Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland , Bellinzona , Switzerland ; University of Groningen, European Research Institute for the Biology of Ageing, University Medical Center Groningen , Groningen , The Netherlands ; IOR, Oncology Institute of Southern Switzerland , Bellinzona , Switzerland ; Università della Svizzera Italiana, Faculty of Biomedical Sciences , Lugano , Italy ; Faculty of Biology and Medicine, University of Lausanne UNIL , Lausanne , Switzerland ; and Department of Medicine, Venetian Institute of Molecular Medicine, University of Padova , Padova , Italy.
Physiol Rev. 2019 Apr 1;99(2):1047-1078. doi: 10.1152/physrev.00020.2018.
Cellular senescence is a permanent state of cell cycle arrest that occurs in proliferating cells subjected to different stresses. Senescence is, therefore, a cellular defense mechanism that prevents the cells to acquire an unnecessary damage. The senescent state is accompanied by a failure to re-enter the cell cycle in response to mitogenic stimuli, an enhanced secretory phenotype and resistance to cell death. Senescence takes place in several tissues during different physiological and pathological processes such as tissue remodeling, injury, cancer, and aging. Although senescence is one of the causative processes of aging and it is responsible of aging-related disorders, senescent cells can also play a positive role. In embryogenesis and tissue remodeling, senescent cells are required for the proper development of the embryo and tissue repair. In cancer, senescence works as a potent barrier to prevent tumorigenesis. Therefore, the identification and characterization of key features of senescence, the induction of senescence in cancer cells, or the elimination of senescent cells by pharmacological interventions in aging tissues is gaining consideration in several fields of research. Here, we describe the known key features of senescence, the cell-autonomous, and noncell-autonomous regulators of senescence, and we attempt to discuss the functional role of this fundamental process in different contexts in light of the development of novel therapeutic targets.
细胞衰老（cellular senescence）是增殖细胞在受到不同应激时发生的一种永久细胞周期停滞状态。因此，衰老（senescence）是一种细胞防御机制，可防止细胞获得不必要的损伤。衰老状态伴随着对有丝分裂刺激无法重新进入细胞周期、增强的分泌表型以及对细胞死亡的抵抗力。衰老（senescence）发生在几个组织中，涉及多种生理和病理过程，如组织重塑、损伤、癌症和衰老。尽管衰老（senescence）是衰老（aging）的原因之一，并且与衰老相关疾病有关，但衰老细胞也可以发挥积极作用。在胚胎发生和组织重塑过程中，衰老细胞对于胚胎的正常发育和组织修复是必需的。在癌症中，衰老（senescence）作为一种有效的屏障来防止肿瘤发生。因此，在衰老组织中通过药理学干预来鉴定和表征衰老的关键特征、诱导癌细胞衰老（senescence）或消除衰老细胞（senescent cells），正在多个研究领域中得到重视。在这里，我们描述了衰老的已知关键特征、衰老的细胞自主和非细胞自主调节因子，并尝试根据新的治疗靶点的发展，讨论该基本过程在不同背景下的功能作用。
