Oxidative stress, mitochondria and mtDNA-mutator mice

The oxidative stress theory of aging, an expansion of the mitochondrial theory of aging, is based around the idea of a vicious cycle, in which somatic mutations of mitochondrial DNA (mtDNA) provoke respiratory chain dysfunction leading to enhanced ROS production and in turn to the accumulation of further mtDNA mutations. Mitochondrial dysfunction and mtDNA mutations are amplified during the course of aging. Recently, results obtained from mtDNA-mutator mice further strengthen the role of mitochondria in the aging process. However, lack of increased oxidative stress in the mtDNA-mutator mice raises doubts in the direct connection of mtDNA mutations with increased ROS production, challenging the oxidative stress theory of aging. The purpose of this short review is to highlight several studies that provide direct evidence that accelerated aging is linked to mtDNA mutations, without an increase in oxidative damage.