title: 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 (O(2)(-)) has long been considered a major cause of aging. O(2)(-) 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 O(2)(-) is not a major determinant of aging in C. elegans.
authors.affiliation: Institute of Healthy Ageing and Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Ryan
authors.initials: R
authors.lastname: Doonan
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: McElwee
authors.forename: Filip
authors.initials: F
authors.lastname: Matthijssens
authors.forename: Glenda A
authors.initials: GA
authors.lastname: Walker
authors.forename: Koen
authors.initials: K
authors.lastname: Houthoofd
authors.forename: Patricia
authors.initials: P
authors.lastname: Back
authors.forename: Andrea
authors.initials: A
authors.lastname: Matscheski
authors.forename: Jacques R
authors.initials: JR
authors.lastname: Vanfleteren
authors.forename: David
authors.initials: D
authors.lastname: Gems
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology; D017353:Gene Deletion; D007527:Isoenzymes / Q000502:physiology; D008017:Life Expectancy; D008954:Models, Biological; D018384:Oxidative Stress; D011972:Receptor, Insulin / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D007527:Isoenzymes; D013481:Superoxides; C113846:SOD-4 protein, C elegans; D013482:Superoxide Dismutase; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin