Targeting Cellular Senescence for Healthier, More Youthful Skin

I’m thrilled to be joined by Dr. Alessandra Zonari to take a deep dive into a breakthrough in skincare science that has caught my attention—OneSkin’s OS-01 peptide. This episode explores how OS-01 targets cellular senescence, the core of aging, potentially transforming skin health – preserving function, not just aesthetics. I’m particularly impressed by OneSkin’s commitment to rigorous research and evidence-based results. Their approach rejuvenates skin function in addition to enhancing its natural radiance, elasticity, and even its microbiome. This could be a significant advancement for individuals managing aging skin or conditions like atopic dermatitis.

Throughout our discussion, we explore the scientific foundation behind OS-01 and its clinical implications and uncover how this peptide may redefine skincare protocols, offering new possibilities for healthier, more radiant skin. Whether you’re a practitioner seeking innovative solutions for patients for ultrasensitive skin or dermatitis, or someone passionate about maintaining skin health, this episode promises insights that could reshape your approach to skincare. And if you’re using OneSkin, I’d be curious to hear from you. You can post a comment wherever you’re listening to this or email me directly at DrKaraFitzgerald.com.

Check out the show notes at www.drkarafitzgerald.com/fxmed-podcast/ for all the relevant links and resources. ~DrKF

In this episode, Dr. Kara Fitzgerald and Dr. Alessandra Zonari explore One Skin’s innovative approach to skin health. They discuss the science behind peptides, particularly the OS-1 peptide, which reduces senescent cells and inflammation. Alessandra shares insights on the clinical applications of One Skin’s products, including benefits for conditions like atopic dermatitis and improvements in skin barrier function. They also touch on the use of retinol, aggressive aesthetic interventions, and the importance of long-term skincare. The episode emphasizes the scientific foundation of One Skin’s products and their potential to enhance both skin aesthetics and overall health.

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. Let me introduce you to our guest. You can see she’s sitting next to me if you’re watching on YouTube. Otherwise, you’re listening wherever you grab your podcasts. This is going to be a fun, cool, interesting, and motivational conversation. Alessandra Zonari is a PhD and the co-founder and chief scientific officer over at OneSkin. You know that I am a huge fan of the OneSkin product line. She earned her master’s degree in stem cell biology, her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil, in collaboration with the 3B’s Research Group in Portugal.

Dr. Kara Fitzgerald: Her PhD work in skin regeneration was awarded best thesis at her university. She did a second postdoc at the University of Coimbra in Portugal, and in 2017 she joined the team at OneSkin, where she dedicated her time to understanding the mechanisms underlying the aging process and developing specifically science-based solutions that can reverse the skin’s biological age. You are also involved in creating the biological age clock, which we’ll talk about as well. The biological age clock for the skin, specifically. She’s co-inventor of five patents and has published over 20 peer-reviewed papers in scientific journals. Alessandra, just welcome, welcome, welcome to New Frontiers.

Dr. Alessandra Zonari: Oh, thank you so much, Dr. Kara. I’m very excited to be here today and to be talking to you.

Dr. Kara Fitzgerald: I love that we’ve had a really nice partnership and we get to share your science. You’re a badass, woman-founded company. You’ve done really neat work in the world of skin rejuvenation and you’re always onto new products and expanding things.

Dr. Kara Fitzgerald: But really, from this firmly rooted in science aspect. I mean, your background is perfect for what you’re doing now. Obviously, a lot of us come to skincare through the lens of wanting our skin to look better. We’re attached to this aesthetic piece, which is interesting because so many of us lather toxic stuff on our skin. So, it might look better, but then we’re uploading parabens and all sorts of junk, and we’re not doing anything around actually reversing the aging of the skin. So talk about how you guys approach that aesthetic piece and what’s unique about it in the OneSkin brand?

Dr. Alessandra Zonari: Yes, we like to say that the aesthetic aspect of the skin is a consequence of healthy skin. So we approach skin through the lens of an important tissue in our body. It’s a vital tissue. People don’t associate how important it is, but it is the barrier protecting our body from all external aggressors. Because of its size, it’s really contributing to what’s happening inside our body.

Dr. Alessandra Zonari: As we are aging, if the skin deteriorates, the function of being this strong skin barrier weakens. We are allowing more pathogens, more inflammation to start to implement in our skin. This may affect our overall health. Our approach is how can we maintain our skin to be as healthy as possible throughout the aging process, so we have a strong organ that can help us navigate the aging process. And, of course, the consequence of that, which we all want, is that your skin will be glowing and looking better, so you will feel more confident about yourself. It’s not only about trying to completely erase wrinkles and make you look younger. It’s more about making your skin behave as younger skin and continue to have this strong function of protecting your inner body.

