Cited by 969Genetics, Aging, and Longevity in Model OrganismsMitochondrial Function and PathologyAutophagy in Disease and Therapy

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A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity

Lee, Siu Sylvia, Lee, Raymond Y.N., Fraser, Andrew G., Kamath, Ravi S., Ahringer, Julie, Ruvkun, Gary·2003·Nature Genetics

DOI 10.1038/ng1056

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Abstract

We report a systematic RNA interference (RNAi) screen of 5,690 Caenorhabditis elegans genes for gene inactivations that increase lifespan. We found that genes important for mitochondrial function stand out as a principal group of genes affecting C. elegans lifespan. A classical genetic screen identified a mutation in the mitochondrial leucyl-tRNA synthetase gene (lrs-2) that impaired mitochondrial function and was associated with longer-lifespan. The long-lived worms with impaired mitochondria had lower ATP content and oxygen consumption, but differential responses to free-radical and other stresses. These data suggest that the longer lifespan of C. elegans with compromised mitochrondria cannot simply be assigned to lower free radical production and suggest a more complex coupling of metabolism and longevity.

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Authors: Lee, S. S., Lee, R. Y. N., Fraser, A. G., Kamath, R. S., Ahringer, J., & Ruvkun, G.
Affiliations: Harvard University (US)
University of Cambridge (GB)
Corresponding author: Ruvkun, Gary
ORCID: Lee, Siu Sylvia
Lee, Raymond Y.N.
Fraser, Andrew G.
Ahringer, Julie
Ruvkun, Gary
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2002-11-25
Volume: 33
Issue: 1
Pages: 40-48
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng1056
OpenAlex: W2155265427
Cited by: 969
References: 47
Citations by year: 2026: 18 · 2025: 20 · 2024: 18 · 2023: 26 · 2022: 34 · 2021: 39 · 2020: 34 · 2019: 30 · 2018: 42 · 2017: 32 · 2016: 40 · 2015: 32 · 2014: 43 · 2013: 26 · 2012: 46
FWCI: 16.56
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust (054523)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: Caenorhabditis elegans, lifespan, longevity, mitochondria, mitochondrial function, leucyl-tRNA synthetase, RNAi screen, ATP levels, oxygen consumption, free radicals, stress response
MeSH terms: Adenosine Triphosphate, Animals, Gene Expression Regulation, Genetic Testing, Leucine-tRNA Ligase, Longevity, Mitochondria, Oxygen Consumption, Stress, Physiological, Caenorhabditis elegans, Genes, Helminth, RNA Interference

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A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity

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