| Literature DB >> 26456335 |
Mark A McCormick1, Joe R Delaney2, Mitsuhiro Tsuchiya1, Scott Tsuchiyama1, Anna Shemorry3, Sylvia Sim3, Annie Chia-Zong Chou3, Umema Ahmed3, Daniel Carr3, Christopher J Murakami3, Jennifer Schleit3, George L Sutphin2, Brian M Wasko3, Christopher F Bennett2, Adrienne M Wang3, Brady Olsen3, Richard P Beyer4, Theodor K Bammler4, Donna Prunkard3, Simon C Johnson3, Juniper K Pennypacker1, Elroy An3, Arieanna Anies1, Anthony S Castanza3, Eunice Choi3, Nick Dang3, Shiena Enerio1, Marissa Fletcher3, Lindsay Fox5, Sarani Goswami3, Sean A Higgins3, Molly A Holmberg6, Di Hu6, Jessica Hui3, Monika Jelic6, Ki-Soo Jeong3, Elijah Johnston3, Emily O Kerr3, Jin Kim6, Diana Kim6, Katie Kirkland3, Shannon Klum3, Soumya Kotireddy5, Eric Liao6, Michael Lim6, Michael S Lin3, Winston C Lo6, Dan Lockshon1, Hillary A Miller3, Richard M Moller5, Brian Muller6, Jonathan Oakes6, Diana N Pak5, Zhao Jun Peng6, Kim M Pham5, Tom G Pollard6, Prarthana Pradeep6, Dillon Pruett6, Dilreet Rai6, Brett Robison1, Ariana A Rodriguez1, Bopharoth Ros6, Michael Sage6, Manpreet K Singh6, Erica D Smith5, Katie Snead6, Amrita Solanky6, Benjamin L Spector6, Kristan K Steffen3, Bie Nga Tchao3, Marc K Ting1, Helen Vander Wende3, Dennis Wang6, K Linnea Welton3, Eric A Westman3, Rachel B Brem1, Xin-Guang Liu7, Yousin Suh8, Zhongjun Zhou9, Matt Kaeberlein10, Brian K Kennedy11.
Abstract
Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging.Entities:
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Year: 2015 PMID： 26456335 PMCID： PMC4862740 DOI： 10.1016/j.cmet.2015.09.008
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287