Dr. Kara Fitzgerald: Awesome. That’s awesome. It’s so essential. And I just want to mention, you’ll likely want to try their product line, and you will get a discount code associated with this podcast. If you use DoctorKara15, you will get 15% off your first purchase at OneSkin.co. You can find this on the show notes at drkarafitzgerald.com and we’ll send this out. I’ll put a pin in that; if I remember, I’ll bring it up again later.

Dr. Kara Fitzgerald: I just want to tell you, that first question brought a lot of thoughts to mind. There’s plenty of science around skin barrier breakdown driving systemic diseases forward because I think it’s the largest organ, right?

Dr. Alessandra Zonari: Yes, it is.

Dr. Kara Fitzgerald: And our immune system is wrapped around, just deep to the skin, so anything that’s entering in when we have this barrier breakdown… People in our space think about the gastrointestinal barrier or the blood-brain barrier all the time. There’s lots of talk around that, but the skin as this barrier that repels UV damaging radiation or, to your point, pathogens, allergens, toxins, all of that, during the aging journey, we become way, way, way more vulnerable. We develop leaky skin, or, those of us treating kids in practice or anybody, we see skin disorders that are leaky by nature, like psoriasis or atopic dermatitis, which I know you guys are looking at. Maybe we can circle back and talk about it. So it’s essential that we’re building the barrier, and it’s a nice reward that as a result of creating true health with our skin, it looks really good also.

Dr. Alessandra Zonari: Exactly. We always say the best reward of treating your skin well is that the appearance will also be better. And also, the way we are targeting, we’re not only improving the skin barrier, but we also improve collagen production. This really improves the texture and firmness of the skin, and this will reflect in a better appearance of the skin as well.

Dr. Kara Fitzgerald: There’s cool research out, and then I want to get into the next question, but this first point brought a lot to my mind. We are hardwired – There was a study published, I think, in 2016, where we were able to look at people and guess their biological age. So we can look at the skin and how healthy somebody looks, and how their skin presents, is reflective of what their true health is. So, your skin is incredibly impeccable.

Dr. Alessandra Zonari: It wasn’t like that. I’m telling you, I suffered a lot with my skin before. I used the wrong products that created more inflammation instead of building this strong barrier. It was not working at all.

Dr. Kara Fitzgerald: In being a customer as well as the person who’s researching and developing these, have you been able to test your skin doing literal biopsies to witness some of the changes? What have you done?

Dr. Alessandra Zonari: No, I haven’t done skin biopsies to measure my own skin’s biological age. I do have images and pictures of how I was before and how it is now. I have very sensitive skin, and it always used to be red and itchy, sometimes burning. I would even spray water to relieve the burning. Many times I went to dermatologists, and they would recommend products that caused more exfoliation or peeling, which was not helpful at all. Since we developed the first version of the OS-01 Face back in the beginning of 2020, I’ve only used OneSkin, and my skin has really improved over the past years.

Dr. Kara Fitzgerald: Wow. Yeah, I can see it. It looks great. Everybody over at your company must be using it too. That’s pretty impressive.

Dr. Alessandra Zonari: Yes, everyone uses OneSkin.

Dr. Kara Fitzgerald: That’s cool. So, peptides. Talk about the journey of screening peptides. Actually, first of all, I guess we could back up and just say what is a peptide? Peptide is a buzzword in our space and more broadly in the longevity space. Everybody’s talking about peptides, but it’s such a generic term. But in fact, you did a massive screening journey to identify what you were going to use. So just talk about what peptides are and what you guys did.

Dr. Alessandra Zonari: Peptides are building blocks of proteins. They are formed by amino acids that, when put together, build a protein. So a small protein will be a peptide, and peptides have biological functions. Usually, a peptide can interact with our cells and activate pathways to either induce more collagen production or other signaling pathways for other things. There are peptides for different things nowadays.

Dr. Alessandra Zonari: So the way we came up with the OS-01 peptide and how we discovered and designed this peptide was by specifically aiming to reduce the senescence burden on the skin. We wanted to reduce the damaged cells that accumulate on the skin and all the negative effects that come with this accumulation, like the release of excessive inflammation. We had a specific target and started with a small library of 200 peptides and we started to look at the effects on the senescent cells in the skin. From this library, we got four hits for peptides that were reducing 10% to nearly 20% of the senescence in the skin. We used an algorithm using AI, although at the time we didn’t call it AI, to look at what these four peptides had and how we could scramble and create new sequences to have a better effect from these peptides.

