Open AccessRapamycin decreases DNA damage accumulation and enhances cell growth of WRN ‐deficient human fibroblasts
Author(s) -
Saha Bidisha,
Cypro Alexander,
Martin George M.,
Oshima Junko
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12190
Subject(s) - werner syndrome , genome instability , biology , autophagy , dna damage , microbiology and biotechnology , premature aging , somatic cell , dna repair , gene knockdown , mutation , cell growth , phenotype , helicase , dna , gene , cancer research , genetics , apoptosis , rna
Summary Werner syndrome (WS), caused by mutations at the WRN helicase gene, is a progeroid syndrome characterized by multiple features consistent with accelerated aging. Aberrant double‐strand DNA damage repair leads to genomic instability and reduced replicative lifespan of somatic cells. We observed increased autophagy in WRN knockdown cells; this was further increased by short‐term rapamycin treatment. Long‐term rapamycin treatment resulted in improved growth rate, reduced accumulation of DNA damage foci and improved nuclear morphology; autophagy markers were reduced to near‐normal levels, possibly due to clearance of damaged proteins. These data suggest that protein aggregation plays a role in the development of WS phenotypes and that the mammalian target of rapamycin complex 1 pathway is a potential therapeutic target of WS.