title: A genomics approach identifies senescence-specific gene expression regulation.
abstract: Replicative senescence is a fundamental tumor-suppressive mechanism triggered by telomere erosion that results in a permanent cell cycle arrest. To understand the impact of telomere shortening on gene expression, we analyzed the transcriptome of diploid human fibroblasts as they progressed toward and entered into senescence. We distinguished novel transcription regulation due to replicative senescence by comparing senescence-specific expression profiles to profiles from cells arrested by DNA damage or serum starvation. Only a small specific subset of genes was identified that was truly senescence-regulated and changes in gene expression were exacerbated from presenescent to senescent cells. The majority of gene expression regulation in replicative senescence was shown to occur due to telomere shortening, as exogenous telomerase activity reverted most of these changes.
authors.affiliation: Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lackner
authors.forename: Makoto T
authors.initials: MT
authors.lastname: Hayashi
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cesare
authors.forename: Jan
authors.initials: J
authors.lastname: Karlseder
mesh_terms: D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D019098:Telomerase / Q000378:metabolism
chemical_list: D019098:Telomerase
keywords: DNA damage; cell cycle; replicative aging; senescence; telomerase expression