Dr. Alessandra Zonari: That generated a new library of 700 new molecules, and we went back to the lab and we screened all of these molecules and the top one was the OS-01 peptide, that we saw consistently reduced up to 40-50% of senescence and the senescence burden, reducing the inflammation that’s being released by the accumulation of senescent cells. This was a design process with a lot of scientific methods to get to this peptide. We didn’t just find the peptide out of nowhere; it was really designed with the purpose of targeting what’s causing skin aging and the accumulation of senescent cells on the skin.

Dr. Kara Fitzgerald: Just to clarify, this is the skin aging phenomenon. There is a  measurable, demonstrable, accumulation of these senescent cells, and they then push forward inflammation. This inflammation breaks the barrier down, creating a feed-forward cycle where toxins, pathogens, etc., get in. There’s a ton of different microbes living on our skin, and when we actually have an intact skin barrier, we foster a healthy microbial distribution. When inflammation kicks in, they become problematic, creating a huge feed-forward problem. Did you see an improvement in the barrier? And to your point, you talked about collagen earlier, your peptide influences all of these?

Dr. Alessandra Zonari: Yes. Going back to some things you mentioned, the accumulation of senescent cells leads to more inflammation on the skin. This inflammation can break down collagen and can also disrupt the skin barrier. Our peptide reduces the amount of senescent cells and reduces the inflammation that’s been secreted by these damaged cells. What this does is allow the healthy cells to proliferate more, produce more collagen, and build a stronger skin barrier. As you mentioned, this skin barrier also protects our skin microbiome. Recently, we ran a study where we sequenced the skin microbiome before using one of our products, the OS-01 Face, and after six weeks, we sequenced it again. It was very interesting to see that after six weeks, the balance of the skin microbiome was healthier than before. This shows that as the skin barrier strengthens, and to your point, the skin microbiome also becomes healthier as a consequence.

Dr. Kara Fitzgerald: That’s very interesting to me, and really validating for what my thinking has been over the years in treating individuals with atopic dermatitis. It seemed to me that if we can turn around atopic dermatitis that the microbiome actually follows. You don’t need to go in there with a topical antimicrobial; you can just focus on the skin and the rest follows. And that’s what you’ve demonstrated. So we could think about OneSkin as a prebiotic for the skin.

Dr. Alessandra Zonari: Yes, it’s kind of like your skin microbiome becomes healthier by using OneSkin products.

Dr. Kara Fitzgerald: Are you going to publish on this microbiome data?

Dr. Alessandra Zonari: Yes, this was recently done. We are preparing the manuscript, and later this year it will be published. Yes.

Dr. Kara Fitzgerald: Since I’ve mentioned atopic dermatitis a few times already, you were doing some in-house investigation around atopic dermatitis. Will that be something you publish? Will you move from focusing on aging to clinical indications such as atopic dermatitis?

Dr. Alessandra Zonari: We know that the effects of our peptide can help with several types of dermatitis and diseases. However, we are still focusing more on the cosmetic and aging process because we’re a small team and cannot do a lot of things simultaneously. Anything related to disease involves an FDA route, which is a longer process. So our focus right now is to build this line of products for a good skin health routine.

Dr. Kara Fitzgerald: I will say from my own experience that I’ve recommended using it, to great effect, in my most sensitive patients who are vulnerable to skin conditions, because it is incredibly well tolerated. I’ve never had a negative report. We have people in our practice with such sensitive skin that we have recipes for them to make their own skin products at home because they can’t have any additives. Even in that arena, people have been able to tolerate OneSkin, which is pretty incredible.

Dr. Alessandra Zonari: That’s awesome. And it’s because after we developed the peptide, when we were formulating our formulas, our goal was to make it a gentle formula. When we are choosing the actives and added ingredients that are going into the formulas, we are always testing on the lab-grown skin and analyzing the levels of inflammation that are caused. Sometimes the combination of some ingredients can raise inflammation, and those won’t go into the formula. We always end up with a gentle formula that is tested in the lab for that.

Dr. Alessandra Zonari: After developing the formula, we always run RIPT (repeat insult patch test), studies on humans to check for sensitization. Before launching our products, we ensure they are safe for sensitive skin because it is very important for us to be safe for sensitive skin as well.

Dr. Kara Fitzgerald: Awesome. I can corroborate that. My practice has drawn some of the most sensitive skin patients, and it’s just been amazing. I’ll also mention, since it’s popping into my head now, that I have xeroderma. I have a filaggrin mutation, which creates at baseline, vulnerability to a leaky barrier and vulnerability to really dry skin. Annoyingly dry skin. This can be worse for those with multiple mutations. That’s part of  atopic dermatitis, etc. etc. But I’ve had really good results. I have ichthyosis vulgaris, the “fish skin” look on my legs sometimes, which is not fun but it’s familiar. I’ve had it my whole life. Your body lotion has turned that around. Yours is the only stuff that’s made a difference for this lifelong condition that I’ve struggled with from having the filaggrin mutation.

