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

• Published in: Experimental gerontology Vol. 43; no. 6; pp. 520 - 529
• Main Authors: Honda, Yoko, Tanaka, Masashi, Honda, Shuji
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.06.2008
• Subjects: Animals; Base Sequence; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Dauer formation; Deletion mutant; Gene Deletion; Gene Expression Regulation, Developmental; Insulin - metabolism; Insulin-Like Growth Factor I - metabolism; Insulin-like signaling; Late-progeny production; Lifespan-extension mutant; Longevity; Longevity - genetics; Longevity - physiology; Metamorphosis, Biological - genetics; MnSOD; Molecular Sequence Data; Mutation; Oxidative Stress; Oxidative-stress resistance; Parasitology - methods; Redox regulation; RNA Interference; Signal Transduction - genetics; Superoxide Dismutase - genetics; Superoxide Dismutase-1; Oxidative-stress resistance; Caenorhabditis elegans; Insulin-like signaling; Lifespan-extension mutant; Redox regulation; MnSOD; Longevity; Dauer formation; Late-progeny production; Deletion mutant
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2008.02.009

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.