Drosophila germ-line modulation of insulin signaling and lifespan

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 d...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-04, Vol.105 (17), p.6368-6373
Main Authors: Flatt, Thomas, Min, Kyung-Jin, D'Alterio, Cecilia, Villa-Cuesta, Eugenia, Cumbers, John, Lehmann, Ruth, Jones, D. Leanne, Tatar, Marc
Format: Article
Language:English
Subjects:
Aging
Animals
Biological Sciences
Caenorhabditis elegans
Cellular biology
Drosophila
Drosophila melanogaster
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Female
females
Gene Expression Regulation
gene induction
Genes, Insect
Germ cells
Germ Cells - cytology
Germ Cells - metabolism
Gonads
hormonal regulation
Insulin
Insulin - metabolism
insulin-like growth factor binding proteins
insulin-like growth factor I
insulin-like growth factor II
insulin-like peptides
Longevity
Male
mutants
Nematodes
Neurons
Ovary - cytology
Peptides
phenotype
Proteins
Receptors
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction
Somatic cells
Stem cells
Testis - cytology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0709128105