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A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging

Mark A. McCormick, Joe R. Delaney, Mitsuhiro Tsuchiya, Scott Tsuchiyama, Anna Shemorry, Sylvia Sim, Annie Chou, Umema Ahmed, Daniel Carr, Christopher J. Murakami, Jennifer Schleit, George L. Sutphin, Brian M. Wasko, Christopher F. Bennett, Adrienne M. Wang

Cell Metabolism · 2015 · ▲ 269 citations

Genomic instability Deregulated nutrient-sensing Caloric restriction Rapamycin / mTOR inhibition Yeast C. elegans
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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 mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">Rapamycin(definition) (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.

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OpenAlex
DOI
10.1016/j.cmet.2015.09.008
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2026-06-13 MST

Cite this

APA
McCormick, M.A., Delaney, J.R., Tsuchiya, M., Tsuchiyama, S., Shemorry, A., Sim, S., Chou, A., Ahmed, U., Carr, D., Murakami, C.J., Schleit, J., Sutphin, G.L., Wasko, B.M., Bennett, C.F., Wang, A.M., Olsen, B., Beyer, R.P., Bammler, T.K., Prunkard, D., &amp; Johnson, S.C. (2015). A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging. <em>Cell Metabolism</em>. https://doi.org/10.1016/j.cmet.2015.09.008
Vancouver
McCormick MA, Delaney JR, Tsuchiya M, Tsuchiyama S, Shemorry A, Sim S, et al. A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging. Cell Metabolism. 2015. doi:10.1016/j.cmet.2015.09.008.
BibTeX
@article{mark2015ACompr, title = {A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging}, author = {Mark A. McCormick and Joe R. Delaney and Mitsuhiro Tsuchiya and Scott Tsuchiyama and Anna Shemorry and Sylvia Sim and Annie Chou and Umema Ahmed and Daniel Carr and Christopher J. Murakami and Jennifer Schleit and George L. Sutphin and Brian M. Wasko and Christopher F. Bennett and Adrienne M. Wang and Brady Olsen and Richard P. Beyer and Theodor K. Bammler and Donna Prunkard and Simon C. Johnson and Juniper K. Pennypacker and Elroy H. An and Arieanna C. Anies and Anthony S. Castanza and Eunice Choi}, journal = {Cell Metabolism}, year = {2015}, doi = {10.1016/j.cmet.2015.09.008}, }

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