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Implications of time-series gene expression profiles of replicative senescence

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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE41714 | GEO | 2013/04/24

SECONDARY ACCESSION(S): PRJNA178010

REPOSITORIES: GEO

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Implications of time-series gene expression profiles of replicative senescence

Project description: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 M-NM-2-galactosidase activity (SA-M-NM-2-gal), and high levels of SA-M-NM-2-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. The analysis of time series gene expression level during replicaive senescence.

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Project description:PUVA pretreatment leads to develop early senescence confirmed by p16, p21 and SA-β-GAL positivity which was completely normalised by longer gap. Indicating that PUVA pretreatment causes conditioning set of genes that led to a marked delay in psoriasis development.

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Complement induced aberrant epigenetic modifications in renal tubular epithelial cells and accelerates senescence after kidney transplantation by Wnt pathway

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