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

BACKGROUND Cellular senescence, 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, p16 INK4a and p21 CIP1/WAF1 . Telomere-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 p16 INK4a and p21 CIP1/WAF1 staining in senescent skin cells revealed low and high expression subgroups that did not correspond to chronological age. Topical HPE significantly reduced high p16 INK4a 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.