How I am Reversing My Skins Aging With Peptides w/ Carolina Reis Oliveira | EP #120

0:00What causes skin aging? In general, from a medical science perspective, what's going on? Skin aging is basically the generation of the skin tissue and it's caused by two processes. I was just blown away by the science and the technology, what you've been building. And I started using it. It is one of the few products I've used consistently, you know, twice a day before years. No, as one has this ability of decreasing up to 40 % the load of senescent cells. That's amazing. What is your skincare protocol? Yeah, like cleanser, see? So... Everybody, Peter Demandis here and welcome to Moon Shots. Today I have a guest who I think about twice a day because I use her product twice a day every day.

0:49It's Dr. Carolina Ries, Oliviara. She's a co -founder and CEO of One Skin. She has a background in stem cell biology, tissue engineering, immunology, and she founded One Skin with four incredible women, all PhDs in this area. It combat age -related disease, particular of the largest organ in our body, our skin. And I love the product. I use it twice a day. Full disclosure, I am an advisor to the company and because I love it so much, super proud that one skin is a sponsor of this podcast. We'll link to one skin and the details down below. But let's jump in to a topic that I've had a lot of energy people, you know, saying your skin looks amazing.

1:37What are you doing? So let's talk about how I'm reversing the age of my skin. Carolina, great to have you. Thank you so much, Peter. So great to be here. Thanks for your support since we launched our product in 2020. So yeah, excited to be back. Yeah, I know it was I met you on our one of our longevity platinum trips up in the Bay area and I was just blown away by the science and the technology what you've been building. And I started using it and I kid you not. It is one of the few products I've used consistently, you know, twice a day for four years. I remember when I was interviewing Larry Page at Google when he first joined the X Prize board back years ago, he said his objective with Google was to create a product that people used at least twice a day like they used their toothbrush.

2:33And if they got to that, that would be super successful. So I know you've gotten to that and I've turned God knows how many people on to once can why because I actually love the product. So where are you today up in the Bay Area? Yeah, I'm in the Bay Area. Fantastic. Continue with the research here. We have an office and a lab in San Francisco. How big is your team at this point? We are about 30 people. Yeah. Amazing. Are your PhD co -founding women still with you on the journey? Yeah. La Sandra, it's my main co -founder that leads the science. Maria and Mariana and Juliana, they were very important partners throughout this journey as well.

3:18We all complement our expertise in some ways. I come from the STEM cell biology, the T -Shown Engineering and the Sanret therapy, the Skin Research Generation, Mariana Bioinformatics and Juliana. She's an expert that also in STEM cell biology. So, yeah. An amazing team. I mean, really blown away. You know, people don't realize skin is the largest organ in your body. Obviously, you know that. And skin care is a massive industry. I should have looked up the number beforehand. You know how big it is as an industry. It's over 200 billion. And then when you focus more anti -aging is around 80 billion.

3:59And it's supposed to grow to, I believe, 150 I'm 2032, so it's definitely growing in a fast pace. Yeah, when I think about, you know, what do I want when I'm, you know, 120 or older? I want to think clearly. I want to have great mobility. I want to have great immunity. And I want to look good, right? So it's cognition, you know, aesthetics, mobility, those are the fundamental things. You can look yourself in the mirror every day. You want to say, oh, you know, I'm doing, I'm doing okay. and you feel good about that. So let's jump into the first general question here, which is, what causes skin aging?

4:41And what is skin aging? What, you know, in general, from a medical science perspective, what's going on? Yeah. So skin aging is basically the generation of the skin tissue and it's caused by two processes. One is the internal aging that's the natural aging process. our cells are constantly dividing and they are accumulating mutations and there is this buildup of inflammation in our body. The other process is the extrinsic agent that's basically all the environmental stressors that we are exposed on a daily basis. So primarily UV exposure but also evolution, obviously smoking and other types of radiation.

