Reversing Skin Aging at the Cellular Level (Carolina Reis Oliveira and Alessandra Zonari, OneSkin)

Dr. Carolina Reis Oliveira and Dr. Alessandra Zonari are the co-founders of OneSkin, a company developing science-backed skincare products to reverse skin aging at the cellular level. In this episode, Carolina and Alessandra tell host Dr. Chris Patil how OneSkin is leveraging recent advances in longevity science to create novel peptides that target senescent cells and inflammation in aged skin. Their lead ingredient, OS-1, is a peptide capable of reducing biological age and senescence burden in human skin models.They explain their rigorous discovery process, including screening peptide libraries in cellular models of skin aging, which were described in a recent paper in Nature Aging. Next, they share how they translated this scientific research into an effective, consumer-friendly skincare product line and brand. Listeners will gain insights into OneSkin’s unique approach bridging cosmetics and cutting-edge geroscience.

Key topics:

Why skin health and appearance are important markers of overall agingThe cellular and molecular changes underlying skin agingHow most skincare products focus on temporary effects vs. targeting root causesScreening peptide libraries in cellular models to discover senolytic/senomorphic candidatesDiscovery and testing of lead peptide OS-1 in 3D skin models and human trialsValidating safety and efficacy to meet cosmetics regulatory requirementsLaunching a science-backed skincare brand and resonating with educated consumersOngoing R&D to expand into new anti-aging applications and delivery methods

Quotes:

Quotes have been lightly edited for clarity.

“Obviously, we look at our skin from the lens of aesthetics or of beauty. But our skin is our largest organ, and its main function is to protect our whole body against pathogens and different types of environmental stressors. As the skin ages and deteriorates, the function also gets compromised.”

“That’s one of the things that we’re interested in and exploring at OneSkin: not only how to improve your appearance, but also how to improve your skin function so it can aid in your overall health.”

“We realized none of the products out there were developed with the rationale of targeting aging itself.”

“When we treat dermal fibroblasts with this peptide, we could decrease the amount of senescent cells by 40–50%.”

“More and more, the population is getting educated. They don’t want just marketing claims, they want to understand and trust brands that can really bring proof.”

“People are more open to say, okay, if I need to put something on my skin, I should use a company that’s actually doing real science.”

“Our primary goal is to continue to be the most innovative company when it comes to skin aging, and to continue to be at the forefront of aging research applied to skin.”

Links to the major podcast platforms:

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This is from their website:

Is there any clinical data available on your Topical Supplements? Has it been published?Updated 4 months ago

While we haven’t published any of our clinical data in a scientific journal yet, we have completed a 12-week clinical study with 22 patients where we collected significantly positive data showing that OS-01 FACE can improve the skin barrier, texture, hydration, and reduce fine lines and wrinkles. You can read more about our 12-week clinical study to evaluate OS-01 FACE [here]
(OneSkin’s 12-Week Clinical Study to Validate the Effects of OS-01 FACE).

My Note: any moisturizer, something from the dollar store, or petroleum jelly, can improve the skin barrier, texture, hydration, and temporarily reduce fine lines and wrinkles.

We also have an ongoing clinical study which is examining our product’s ability to reduce the skin’s biological age over 6 months, along with a clinical study evaluating the effects of OS-01 EYE. We can’t wait to share the results!

My note: If they publish in a journal it will be a conflict of interest, just like their ex vivo skin study which they published in a very obscure, low impact journal. PMID:37217561

Color me unimpressed.

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Skepticism is always warranted, even more so when it comes to skin aging “cosmeceuticals”.

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Skepticism is always warranted. However, as I’ve mentioned before. This stuff works, it really does. I can understand the fatigue from trying various products over the years. I tried this out of curiosity after reading about the founders background.
Since I’ve been using it it’s spread around my circle of friends, both woman and men. There’s an easy way to ‘prove’ it works or not and that’s try it for yourself.

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How large is the peptide? One problem with peptides is it is difficult to get larger peptides from the surface of the skin into the epidermal cells or into the dermis. The skin is a pretty good barrier.

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I’m not sure - perhaps check their scientific publications:

On a separate tangent… In the podcast, its interesting that they are looking at using the peptides (and other senolytics) for hair loss… as senescent cells are also implicated in hair loss.

