Institute of Ageing Research, School of Medicine, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.
Department of Immunology, Monash University Faculty of Medicine, Melbourne, Vitoria 3004, Australia.
Cells. 2019 Jan 15;8(1):54. doi: 10.3390/cells8010054.
Telomeres with G-rich repetitive DNA and particular proteins as special heterochromatin structures at the termini of eukaryotic chromosomes are tightly maintained to safeguard genetic integrity and functionality. Telomerase as a specialized reverse transcriptase uses its intrinsic RNA template to lengthen telomeric G-rich strand in yeast and human cells. Cells sense telomere length shortening and respond with cell cycle arrest at a certain size of telomeres referring to the "Hayflick limit." In addition to regulating the cell replicative senescence, telomere biology plays a fundamental role in regulating the chronological post-mitotic cell ageing. In this review, we summarize the current understandings of telomere regulation of cell replicative and chronological ageing in the pioneer model system and provide an overview on telomere regulation of animal lifespans. We focus on the mechanisms of survivals by telomere elongation, DNA damage response and environmental factors in the absence of telomerase maintenance of telomeres in the yeast and mammals.
端粒是真核染色体末端富含 G 的重复 DNA 和特定蛋白质组成的特殊异染色质结构,它们被紧密地维持着,以保障遗传完整性和功能。端粒酶作为一种特殊的逆转录酶,利用其内在的 RNA 模板来延长酵母和人类细胞中端粒富含 G 的链。当端粒缩短到一定大小时,细胞会感知到这一情况,并通过细胞周期停滞来做出反应,这被称为“海弗利克极限”。除了调节细胞复制性衰老外,端粒生物学在调节有丝分裂后细胞的程序性衰老方面也起着基础性的作用。在这篇综述中,我们总结了端粒在先锋模型系统中对细胞复制性和程序性衰老的调控的最新认识,并概述了端粒对动物寿命的调控。我们重点关注了在酵母和哺乳动物中端粒酶缺失的情况下,通过端粒延长、DNA 损伤反应和环境因素来维持端粒的生存机制。