5:28Both of these processes, they cause damage in our cells and in our direct and our DNA or proteins, they increase the production of free radicals. And these all contributes to the accumulation of these old cells that we call the like senescent cells or zombie cells. And the main problem of these old cells or senescent cells is that they start to create inflammation. And the inflammation that they create basically leads to collagen breakdown, leads to dysregulation melanin synthesis. And this consequently leads to sagging wrinkles, dark spots. So if you are going to simplify, we can say that senescent cells accumulation is one of the main drivers of skin aging.

6:22There are several ways that we can lead to senescence. And the interesting part is that when we are young, our body is able to recognize those senescent cells and clear them out of the way. So our immune system is supposed to do this well, but as we grow older and we accumulate more and more of those senescent cells, the inflammation becomes too appointed that it overwhelms our immune system, our immune system gets deficient and they accumulate. And that's when it leads to those, these functions that in the skin we see signs of aging and obviously it's also associated with skin cancer, but in other tissues in our body, the accumulation of those cells is associated with several age related diseases.

7:13So it could be heart diseases, brain diseases. So this is considered one of the main hallmarks of aging because it's not, it happens throughout our body, our bodies, and then that's why we are very interested in how we decrease the amount of those zombie cells in our skin. Yeah, the way I learned it, let me balance this off you for feedback, is, you know, for human cells at least, we typically have something called the hayflick limit, which is the number of times a cell can divide. And I think that is like 50 cell divisions that are about to be implemented. And at the end of 50 cell divisions, cells should have the decency to die.

8:00You've done your job, you've divided, okay, now go away. But two other outcomes can occur. One, they can go immortal and become cancers, which is not a good thing. Or the second thing, like you said, they can become senile cells, also known as zombie cells, grouchy old man cells. and as those cells are sitting there not dying, they're sort of like in this, this, again, zombie state, and they're just pumping out inflammatory molecules that are recruiting other cells around them and causing this inflammation. And I think it's your innate, your natural killer cells, your innate immune system that's supposed to find those.

8:45I know I've, you know Dr. Bob Haruri, who's the CEO of Cellularity, and we've been talking about the idea of supplementing your NK cell population to help you with senescence and cancer and so forth. But I think the point you made is as we get older there's a concept called immuno -exhaustion where your immune system is just getting exhausted. It's fighting against all these viruses, it's fighting against, you know, all the increasing senescent cells and it can't catch up. So then you need to do something else. So, all right, so let's talk about, let's dive into it, you know, you developed a compound to find and zap senescent cells.

9:36So when you're doing your doctoral work and you're laying down the foundation for one skin and the OS one product. Did you set out to focus on senescent cells or yeah, talk to me about that? Yeah, no, actually we started, well, back in Brazil we were doing something else. We were growing human tissues derived from stem cells to replace animal testing. very different when that first endeavor didn't work out but we got the opportunity to move to the US and focus primarily on skin and at that point we decided to use our expertise to grow human skins in the lab and test any anti -aging product that we're already in the market to measure if they could actually promote any age reversal effect.

10:30So because we're able to measure the age of the skin by reading the epigenetic signature, we could determine if a skin is like 50 years old, we can test a given product and we can measure how many years that product would reduce, hopefully reduce the age of the skin. What we found really fast is that most products that are there claiming to be anti -aging, most of them cannot decrease the age of the skin, some can accelerate the age of this end. And none of them were actually targeting what we believed to be one of the primary causes of aging. So we saw that the industry that's claiming to be anti -aging is completely outdated.

11:18They haven't evolved in their approach. And we, because we were studying so much about aging and we were seeing a lot going on in the, you know, salver programming, cellular senescence and different strategy to target the fundamental, you know, mechanisms that are driving aging. We realized there was a better way to actually address this problem to target aging at the source. So that point we decided to shift from being like a testing company to actually a company that would search for new molecules, more specifically peptides. We were interested in peptides because it's already commonly used in cosmetics.

12:01And for those who don't know, peptides basically are the building blocks of a protein. If you think in that way, it's like a small sequence of amino acids. And for example, insulin is a peptide and peptides can have this effect of entering the cell and act as a messenger so they can activate certain pathways or suppress others. And we were looking for peptides that could selectively, you know, switch off senescent cells or decrease the burden of senescent cells. So we spent the first five years of one skin just doing the research in order to find this peptide. I mean using the platform you had created for testing everybody else, right?

