title: Drosophila germ-line modulation of insulin signaling and lifespan.
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.
authors.affiliation: Division of Biology and Medicine, Department of Ecology and Evolutionary Biology, Brown University, Box G-W, Providence, RI 02912, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Flatt
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Min
authors.forename: Cecilia
authors.initials: C
authors.lastname: D'Alterio
authors.forename: Eugenia
authors.initials: E
authors.lastname: Villa-Cuesta
authors.forename: John
authors.initials: J
authors.lastname: Cumbers
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehmann
authors.forename: D Leanne
authors.initials: DL
authors.lastname: Jones
authors.forename: Marc
authors.initials: M
authors.lastname: Tatar
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D017344:Genes, Insect; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008136:Longevity; D008297:Male; D010053:Ovary / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013737:Testis / Q000166:cytology
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D012333:RNA, Messenger