P38 (MAPK) stress signalling in replicative senescence in fibroblasts from progeroid and genomic instability syndromes.

ABSTRACT: Werner Syndrome (WS) is a human segmental progeria resulting from mutations in a DNA helicase. WS fibroblasts have a shortened replicative capacity, an aged appearance, and activated p38 MAPK, features that can be modulated by inhibition of the p38 pathway. Loss of the WRNp RecQ helicase has been shown to result in replicative stress, suggesting that a link between faulty DNA repair and stress-induced premature cellular senescence may lead to premature ageing in WS. Other progeroid syndromes that share overlapping pathophysiological features with WS also show defects in DNA processing, raising the possibility that faulty DNA repair, leading to replicative stress and premature cellular senescence, might be a more widespread feature of premature ageing syndromes. We therefore analysed replic

SUBMITTER: Tivey HS 

PROVIDER: S-EPMC3627027 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature