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Resources » Paper

McCormick MA et al. (2015) Cell Metab "A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging."

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  • Comments on McCormick MA et al. (2015) Cell Metab "A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging." (0)

  • Overview

    PMID:
    26456335
    DOI:
    10.1016/j.cmet.2015.09.008
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00050035

    McCormick MA, Delaney JR, Tsuchiya M, Tsuchiyama S, Shemorry A, Sim S, Chou AC, Ahmed U, Carr D, Murakami CJ, Schleit J, Sutphin GL, Wasko BM, Bennett CF, Wang AM, Olsen B, Beyer RP, Bammler TK, Prunkard D, Johnson SC, Pennypacker JK, An E, Anies A, Castanza AS, Choi E, Dang N, Enerio S, Fletcher M, Fox L, . . . Kennedy BK (2015). A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging. Cell Metab, 22, 895-906. doi:10.1016/j.cmet.2015.09.008

    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.

    Authors: McCormick MA, Delaney JR, Tsuchiya M, Tsuchiyama S, Shemorry A, Sim S, Chou AC, Ahmed U, Carr D, Murakami CJ, Schleit J, Sutphin GL, Wasko BM, Bennett CF, Wang AM, Olsen B, Beyer RP, Bammler TK, Prunkard D, Johnson SC, Pennypacker JK, An E, Anies A, Castanza AS, Choi E, Dang N, Enerio S, Fletcher M, Fox L, Goswami S, Higgins SA, Holmberg MA, Hu D, Hui J, Jelic M, Jeong KS, Johnston E, Kerr EO, Kim J, Kim D, Kirkland K, Klum S, Kotireddy S, Liao E, Lim M, Lin MS, Lo WC, Lockshon D, Miller HA, Moller RM, Muller B, Oakes J, Pak DN, Peng ZJ, Pham KM, Pollard TG, Pradeep P, Pruett D, Rai D, Robison B, Rodriguez AA, Ros B, Sage M, Singh MK, Smith ED, Snead K, Solanky A, Spector BL, Steffen KK, Tchao BN, Ting MK, Vander Wende H, Wang D, Welton KL, Westman EA, Brem RB, Liu XG, Suh Y, Zhou Z, Kaeberlein M, Kennedy BK


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