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A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity
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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“Unexpectedly, reduced mitochondrial function can, in some circumstances, increase lifespan.”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [36]
In the citing paper
“Paradoxically, it is the impairment of mitochondrial function and associated lower ATP levels that prolongs lifespan in worms (Dillin et al., 2002; Lee et al., 2003).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Lee et al., 2003
In the citing paper
“an unbiased search for genes that extend lifespan has identified a disproportionate number of genes that function in mitochondrial metabolism(273)”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [273]
In the citing paper
“By contrast, knockdown experiments that target other components of the electron transport chain, including essential elements of complexes I, III and IV, lead to lifespan extension in worms 99, 100 .”
From The common biology of cancer and ageing (2007) · cites this paper as [100]
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Metadata
- 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
- Venue
- Nature Genetics
- Published
- 2002-11-25
- Volume
- 33
- Issue
- 1
- Pages
- 40-48
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- 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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