Authors: Honda, Yoko; Tanaka, Masashi; Honda, Shuji
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.
Keywords: Adaptation, Physiological; Aging/physiology; Animals; Caenorhabditis elegans/radiation effects; Caenorhabditis elegans Proteins/physiology; Gene Expression Regulation/*physiology; Humans; Hyperoxia; Larva; Longevity/*physiology; Mutation; Oligonucleotide Array Sequence Analysis; Oxidative Stress/*physiology; Receptor, IGF Type 1/physiology; Superoxide Dismutase/physiology; Transcription Factors/physiology|
Journal: Geriatr Gerontol Int Volume: 10 Suppl 1 Pages: S59-69 Date: July 16, 2010 PMID: 20590843 |
Honda, Yoko, Tanaka, Masashi, Honda, Shuji (2010) Redox regulation, gene expression and longevity. Geriatr Gerontol Int 10 Suppl 1: S59-69.
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