Dr. Alessandra Zonari: It’s interesting that you mention the body lotion because most people take care of their facial skin and forget the rest of their body. Usually because they don’t have any conditions like yours or a disease, so they just forget. And later in life, when we’re 60+, skin starts to get super thin and crepey, and more prone to tearing and bruising. That’s when people realize they need something for their body. But protecting the skin on your body early on to maintain this strong skin barrier will be important in the aging process so you can avoid having this excessive thinning of the skin, where it becomes so fragile, later on in life.

Dr. Alessandra Zonari: For our body lotion, we did a very interesting clinical study as well. The manuscript is under review and it will be published pretty soon. We analyzed the effect of using our body lotion on elderly people, aged 60 to 90 years old and we measured the improvement of the skin barrier with instruments. They perceived a better overall appearance on the skin on the arms and legs. And interestingly, we measured cytokine levels, indicating the level of inflammation in their blood, both at baseline and after three months. In the study, we had two groups: one that was treating with OS-01 Body, and another group that was using a moisturizer without active peptides. The participants didn’t know which product they were using.

Dr. Alessandra Zonari:The perception of better skin was higher in the group using OS-01, the instrument measurements confirmed improved skin barrier function on the group that used OS-01, and the inflammatory levels, after 3 months of use, were maintained and decreased at some level, while the levels in the other group trended to increase or was not changing that much. This really speaks to this correlation that having stronger skin protecting your body can really help your inner health and help reduce inflammation throughout the body.

Dr. Kara Fitzgerald: That is so cool. I look forward to seeing that study. And you just think about, that’s only in three months time and to your point, think about always working on it, always rebuilding it. As I mentioned earlier, I’m recording this from Mexico where the sun in Baja is incredibly intense. We’re inching towards the equator down here and there’s loads of skin damage here, loads of sun damage. The more that we can protect our barrier, the more we’re going to minimize that change as well.

Dr. Alessandra Zonari: More than just having these products like ours that can repair this damage, but the most important is avoiding the formation of this damage. The use of our products is helping, because the peptide can also help in turning on DNA repair pathways, it can help to avoid accumulating damage.  It keeps the healthy cells from becoming late senscent and producing that inflammation. Besides that, it’s very important, especially in areas with high sun exposure, to use sunscreen and protect your skin from sun damage. A lot of times, we may think about this later in life and it can be a little bit late, but starting early is key. The more you protect your skin from accumulating and forming new damage from the beginning, the better your skin will look as you age.

Dr. Kara Fitzgerald: And you have the sunscreen base topical available and when is the body topical going to be out?

Dr. Alessandra Zonari: It’s coming up. We launched the Face SPF last year. Both of them are mineral, non-nano zinc oxide. We’re launching our Body sunscreen on May 15th. It’s 100% mineral, it’s water-resistant for 80 minutes, broad spectrum, and it also contains the peptides. So, besides protecting from UV radiation, it’s also nourishing your skin with the peptide to repair damage and protect against new damage from excessive UV. It also has a nice blend of antioxidants to fight free radicals. It’s a very nice and glowy formula that does not leave a white cast. We’re very excited about this new product, and it will be available next week. One week from this recording.

Dr. Kara Fitzgerald: I can’t wait. I have a care package coming my way. I can not wait. I’m such a dedicated user of the lotion. To have the SPF added…

Dr. Alessandra Zonari: Especially now, living in Mexico, you will love the OS-O1 Body SPF.

Dr. Kara Fitzgerald: Yeah. Just going back to the conversation around senescent cells, getting at the heart of the heart of the hallmarks of aging, and the extraordinary turnaround you saw as you were researching it. The peptide was really dropping senescent cells like a stone in your early research. You guys have just published in the journal Aging out of Nature looking at this. Give us the lowdown on this publication. Before you jump in, I want to remind my audience, please circle over to the show notes and the studies we’ve already mentioned that are available will be parked on the show notes page at drkarafitzgerald.com so you’ll have access to all of this awesome science.

Dr. Alessandra Zonari: Yes, this specific publication you’re mentioning, we’re very proud of because it’s a scientific manuscript. It describes the whole experiments we did to understand skin aging, to screen for the OS-01 peptide, and all the mechanisms. It shows what the OS-01 peptide is doing when it’s in contact with the skin. It shows how it is reducing the senescence burden, reducing inflammation, and reducing the markers of senescence, allowing the skin to produce more collagen, and getting that skin barrier stronger. We also measured the biological age of the skin in this manuscript, and we can see that after treatment with the peptide, not only are the aspects I mentioned improved, but also the biological age of the skin is younger after the treatment.

