Present addresses: M. Giannakou, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. M. Goss, Biochemical Pharmacology, William Harvey Research Institute, Charterhouse Square, London, EC1M 6BQ, UK.
dFOXO-independent effects of reduced insulin-like signaling in Drosophila
Article first published online: 6 MAY 2011
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland
Volume 10, Issue 5, pages 735–748, October 2011
How to Cite
Slack, C., Giannakou, M. E., Foley, A., Goss, M. and Partridge, L. (2011), dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Aging Cell, 10: 735–748. doi: 10.1111/j.1474-9726.2011.00707.x
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
- Issue published online: 14 SEP 2011
- Article first published online: 6 MAY 2011
- Accepted manuscript online: 28 MAR 2011 01:01PM EST
- Accepted for publication 20 March 2011
- insulin signaling
The insulin/insulin-like growth factor-like signaling (IIS) pathway in metazoans has evolutionarily conserved roles in growth control, metabolic homeostasis, stress responses, reproduction, and lifespan. Genetic manipulations that reduce IIS in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse have been shown not only to produce substantial increases in lifespan but also to ameliorate several age-related diseases. In C. elegans, the multitude of phenotypes produced by the reduction in IIS are all suppressed in the absence of the worm FOXO transcription factor, DAF-16, suggesting that they are all under common regulation. It is not yet clear in other animal models whether the activity of FOXOs mediate all of the physiological effects of reduced IIS, especially increased lifespan. We have addressed this issue by examining the effects of reduced IIS in the absence of dFOXO in Drosophila, using a newly generated null allele of dfoxo. We found that the removal of dFOXO almost completely blocks IIS-dependent lifespan extension. However, unlike in C. elegans, removal of dFOXO does not suppress the body size, fecundity, or oxidative stress resistance phenotypes of IIS-compromised flies. In contrast, IIS-dependent xenobiotic resistance is fully dependent on dFOXO activity. Our results therefore suggest that there is evolutionary divergence in the downstream mechanisms that mediate the effects of IIS. They also imply that in Drosophila, additional factors act alongside dFOXO to produce IIS-dependent responses in body size, fecundity, and oxidative stress resistance and that these phenotypes are not causal in IIS-mediated extension of lifespan.