Author Summary Top
An unequivocal demonstration that mitochondria are important for lifespan comes from studies with the nematode Caenorhabditis elegans. Mutations in mitochondrial proteins such as ISP-1 and NUO-6, which function directly in mitochondrial electron transport, lead to a dramatic increase in the lifespan of this organism. One theory proposes that toxicity of mitochondrial reactive oxygen species (ROS) is the cause of aging and predicts that the generation of the ROS superoxide should be low in these mutants. Here we have measured superoxide generation in these mutants and found that it is in fact elevated, rather than reduced. Furthermore, we found that this elevation is necessary and sufficient for longevity, as it is abolished by antioxidants and induced by mild treatment with oxidants. This suggests that superoxide can act as a signal triggering cellular changes that attenuate the effects of aging. This idea suggests a new model for the well-documented correlation between ROS and the aged phenotype. We propose that a gradual increase of molecular damage during aging triggers a concurrent, gradually intensifying, protective superoxide response.
This strikes me as pretty earth-shaking in the world of aging research, since the former putative cause of aging, namely oxygen radicals, are seen in this experiment as inducing longevity rather than aging. The free radical theory of aging looks defeated.
This also makes sense of some phenomena such as hormesis as well as the fact that antioxidant supplements seem to promote aging. Exercise also fits into this scenario, since it increases generation of reactive oxygen species yet promotes longevity (or retards aging, however you want to look at it).