Dr. Alessandra Zonari: This peer-reviewed journal, if you look at the publication, it’s the result of five years of research. It contains tons of data, and it was peer-reviewed by renowned scientists in the field of aging. It takes time to get this type of research published in this kind of journal, so it’s scientifically proven now. The whole research was reviewed by peers that have knowledge and are studying aging. You can find this publication on our website. It’s very deep because we use a lot of technical terms, but we also have blogs on our website that digest the content of the publication.

Dr. Alessandra Zonari: This is something that you wouldn’t usually find on other skincare brands, that they have a unique molecule that has been so deeply researched using scientific methodologies, compared to controls, and well-determined to validate the efficacy of a new ingredient in their products.

Dr. Kara Fitzgerald: It’s an incredible journey. I know that moving through the peer review process can take a really long time, and it’s a huge accomplishment. We will link to not only the paper, but the blogs on your site from our website so people can find them and access some of that cool content.

Dr. Kara Fitzgerald: We’ve talked about some of the new clinical work you have. We just talked about the change in inflammation markers and the drop in those, and the change in biological age. You have some OS-01 Eye clinical data. Let’s talk about that. You have data on sunburn and hyperpigmentation. And you have some findings on the  OS-01 Face topical and biological aging. It’s just one of the neatest things to bring it up again —you’re a badass bunch of women scientists. You’re a small, scrappy team, like we are. There’s not a lot of us but we try to make the most of thinking it through and doing the science. You’re always up to doing some really cool science. So give me the lowdown on all of these projects you have happening.

Dr. Alessandra Zonari: Yes, we’re absolutely passionate about science and having the data before launching our products. All our products go through extensive research in the lab, and we run clinical studies with all of them as well. One recent publication is also available in a peer-reviewed journal. It’s about the OS-01 Face formula. It was a very interesting clinical study because we did a split-face trial where participants used the OS-01 complete formula containing the peptide on one side of their face, and on the other side of their face they used the full formula without the peptide, and they didn’t know which side was which. We used instruments to measure improvements in the skin, and the improvement in the skin barrier that was measured by instruments was only present on the side that contained the peptide. This really shows that the results we were getting in the lab are now translating to when you apply the product on people’s faces. Not only did we see improvement on the skin barrier, we also saw significant improvement in the texture of the skin and in reducing fine lines on the side that contained the peptide. And we recently published this clinical study.

Dr. Kara Fitzgerald: How long was that intervention for? How long did you run it?

Dr. Alessandra Zonari: We collected data after six weeks and 12 weeks. After six weeks, we already saw improvement in the skin barrier, which was even better after 12 weeks of use. The eye cream is also a very interesting formula, because first of all, we weren’t planning to develop an eye cream because the face formula is safe enough to use on your whole face, including the eye area, and we do see in clinical studies improvement in the skin around the eye. But with more research on the skin around the eye we found another study, not done by OneSkin, that measured the biological age of the skin around the eye and also in different parts of your face, and the biological age of the skin under the eye and on the eyelid is 20 to 30 years older than the skin right on the temples.

Dr. Alessandra Zonari: We know that the skin around the eyes is thinner and accumulates more damage, which is why it’s the first place we start seeing the signs of aging, but we had no idea there was an accumulation of more damage and cellular senescence, leading to a higher biological age of the skin around the eye. So we started developing a new formula with a higher concentration of the peptide. The research involved testing on eyelid skin that we received from blepharoplasty surgeries, and we were able to optimize this formula to improve collagen production around the eye , even more than the OS-01 Face, and reduce the senescence burden. And then we ran a specific clinical study looking just at the area around the eye. We measured 4 weeks and 12 weeks time, and after 12 weeks, we saw improvement in the skin barrier function, but also we saw an improvement in the firmness of the skin around the eye, on the hydration, all measured by instruments. I like to point out the results from instrument measures because they are not biased.

Dr. Kara Fitzgerald: Not biased. Yeah.

Dr. Alessandra Zonari: Most companies rely on consumer perception, saying “99% of customers feel their skin is looking better.” We also have this data, but we like to understand why they think their skin is looking better and what’s really changing. In all of our clinical studies we use instruments to measure improvements in elasticity, hydration, and skin barrier function. In the before and afters of the eye cream, our board of dermatologists were very impressed with the improvements the eye cream provided to the skin around the eye. This will be published soon. The manuscript is under preparation. We like to publish our data to get this scientific validation of the process, so we’ll have a blog explaining the clinical study, which will be published soon.

