title: Redox regulation, gene expression and longevity.
abstract: 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.
authors.affiliation: Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. yhonda@center.tmig.or.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Honda
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Shuji
authors.initials: S
authors.lastname: Honda
mesh_terms: 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
chemical_list: 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