The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
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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In the citing paper
“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]
Citations
Cites
Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413
Systematic functional analysis of the Caenorhabditis elegans genome using RNAi
Kamath, R. S., Fraser, A. G., Yan, D., Poulin, G. B., Durbin, R. M., Gotta, M., Kanapin, A. A., Bot, N. L., Moreno, S., Sohrmann, M., et al. (2003) · Nature · doi:10.1038/nature01278 · Cited by 3,618
Self-citationA C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060
Kimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997) · Science · doi:10.1126/science.277.5328.942 · Cited by 2,250
Self-citationOgg, S., Paradis, S., Gottlieb, S., Patterson, G. I., Lee, L., Tissenbaum, H. A., & Ruvkun, G. (1997) · Nature · doi:10.1038/40194 · Cited by 1,935
Self-citationFunctional genomic analysis of C. elegans chromosome I by systematic RNA interference
Fraser, A. G., Kamath, R. S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M., & Ahringer, J. (2000) · Nature · doi:10.1038/35042517 · Cited by 1,720
Self-citationLin, K., Dorman, J. B., Rodan, A. R., & Kenyon, C. J. (1997) · Science · doi:10.1126/science.278.5341.1319 · Cited by 1,501
Longevity, senescence and the genome
(1995) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(95)90026-8 · Cited by 1,403
Genetic pathways that regulate ageing in model organisms
Guarente, L., & Kenyon, C. J. (2000) · Nature · doi:10.1038/35041700 · Cited by 1,337
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Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185
Broken Limits to Life Expectancy
Oeppen, J., & Vaupel, J. W. (2002) · Science · doi:10.1126/science.1069675 · Cited by 2,819
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease
Tönnies, E., & Trushina, E. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161088 · Cited by 1,750
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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