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PMID: 18434551 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Drosophila germ-line modulation of insulin signaling and lifespan.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 17 ·2008-04-29 ·Pages 6368-73

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.

MeSH Terms
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
Chemicals
Drosophila Proteins Insulin RNA, Messenger
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Flatt Thomas
Division of Biology and Medicine, Department of Ecology and Evolutionary Biology, Brown University, Box G-W, Providence, RI 02912, USA.
Min Kyung-Jin
D'Alterio Cecilia
Villa-Cuesta Eugenia
Cumbers John
Lehmann Ruth
Jones D Leanne
Tatar Marc
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0709128105
Published
2008-04-29
Epub
2008-00-23
Pages
6368-73
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2359818
Subset
IM
Grants
NIA NIH HHS · R37 AG024360 · United States
NIA NIH HHS · R01 AG021953 · United States
NIA NIH HHS · R01 AG024360 · United States
Howard Hughes Medical Institute · United States
NIA NIH HHS · AG021953 · United States
NIA NIH HHS · AG024360 · United States
NIA NIH HHS · R01 AG028092 · United States
External Links
PubMed source DOI: 10.1073/pnas.0709128105 PMC Full Text View journal details
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