title: Extension of replicative lifespan in WI-38 human fibroblasts by dexamethasone treatment is accompanied by suppression of p21 Waf1/Cip1/Sdi1 levels.
abstract: Numerous studies have shown that supplementation of the growth medium of human fibroblasts with dexamethasone at physiologic concentrations extends replicative lifespan up to 30%. While this extension of lifespan has been used to probe various aspects of the senescent phenotype, no mechanism for the increased lifespan of human fibroblasts grown in the presence of dexamethasone has ever been identified. In the present study we present evidence that the extended lifespan of human lung fibroblasts (WI-38 cells) that occurs when these cells are maintained in culture medium supplemented with dexamethasone is accompanied by a suppression of p21(Waf1/Cip1/Sdi1) levels, which normally increase as these cells enter senescence, while p16(INK4a) levels are unaffected. These results suggest that the delay of senescence in cultures grown in the presence of dexamethasone is due to a suppression of the senescence related increase in p21(Waf1/Cip1/Sdi1). These results are consistent with models of replicative senescence in which p53 and p21(Waf1/Cip1/Sdi1) play a role in the establishment of the senescent arrest.
authors.affiliation: Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA.
authors.forename: Madhu
authors.initials: M
authors.lastname: Mawal-Dewan
authors.forename: Lorenza
authors.initials: L
authors.lastname: Frisoni
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Cristofalo
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D003470:Culture Media / Q000737:chemistry; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans
chemical_list: C493956:CDKN1A protein, human; D003470:Culture Media; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D003907:Dexamethasone