Levels and location are crucial in determining the effect of ROS on lifespan

Abstract

Reactive oxygen species (ROS) cause molecular damage that accumulates with age and have been proposed to be one of the primary causes of aging. However, recent work indicates that ROS have beneficial roles in an organism and that the relationship between ROS and aging is complex. We have shown that increasing ROS levels or oxidative damage does not necessarily lead to decreased lifespan. We have also shown that in some cases increasing ROS can promote longevity. Further investigation of the factors that determine the effect of ROS on lifespan demonstrate that both the levels and location of ROS are important in predicting the impact of ROS on longevity. Increasing superoxide levels in the cytoplasm results in decreased lifespan, while increasing superoxide levels in the mitochondria leads to increased lifespan. Within the mitochondria, mild elevation of superoxide levels promote longevity, while high levels of superoxide are toxic. Thus, a new paradigm is emerging in which ROS are neither good nor bad but levels and location makes it so.