Department of Dermatology, Mayo Clinic, Rochester, Minnesota.
Center for Regenerative Biotherapeutics, Mayo Clinic, Rochester, Minnesota.
Dermatol Surg. 2024 Nov 1;50(11S):S160-S165. doi: 10.1097/DSS.0000000000004426. Epub 2024 Oct 4.
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.
To evaluate the cellular and molecular effects of topical HPE for skin rejuvenation after 12 weeks of twice daily use.
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.
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.
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.
细胞衰老,即具有分泌表型的不可逆细胞周期停滞,是皮肤衰老的一个标志。再生外泌体为基础的方法,如局部人血小板提取物(HPE),正在被开发用于针对与年龄相关的皮肤功能障碍。
评估局部 HPE 在每日两次使用 12 周后对皮肤年轻化的细胞和分子作用。
对皮肤活检标本进行组织学评估,以检测衰老标志物 p16INK4a 和 p21CIP1/WAF1。端粒相关焦点、端粒共结合和 DNA 损伤标志物 γH2AX 也进行了评估。RNA 测序评估了衰老相关分泌表型(SASP)和细胞外基质途径。
衰老皮肤细胞中的 p16INK4a 和 p21CIP1/WAF1 染色显示低表达和高表达亚组,与实际年龄无关。局部 HPE 可显著减少真皮中高 p16INK4a 细胞(p =.02)。局部 HPE 后端粒损伤也减少(p =.03)。在基线时具有高衰老细胞的患者中,促炎 SASP 减少了 40%。细胞外基质重塑途径,包括胶原蛋白和弹性纤维,被上调。
局部 HPE 应用于完整皮肤,在每日两次使用 12 周后可减少衰老信号和衰老相关的端粒损伤,针对皮肤长寿或健康老化的途径。