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Implications of time-series gene expression profiles of replicative senescence.

Authors
Kim, YM; Byun, HO; Jee, BA; Cho, H; Seo, YH; Kim, YS; Chung, HY; Woo, HG; Yoon, G
Citation
Aging cell, 12(4):622-634, 2013
Journal Title
Aging cell
ISSN
1474-97181474-9726
Abstract
Although senescence has long been implicated in aging-associated pathologies, it is not clearly understood how senescent cells are linked to these diseases. To address this knowledge gap, we profiled cellular senescence phenotypes and mRNA expression patterns during replicative senescence in human diploid fibroblasts. We identified a sequential order of gain-of-senescence phenotypes: low levels of reactive oxygen species, cell mass/size increases with delayed cell growth, high levels of reactive oxygen species with increases in senescence-associated β-galactosidase activity (SA-β-gal), and high levels of SA-β-gal activity. Gene expression profiling revealed four distinct modules in which genes were prominently expressed at certain stages of senescence, allowing us to divide the process into four stages: early, middle, advanced, and very advanced. Interestingly, the gene expression modules governing each stage supported the development of the associated senescence phenotypes. Senescence-associated secretory phenotype-related genes also displayed a stage-specific expression pattern with three unique features during senescence: differential expression of interleukin isoforms, differential expression of interleukins and their receptors, and differential expression of matrix metalloproteinases and their inhibitory proteins. We validated these phenomena at the protein level using human diploid fibroblasts and aging Sprague-Dawley rat skin tissues. Finally, disease-association analysis of the modular genes also revealed stage-specific patterns. Taken together, our results reflect a detailed process of cellular senescence and provide diverse genome-wide information of cellular backgrounds for senescence.
MeSH terms
Animals*Cell AgingCell CycleCell DeathCell SizeDiploidyEnzyme ActivationFibroblasts/cytology/enzymology/*metabolismGene Expression RegulationHumansInterleukins/genetics/metabolismMatrix Metalloproteinase 12/genetics/metabolismPhenotypeRatsRats, Sprague-DawleyReactive Oxygen Species/metabolismTime Factors*Transcriptomebeta-Galactosidase/genetics/metabolism
DOI
10.1111/acel.12087
PMID
23590226
Appears in Collections:
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
변, 해옥김, 유선우, 현구윤, 계순
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