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Citation
Zheng, X., Yang, Z., Yue, Z., Alvarez, J.D., Sehgal, A. (2007). FOXO and insulin signaling regulate sensitivity of the circadian clock to oxidative stress.  Proc. Natl. Acad. Sci. U.S.A. 104(40): 15899--15904.
FlyBase ID
FBrf0216135
Publication Type
Research paper
Abstract

Circadian rhythms can be regulated by many environmental and endogenous factors. We show here a sensitivity of circadian clock function to oxidative stress that is revealed in flies lacking the foxo gene product. When exposed to oxidative stress, wild-type flies showed attenuated clock gene cycling in peripheral tissues, whereas foxo mutants also lost behavioral rhythms driven by the central clock. FOXO is expressed predominantly in the fat body, and transgenic expression in this tissue rescued the mutant behavioral phenotype, suggesting that foxo has non-cell-autonomous effects on central circadian clock function. Overexpression of signaling molecules that affect FOXO activity, such as the insulin receptor or Akt, in the fat body also increased susceptibility of the central clock to oxidative stress. Finally, foxo mutants showed a rapid decline in rest:activity rhythms with age, supporting the idea that the increase of oxidative stress contributes to age-associated degeneration of behavioral rhythms and indicating the importance of FOXO in mitigating this deterioration. Together these data demonstrate that metabolism affects central clock function and provide a link among insulin signaling, oxidative stress, aging, and circadian rhythms.

PubMed ID
PubMed Central ID
PMC2000406 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Aberrations (2)
    Alleles (11)
    Genes (8)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (7)