Division of Cancer Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Cancer Sci. 2013 May;104(5):525-30. doi: 10.1111/cas.12118. Epub 2013 Mar 11.
Cellular senescence is the state of irreversible cell cycle arrest that can be induced by a variety of potentially oncogenic stimuli and has therefore long been considered to suppress tumorigenesis, acting as a guardian of homeostasis. However, surprisingly, emerging evidence reveals that senescent cells also promote secretion of a series of inflammatory cytokines, chemokines, growth factors and matrix remodeling factors, which alter the local tissue environment and contribute to chronic inflammation and cancer. This newly identified senescence phenotype, termed the senescence-associated secretory phenotype (SASP) or the senescence-messaging secretome (SMS), is induced by DNA damage that promotes the induction of cellular senescence. All of these senescence-associated secreting factors are involved in homeostatic disorders such as cancer. Therefore, it is quite possible that accumulation of senescent cells during the aging process in vivo might contribute to age-related increases in homeostatic disorders. In this review, current knowledge of the molecular and cellular biology of cellular senescence is introduced, focusing on its positive and negative roles in controlling tissue homeostasis in vivo.
细胞衰老（cellular senescence）是一种不可逆的细胞周期停滞状态，可由多种潜在致癌刺激诱导，因此长期以来一直被认为可抑制肿瘤发生，起到维持体内平衡的守护者作用。然而，令人惊讶的是，新出现的证据表明，衰老细胞也会促进一系列炎症细胞因子、趋化因子、生长因子和基质重塑因子的分泌，这些因子改变了局部组织环境，导致慢性炎症和癌症。这种新发现的衰老表型被称为衰老相关分泌表型（SASP）或衰老信息传递组（SMS），是由促进细胞衰老的 DNA 损伤诱导的。所有这些与衰老相关的分泌因子都参与了体内平衡紊乱，如癌症。因此，在体内衰老过程中衰老细胞的积累可能会导致与年龄相关的体内平衡紊乱增加，这是非常有可能的。在这篇综述中，引入了细胞衰老的分子和细胞生物学的最新知识，重点介绍了其在控制体内组织平衡方面的积极和消极作用。
