2.11. MODEL FOR MITOCHONDRIAL DISEASE AND AGING
These considerations suggest that mitochondrial disease and aging may be closely related processes, the time course of which is determined by the individual's initial bioenergetic genotype (Fig. 2.1). If the individual's mitochondrial genotype is good, then he will start with a high bioenergetic capacity at birth, but if his genotype incorporates a deleterious mutation, then he will start at a lower energetic capacity, though still above tissue energetic thresholds and free of clinical symptoms. As the individual ages, ROS from the mitochondria will continue to damage the mtDNA resulting in somatic mutations. As the mitochondrial bioenergetic capacity declines, this further increases ROS production and the mtDNA mutation rate. Ultimately, the mitochondrial energy capacity is no longer sufficient to sustain normal tissue function, the organs begin to fail, and ultimately the individual dies.
This hypothesis predicts that antioxidants such as MnTBAP might inhibit ROS damage to the mtDNA and other macromolecules, thus slowing the progression of mitochondrial energy decline. If so, then such drugs may not only help treat mitochondrial disease patients but also may ameliorate some of the worst ravages of the aging process.