Perhaps a chance for people to test out the OneSkin product on hair loss situations, or other senolytics in that type of application… Senolytics Topically Administered to Skin for Antiaging Effects

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One-Skin is not cheap but David Sinclair in passing endorsed them. I wish they send out some samples, that’s how cosmetics move

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Not everyone is thrilled: AMAZON

Even the Vine reviewer who received it for free wasn’t impressed:

“I have used this product for 12 weeks now, and have not noticed any improvement in my skin versus any other (significantly cheaper) lotion or moisturizer. In addition, I often experienced dry skin (peeling and flaking) around my mouth. I’ll pass.”

So, in their literature, they are comparing it with retinol which is not the same as tretinoin(Retin-A). Which by the way actually works though it is too strong for some people.

“Retin-A is much stronger than retinol and can be used directly by the skin. Retinol needs to be converted into retinoic acid before it can be used by the skin.”

One of the main hallmarks of aging is skepticism. :grin:

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I wonder if topical, or oral, ACE inhibitors would help skin…

Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.

https://www.sciencedirect.com/science/article/abs/pii/S0006291X13018640?via%3Dihub

Hmm… Being using oneskin body, face and eye creams for a couple of years. Results are very minimal if any. Frankly did split testing vs Rapamycin cream 0.2 % and retin A 0.1 % and it is not a winner. Retin A is followed by Rapamycin. Further it is loaded with various ingredients so it is unclear what does what. it caused allergic reaction and red bumps.

The compound losartan cream inhibits scar formation via TGF-β/Smad pathway | Scientific Reports (nature.com)

The role of angiotensin receptor blocker in wound healing and cutaneous fibrosis has become a hotspot in recent years. We have developed a losartan cream that is comparable to triamcinolone ointment in inhibiting scarring. Considering the effects of chitosan and asiaticoside on wound healing and scarring, we added them to the losartan cream this time and improved the formula, expecting to get a better anti-scarring effect. The effects of creams were investigated on mouse scar model with triamcinolone ointment, onion extract gel, and commercial asiaticoside cream set as positive controls. A preliminary exploration of the mechanism involved in TGF-β/Smad pathway was performed in vivo and in vitro. With all results of anti-scarring, the compound losartan cream (containing chitosan, asiaticoside, and losartan) shows the best effect, followed by the chitosan asiaticoside cream. The treatment of the compound losartan cream inhibited expression of TGF-β1, collagen, and Smads, and decreased phosphorylation of Smad in vivo. These inhibitory effects were also confirmed in vitro. Our findings indicated that the compound losartan cream could inhibit scarring via TGF-β/Smad pathway. This cream might be an effective option for scar treatment.

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Pycnogenol works in several different ways, including ACE inhibition. It is is the brand name of a supplement made from extracts of the French maritime pine bark. It contains 65-75% procyanidins, compounds with antioxidant and anti-inflammatory effects.

There are skin serums that contain Pycnogenol. For example, The Ordinary has a 5% Pycnogenol:

Pycnogenol 5% | The Ordinary

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I tried it around 2005-ish. I was not impressed. I’ve found that topical antioxidants provide minimal benefit, if any, if one is already using an rx retinoid and a decent sunscreen.

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Thanks - I was going to give it a try, but already using tretinoin and a good sunscreen :slight_smile:

I have tried just about everything and found minimal additional benefit until topical rapamycin.

But, if you want to try something else that is relatively cheap, you could add The Ordinary matrixyl and argireline. I am not convinced that they do more than temporary plumping but they might provide some visible benefit during the day if you use them in the morning.

I’ve been using various “actives” in Korean skin care products and the only ones so far that I want to keep in my routine are the ones with isolated cica compounds (madecassoside, madecassic acid, asiatic acid, etc.). They are anti-inflammatory, among other things. They are great in moisturizers on top of tretinoin or tazarotene. They seem to keep irritation at bay.

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RapAdmin, Do you know if this refers to oral administration or topical administration?

Topical

Full paper is here: Sci-Hub | Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles | 10.1016/j.bbrc.2013.10.162

To examine the effect of enalapril maleate, its treatment was started at 1 week after 10-week irradiation. One hundred microliters of 1% w/v enalapril maleate dissolved in 30 vol% ethanol solution or 30 vol% ethanol (control) was applied 5 times a week for 6 consecutive weeks to the whole dorsal skin of each of the mice. Each of the experimental groups and the control group comprised 5 or 6 mice.

Seems like it would be a candidate to add to a DIY Cream, its cheap as dirt from India (remember, 82 rupees to the US $):

Perhaps someone familiar with these measures can translate the measures into mg of enalapril maleate? ( One hundred microliters of 1% w/v enalapril maleate dissolved in 30 vol% ethanol solution)

Source from the usual suppliers: Buy Rapamycin Online - List of Reliable Pharmacies

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