Groningen Research Institute of Pharmacy, Chemical and Pharmaceutical Biology, University of Groningen, Groningen, the Netherlands; European Institute for the Biology of Aging (ERIBA), University Medical Center Groningen (UMCG), University of Groningen, Groningen, the Netherlands.
Groningen Research Institute of Pharmacy, Chemical and Pharmaceutical Biology, University of Groningen, Groningen, the Netherlands.
J Mol Biol. 2019 Jul 12;431(15):2629-2643. doi: 10.1016/j.jmb.2019.05.036. Epub 2019 May 31.
Cellular senescence is a state of stable cell cycle arrest arising in response to DNA and mitochondrial damages. Senescent cells undergo morphological, structural and functional changes that are influenced by a number of variables, including time, stress, tissue, and cell type. The heterogeneity of the senescent phenotype is exemplified by the many biological properties that senescent cells can cover. The advent of innovative model organisms has demonstrated a functional role of senescent cells during embryogenesis, tissue remodeling, tumorigenesis and aging. Importantly, prolonged and aberrant persistence of senescent cells is often associated with tissue dysfunction and pathology, and is partially the consequence of mechanisms that enhance survival and resistance to cell death. Here, we describe the main molecular players involved in promoting survival of senescent cells, with particular emphasis on the regulation of senescence-associated anti-apoptotic pathways. We discuss the consequences these pathways have in providing resistance to intrinsic and extrinsic pro-apoptotic signals. Finally, we highlight the importance of these pathways in the development of targets for senolytic interventions.
细胞衰老（Cellular senescence）是一种稳定的细胞周期停滞状态，是对 DNA 和线粒体损伤的反应。衰老细胞会经历形态、结构和功能的变化，这些变化受到许多变量的影响，包括时间、压力、组织和细胞类型。衰老表型的异质性体现在衰老细胞可以涵盖的许多生物学特性上。创新模型生物的出现证明了衰老细胞在胚胎发生、组织重塑、肿瘤发生和衰老过程中的功能作用。重要的是，衰老细胞的长期和异常持续存在通常与组织功能障碍和病理学有关，并且部分是增强生存和抵抗细胞死亡的机制的结果。在这里，我们描述了促进衰老细胞存活的主要分子参与者，特别强调了调节衰老相关抗细胞凋亡途径。我们讨论了这些途径在提供对内在和外在促凋亡信号的抵抗方面的后果。最后，我们强调了这些途径在开发衰老干预的目标中的重要性。
