Drosophila germ-line modulation of insulin signaling and lifespan.

Authors: Flatt T; Min KJ; D'Alterio C; Villa-Cuesta E; Cumbers J; Lehmann R; Jones DL; Tatar M

Abstract: Ablation of germ-line precursor cells in Caenorhabditis elegans extends lifespan by activating DAF-16, a forkhead transcription factor (FOXO) repressed by insulin/insulin-like growth factor (IGF) signaling (IIS). Signals from the gonad might thus regulate whole-organism aging by modulating IIS. To date, the details of this systemic regulation of aging by the reproductive system are not understood, and it is unknown whether such effects are evolutionarily conserved. Here we report that eliminating germ cells (GCs) in Drosophila melanogaster increases lifespan and modulates insulin signaling. Long-lived germ-line-less flies show increased production of Drosophila insulin-like peptides (dilps) and hypoglycemia but simultaneously exhibit several characteristics of IIS impedance, as indicated by up-regulation of the Drosophila FOXO (dFOXO) target genes 4E-BP and l (2)efl and the insulin/IGF-binding protein IMP-L2. These results suggest that signals from the gonad regulate lifespan and modulate insulin sensitivity in the fly and that the gonadal regulation of aging is evolutionarily conserved.

Keywords: Animals; Drosophila Proteins/genetics/metabolism; Drosophila melanogaster/genetics/*metabolism; Female; Gene Expression Regulation; Genes, Insect; Germ Cells/cytology/*metabolism; Insulin/*metabolism; *Longevity; Male; Ovary/cytology; RNA, Messenger/genetics/metabolism; Signal Transduction; Testis/cytology
Journal: Proceedings of the National Academy of Sciences of the United States of America
Volume: 105
Issue: 17
Pages: 6368-73
Date: April 25, 2008
PMID: 18434551
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Citation:

Flatt T, Min KJ, D'Alterio C, Villa-Cuesta E, Cumbers J, Lehmann R, Jones DL, Tatar M (2008) Drosophila germ-line modulation of insulin signaling and lifespan. Proceedings of the National Academy of Sciences of the United States of America 105: 6368-73.


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