Dr. Kara Fitzgerald: Okay, cool. All right. We’ll link to whatever we can on the product. It seems super interesting that the eye skin is aging in an accelerated manner. I can always tell when I’m dehydrated because I see a difference in my eyelids. That’s my window into the fact that I haven’t drunk enough water. I can just see it in my eyes.  It makes total sense that the area around the eye would age faster. I can see it in myself. I’ve always been really dubious about buying another product, but the fact that you’ve designed it specifically for that skin and tested it and demonstrated the difference is extremely important.

Dr. Kara Fitzgerald: The question that popped into my head, and others might be thinking about it as well, is would it be more beneficial to use this higher peptide everywhere else?

Dr. Alessandra Zonari: I mean…

Dr. Kara Fitzgerald: Or is it not–

Dr. Alessandra Zonari: It has benefits of having more, but the rest of the skin may not need as much. Depending on how your skin is, you’d be paying more for something your skin doesn’t need at that moment. We do have customers who use the eye cream on their whole face, which is allowed, but depending on where you’re starting your skin health journey, if the  skin around your eyes is still very good and strong, you can use OS-01 Face around the eyes. If you’re already seeing signs of aging around the eyes and want to boost the effect, using both products is better. Often, because it comes in a smaller bottle, people use the eye cream on lines around the mouth or a bit on the neck, but I wouldn’t use it as your full moisturizer because there’s no need for that.

Dr. Kara Fitzgerald: Okay. I do like it. I’m glad to have the backstory on the formulation difference. I’m really diligent about the body and the face, but I’m going to be extra diligent about the eyes too, since I have this clear indicator. I can tell when my eyes aren’t happy.

Dr. Alessandra Zonari: Exactly, yeah.

Dr. Kara Fitzgerald: So, you’re working on an at-home bio age clock so we can all do this easily. You don’t have to be a physician to order it or be in the laboratory setting. Talk about that.

Dr. Alessandra Zonari: During our research phase in developing OS-01, we wanted a way to quantify if this new molecule that we found was truly rejuvenating the skin. The way we decided to do this was to measure and see changes in the biological age of the skin. There are already several molecular clocks out there that measure biological age, usually using blood or saliva samples. Here, we wanted to be specific to the skin, so we looked at 500 DNA samples of skin from very young to old age to understand what epigenetic changes are happening on the DNA.

Dr. Alessandra Zonari: Epigenetics is actually what’s telling the DNA to express. Gene expression depends on this epigenetics. So our DNA doesn’t change with aging, but what the DNA is expressing changes and it is regulated by epigenetics. That’s what we are measuring to determine the biological age. We developed a clock, called MolClock, specific for the skin tissue. Using this algorithm in the lab, we are able to quantify that OS-01 can reverse the biological age of the skin. We’re now running a clinical study to see this in humans.

Dr. Alessandra Zonari: We intend to make this available for customers soon, but there’s still a lot of research to be done. So far, the way that we have developed the algorithm, it needs a full sample of your skin, meaning the epidermis and the dermis, which requires a full biopsy—which is not consumer-friendly. So we are now working on a version of the clock that can read biological age using non-invasive collection methods, like tape to collect some skin samples. We have some very interesting preliminary data that has already come up, but the study isn’t finished yet, so I don’t want to talk about it right now. We are working on that and trying to find ways for people to check their skin health by knowing the biological age of their skin. Usually, if the biological age is older than your chronological age, it means your skin is aging faster than it should be. We always want to keep the biological age the same or younger than your chronological age.

Dr. Kara Fitzgerald: Sure, sure. For your study, I think that you just referenced that in as little as four weeks, we could potentially see a drop. How long would you recommend using it to achieve optimal results? How long do we want to stay with it? Well, we want to stay with it long-term, but when would we actually expect to see the best outcome?

Dr. Alessandra Zonari: The best outcome that we measure in our clinical studies is 12 weeks. We usually recommend that. There are people who see results in one to two weeks, but we definitely recommend 12 weeks because that’s where we have more substantial data on results. Aging is a process that never stops. You are always aging and always encountering more stressors that are in contact with your skin, so it’s important to keep treating your skin every day and for the long term. It’s not that you will use our products for three months, see results, and then you’re done. You need to continue nurturing and giving the right ingredients to your skin so it can always be functioning at that level or younger, and always fighting the aging process.

Dr. Kara Fitzgerald: Yeah, absolutely. Anybody listening to this who’s using OneSkin, I’d be curious to hear from you. You can post a comment wherever you’re listening to this or email me directly at DrKaraFitzgerald.com. I know that I’ve recommended this time and again for people with skin conditions. I know you guys at OneSkin can’t, but I can as a clinician who’s not working at OneSkin. I do because I see it really well-tolerated. So, I’m curious if anyone’s using it from my space, I’d love to hear what your experience has been and how well you’ve tolerated it. You get anecdotal reports, though. I’m sure people are calling you and saying, “Hey, I just used this and….”

