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Multiple-stress analysis for isolation of Drosophila longevity genes

Wang, Horng-Dar and Kazemi-Esfarjani, Parsa and Benzer, Seymour (2004) Multiple-stress analysis for isolation of Drosophila longevity genes. Proceedings of the National Academy of Sciences of the United States of America, 101 (34). pp. 12610-12615. ISSN 0027-8424. PMCID PMC515105.

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Long-lived organisms tend to be more resistant to various forms of environmental stress. An example is the Drosophila longevity mutant, methuselah, which has enhanced resistance to heat, oxidants, and starvation. To identify genes regulated by these three stresses, we made a cDNA library for each by subtraction of "unstressed" from "stressed" cDNA and used DNA hybridization to identify genes that are regulated by all three. This screen indeed identified 13 genes, some already known to be involved in longevity, plus candidate genes. Two of these, hsp26 and hsp27, were chosen to test for their effects on lifespan by generating transgenic lines and by using the upstream activating sequence/GAL4 system. Overexpression of either hsp26 or hsp27 extended the mean lifespan by 30%, and the flies also displayed increased stress resistance. The results demonstrate that multiple-stress screening can be used to identify new longevity genes.

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Additional Information:© 2004 by the National Academy of Sciences. Contributed by Seymour Benzer, July 6, 2004. Published online before print August 12, 2004, 10.1073/pnas.0404648101 We thank members of the Benzer laboratory, including P. Kapahi, T. Brummel, D. Walker, D. Tracey, and B. Al-Ansi, for helpful discussions and comments on the manuscript. We are grateful for technical support from T. Gill, G. Kwan, C. Lai, P. Karayan, A. Lam, A. Dinh, U. Zimmermann, J. Silverlake, R. Young, and V. Sapin. We also thank A. Cameron and E. Davidson for use of the California Institute of Technology Genome Technology facility. This work was supported by a National Research Service Award from the National Institute of Aging (Grant AG05890 to H.-D.W.), grants from Hereditary Disease Foundation and the Wills Foundation (to P.K.-E.), and grants to S.B. from the National Institutes of Health (Grant AG16630), the National Science Foundation (Grant MCB-9907939), and the Ellison Foundation.
Funding AgencyGrant Number
NIH Predoctoral FellowshipAG05890
Hereditary Disease FoundationUNSPECIFIED
Wills FoundationUNSPECIFIED
Ellison Medical FoundationUNSPECIFIED
Subject Keywords:aging, heat-shock proteins hsp26 and hsp27, chaperones, paraquat, starvation, life-span extension, C-dependent activation, heat-shock proteins, caenorhabditis-elegans, oxidative stress, extended life, cytochrome-C, polyglutamine toxicity, superoxide-dismutase, paraquat resistance
Issue or Number:34
PubMed Central ID:PMC515105
Record Number:CaltechAUTHORS:WANpnas04b
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1132
Deposited By: Tony Diaz
Deposited On:22 Dec 2005
Last Modified:02 Oct 2019 22:40

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