Velarde Michael C, Demaria Marco
Buck Institute for Research on Aging, Novato, Calif., USA.
Gerontology. 2016;62(5):513-8. doi: 10.1159/000444877. Epub 2016 Apr 1.
Senescent cells are induced by a wide variety of stimuli. They accumulate in several tissues during aging, including the skin. Senescent cells secrete proinflammatory cytokines, chemokines, growth factors, and proteases, a phenomenon called senescence-associated secretory phenotype (SASP), which are thought to contribute to the functional decline of the skin as a consequence of aging. Due to the potential negative effects of the SASP in aged organisms, drugs that selectively target senescent cells represent an intriguing therapeutic strategy to delay aging and age-related diseases. Here, we review studies on the role of senescent cells in the skin, with particular emphasis on the age-related mechanisms and phenotypes associated with excessive accumulation of cellular senescence. We discuss the aberrant behavior of senescent cells in aging and how the different signaling pathways associated with survival and secretion of senescent cells can be engaged for the development of targeted therapies.
衰老细胞可由多种刺激诱导产生。它们在衰老过程中在包括皮肤在内的多种组织中积累。衰老细胞分泌促炎细胞因子、趋化因子、生长因子和蛋白酶，这种现象称为衰老相关分泌表型（SASP），人们认为这会导致皮肤因衰老而出现功能衰退。由于SASP在衰老生物体中具有潜在的负面影响，选择性靶向衰老细胞的药物代表了一种有趣的治疗策略，可延缓衰老及与年龄相关的疾病。在此，我们综述了关于衰老细胞在皮肤中的作用的研究，特别强调与细胞衰老过度积累相关的衰老机制和表型。我们讨论了衰老细胞在衰老过程中的异常行为，以及如何利用与衰老细胞存活和分泌相关的不同信号通路来开发靶向治疗方法。
