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]
卷期号:28 (6): 436-453 被引量:1414
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. It can degrade nonspecific (general autophagy) or specific (selective autophagy) targets [149García-Prat L. et al.Autophagy maintains stemness by preventing senescence.Nature. 2016; 529: 37-42Crossref PubMed Scopus (158) Google Scholar]. cholesterol-enriched microdomains of the plasma membrane [119Ohno-Iwashita Y. et al.Plasma membrane microdomains in aging and disease.Geriatr. Gerontol. Int. 2010; 10: S41-S52Crossref PubMed Scopus (24) Google Scholar]. state of permanent cell cycle arrest in response to different damaging stimuli [2Muñoz-Espín D. Serrano M. Cellular senescence: from physiology to pathology.Nat. Rev. Mol. Cell Biol. 2014; 15: 482-496Crossref PubMed Scopus (380) Google Scholar]. robust response of the cells to the presence of DNA damage. regulatory mechanism of genes that affects their transcription. 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. Acta. 2015; 1847: 1373-1379Crossref PubMed Scopus (0) Google Scholar, 143Passos J.F. et al.Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence.PLoS Biol. 2007; 5: 1138-1151Crossref Scopus (0) Google Scholar]. selective autophagy of mitochondria [146Dalle Pezze P. et al.Dynamic modelling of pathways to cellular senescence reveals strategies for targeted interventions.PLoS Comput. Biol. 2014; 10e1003728Crossref PubMed Scopus (0) Google Scholar]. protein structure surrounding the interior of the nuclear membrane that supports the structural integrity and shape of the nucleus [154Chandra T. Kirschner K. Chromosome organisation during ageing and senescence.Curr. Opin. Cell Biol. 2016; 40: 161-167Crossref PubMed Scopus (7) Google Scholar]. high-throughput techniques including genomics, proteomics, transcriptomics, metabolomics, and so on. regulatory mechanism in which a protein suffers modifications (such as methylations, phosphorylations, acetylations, shedding, etc.) that affect its function. molecular biology technique used to amplify and detect small amounts of mRNA from a particular protein and to quantify them [161Pfaffl M.W. Relative quantification.in: Dorak T. Real Time PCR. International University, 2006: 63-82Google Scholar]. by-products of mitochondrial respiration [143Passos J.F. et al.Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence.PLoS Biol. 2007; 5: 1138-1151Crossref Scopus (0) Google Scholar]. activity of the β-galactosidase enzyme detectable at pH 6.0 4′,6-diamidino-2-phenylindole (DAPI) intense nuclear foci enriched in repressive epigenetic marks [153Chandra T. et al.Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation.Mol. Cell. 2012; 47: 203-214Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar]. set of molecules secreted by senescent cells. It includes extracellular matrix-remodeling enzymes and inflammatory molecules [3Sharpless N.E. Sherr C.J. Forging a signature of in vivo senescence.Nat. Rev. Cancer. 2015; 15: 397-408Crossref PubMed Scopus (131) Google Scholar]. proteolytic release of the extracellular domain of transmembrane proteins [75Morancho B. et al.Role of ADAM17 in the non-cell autonomous effects of oncogene-induced senescence.Breast Cancer Res. 2015; 17: 106Crossref PubMed Scopus (2) Google Scholar]. increased expression of a gene requiring the presence of another protein called a ‘transactivator’. regulatory mechanism in which the transcription of the gene is either activated or repressed, for instance by transcription factors or repressors. regulatory mechanism in which the translation of an mRNA into protein is either enhanced or reduced. response of the ER against accumulation and aggregation of proteins that occurs as a consequence of multiple factors, such as oxidative stress, mutation, infection, and lack of chaperons [105Pluquet O. et al.The unfolded protein response and cellular senescence. A review in the theme: cellular mechanisms of endoplasmic reticulum stress signaling in health and disease.Am. J. Physiol. Cell Physiol. 2015; 308: C415-C425Crossref PubMed Scopus (37) Google Scholar].
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