Inhibition of matrix metalloproteinase expression by selective clearing of senescent dermal fibroblasts attenuates ultraviolet-induced photoaging

• Published in: Biomedicine & pharmacotherapy Vol. 150; p. 113034
• Main Authors: Kim, Haesoo, Jang, Jeehee, Song, Min Ji, Park, Chi-Hyun, Lee, Dong Hun, Lee, Si-Hyung, Chung, Jin Ho
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-06-2022; Elsevier
• Subjects: Fibroblast; Inflammation; Photoaging; Senescent cell; Senolytic drug; UVSF; CXCL12; CCL7; CCL5; Senescent cell; OPG; Senolytic drug; NHDF; Inflammation; Photoaging; SASP; Fibroblast
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113034

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Photoaging mainly occurs due to ultraviolet (UV) radiation, and is accompanied by increased secretion of matrix metalloproteinases (MMPs) and degradation of collagen. UV radiation induces cell senescence in the skin; however, the role of senescent cells in photoaging remains unclear. Therefore, to elucidate the role of senescent cells in photoaging, we evaluated the effect of senolytics in a photoaging mouse model and investigated the underlying mechanism of their antiaging effect. Both UV-induced senescent human dermal fibroblasts and a photoaging mouse model, ABT-263 and ABT-737, demonstrated senolytic effects on senescent fibroblasts. Moreover, we found that several senescence-associated secretory phenotype factors, such as IL-6, CCL5, CCL7, CXCL12, and SCF, induced MMP-1 expression in dermal fibroblasts, which decreased after treatment with ABT-263 and ABT-737 in vivo and in vitro. Both senolytic drugs attenuated the induction of MMPs and decreased collagen density in the photoaging mouse model. Our data suggest that senolytic agents reduce UV-induced photoaging, making strategies for targeting senescent dermal fibroblasts promising options for the treatment of photoaging.
•Secretory phenotypes from UV-induced senescent fibroblasts induced MMP-1 expression.•Treatment with senolytic drugs attenuated collagen degradation in photoaged mice.•Elimination of senescent cells in photoaged skin exhibited an antiaging effect.