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

Dermatol Surg. 2024 Nov 1;50(11S):S160-S165. doi: 10.1097/DSS.0000000000004426. Epub 2024 Oct 4.

Abstract

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, p16INK4a and p21CIP1/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: 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.

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Aged
  • Blood Platelets* / metabolism
  • Cellular Senescence* / drug effects
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Exosomes* / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Rejuvenation
  • Senescence-Associated Secretory Phenotype
  • Signal Transduction / drug effects
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Skin Aging* / drug effects
  • Telomere / drug effects

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21