12:56Yeah, exactly. First we developed this platform that one we can replicate the skin aging the lab. so we can replicate a very young skin to a very old skin. So we understand exactly what is changing in that process. And we can measure the age of the skin. The second is that we use that this cells derived from progeria donors. So progeria is a rare and genetic disorder that children age really fast. And they accumulate senescent cells really fast. So we use cells derived from those donors to screen peptides. So we test over 900 peptides, but initially we partnered with this university in Brazil.

13:43They were studying antimicrobial peptides and they had a library of 200 peptides. We decided to test them against these pergierous cells. And in that first round of screening, we found four hits. So basically four peptides that perform the better. And then we use an algorithm that helped us to do permutations. So changing the sequence of the amino acids in a way that we could optimize the efficiency and we generated another 700 peptides out of those four. And we test again against the same previous cells. That's where that's when we found OS one and OS one has this ability of decreasing up to 40 % the load of SNS and cells.

14:34That's amazing. Yeah. So how, so we talk about peptides and again, just to remind folks, you know, and amino acid is a basic building block and your DNA codes for basically proteins which are made up of of the sequence of amino acids and those proteins can be, you know, hundreds or thousands, tens of thousands of amino acids long and they're assembled in your ribosomes. But the signaling peptides are rather small, right? They're short sequence amino acids. So what size amino acids, how many, what size peptides, how many amino acids were the range of them that you were testing? Yeah, they range us between 10 and 14 because also to be able to penetrate the skin.

15:24There is a limit in the molecular weight. So, OS 1 is 10 amino acids. So it's over a little bit over 1000 doubters. And because of the polarity and the confirmation of the peptide, we can guarantee the penetration of the peptide throughout the straddle corneum, the skin barrier. But obviously, if you get to a bigger peptide, it becomes more challenging. You need to use the sophisticated delivery system. So luckily, OS1 is a size that we can apply top plea and we can detect the penetration up to the dermal layer. that's the layer that contains the fibroblast that produce collagen, gives like the firmness and the structure of the skin.

16:13So that's great. So 10 amino acids and I am curious, I never asked you this question. Were you able to like patent that amino acid sequence as a as a aging product? Yeah. So we definitely, we have a patent on the, there is a motif that we believe that it's important for this function and there are variations around this motif that we can patent. So we have a patent mainly focus on skin and senescence, but we even have been exploring for other applications as well as like metabolic disorders and inflammation. inflammation because one of the main ways that the peptide works is like decreasing inflammation.

17:02So when we treated those berygeria cells with the peptide, we see that there is overall decrease in the secretion that the senescent cells are producing in terms of the inflammation and that really helps in any, you know, many other conditions. So, I'll see you later. Yeah, so let me ask you a question. So I use the OS1 product. I said that on my skin. But I also have an OS1 body lotion and an eye lotion, and then a sort of sun screen and so forth. When I'm using OS1 and, okay, do my face in the morning and at night for a sleep, And then I'm putting the OS 1 body lotion on my arms and my legs.

17:53Is it my imagination that it's going beyond just my skin? Is it giving me an overall senescent protection for other organs in my body? We can't actually we have measured already the blood of individuals that have been using the product for many, many years and we couldn't detect the peptide in the blood, which is good because obviously this could have other implications, good or bad that as a cosmetic company, as a skincare company, we shouldn't be there. But what we see is that by protecting your skin and strengthening your skin indirectly, you are decreasing the inflammation of your body because your skin is your largest organ and as it accumulates damage and accumulates senes and cells and as the skin barrier weakens there is an increase that read in the inflammation that comes from our skin and even low levels of inflammation coming from our skin can compromise on internal levels of inflammation so that's an interesting one of the interesting since studies that we did was actually the body lotion that we recruited elderly people from 60 to 85 years old.

