The superoxide free radical (O(2)(•-)) has been viewed as a likely major contributor to aging. If this is correct, then superoxide dismutase (SOD), which removes O(2)(•-), should contribute to longevity assurance. In Caenorhabditis elegans, overexpression (OE) of the major cytosolic Cu/Zn-SOD, sod-1, increases life span. But is this increase caused by enhanced antioxidant defense? sod-1 OE did not reduce measures of lipid oxidation or glycation and actually increased levels of protein oxidation. The effect of sod-1 OE on life span was dependent on the DAF-16/FoxO transcription factor (TF) and, partially, on the heat shock TF HSF-1. Similarly, overexpression of sod-2 (major mitochondrial Mn-SOD) resulted in life-span extension that was daf-16 dependent. sod-1 OE increased steady-state hydrogen peroxide (H(2)O(2)) levels in vivo. However, co-overexpression of catalase did not suppress the life-span extension, arguing against H(2)O(2) as a cause of longevity. sod-1 OE increased hsp-4 expression, suggesting increased endoplasmic reticulum (ER) stress. Moreover, longevity was partially suppressed by inactivation of ire-1 and xbp-1, mediators of the ER stress response. This suggests that high levels of SOD-1 protein may challenge protein-folding homeostasis, triggering a daf-16- and hsf-1-dependent stress response that extends life span. These findings imply that SOD overexpression increases C. elegans life span, not by removal of O(2)(•-), but instead by activating longevity-promoting transcription factors.
Pubmed ID: 21839827 RIS Download
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View all literature mentionsCaenorhabditis elegans with name wuEx125 [sod-1 gDNA rol-6(su1006)] from WB.
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