Dr. Alessandra Zonari: Yeah, we have a lot of customer reviews saying it helped with different skin conditions. As you mentioned, our product is not meant, or advertised, to treat any skin condition, but because of the nature of the product, it can help and we know it’s safe for sensitive skin.

Dr. Kara Fitzgerald: Yeah. I have a little bit of nummular dermatitis too, and it’s been helpful. Just going back to the pesky filaggrin mutation. What about elsewhere? Hair… Are you looking at using this peptide in the body elsewhere?

Dr. Alessandra Zonari: Yeah. Because the peptide is targeting cellular senescence, which is a common driver of aging not only in the skin, but in different tissues, it has the potential to be applied and developed for other indications beyond the skin. We have been focusing right now on skin. We have data on other conditions and applications from when we started, but we are not exploring this right now. We’re keeping our focus on skin. Yeah.

Dr. Kara Fitzgerald: That’s so fascinating. Like, of course you could use this internally, right? I mean, the sky’s the limit of what this could be. But yeah, that’ll require a much bigger team.

Dr. Alessandra Zonari: It’s a whole different thing. The desire is there, but when we realized what we could really do, we decided to be a skin longevity company where you can rely on our research to bring the best products to maintain your skin health. We are on this mission to maintain skin health and even to understand how we can improve our products. In two to three years from now, how can this product be even better than what we have right now? We continue screening for new molecules, we continue doing deep basic research on skin aging biology, to continue bringing the latest innovations and the best products to maintain your skin health.

Dr. Kara Fitzgerald: Super interesting. You guys could partner with somebody, though. I’m sure you get a ton of inquiries in that arena. People are always talking about retinol as the gold standard intervention for skin, but it’s a mixed bag for sure. What do you think about it? Do you advise people to use it in conjunction with OneSkin, not to use it at all? What do you think about it?

Dr. Alessandra Zonari: Retinol has been the gold standard for a long time, but for sensitive skin, it’s a big no because it just causes more irritation. The nature of retinol is to induce cell turnover in your skin, which can break the skin barrier for a period. When you already have sensitive skin, it keeps that barrier compromised, increasing inflammation and redness so you don’t see the benefits of retinol.

Dr. Kara Fitzgerald: It could be pro-aging.

Dr. Alessandra Zonari: Yeah, it can be accelerating because your skin is more sensitive to damage, so you’re actually doing the opposite of what you had intended when you started using retinol. For more resilient skin, retinol has benefits of inducing cell turnover, it also induces collagen production, but it doesn’t target the thing that causes aging of the skin. So we always say to associate it with OS-01 because OS-01 will complement areas that retinol doesn’t target and can even counteract some of the side effects of retinol.

Dr. Alessandra Zonari: So, you can use OS-01 in conjunction with retinol, or you can replace retinol, especially if you have sensitive skin. Or even if you don’t have sensitive skin, you can get pretty good results by using only OS-01. It was very interesting in the beginning, because I was still facing a lot of my skin problems and I had retinol prescribed for me several times and I could never tolerate it. When I saw the effect of retinol in the lab, with the peeling effect and how it induced inflammation, everything  made sense in my head. Our take on retinol is that it has benefits, but it’s not for everyone. It doesn’t target skin aging, so you may want to combine it with a product that’s targeting this accumulation of senescent cells. And if you don’t tolerate retinol, don’t keep pushing your skin; there are alternatives to retinol.

Dr. Kara Fitzgerald: It’s almost like for some people… I used retinol for a little while and definitely had what you did. I had this terrible burn response, and I think there’s a continuum of strengths, so I could use a micro strength. I don’t think my skin is quite as sensitive as what you’re describing your skin as, at least on my face. So maybe an appropriate amount of retinol might have a hormetic effect.

Dr. Alessandra Zonari: Yeah.

Dr. Kara Fitzgerald:It’s causing a little damage but then your body responds favorably. But it’s not actually getting at cellular senescence or the underlying mechanisms of aging.

Dr. Alessandra Zonari: Exactly. That’s why the combination can be very interesting.

Dr. Kara Fitzgerald: Interesting. Yeah, that makes sense. We talked about now being the time to start, whatever your age is, so that you don’t end up having to attempt to undo the damage that’s already there, and using it on our body as well. What about people who are interested in using more aggressive aesthetic treatments, like Botox or fillers? What do you think about microneedling? I was just talking to a friend of mine who has a clinic and they’re using exosomes and microneedling, some of the more biohacking type interventions and some of the mainstream interventions, like botox. What do you think about those through this OneSkin lens?

