Redox regulation, gene expression and longevity.
Lifespan can be lengthened by genetic and environmental modifications. Study of these might provide valuable insights into the mechanism of aging. Low doses of radiation and short-term exposure to heat and high concentrations of oxygen prolong the lifespan of the nematode Caenorhabditis elegans. These might be caused by adaptive responses to harmful environmental conditions. Single-gene mutations have been found to extend lifespan in C. elegans, Drosophila and mice. So far, the best-characterized system is the C. elegans mutant in the daf-2, insulin/IGF-I receptor gene that is the component of the insulin/IGF-I signaling pathway. The mutant animals live twice as long as the wild type. The insulin/IGF-I signaling pathway regulates the activity of DAF-16, a FOXO transcription factor. However, the unified explanation for the function of DAF-16 transcription targets in the lifespan extension is not yet fully established. As both of the Mn superoxide dismutase (MnSOD) isoforms (sod-2 and sod-3) are found to be targets of DAF-16, we attempted to assess their functions in regulating lifespan and oxidative stress responsivity. We show that the double deletions of sod-2 and sod-3 genes induced oxidative-stress sensitivity but do not shorten lifespan in the daf-2 mutant background, indicating that oxidative stress is not necessarily a limiting factor for longevity. Furthermore, the deletion in the sod-3 gene lengthens lifespan in the daf-2 mutant. We conclude that the MnSOD systems in C. elegans fine-tune the insulin/IGF-I-signaling based regulation of longevity by acting not as anti-oxidants but as physiological-redox-signaling modulators.
Honda
Yoko
Y
Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. yhonda@center.tmig.or.jp
Tanaka
Masashi
M
Honda
Shuji
S
D000222:Adaptation, Physiological; D000375:Aging / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018496:Hyperoxia; D007814:Larva; D008136:Longevity / Q000502:physiology*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000502:physiology; D013482:Superoxide Dismutase / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D000099156:Superoxide Dismutase 2
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D017526:Receptor, IGF Type 1; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C108831:daf-16 protein, C elegans; C525107:Sod-3 protein, C elegans