Reference Report

Reference
Citation	Sun, X., Komatsu, T., Lim, J., Laslo, M., Yolitz, J., Wang, C., Poirier, L., Alberico, T., Zou, S. (2012). Nutrient-dependent requirement for SOD1 in lifespan extension by protein restriction in Drosophila melanogaster. Aging Cell 11(5): 783--793. (Export to RIS)
FlyBase ID	FBrf0219634
Publication Type	Research paper
PubMed ID	22672579
PubMed Abstract	Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low-sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low-calorie diets both reduced target of rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly, rapamycin decreased lifespan in sod1 mutant but not wild-type males fed the standard, HS-LP, and low-calorie diets, whereas antioxidant N-acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions.
DOI	10.1111/j.1474-9726.2012.00842.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 (8)
	foxo²¹ foxo²⁵ Scer\GAL4^cad-md509 Scer\GAL4^da.G32 Scer\GAL4^da.Switch.PT Sod^{dsRNA.Scer\UAS.cHa} Sodⁿ¹ Sod^Scer\UAS.cAa
Constructs (4)
	P{da-GSGAL4.T} P{GAL4-da.G32} P{UAS-Sod.A} P{UAS-Sod.IR}
Genes (12)
	Acon ade3 Cat foxo Irp-1A Irp-1B Pepck Prx2540-2 S6k Scer\GAL4 Sod Sod2
Insertions (1)
	P{GawB}cad^md509