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.
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.
Doonan
Ryan
R
Institute of Healthy Ageing and Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom.
McElwee
Joshua J
JJ
Matthijssens
Filip
F
Walker
Glenda A
GA
Houthoofd
Koen
K
Back
Patricia
P
Matscheski
Andrea
A
Vanfleteren
Jacques R
JR
Gems
David
D
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*
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