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Hallmarks of Cellular Senescence

衰老 生物 细胞生物学 细胞衰老 表型 细胞老化 计算生物学 端粒 遗传学 DNA 基因
作者
Alejandra Hernandez‐Segura,Jamil Nehme,Marco Demaria
出处
期刊:Trends in Cell Biology [Elsevier BV]
卷期号:28 (6): 436-453 被引量:2565
标识
DOI:10.1016/j.tcb.2018.02.001
摘要

The phenotype associated with cellular senescence is highly variable and heterogeneous. Senescent cells show common marks, but mechanisms behind these marks are not widely conserved among all the senescence programs. Lack of universal or program-specific markers is a major limitation for the identification and the targeting of senescent cells in vitro and in vivo. Technological advancements or more systematic approaches need to address difficulties associated with the study of cellular senescence. Cellular senescence is a permanent state of cell cycle arrest that promotes tissue remodeling during development and after injury, but can also contribute to the decline of the regenerative potential and function of tissues, to inflammation, and to tumorigenesis in aged organisms. Therefore, the identification, characterization, and pharmacological elimination of senescent cells have gained attention in the field of aging research. However, the nonspecificity of current senescence markers and the existence of different senescence programs strongly limit these tasks. Here, we describe the molecular regulators of senescence phenotypes and how they are used for identifying senescent cells in vitro and in vivo. We also highlight the importance that these levels of regulations have in the development of therapeutic targets. Cellular senescence is a permanent state of cell cycle arrest that promotes tissue remodeling during development and after injury, but can also contribute to the decline of the regenerative potential and function of tissues, to inflammation, and to tumorigenesis in aged organisms. Therefore, the identification, characterization, and pharmacological elimination of senescent cells have gained attention in the field of aging research. However, the nonspecificity of current senescence markers and the existence of different senescence programs strongly limit these tasks. Here, we describe the molecular regulators of senescence phenotypes and how they are used for identifying senescent cells in vitro and in vivo. We also highlight the importance that these levels of regulations have in the development of therapeutic targets. functional decline or an organism throughout life [1López-Otín C. et al.The hallmarks of aging.Cell. 2013; 153: 1194-1217Abstract Full Text Full Text PDF PubMed Scopus (2013) Google Scholar]. process that allows a gene to encode different mRNA products by differentially using exons and excluding introns in a primary transcript to give rise to different processed mRNAs. normal physiological form of cell death [82Ryu S.J. et al.Failure of stress-induced downregulation of Bcl-2 contributes to apoptosis resistance in senescent human diploid fibroblasts.Cell Death Differ. 2007; 14: 1020-1028Crossref PubMed Scopus (34) Google Scholar]. intracellular degradation system. 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It includes methylation of DNA, post-translational modification of histones, and other chromatin-remodeling events [1López-Otín C. et al.The hallmarks of aging.Cell. 2013; 153: 1194-1217Abstract Full Text Full Text PDF PubMed Scopus (2013) Google Scholar]. chromatin enriched in repressive marks. protein complex formed by caspase-1 and adaptor proteins. set of chemical reactions that occurs in an organism to obtain energy and building materials or to use them to build different and more complex structures. condition in which the regulation of mitochondrial homeostasis, production of mitochondrial metabolites, mitochondrial membrane potential, and ROS generation are altered [95Correia-Melo C. Passos J.F. Mitochondria: are they causal players in cellular senescence?.Biochim. Biophys. 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