Oxidative stress and aging--the use of superoxide dismutase/catalase mimetics to extend lifespan.

To date, more than 40 genes have been identified in the nematode Caenorhabditis elegans, which, when mutated, lead to an increase in lifespan. Of those tested, all confer an increased resistance to oxidative stress. In addition, the lifespan of C. elegans can also be extended by the administration of synthetic superoxide dismutase/catalase mimetics. These compounds also appear to confer resistance to oxidative damage, since they protect against paraquat treatment. The protective effects of these compounds are apparent with treatment during either development or adulthood. These findings have demonstrated that pharmacological intervention in the aging process is possible and that these compounds can provide important information about the underlying mechanisms. To date, such interventions have targeted known processes rather than screening compound libraries because of the limitations of assessing lifespan in nematodes. However, we have recently developed a microplate-based assay that allows for a rapid and objective score of nematode survival at rates many times higher than previously possible. This system now provides the opportunity to perform high-throughput screens for compounds that affect nematode survival in the face of acute oxidative stress and will facilitate the identification of novel drugs that extend nematode lifespan.