Modulation of longevity and diapause by redox regulation mechanisms under the insulin-like signaling control in Caenorhabditis elegans.

Authors: Honda Y; Tanaka M; Honda S

Abstract: In Caenorhabditis elegans, the downregulation of insulin-like signaling induces lifespan extension (Age) and the constitutive formation of dauer larvae (Daf-c). This also causes resistance to oxidative stress (Oxr) and other stress stimuli and enhances the expression of many stress-defense-related enzymes such as Mn superoxide dismutase (SOD) that functions to remove reactive oxygen species in mitochondria. To elucidate the roles of the two isoforms of MnSOD, SOD-2 and SOD-3, in the Age, Daf-c and Oxr phenotypes, we investigated the effects of a gene knockout of MnSODs on them in the daf-2 (insulin-like receptor) mutants that lower insulin-like signaling. In our current report, we demonstrate that double deletions of two MnSOD genes induce oxidative-stress sensitivity and thus ablate Oxr, but do not abolish Age in the daf-2 mutant background. This indicates that Oxr is not the underlying cause of Age and that oxidative stress is not necessarily a limiting factor for longevity. Interestingly, deletions in the sod-2 and sod-3 genes suppressed and stimulated, respectively, both Age and Daf-c. In addition, the sod-2/sod-3 double deletions stimulated these phenotypes in a similar manner to the sod-3 deletion, suggesting that the regulatory pathway consists of two MnSOD isoforms. Furthermore, hyperoxic and hypoxic conditions affected Daf-c in the MnSOD-deleted daf-2 mutants. We thus conclude that the MnSOD systems in C. elegans fine-tune the insulin-like-signaling based regulation of both longevity and dauer formation by acting not as antioxidants but as physiological-redox-signaling modulators.

Keywords: Animals; Base Sequence; Caenorhabditis elegans/genetics/*metabolism; Caenorhabditis elegans Proteins/genetics/*metabolism; Gene Deletion; *Gene Expression Regulation, Developmental; Insulin/metabolism; Insulin-Like Growth Factor I/metabolism; Longevity/genetics/*physiology; Metamorphosis, Biological/genetics; Molecular Sequence Data; Mutation; Oxidative Stress; Parasitology/methods; RNA Interference; Signal Transduction/genetics; Superoxide Dismutase/genetics
Journal: Experimental gerontology
Volume: 43
Issue: 6
Pages: 520-9
Date: April 15, 2008
PMID: 18406553
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Citation:

Honda Y, Tanaka M, Honda S (2008) Modulation of longevity and diapause by redox regulation mechanisms under the insulin-like signaling control in Caenorhabditis elegans. Experimental gerontology 43: 520-9.


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