A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging
- McCormick, Mark A.
- Delaney, Joe R.
- Tsuchiya, Mitsuhiro
- Tsuchiyama, Scott
- Shemorry, Anna
- Sim, Sylvia
- Chou, Annie Chia-Zong
- Ahmed, Umema
- Carr, Daniel
- Murakami, Christopher J.
- Schleit, Jennifer
- Sutphin, George L.
- Wasko, Brian M.
- Bennett, Christopher F.
- Wang, Adrienne M.
- Olsen, Brady
- Beyer, Richard P.
- Bammler, Theodor K.
- Prunkard, Donna
- Johnson, Simon C.
- Pennypacker, Juniper K.
- An, Elroy
- Anies, Arieanna
- Castanza, Anthony S.
- Choi, Eunice
- Dang, Nick
- Enerio, Shiena
- Fletcher, Marissa
- Fox, Lindsay
- Goswami, Sarani
- Higgins, Sean A.
- Holmberg, Molly A.
- Hu, Di
- Hui, Jessica
- Jelic, Monika
- Jeong, Ki-Soo
- Johnston, Elijah
- Kerr, Emily O.
- Kim, Jin
- Kim, Diana
- Kirkland, Katie
- Klum, Shannon
- Kotireddy, Soumya
- Liao, Eric
- Lim, Michael
- Lin, Michael S.
- Lo, Winston C.
- Lockshon, Dan
- Miller, Hillary A.
- Moller, Richard M.
- Muller, Brian
- Oakes, Jonathan
- Pak, Diana N.
- Peng, Zhao Jun
- Pham, Kim M.
- Pollard, Tom G.
- Pradeep, Prarthana
- Pruett, Dillon
- Rai, Dilreet
- Robison, Brett
- Rodriguez, Ariana A.
- Ros, Bopharoth
- Sage, Michael
- Singh, Manpreet K.
- Smith, Erica D.
- Snead, Katie
- Solanky, Amrita
- Spector, Benjamin L.
- Steffen, Kristan K.
- Tchao, Bie Nga
- Ting, Marc K.
- Vander Wende, Helen
- Wang, Dennis
- Welton, K. Linnea
- Westman, Eric A.
- Brem, Rachel B.
- Liu, Xin-guang
- Suh, Yousin
- Zhou, Zhongjun
- Kaeberlein, Matt
- Kennedy, Brian K.
DOIAbstract
SummaryMany 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 LOS...
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