Senotherapeutic peptide reduces skin biological age and improves skin health markers

Abstract

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 skincare. 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.

Meeting Report: Aging Research and Drug Discovery

“…The CSO of OneSkin Alessandra Zonari presented their latest findings regarding Peptide 14, identified through a cell-based screening. Treatment of aged skin with Peptide 14 caused a reduction in senescence and inflammatory markers and led to an increase in skin health with higher efficiency than rapamycin treatment [38]. Sibylle Jäger, L'Oreal Research and Innovation, presented a novel salicylic acid derivative C8-SA is known to promote longevity in C. elegans and prevent oxidative damage in humans by stimulating endogenous antioxidant defenses in an AMPK DAF-16 dependent manner (unpublished, L'Oreal).…”

Cellular Senescence in Aging, Tissue Repair, and Regeneration

“…68 A proprietary topically delivered senotherapeutic peptide reduces skin biological age and improves skin health markers in ex vivo human skin models. 97…”