title: Superoxide dismutase is dispensable for normal animal lifespan.
abstract: Reactive oxygen species (ROS) are toxic oxygen-containing molecules that can damage multiple components of the cell and have been proposed to be the primary cause of aging. The antioxidant enzyme superoxide dismutase (SOD) is the only eukaryotic enzyme capable of detoxifying superoxide, one type of ROS. The fact that SOD is present in all aerobic organisms raises the question as to whether SOD is absolutely required for animal life and whether the loss of SOD activity will result in decreased lifespan. Here we use the genetic model organism Caenorhabditis elegans to generate an animal that completely lacks SOD activity (sod-12345 worms). We show that sod-12345 worms are viable and exhibit a normal lifespan, despite markedly increased sensitivity to multiple stresses. This is in stark contrast to what is observed in other genetic model organisms where the loss of a single sod gene can result in severely decreased survival. Investigating the mechanism underlying the normal lifespan of sod-12345 worms reveals that their longevity results from a balance between the prosurvival signaling and the toxicity of superoxide. Overall, our results demonstrate that SOD activity is dispensable for normal animal lifespan but is required to survive acute stresses. Moreover, our findings indicate that maintaining normal stress resistance is not crucial to the rate of aging.
authors.affiliation: Department of Biology,  McGill University, Montreal, QC,  Canada H3A 1B1.
authors.forename: Jeremy Michael
authors.initials: JM
authors.lastname: Van Raamsdonk
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hekimi
mesh_terms: D000332:Aerobiosis / Q000187:drug effects; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D005838:Genotype; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000633:toxicity; D016019:Survival Analysis
chemical_list: D013481:Superoxides; D013482:Superoxide Dismutase