr. Carolina Reis Oliveira: That’s a very good point. Yeah, there are so many variants and we could still see improvement in hydration and the skin barrier, as we said, we measure through an instrument. So it’s quantifiable. And another area was tone because with obviously aging everyone, experiences more like dark spots and sun spots and the product helps controlling that melanin production that also gets deregulated with the presence of senescent cells.

Dr. Kara Fitzgerald: I think the cool thing about one of the studies that you did was that you compared the base ingredients, which are smart. You have a smart design of base compared to the full product with the OS1 peptide. So you showed some benefits on both sides, but obviously the OS1 peptide formulation well outperformed it. What are some of the other key ingredients that you think make the product perform as a whole along with the OS1?

Dr. Carolina Reis Oliveira: Yeah, we have several important support ingredients. Some oils that we brought from the Amazon rainforest.

Dr. Kara Fitzgerald: Oh, cool.

Dr. Carolina Reis Oliveira: Yeah, we have Pau Mulato oil, Pracaxi oil and they are very anti-inflammatory and rich in antioxidants, very calming and soothing for your skin as well. So as I said, people that sometimes have eczema or some kind of rashes, they see an improvement, they see a calming in their skin. And then we have niacinamide that’s kind of classic. Allantoin, it’s very calming and soothing as well. Vitamin E, I think these are the… And hyaluronic acid. We have three different molecular weights of hyaluronic acid, one that is very large molecular weight that’s going to just form a barrier on top of your skin and retain moisture and some low molecular weight that can actually penetrate in the skin and activate your skin to produce more hyaluronic acid.

Dr. Kara Fitzgerald: Which is kind of the classic… I think of it as a sandwich. So you have an occlusive that keeps things in and then you also humectant that gets in there. Fabulous. There’s studies happening trying to figure out barrier repair products to inhibit the allergic march, eczema to asthma, to food allergies, et cetera. And there hasn’t been success. I guess I can’t help but wonder how yours might perform with this evidence that can improve barrier. Yeah. Do you have some thoughts?

Dr. Carolina Reis Oliveira: Yeah, that’s a very interesting point because I think as you mentioned, when you want to improve the barrier, it can’t be only on the surface. We need something that will be more active. So our actives, like the peptides and the hyaluronic acid that can penetrate the skin that will work from the inside out and help your skin to actually repair the skin barrier, more so than creating a physical barrier just with those emollients, that’s what in the long term will help your skin to recover from some of the distress that the skin is experiencing.

Dr. Kara Fitzgerald: It’d be interesting to see. I know the research they were looking at was exclusively in ceramide products and I think there is a place for ceramides for sure, but the outcomes weren’t very exciting.

Dr. Carolina Reis Oliveira: Yeah. And by the way, we have another interesting study and we can talk. So basically we are focused on skin health as a whole, so that’s why we have a face and a body product and one of our hypothesis and aim with our company is that we need to show that your skin health impacts your overall health as a whole. So as you age and you start to accumulate more senescent cells and you start to get your skin barrier compromised, you also have more release of inflammatory signals coming from your skin and because your skin is your largest organ can actually impact your levels of inflammation systemically. So our hypothesis is that if we treat our skin topically and if we’re able to repair the skin barrier and reduce the levels of inflammation coming from senescent cells, can we help lower our inflammation in the blood systemically? So we are running this study in which we collect blood before the patients start using the product topically and after three months we collect blood again to measure the impact of a topical treatment on circulating inflammatory levels.

And I think this is totally correlated with the skin barrier and definitely a very interesting way to show that your skin is much more than we think. It’s not just a barrier, but it’s an organ that’s actually super connected with our internal body.

Dr. Kara Fitzgerald: Huge. That’s so interesting. So is that study underway right now? Do you have anything to-

Dr. Carolina Reis Oliveira: Yeah.

Dr. Kara Fitzgerald: Okay. So you can’t report on it.

Dr. Carolina Reis Oliveira: Yeah, we should end now, end of June. So we hope to have the… But the preliminary, because some participants already finished and we already see some very interesting trends in decreasing some key inflammatory cytokines upon the treatment.

