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

Nature Genetics

Volumn 33, Issue 1, 2003, Pages 40-48

  Lee, Siu Sylvia ^a   Lee, Raymond Y N ^a,c   Fraser, Andrew G ^b   Kamath, Ravi S ^b   Ahringer, Julie ^b   Ruvkun, Gary ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; FREE RADICAL; LEUCINE TRANSFER RNA LIGASE; OXYGEN; RNA;

ARTICLE; CAENORHABDITIS ELEGANS; CONTROLLED STUDY; GENE FUNCTION; GENE IDENTIFICATION; GENE INACTIVATION; GENE MUTATION; GENETIC SCREENING; LIFESPAN; LONGEVITY; METABOLISM; MITOCHONDRION; NONHUMAN; OXYGEN CONSUMPTION; PRIORITY JOURNAL; STRESS;

ADENOSINE TRIPHOSPHATE; ANIMALS; CAENORHABDITIS ELEGANS; GENE EXPRESSION REGULATION; GENES, HELMINTH; GENETIC SCREENING; LEUCINE-TRNA LIGASE; LONGEVITY; MITOCHONDRIA; OXYGEN CONSUMPTION; RNA INTERFERENCE; STRESS;

CAENORHABDITIS ELEGANS; INVERTEBRATA; NEMATODA;

EID: 0037228016     PISSN: 10614036     EISSN: None     Source Type: Journal    
DOI: 10.1038/ng1056     Document Type: Article

References (46)

1. Rose, M.R. Genetics of aging in Drosophila. Exp. Gerontol. 34, 577-585 (1999).
2. Guarente, L. & Kenyon, C. Genetic pathways that regulate ageing in model organisms. Nature 408, 255-262 (2000).
3. Finch, C.E. Longevity, Senescence, and the Genome (The University of Chicago, Chicago, 1990).
4. Kimura, K.D., Tissenbaum, H.A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942-946 (1997).
5. Kenyon, C., Chang, J., Gensch, E., Rudner, A. & Tabtiang, R. A C elegans mutant that lives twice as long as wild type. Nature 366, 461-464 (1993).
6. Morris, J.Z., Tissenbaum, H.A. & Ruvkun, G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans, Nature 382, 536-539 (1996).
7. Pierce, S.B. et al. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev. 15, 672-686 (2001).
8. Ogg, S. et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994-999 (1997).
9. Lin, K., Dorman, J.B., Rodan, A. & Kenyon, C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278, 1319-1322 (1997).
10. Lakowski, B. & Hekimi, S. The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 95, 13091-13096 (1998).
11. Lakowski, B. & Hekimi, S. Determination of life-span in Caenorhabditis elegans by four clock genes. Science 272, 1010-1013 (1996).
12. Ewbank, JJ. et al. Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1. Science 275, 980-983 (1997).
13. Jonassen, T., Larsen, P.L. & Clarke, C.F. A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants. Proc. Natl. Acad. Sci. USA 98, 421-426 (2001).
14. Ahmed, S., Alpi, A., Hengartner, M.O. & Gartner, A. C. elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein. Curr. Biol. 11, 1934-1944 (2001).
15. Lim, C.S., Mian, I.S., Dernburg, A.F. & Campisi, J. C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p. Curr Biol. 11, 1706-1710 (2001).
16. Benard, C. et al. The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length. Development 128, 4045-4055 (2001).
17. Fraser, A.G. et al. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325-330 (2000).
18. Kamath, R. et al. Systematic functional analysis of the C. elegans genome using RNAi. Nature (in press, 2002).
19. Friedman, D.B. & Johnson, T.E. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118, 75-86 (1988).
20. Tsang, W.Y. & Lemire, B.D. Mitochondrial genome content is regulated during nematode development. Biochem. Biophys. Res. Commun. 291, 8-16 (2002).
21. Lee, R.Y., Hench, J. & Ruvkun, G. Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr. Biol. 11, 1950-1957 (2001).
22. Kelly, W.G., Xu, S., Montgomery, M.K. & Fire, A. Distinct requirements for somatic and germline expression of a generally expressed Caenorhabditis elegans gene. Genetics 146, 227-238 (1997).
23. Tzagoloff, A., Gatti, D. & Gampel, A. Mitochondrial aminoacyl-tRNA synthetases. Prog. Nucleic Acid Res. Mol. Biol. 39, 129-158 (1990).
24. Okimoto, R., Macfarlane, J.L., Clary, D.O. & Wolstenholme, D.R. The mitochondrial genomes of two nematodes, Caenorhabditis elegans and Ascaris suum. Genetics 130, 471-498 (1992).
25. Labrousse, A.M., Zappaterra, M.D., Rube, D.A. & van der Bliek, A.M. C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol. Cell 4, 815-826 (1999).
26. Feng, J., Bussiere, F. & Hekimi, S. Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev. Cell 1, 633-644 (2001).
27. Hekimi, S., Lakowski, B., Barnes, T.M. & Ewbank, J.J. Molecular genetics of life span in C. elegans: How much does it teach us? Trends Genet. 14, 14-20 (1998).
28. Pearl, R. The Rate of Living (University of London Press, London, 1928).
29. Finkel, T. & Holbrook, N.J. Oxidants, oxidative stress and the biology of ageing. Nature 408, 239-247 (2000).
30. Lithgow, G.J., White, T.M., Melov, S. & Johnson, T.E. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc. Natl. Acad. Sci. USA 92, 7540-7544 (1995).
31. Honda, Y. & Honda, S. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 13, 1385-1393 (1999).
32. Larsen, P.L. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 90, 8905-8909 (1993).
33. Kumar, A. et al. Subcellular localization of the yeast proteome. Genes Dev. 16, 707-719 (2002).
34. Tsang, W.Y., Sayles, L.C., Grad, L.I., Pilgrim, D.B. & Lemire, B.D. Mitochondrial respiratory chain deficiency in Caenorhabditis elegans results in developmental arrest and increased life span. J. Biol. Chem. 276, 32240-32246 (2001).
35. Maechler, P. & Wollheim, CB. Mitochondrial function in normal and diabetic βcells. Nature 414, 807-812 (2001).
36. Wallace, D.C. Mitochondrial diseases in man and mouse. Science 283, 1482-1488 (1999).
37. Griparic, L. & van der Bliek, A.M. The many shapes of mitochondrial membranes. Traffic 2, 235-244 (2001).
38. Paumard, P. et al. The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J. 21, 221-230 (2002).
39. Senoo-Matsuda, N. et al. A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans. J. Biol. Chem. 276, 41553-41558 (2001).
40. Osiewacz, H.D. Genes, mitochondria and aging in filamentous fungi. Ageing Res. Rev. 1, 425-442 (2002).
41. Kirchman, P.A., Kim, S., Lai, C.Y. & Jazwinski, S.M. Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae. Genetics 152, 179-190 (1999).
42. Jazwinski, S.M. New clues to old yeast. Mech. Ageing Dev. 122, 865-882 (2001).
43. Vanfleteren, J.R. & Braeckman, B.P. Mechanisms of life span determination in Caenorhabditis elegans. Neurobiol. Aging 20, 487-502 (1999).
44. Lin, S.J. et al. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418, 344-348 (2002).
45. Rogina, B., Reenan, R.A., Nilsen, S.P. & Helfand, S.L. Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290, 2137-2140 (2000).
46. Braeckman, B.P., Houthoofd, K., De Vreese, A. & Vanfleteren, J.R. Assaying metabolic activity in ageing Caenorhabditis elegans. Mech. Ageing Dev. 123, 105-119 (2002).