Data on OneSkin's Peptide 14, a Topical Senotherapeutic, in Human Skin Models and Skin Biopsies

You might recall that OneSkin recently launched a cosmetic product claimed to reduce levels of senescent cells in aged skin, as measured by the usual markers for cellular senescence, such as p16 expression and senescence-associated β-galactosidase. Removal of senescent cells is more or less literal rejuvenation, given that the accumulation of such cells drives chronic inflammation, tissue dysfunction, and degenerative aging. Clearance of a large fraction of senescent cells via senolytic drugs has been shown to extend life and turn back measures of aging in a number of animal studies.

The OneSkin product contains a bunch of the usual things one puts into skin care products, all of which can be safely ignored, but the core of it is peptide 14, also called OS-01 and decapeptide-52. This may or may not be a senolytic compound, capable of selectively destroying senescent cells to some degree. The evidence presented in today's preprint paper suggests that the observed effect on markers of cellular senescence is more likely achieved by preventing at least some cells from entering the senescent state.

In this, the use of peptide 14 might be similar in outcome to the topical application of rapamycin. In that case, researchers are fairly confident that no direct destruction of senescent cells is taking place, only a reduction in senescent cell creation and activity. This can be enough in aged skin to allow existing processes of senescent cell clearance to catch up over a timescale of a few months, and meaningful reduce the number of these errant cells and their impact on tissue function. Interestingly, the OneSkin folk used rapamycin as a positive control, and found it worsened aspects of their skin models even as it lowered markers of cellular senescence - so perhaps not something to dive into until more data has accumulated.

Looking at the meat of the data in this preprint, peptide 14 performs as well or better than topical rapamycin in reducing markers of cellular senescence, at least in skin models and in skin biopsies taken from older volunteers. Formal trials and resulting human data are pending - though the product is available for anyone who wants to give it a try. Given the existing data, it will be interesting to see how the product performs in older people in comparison to topical rapamycin use.

Senotherapeutic peptide reduces skin biological age and improves skin health markers

Skin aging has been primarily related to aesthetics and beauty. Therefore, interventions have focused on reestablishing skin appearance, but not necessarily skin health, function, and resilience. Recently, cellular senescence was shown to play a role in age-related skin function deterioration and influence organismal health and, potentially, longevity.

In the present study, a two-step screening was performed to identify peptides capable of reducing cellular senescence in human dermal fibroblasts (HDF) from Hutchinson-Gilford Progeria (HGPS) patients. From the top four peptides of the first round of screening, we built a 764-peptide library using amino acid scanning, of which the second screen led to the identification of peptide 14. Peptide 14 effectively decreased HDF senescence induced by HGPS, chronological aging, ultraviolet-B radiation, and etoposide treatment, without inducing significant cell death, and likely by modulating longevity and senescence pathways.

We further validated the effectiveness of peptide 14 using human skin equivalents and skin biopsies, where peptide 14 promoted skin health and reduced senescent cell markers, as well as the biological age of samples, according to the Skin-Specific DNA methylation clock, MolClock. Topical application of peptide 14 outperformed Retinol treatment, the current gold-standard in "anti-aging" skin care. Finally, we determined that peptide 14 is safe for long-term applications and also significantly extends both the lifespan and healthspan of C. elegans worms tested in two independent testings. This highlights the potential for geroprotective applications of the senotherapeutic compounds identified using our screening platform beyond the skin.

Comments

I'm glad you seem to be cautious optimistic Reason for this product. First I'd like to try it if it gives measurable results. Second, it should give a needed boost to the rejuvenation market.

Posted by: Robert at November 6th, 2020 3:44 PM

Yes I suppose part of it is senescent cells, however... there is also some sort of cross-linking of collagen going on in the extra cellular spaces, correct?

And for that, science has developed this new technology called "lytec". The groups working on PROTACs developed this.

To hear more about this I recommend the recent a16z podcast where they discuss biotech advancements, with a focus on PROTACs.

Very cool science where they are hacking the existing machinery that degrades unwanted proteins using the proteasome.

Lytecs use the lysosome.

Write something up on this please!

Posted by: Matt at November 7th, 2020 2:42 AM

Is there any reason why Oisin couldn't produce a cosmetic product quickly too?

Posted by: Jimofz at November 7th, 2020 3:13 AM

@Jimofz: Three reasons. One, our gene therapy can't be marketed as a cosmetic; it needs to go though clinical trial as an FDA-approved therapeutic for a disease indication. Two, our PLV (proteo-lipid vehicle, a lipid-based nanoparticle) won't easily penetrate the stratum corneum layer of the skin (unlike small molecules). Third, like the problem Unity had with killing SnCs in the knee joint, if you try to kill senescent cells locally, you run the risk that the SnCs in the rest of the body will still inhibit the stem cells locally, preventing regeneration. The skin might be somewhat different, but at the moment we think that systemic administration of senolytics are to be preferred over local. Note that OneSkin's product is seemingly mostly a senomorphic, rather than a senolytic. Full disclosure: I use it.

Posted by: Gary at November 7th, 2020 6:05 PM

I find it odd that a small molecule drug is regarded by the FDA as "cosmetic" yet a gene therapy having the same effect is a drug. Still, I guess that's the world we live in.

Personally I agree with Reason in thinking that Senolytics won't do much for the youthful appearance of skin in the 25-50 age bracket. Finding small molecule drugs to activate regnerative cells in the skin might be a more useful approach:

https://www.genengnews.com/news/progenitors-of-regeneration-for-severely-damaged-skin-identified/

Posted by: jimofoz at November 9th, 2020 5:51 AM

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