Dr. Kara Fitzgerald: Can you share any of them yet? I’m so curious to see what you’ve changed or to hear what you’ve changed.

Dr. Carolina Reis Oliveira: Yeah, I think I’ll hold just because things can change where you have the whole-

Dr. Kara Fitzgerald: Fair, totally fair. Yeah, definitely. Definitely.

Dr. Carolina Reis Oliveira: We can do second episode.

Dr. Kara Fitzgerald: We can do a second. Yeah. Yeah. Well you have a couple of papers coming out that we should talk about and anything that comes out we can link to on the show notes folks, we will. We’ll make sure that you’re in the know with this cool product line. So you alluded to people using this for eczema. I mean obviously as a clinician and there’s a lot of doctors and clinicians who are listening to this podcast. So not only are they thinking about using it for themselves, but they’re going to be thinking about prescribing it to their patients. Have you looked at using OneSkin for eczema or for other skin conditions?

Dr. Carolina Reis Oliveira: Yeah. Not on a clinical study. So all the data that we have is still anecdotal. But I think we definitely need results or studies to prove this hypothesis. I think the whole rationale behind improving the skin barrier makes sense. But obviously eczema has more… It’s a more of a complex condition, so there will be other factors that could interfere as well. Another thing that I think we saw that was interesting, mainly from the body product and a lot of people during the aging process, they experienced a lot of itching and flakiness and skin gets really fragile, tends to tear really easily. So we did see a lot of improvement in terms of improving the skin resilience and decreasing itchiness. And so the skin is recovered to that health and I would say strong state again. So that-

Dr. Kara Fitzgerald: Very impressive.

Dr. Carolina Reis Oliveira: Helped many patient participants as well.

Dr. Kara Fitzgerald: I mean, I can say that certainly the variables that you’re measuring, barrier, the hydration status, these are all the classic measurements that they use in products designed specifically to treat eczema or atopic dermatitis. So it seems to me that I’ll make the leap that it would be absolutely reasonable to try and it’s really… It’s very gentle.

Dr. Carolina Reis Oliveira: It’s very gentle. Even if you had a child that has a problem, we haven’t tested, so we don’t publicly recommend, but I would say that’s safe for a child though or yeah.

Dr. Kara Fitzgerald: Yeah. Okay. That’s just really exciting. All right. We’ve covered a lot. Let me think. Oh, the other question I wanted to ask you was, we’re thinking about the skin microbiome a lot and the influence on either accelerated aging or decelerated aging. So again, my coming from a background of thinking about allergic disease and atopic dermatitis, there’s always a dysbiotic microbiome that’s involved in the process. And I’m curious if you’ve looked at changes to the microbiome with OneSkin?

Dr. Carolina Reis Oliveira: Yeah, that’s a great question. Again, and we actually have a clinical study ongoing as well to measure change in the skin microbiome after people are using the product because it’s really hard to mimic the microbiome in vitro. So that’s something that we cannot assess with our tools in the lab. But we are also curious, and there are many studies showing that your microbiome changes with the aging process and obviously when you are experiencing any of those conditions. So we want to understand a little bit more of the impact of our product after a certain period. So I’ll add…

Dr. Kara Fitzgerald: Keep me posted. I have to say that paying attention to that literature for a while, and correct me if I’m wrong, but my conclusion was that it’s more… If we correct the imbalance in the skin, sort of the underlying imbalance, then the microbiome tends to follow. So going in after an imbalanced microbiome with some sort of antimicrobial or trying to eradicate and rebuild is probably not the approach. It may be the inside-out rebuilding of the skin itself, that may change it, and your study would actually confirm that or dispute it.

Dr. Carolina Reis Oliveira: Yeah. Yeah. I think it as always is kind of a two-way approach. I think it’s a little harder to actually add the right amount of microbes to your skin that you need with a topical product. There are so many variables and that it’s hard to guarantee the delivery of the right ones to your skin. So I would agree with you that when your skin is in a good homeostasis state that the direct consequence is that your microbiome will respond and will… Because the default when we are healthy and young is that everything is in harmony. So that’s a consequence of having a healthy skin is that your microbiome would complement that. Yeah.

