Drosophila germ-line modulation of insulin signaling and lifespan

doi:10.1073/pnas.0709128105

Drosophila germ-line modulation of insulin signaling and lifespan

^†Division of Biology and Medicine, Department of Ecology and Evolutionary Biology, Brown University, Box G-W, Providence, RI 02912;
^‡Department of Biological Sciences, University of Alaska, Anchorage, AK 99508;
^§The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 N. Torrey Pines Road, La Jolla, CA 92037; and
^¶Howard Hughes Medical Institute, Developmental Genetics Program, Skirball Institute of Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, New York, NY 10016

Edited by Allan C. Spradling, Carnegie Institution of Washington, Baltimore, MD, and approved March 6, 2008 (received for review September 25, 2007)

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.

Footnotes

^‖To whom correspondence should be addressed. E-mail: marc_tatar{at}brown.edu
Author contributions: T.F., R.L., D.L.J., and M.T. designed research; T.F., K.-J.M., C.D., E.V.-C., J.C., and D.L.J. performed research; R.L. and D.L.J. contributed new reagents/analytic tools; T.F. analyzed data; and T.F., R.L., D.L.J., and M.T. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0709128105/DCSupplemental.