Modulation of longevity and diapause by redox regulation mechanisms under the insulin-like signaling control in Caenorhabditis elegans.
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.
Honda
Yoko
Y
Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashiku, Tokyo 173-0015, Japan.
Tanaka
Masashi
M
Honda
Shuji
S
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008675:Metamorphosis, Biological / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress; D010274:Parasitology / Q000379:methods; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2