Dr. Kara Fitzgerald: It’s like synergistic, symbiotic relation, but beneficial relationship. Well, we’ve covered a lot. I’m really, really, really excited to get to talk to you and I look forward to other conversations as you are so committed in moving the science forward. I just hope you blow this field right up. It needs it. Anything else that you want to add? Yeah, we’ve covered quite a bit. I’m thrilled about the clock. I’m thrilled about all the papers. Every question that I had, you’re already researching it, so what else?

Dr. Carolina Reis Oliveira: Yeah, I mean maybe just touch on what we are developing next.

Dr. Kara Fitzgerald: Yeah, good, good.

Dr. Carolina Reis Oliveira: Yeah, that’s also super interesting, and as we think of the impact of senescent cells in other conditions, I think another one that’s really close to what we are doing is hair loss as it’s associated with aging. Your scalp is a continuation of your skin, and there are several studies actually showing that senescent cells impact hair loss and even graying hair. So I think it’s so fascinating when you think that, okay, if we can actually target aging at the root cause, we can solve so many things that we are experiencing with one kind of, the same target. So we have just started researching hair follicle growth and the impact of senescent cells and testing our peptide in combination with other ingredients to evaluate whether we could also treat or prevent hair loss as well.

Dr. Kara Fitzgerald: Wow. Anything to report? Is this-

Dr. Carolina Reis Oliveira: Yeah. It’s too early. It’s too early.

Dr. Kara Fitzgerald: Very exciting.

Dr. Carolina Reis Oliveira: So yeah, this one is probably going to take a while. Yeah, I think the other closest product that we are bringing to the market will be a sunscreen that also has the peptide, right? So I think obviously we know that sunscreen is the best defense against aging. You need to choose well, also sunscreen can be sometimes a little toxic in some ways, such as mineral ones. But I think combining a sunscreen with our peptide is basically having a two-way defense against sun damage. Because sometimes when the sunscreen cannot be effective and you accumulate sun damage, then the peptide has this ability to repair or to help your cells to repair the damage more efficiently. So we’ll be like a duo that will work super well to again, continue to promote the skin health.

Dr. Kara Fitzgerald: Perfect. Keep us posted on that. Really exciting. All of it. All right, Carolina, thanks again for joining me on New Frontiers. Folks, again, you will find all of the information we covered in the show notes, the links to the papers, et cetera. So thank you.

Dr. Carolina Reis Oliveira: Thank you Dr. Kara. So fun this conversation.

Carolina Reis Oliveira, PhD, is co-founder and CEO of OneSkin. She holds her Ph.D. in Immunology from the Federal University of Minas Gerais in collaboration with Rutgers University and is an alumnus of IndieBio, the world’s leading biotechnology accelerator. In 2016, Carolina relocated to Silicon Valley from Latin America to co-found OneSkin, and to lead the development of the company’s disruptive longevity technologies.

OneSkin was founded by 4 scientists united in their passion to develop solutions to prolong human healthspan. Carolina Carolina Reis Oliveira, PhD, Alessandra Zonari, PhD, Mariana Boroni, PhD, and Juliana Carvalho, PhD, had a shared vision – to create technologies that help people age in a healthy and vibrant way, so that they can live their best lives, every day. They believe there’s no reason you can’t be dancing on a table at 80 years young. Fueled by their passion for science and their love of life, these women scientists embarked upon a journey to forever transform the way humans experience aging. Troubled by the reality that so many people, including some of their loved ones, spend a considerable portion of their lives in poor health due to age-related disease, they set out to create technologies that slow down or even reverse the aging process.

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Summary of OS-01 FACE 12 week clinical study

Dave Asprey, The Human Upgrade

OneSkin R&D

OS-01 Key Data (all products)

OS-01 EYE 1 Pager

Article: How the OS-01 Peptide Works to Reverse Skin’s Biological Age

Most Toxic Ingredients in Common Skincare Products:

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• Younger You book
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