19:19These are people that already have a very fragile skin. And we collect blood at the baseline and they use the body lotion and the face for three three months. And then we collect blood again. And we saw decrease in some inflammatory cytokines just by treating the skin topically. So that's a very interesting concept that most people are not aware that obviously your skin is impacting our our body internally, but in a very important way. So a lot of those inflammatory cytokines, they are related to chronic diseases. So if you're elevated in your blood, you are more susceptible to develop of, um, yes, such a disease.

20:03And so that's a, that's a very interesting point that the, uh, the product helps. Everybody wants to take a short break from our episode to talk about a company that's very important to me and could actually save your life or the life of someone that you love. Companies called Fountain Life. And it's a company I started years ago with Tony Robbins and a group of very talented physicians. You know, most of us don't actually know what's going on inside our body. You were all optimists. Until that day, when you have a pain in your side, you go to the physician and they burn in the room and they say, listen, I'm sorry to tell you this, but you have this stage three or four going on.

20:40And you know, it didn't start that morning. It probably was a problem that's been going on for some time, but because we never look, we don't find out. So what we built at Fountain Life was the world's most advanced diagnostic centers. as we have four across the US today, and we're building 20 around the world. These centers give you a full body MRI, a brain, a brain vasculature, an AI -nabled coronary CT looking for soft plaque, dexascan, a grail blood cancer test, a full executive blood workup. It's the most advanced workup you'll ever receive. 150 gigabytes of data that then go to our AI's and our physicians to find any disease at the very beginning when it's solvable.

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22:06Really it's something that is, for me, one of the most important things I offer my entire family, the CEOs of my companies, my friends, it's a chance to really add decades onto our healthy life spans. Go to fountainlife .com, backslash, Peter. It's one of the most important things I can offer to you as one of my listeners. All right, let's go back to our episode. Because you've got a platform for measurement, I mean, you had, so first of all, I think you said 40 % reduction in senescent cells in the skin, which is huge. You have to have compared yourself to other skin creams out there. How do you fare against the other?

22:52I just don't know the field. All I know is I love your product and it works for me. But so what are the other leading products? How do you compare to those? What can you say about that in your testing? Yeah, great question. So there are a few things that we learned as we're testing on their products. There are some products that they claim to be anti -aging, but they are full of toxic ingredients that they can actually be causing more damage than good to your skin. So some of them when we apply on top of the same in the lab and we look at the histology like a cross -section of the skin. The cells are completely degenerating, the cells are dying, there is a lot of inflammation, so unfortunately some products are really causing more damage to our skin.

23:45Other products known to have vitamin C or other ingredients like glycolytic acid, they can be good for your skin. So some can promote like a light exfoliation or vitamin C can fight, can work as an antioxidant and fight the free radicals, but they are not addressing senescent cells. This similarly, the main product that's used as an anti -aging is retinol like acid or retina in or retinous. This is known as a very effective ingredient, basically induces cell turnover. So the retina, they bind to several receptors in eye skin and causes this cell renewal. And for most people you're gonna see your skin initially peeling off, so you are growing a newer fresh skin.

24:41A lot of can't tolerate a lot of people become more sensitive because while we are renew your skin you're basically exposing your skin because the barrier is completely removed but similar to the other ingredients it's not decreasing the load of senescent cells so all of them they can help in some way but you would still need a product like ours that is targeting senescent cells. Otherwise, you're treating the symptoms and the driver is still there promoting pumping that inflammation that it's accelerating aging. Is there any product you found that is competitive with what you do or do you feel like your the number one product out there in terms of of of senescent cell reduction.

25:34So far as far as I know we are the only ones that are completely focused on cellular senescence there are other companies claiming that they focus on senescence but I haven't seen any data. So I think because we've been studying this for like the past eight years it's very challenging to get to something as we got today. So first you need to find an ingredient that is effective and it's we have tests like several common I would say Lone Gavri, Molycus, so for example, metforamine or rapid micein or NMN and some of them work for reducing senescent cells but when comes to the concentration that you need to deliver to the skin to be effective.

