Premium
No Increase in Senescence‐Associated β‐Galactosidase Activity in Werner Syndrome Fibroblasts after Exposure to H 2 O 2
Author(s) -
MAGALHÃES JOÃO PEDRO,
MIGEOT VALÉRIE,
MAINFROID VÉRONIQUE,
LONGUEVILLE FRANÇOISE,
REMACLE JOSÉ,
TOUSSAINT OLIVIER
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1297.066
Subject(s) - senescence , fibroblast , werner syndrome , in vitro , hydrogen peroxide , oxidative stress , in vivo , chemistry , microbiology and biotechnology , andrology , biology , medicine , biochemistry , genetics , rna , helicase , gene
A bstract : Normal human diploid fibroblasts (HDFs) exposed to a single H 2 O 2 subcytotoxic stress display features of premature senescence, termed stress‐induced premature senescence (SIPS). In this work, our aim was to study SIPS in Werner syndrome (WS) fibroblasts, derived from a patient with WS, a disease resembling accelerated aging. The subcytotoxic dose for WS fibroblasts was found to be inferior to that of normal HDFs, indicating WS fibroblasts are more sensitive to hydrogen peroxide than normal HDFs. SA β‐gal activity has been shown to occur both in vitro and in vivo , and we studied the proportion of WS cells positive for SA β‐gal. Intriguingly, the percentage of positive cells did not increase with the dose of H 2 O 2 used. Contrary to other HDFs, the DNA‐binding activity of p53 in WS fibroblasts did not increase in SIPS. We found, based on our results, that WS fibroblasts feature an altered stress response and do not reach SIPS from H 2 O 2 . We suggest that the proportion of cells that in normal HDFs would enter SIPS instead die in WS fibroblasts. Last, we propose that aging derives from a loss of integrity of the chromatin structure, which occurs faster in WS patients.