Dr. Alessandra Zonari: I think they are very complementary and serve different purposes. Our product helps your skin behave as younger skin, and continue building this protective barrier for your body. Depending on the level of skin damage that you have, or if you have fine lines or deep wrinkles that you already have, if it’s something that’s annoying or you don’t like, you would need to use other interventions as well to have better aesthetic results. Botox, for example, paralyzes muscles so your muscle does not move and the skin does not move so you don’t see the lines being formed. There are positive sides of this because immediately you look younger, just because you are not showing those lines. But your skin is not behaving as younger skin.

Dr. Alessandra Zonari: So if you want to use botox, using OS-01 is also beneficial because it will do the things Botox is not doing: making sure your skin continues to produce collagen and maintain a strong skin barrier to protect your body. Depending on when you start on your journey, you can avoid using a lot of Botox by taking care of your skin early on to make sure it functions better. I’m more on the side of this natural aging, so I’m not very excited about using a lot of Botox, and paralyzing and getting that face expression all the time. And there are other things you can do, combining microneedling and some lasers that can help boost collagen production, but again, they are not targeting what’s driving aging. So they can be used complimentary to obtain a better result on the status of your skin, and OneSkin is very well tolerated with different procedures.

Dr. Kara Fitzgerald: Okay. Yeah, that makes a lot of sense. I don’t think there are that many listeners using Botox, there are probably some, but microneedling has a place in our world, along with some of the more creative uses of it, like with exosomes.

Dr. Kara Fitzgerald: Well, we’ve got a lot of goodies I just want to mention again. We’ve got a 15% discount if you want to jump in and try OneSkin. Definitely, definitely do it. Use the code DRKARA15 to get this discount. Let me know what you think of the product. I’ve been a big fan of you guys since I first heard about you when you first came out. I was very excited about what you were all about and your commitment to science, which just continues. I’m happy to hear about all of your updates. Again, all of the content, they have a really cool video on the peptide, we’re going to link it in our show notes so you can easily get over to their website and find it.  We’ll also include the research on the body lotion and their line of products, all of that will be available. And then again, all published studies so far will be anchored on the show notes.

Dr. Kara Fitzgerald: Again, I’m thrilled to use the product and I’m just absolutely thrilled to be able to connect with you today, Alessandra. Thanks for all your hard work over there at OneSkin. I just want to give you a minute if there’s anything else you want to add. Otherwise, just hats off to you.

Dr. Alessandra Zonari: Thank you so much for your support. As you said, it’s been years already, and we really appreciate you taking the time to explain a little bit about our science to your community. As a scientist, and today you might have noticed, I tend to talk too much about the science, and simplifying this for the audience is very important and you’ve been great at helping spread this message.

Dr. Alessandra Zonari: One thing we want to spread is this message of taking care of your skin, thinking about what an important organ it is to your body, and taking care of your skin health. When we are aging we think about taking care of our heart and liver, and sometimes we neglect the skin as an important organ. But it’s important for your longevity and we are here to create products that support skin health and help people embrace aging, and navigate the path of aging feeling good about themselves. We’re all about bringing this good feeling and seeing everyone aging at their best and continuing to enjoy their lives, regardless of their age.

Dr. Kara Fitzgerald: Awesome, I love it. Thanks so much for coming. We’ll continue to be in the mix together and keep everyone posted as OneSkin moves forward in their efforts to reverse biological skin aging.

OneSkin co-founder and Chief Scientific Officer, Alessandra Zonari, PhD joined the early team in 2017 dedicating her time to understanding the underlying mechanism of the aging process and developing solutions to reverse skin’s biological age. Zonari is the co-inventor of five patents and has published more than 20 peer-reviewed papers in scientific journals.

alessandra@oneskin.co

Animated science video explaining how OS-01 works

Study: Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models

Blog: Pressing the Pause Button on Aging Skin: OS-01 BODY’s 12-Week Clinically Validated Results

Study: In vitro and in vivo toxicity assessment of the senotherapeutic Peptide 14

Study: Highly accurate skin-specific methylome analysis algorithm as a platform to screen and validate therapeutics for healthy aging

MolClock: Estimate DNA methylation age of Skin Tissues

Study: Double-blind, vehicle-controlled clinical investigation of peptide OS-01 for skin rejuvenation

OneSkin Blog: Senotherapeutics, Senolytics, and Senomorphics — What are they and what is OS-01?

OneSkin Product PDF

Podcast: Disrupting Anti-Aging Skincare by Targeting Senescent Cells

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

Blog: Why Skin Health is the Ultimate Test of Longevity

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

Bio Age Lab Test

Bio Age Self Assessment Quiz

Younger You Group Program

Younger You book

Better Broths and Healing Tonics book