26:26So the ability to penetrate the skin and the stability of those molecules over time, different pHs, it's very tricky to check all of those boxes. But there is rubber mice in cream out there, you need prescription. We tested rapamycin in our skin and what we saw is that if there is a very... there is a tight dose that the rapamycin works well. If you increase a little bit, it is already causing a little bit of toxicity. So one need to be careful when you're using a rapamycin cream because we know that it can be, you know, suppressed and it can be toxic. depending on the concentration. Is there any limit on the Onescom cream?

27:18I use it twice a day. Is there any value in using it three times a day? Or does it still work? But once a day, help me understand that. Yeah, there is for the face product, we optimize it those like for twice a day. We haven't tested like three times or more a day because it's almost like not the people wouldn't be able to do that. Interesting, we have tried to increase the concentration of the peptide for the face cream, who didn't necessarily lead to a better result. For the eye cream, which is a different formulation, and one very interesting data that we have around the skin on the eyes, is that if you measure the biological age just under or above your eyes, it's 20 to 30 years older than the skin around your temple or forehead.

28:16So because the skin is much thinner, it's moving all the time, accumulate more senescent cells, it's more delicate. It's a different, I would say, skin composition that requires a different product. So for that product, we used eyelid schemes that we got in partnership with like surgeons that we were doing like blepharoplastic surgeries. And we developed that specific formula to increase the collagen, and decrease the senescence load around the eye. So for that product, we increased the concentration of OS1 peptide. and we saw an improvement in the results in collagen production and reduction in P16.

29:03That's one of the main markers of cellulose innocence. So, some people what they do instead of using the face cream, they use the eye in their whole face or their neck, whatever it's there, they're most concerned about. I think if you have a healthy skin, the face should be good for you. Obviously, for areas that you need a little bit more. And how does the body cream differ from the face cream? Yeah, the body cream also has different ingredients. So there are ingredients that are more hydrating that you couldn't necessarily use on your face because it could potentially clog some pores. So we have this ingredient like derived from mushrooms that can hold water 400 times more than hyaluronic acid, which is like known as one of the main that can hydrate the skin.

30:01There is so far a vein that's also known as a long chievery, molecule is present in broccoli, but it has a lot of antioxidants, and some people even use for like treating cancer. And it has a lower concentration of the peptide. Again, because your body is not as exposed as your face, we optimize for the skin of their body. And one of the interesting things that we have seen with the body as well is that a lot of people, they get this fragile skin and if people have conditions like diabetes, it is they can have some wounds that won't heal. And by using the body lotion, we even got recently a review that the people were able to close that wound, not applying on the open wound, we never suggest that, but if you apply around, you're basically decreasing that inflammation and the skin is recovering that ability to heal.

31:00So it's, we have seen a lot of people reporting that kind of benefit to it. First, it's really exciting to see. Carolina, are you continuing your underlying R &D to find other molecules that perform even better? Do you have a sort of, and are you using AI in that search to look for that? Give me an understanding of where one skin is a company is going. Yeah, absolutely. We continue to test new molecules. Right now we believe that peptides are the main molecule that we can deliver to consumers. In the near term, there are other technologies as cell reprogramming, which still has a lot of challenge in terms of translation to consumers.

31:51So we continue to focus on peppermint. And when you talk about cell cellular reprogramming, you're talking about the work that David Sinclair has done on epigenetic reprogramming on reversing the epigenome of those cells to a younger state. Yeah, some people can do it with CRISPR as well. You can use it like viral vectors, mRNAs. There are a few companies working on that. The translation to consumers mainly as skincare products is still challenging. So we are mainly focused on peptides and other molecules that can be delivered in this skin, but always looking how we can optimize, again, the reduction of senescent cells, how we can reduce more the biological age of the skin.

32:39Because with OS1 peptide, we showed that we could decrease the biological age in 2 .5 years in the lab. This was over a course of five days, obviously a very controlled experimental condition. We have been testing now in humans the biological age after using the products for 12 years. And we have found that we could reduce 3 .3 years after using the product for 12 months. We are repeating the study with a larger cohort, so we hope to see even like a higher decrease in the biological age. But right now that's what we have, but we want to obviously develop the next generation of our product. One of the things that we are also looking to is encapsulating the peptide so we can penetrate and can be delivered in a more sustainable way.