Misexpression screen delineates novel genes controlling Drosophila lifespan

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In an initial preliminary screen we identified factors associated with controlling Drosophila aging by examining longevity in adults where EP elements induced over-expression or antisense-RNA at genes adjacent to each insertion. Here, we study 45 EP lines that initially showed at least 10% longer mean lifespan than controls. These 45 lines and a daughterless (da)-Gal4 stock were isogenized into a CS10 wild-type background. Sixteen EP lines corresponding to 15 genes significantly extended lifespan when their target genes were driven by da-Gal4. In each case, the target genes were seen to be over-expressed. Independently derived UAS-gene transgenic stocks were available or made for two candidates: ImpL2 which is ecdysone-inducible gene L2, and CG33138, 1,4-alpha-glucan branching enzyme. With both, adult lifespan was increased upon over-expression via the GeneSwitch inducible Gal4 driver system. Several genes in this set of 15 correspond to previously discovered longevity assurance systems such as insulin/IGF-1 signaling, gene silencing, and autophagy; others suggest new potential mechanisms for the control of aging including mRNA synthesis and maturation, intracellular vesicle trafficking, and neuroendocrine regulation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Publisher
ELSEVIER IRELAND LTD
Issue Date
2012-05
Language
English
Article Type
Article
Keywords

STRESS RESISTANCE; ALZHEIMER-DISEASE; EXTENDED LIFE; MOUSE MODEL; C-ELEGANS; MELANOGASTER; INSULIN; LONGEVITY; PROTEIN; SYSTEM

Citation

MECHANISMS OF AGEING AND DEVELOPMENT, v.133, no.5, pp.234 - 245

ISSN
0047-6374
DOI
10.1016/j.mad.2012.02.001
URI
http://hdl.handle.net/10203/104573
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