Against the oxidative damage theory of aging: Superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans

Abstract

The superoxide radical (O2-) has long been considered a major cause of aging. O2- in cytosolic, extracellular, and mitochondrial pools is detoxified by dedicated superoxide dismutase (SOD) isoforms. We tested the impact of each SOD isoform in Caenorhabditis elegans by manipulating its five sod genes and saw no major effects on life span. sod genes are not required for daf-2 insulin/ IGF-1 receptor mutant longevity. However, loss of the extracellular Cu/ZnSOD sod-4 enhances daf-2 longevity and constitutive diapause, suggesting a signaling role for sod-4. Overall, these findings imply that O2- is not a major determinant of aging in C. elegans. © 2008 by Cold Spring Harbor Laboratory Press.