Reference Report

Reference
Citation	Slack, C., Giannakou, M.E., Foley, A., Goss, M., Partridge, L. (2011). dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Aging Cell 10(5): 735--748. (Export to RIS)
FlyBase ID	FBrf0215229
Publication Type	Research paper
PubMed ID	21443682
PubMed 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.
DOI	10.1111/j.1474-9726.2011.00707.x
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Aging Cell
Title	Aging Cell
Publication Year	2002-
ISBN/ISSN	1474-9718 1474-9728
Data from Reference
Alleles (19)
	chico¹ foxo²¹ foxo²⁵ foxo^BG01018 foxo^{Scer\UAS.P\T.cSa} foxo^W24 foxo^Δ94 Ilp2¹ Ilp3¹ Ilp5¹ InR^{K1409A.Scer\UAS} Lnk^Del29 Pi3K92E^{D954A.Scer\UAS.T:Hsap\MYC} rpr^Scer\UAS.C Scer\GAL4^da.G32 Scer\GAL4^da.Switch.PT Scer\GAL4^ey.PH Scer\GAL4^Ilp3.PB Scer\GAL4^{mat.αTub67C.T:Hsim\VP16}
Constructs (9)
	P{da-GSGAL4.T} P{Dp110^D954A} P{GAL4-da.G32} P{GAL4-ey.H} P{Ilp3-Gal4.B} P{matα4-GAL-VP16} P{UAS-InR.K1409A} P{UASp-foxo.S} P{UAS-rpr.C}
Genes (12)
	chico foxo Ilp2 Ilp3 Ilp5 InR Lnk Pi3K92E rpr Scer\GAL4 Thor Yp2
Insertions (2)
	P{GT1}foxo^BG01018 P{lacW}foxo^W24
Natural transposons (1)
	P-element