Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle upon Tyne NE4 5PL, UK.
Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Newcastle upon Tyne NE4 5PL, UK.
EBioMedicine. 2017 Jul;21:14-20. doi: 10.1016/j.ebiom.2017.03.027. Epub 2017 Mar 21.
Telomeres are protective structures present at the ends of linear chromosomes that are important in preventing genome instability. Telomeres shorten as a result of cellular replication, leading to a permanent cell cycle arrest, also known as replicative senescence. Senescent cells have been shown to accumulate in mammalian tissue with age and in a number of age-related diseases, suggesting that they might contribute to the loss of tissue function observed with age. In this review, we will first describe evidence suggesting a key role for senescence in the ageing process and elaborate on some of the mechanisms by which telomeres can induce cellular senescence. Furthermore, we will present multiple lines of evidence suggesting that telomeres can act as sensors of both intrinsic and extrinsic stress as well as recent data indicating that telomere-induced senescence may occur irrespectively of the length of telomeres.
端粒是线性染色体末端的保护结构,对于防止基因组不稳定非常重要。由于细胞复制,端粒会缩短,导致永久性的细胞周期停滞,也称为复制性衰老。衰老细胞随着年龄的增长在哺乳动物组织中积累,并且在许多与年龄相关的疾病中积累,这表明它们可能导致与年龄相关的组织功能丧失。在这篇综述中,我们首先描述了衰老在衰老过程中起关键作用的证据,并详细阐述了端粒诱导细胞衰老的一些机制。此外,我们还提供了多个证据表明端粒可以作为内在和外在应激的传感器,以及最近的数据表明,端粒诱导的衰老可能与端粒的长度无关。