Rapamycin decreases DNA damage accumulation and enhances cell growth of WRN-deficient human fibroblasts
Article first published online: 5 FEB 2014
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 3, pages 573–575, June 2014
How to Cite
Saha, B., Cypro, A., Martin, G. M. and Oshima, J. (2014), Rapamycin decreases DNA damage accumulation and enhances cell growth of WRN-deficient human fibroblasts. Aging Cell, 13: 573–575. doi: 10.1111/acel.12190
- Issue published online: 23 MAY 2014
- Article first published online: 5 FEB 2014
- Accepted manuscript online: 6 DEC 2013 05:56AM EST
- Manuscript Accepted: 30 NOV 2013
- NIH. Grant Number: R24CA78088/R24AG042328
- Ellison Medical Foundation
- American Heart Association
- DNA damage;
- mammalian target of rapamycin;
- Werner syndrome
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.