Topical Platelet Exosomes Reduce Senescence Signaling in Human Skin: An Exploratory Prospective Trial

BACKGROUND: Cellular senescence(definition), an irreversible cell cycle arrest with secretory phenotype, is a hallmark of skin aging. Regenerative exosome-based approaches, such as topical human platelet extract (HPE), are emerging to target age-related skin dysfunction. OBJECTIVE: To evaluate the cellular and molecular effects of topical HPE for skin rejuvenation after 12 weeks of twice daily use. METHODS: Skin biopsies were obtained for histological evaluation of senescence markers, p16INK4a and p21CIP1/WAF1. Telomere(definition)-associated foci, coassociation of telomeres, and DNA damage marker, γH2AX, were assessed. RNA sequencing evaluated senescence associated secretory phenotype (SASP) and extracellular matrix pathways. RESULTS: p16INK4a and p21CIP1/WAF1 staining in senescent skin cells revealed low and high expression subgroups that did not correspond to chronological age. Topical HPE significantly reduced high p16INK4a cells in the dermis (p = .02). There was also a decrease in telomere damage after topical HPE (p = .03). In patients with high senescent cells at baseline, there was a 40% reduction in proinflammatory SASP. Extracellular matrix remodeling pathways, including collagen and elastic fibers, were up-regulated. CONCLUSION: Topical HPE, applied on intact skin, reduced senescence signaling and senescence-associated telomere damage after 12 weeks of twice daily use, targeting a path for skin longevity or healthy skin aging.