ArticleCell metabolism2015
A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging.
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Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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160citing papers in PubMed
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160 citing papers in PubMed, 266 citations in OpenAlex.
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- Overexpression of Ssd1 and calorie restriction extend yeast replicative lifespan by preventing deleterious age-dependent iron uptake.bioRxiv : the preprint server for biology · 2025Article
- Design principles of gene circuits for longevity.Trends in cell biology · 2025Review
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- Qarles: a web server for the quick characterization of large sets of genes.NAR genomics and bioinformatics · 2025Article
- Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species.Aging cell · 2025Article
- Disturbances in cell wall biogenesis as a key factor in the replicative aging of budding yeast.Biogerontology · 2025Article
- The core genetic drivers of chronological aging in yeast are universal regulators of longevity.Microbial cell (Graz, Austria) · 2025Article
- Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics.npj aging · 2024Review
- The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging.Nature communications · 2024Article
- Lifespan regulation by targeting heme signaling in yeast.GeroScience · 2024Article
100 more citing papers are in PubMed but not listed here.
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Authors and funding
81 authors at 5 institutions in 3 countries.
Mark A McCormickBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Joe R DelaneyDepartment of Pathology, University of Washington, Seattle, WA 98195, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Mitsuhiro TsuchiyaBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Scott TsuchiyamaBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Anna ShemorryDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Sylvia SimDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Annie Chia-Zong ChouDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Umema AhmedDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Daniel CarrDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Christopher J MurakamiDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Jennifer SchleitDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
George L SutphinDepartment of Pathology, University of Washington, Seattle, WA 98195, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Brian M WaskoDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Christopher F BennettDepartment of Pathology, University of Washington, Seattle, WA 98195, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Adrienne M WangDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Brady OlsenDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Richard P BeyerDepartment of Occupational and Environmental Health Sciences, University of Washington, Seattle, WA 98195, USA.
Theodor K BammlerDepartment of Occupational and Environmental Health Sciences, University of Washington, Seattle, WA 98195, USA.
Donna PrunkardDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Simon C JohnsonDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Juniper K PennypackerBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Elroy AnDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Arieanna AniesBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Anthony S CastanzaDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Eunice ChoiDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Nick DangDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Shiena EnerioBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Marissa FletcherDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Lindsay FoxDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Sarani GoswamiDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Sean A HigginsDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Molly A HolmbergMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Di HuMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Jessica HuiDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Monika JelicMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Ki-Soo JeongDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Elijah JohnstonDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Emily O KerrDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Jin KimMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Diana KimMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Katie KirklandDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Shannon KlumDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Soumya KotireddyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Eric LiaoMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Michael LimMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Michael S LinDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Winston C LoMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Dan LockshonBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Hillary A MillerDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Richard M MollerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Brian MullerMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Jonathan OakesMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Diana N PakDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Zhao Jun PengMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Kim M PhamDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Tom G PollardMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Prarthana PradeepMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Dillon PruettMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Dilreet RaiMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Brett RobisonBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Ariana A RodriguezBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Bopharoth RosMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Michael SageMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Manpreet K SinghMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Erica D SmithDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Katie SneadMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Amrita SolankyMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Benjamin L SpectorMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Kristan K SteffenDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Bie Nga TchaoDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Marc K TingBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Helen Vander WendeDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Dennis WangMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
K Linnea WeltonDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Eric A WestmanDepartment of Pathology, University of Washington, Seattle, WA 98195, USA.
Rachel B BremBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Xin-Guang LiuAging Research Institute, Guangdong Medical College, Dongguan 523808, Guangdong, P.R. China.
Yousin SuhAging Research Institute, Guangdong Medical College, Dongguan 523808, Guangdong, P.R. China; Department of Genetics, Albert Einstein College of Medicine, New York, NY 10461, USA.
Zhongjun ZhouDepartment of Biochemistry, University of Hong Kong, Hong Kong.
Matt KaeberleinDepartment of Pathology, University of Washington, Seattle, WA 98195, USA. Electronic address: kaeber@uw.edu.
Brian K KennedyBuck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: bkennedy@buckinstitute.org.
University of Washington · USBuck Institute for Research on Aging · USAlbert Einstein College of Medicine · USGuangdong Medical College · CNUniversity of Hong Kong · HK
Funding
SPECIFICITY OF OXYGEN DNA DAMAGE AND MUTAGENESISP01AG001751 · NIA · UNIVERSITY OF WASHINGTON · PI PRUSKY, GLEN THOMAS · 1985 to 2021
$29.6MUniversity of Washington Nathan Shock Center of Excellence in the Basic Biology of AgingP30AG013280 · NIA · UNIVERSITY OF WASHINGTON · PI Michael MacCoss · 1995 to 2026
$27.1MTRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0MGENETIC APPROACHES TO AGING RESEARCHT32AG000057 · NIA · UNIVERSITY OF WASHINGTON · PI RABINOVITCH, PETER S · 1985 to 2019
$14.2MTraining in Basic Research on Aging and Age-Related DiseaseT32AG000266 · NIA · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Lisa M Ellerby · 1998 to 2026
$13.8MEnvironmetal Pathology/Toxicology Training ProgramT32ES007032 · NIEHS · UNIVERSITY OF WASHINGTON · PI FAUSTMAN, ELAINE M, ROSENFELD, MICHAEL E · 1985 to 2023
$10.7MSystem approaches to determine mechanisms underlying yeast replicative agingR01AG043080 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI KENNEDY, BRIAN K · 2012 to 2016
$3.0MDefining the Mechanisms of genotype-dependent responses to caloric restrictionR01AG039390 · NIA · UNIVERSITY OF WASHINGTON · PI KAEBERLEIN, MATT · 2011 to 2015
$1.5MGenome-wide Analysis of Aging in YeastR01AG025549 · NIA · UNIVERSITY OF WASHINGTON · PI KENNEDY, BRIAN K · 2006 to 2010
$1.5MNIA NIH HHS P01 AG001751NIA NIH HHS P30 AG013280NIA NIH HHS P30AG013280NIA NIH HHS R01 AG025549NIA NIH HHS R01AG025549NIA NIH HHS R01 AG039390NIA NIH HHS R01AG039390NIA NIH HHS R01 AG043080NIA NIH HHS R01AG043080NIA NIH HHS T32 AG000057NIA NIH HHS T32AG000057NIA NIH HHS T32 AG000266NIA NIH HHS T32AG000266NIEHS NIH HHS T32 ES007032NIEHS NIH HHS T32ES007032NIGMS NIH HHS T32 GM007270
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.
Indexed as
AgingAnimalsBasic-Leucine Zipper Transcription FactorsCaenorhabditis elegansCaloric RestrictionDNA DamageGene DeletionGene Expression RegulationGenomeLongevityNuclear Pore Complex ProteinsRNA, TransferSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTOR Serine-Threonine KinasesBasic-Leucine Zipper Transcription FactorsGCN4 protein, S cerevisiaeLos1 protein, S cerevisiaeNuclear Pore Complex ProteinsRNA, TransferSaccharomyces cerevisiae ProteinsTOR Serine-Threonine Kinases
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