Ageing Research Laboratories, Faculty of Medical Sciences, Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Molecular Biology and Genetics, Arts and Sciences Faculty, Near East University, Nicosia, Turkey.
Antioxid Redox Signal. 2021 Feb 1;34(4):308-323. doi: 10.1089/ars.2020.8048. Epub 2020 Apr 27.
Cell senescence was originally defined by an acute loss of replicative capacity and thus believed to be restricted to proliferation-competent cells. More recently, senescence has been recognized as a cellular stress and damage response encompassing multiple pathways or senescence domains, namely DNA damage response, cell cycle arrest, senescence-associated secretory phenotype, senescence-associated mitochondrial dysfunction, autophagy/mitophagy dysfunction, nutrient and stress signaling, and epigenetic reprogramming. Each of these domains is activated during senescence, and all appear to interact with each other. Cell senescence has been identified as an important driver of mammalian aging. Activation of all these senescence domains has now also been observed in a wide range of post-mitotic cells, suggesting that senescence as a stress response can occur in nondividing cells temporally uncoupled from cell cycle arrest. Here, we review recent evidence for post-mitotic cell senescence and speculate about its possible relevance for mammalian aging. Although a majority of senescence domains has been found to be activated in a range of post-mitotic cells during aging, independent confirmation of these results is still lacking for most of them. To define whether post-mitotic senescence plays a significant role as a driver of aging phenotypes in tissues such as brain, muscle, heart, and others. 34, 308-323.
细胞衰老最初被定义为复制能力的急性丧失，因此被认为仅限于增殖能力细胞。最近，衰老已被认为是一种细胞应激和损伤反应，包括多种途径或衰老域，即 DNA 损伤反应、细胞周期停滞、衰老相关分泌表型、衰老相关线粒体功能障碍、自噬/线粒体自噬功能障碍、营养和应激信号以及表观遗传重编程。在衰老过程中，这些域中的每一个都被激活，而且似乎都相互作用。细胞衰老已被确定为哺乳动物衰老的重要驱动因素。目前，所有这些衰老域的激活也在广泛的有丝分裂后细胞中观察到，这表明衰老作为一种应激反应可以发生在与细胞周期停滞暂时脱偶的非分裂细胞中。在这里，我们回顾了最近关于有丝分裂后细胞衰老的证据，并推测了它对哺乳动物衰老的可能相关性。虽然大多数衰老域已在衰老过程中的一系列有丝分裂后细胞中被发现被激活，但其中大多数仍缺乏独立的确认。为了确定有丝分裂后衰老是否作为大脑、肌肉、心脏和其他组织等组织衰老表型的驱动因素发挥重要作用。34, 308-323.
