Author(s): Mawal-Dewan M; Frisoni L; Cristofalo VJ; Sell C

Title: Extension of replicative lifespan in WI-38 human fibroblasts by dexamethasone treatment is accompanied by suppression of p21(Waf1/Cip1/Sdi1) levels

Source: EXPERIMENTAL CELL RESEARCH 285 (1): 91-98

Date: 2003 APR 15

Document Type: Journal : Article

DOI: 10.1016/S0014-4827(03)00013-2

Language: English

LCR: 19   CR: 28   LCS: 1   GCS: 7   SCS: 

Comment:  

Address: Lankenau Inst Med Res, Wynnewood, PA 19096 USA.

Reprint: Sell, C, Lankenau Inst Med Res, 100 Lancaster Ave, Wynnewood, PA 19096
USA.

E-mail:  

Author Keywords: senescence; dexamethasone; p21; p16; p53; lifespan

KeyWords Plus: HUMAN-DIPLOID FIBROBLASTS; SENESCENT HUMAN-FIBROBLASTS; DEPENDENT KINASE INHIBITOR; CELLULAR SENESCENCE; DNA-SYNTHESIS; HUMAN-CELLS; EXPRESSION; SPAN; COLLAGENASE; FEATURES

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. (C) 2003 Elsevier Science (USA). All rights reserved.