dFOXO-independent effects of reduced insulin-like signaling in drosophila

Cathy Slack, Maria E. Giannakou, Andrea Foley, Martin Goss, Linda Partridge

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish
Pages735-748
Number of pages14
JournalAging Cell
Volume10
Issue number5
Early online date14 Sep 2011
DOIs
Publication statusPublished - Oct 2011

Fingerprint

Caenorhabditis elegans
Drosophila
Body Size
Insulin
Phenotype
Diptera
Fertility
Oxidative Stress
Physiological Stress
Somatomedins
Xenobiotics
Drosophila melanogaster
Reproduction
Fruit
Homeostasis
Transcription Factors
Animal Models
Alleles
Growth

Bibliographical note

Re‐use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

Keywords

  • Aging
  • Drosophila
  • FOXO
  • Insulin signaling

Cite this

Slack, Cathy ; Giannakou, Maria E. ; Foley, Andrea ; Goss, Martin ; Partridge, Linda. / dFOXO-independent effects of reduced insulin-like signaling in drosophila. In: Aging Cell. 2011 ; Vol. 10, No. 5. pp. 735-748.
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dFOXO-independent effects of reduced insulin-like signaling in drosophila. / Slack, Cathy; Giannakou, Maria E.; Foley, Andrea; Goss, Martin; Partridge, Linda.

In: Aging Cell, Vol. 10, No. 5, 10.2011, p. 735-748.

Research output: Contribution to journalArticle

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