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

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dc.contributor.authorWasko, Brian
dc.date.accessioned2020-10-20T15:25:12Z
dc.date.available2020-10-20T15:25:12Z
dc.date.issued2015
dc.description.abstractMany 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 non-additive 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.en_US
dc.identifier.citationMcCormick, Mark A et al. “A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging.” Cell metabolism vol. 22,5 (2015): 895-906. doi:10.1016/j.cmet.2015.09.008en_US
dc.identifier.urihttps://hdl.handle.net/10657.1/2531
dc.publisherCell Metaben_US
dc.subjectS. cerevisiae, lifespan, aging, los1, tRNA transport, Rad53, mTORen_US
dc.titleA Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Agingen_US
dc.typeArticleen_US

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Brian Wasko