Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea; Institute of Human-Environmental Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea.
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea; Institute of Human-Environmental Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea.
Biomed Pharmacother. 2022 Jun;150:113034. doi: 10.1016/j.biopha.2022.113034. Epub 2022 Apr 28.
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.
光老化主要是由于紫外线（UV）辐射引起的，同时伴随着基质金属蛋白酶（MMPs）分泌增加和胶原蛋白降解。UV 辐射会诱导皮肤细胞衰老；然而，衰老细胞在光老化中的作用尚不清楚。因此，为了阐明衰老细胞在光老化中的作用，我们在光老化小鼠模型中评估了衰老细胞清除剂的作用，并研究了其抗衰老作用的潜在机制。UV 诱导的人真皮成纤维细胞衰老和光老化小鼠模型（ABT-263 和 ABT-737）均对衰老的成纤维细胞表现出衰老细胞清除作用。此外，我们发现几种衰老相关分泌表型因子，如 IL-6、CCL5、CCL7、CXCL12 和 SCF，可诱导真皮成纤维细胞中 MMP-1 的表达，而在用 ABT-263 和 ABT-737 进行体内和体外治疗后，其表达减少。两种衰老细胞清除剂均可减轻光老化小鼠模型中 MMP 的诱导，并减少胶原蛋白密度。我们的数据表明，衰老细胞清除剂可减轻 UV 诱导的光老化，因此针对衰老真皮成纤维细胞的策略可能是治疗光老化的一种有前途的选择。
