MtDNA mutations, functional decline and turnover of mitochondria in aging.

Aging is a complex biological process that involves gradual function deterioration in various tissues and organs of an individual. Mitochondrial function decline can lead to cellular overproduction of reactive oxygen species (ROS) and increase in oxidative damage to biological molecules in the aging process. We have hypothesized that increased production of ROS by the mitochondria in affected tissues in patients with mitochondrial diseases and elderly subject results in increased oxidative stress and oxidative damage. Due to the similarity of human aging process to diseases related to bioenergetic function decline and mitochondrial DNA (mtDNA) alterations, aging is sometimes viewed as a "chronic" version of such diseases. Recent studies have also established that the expression profiles of several clusters of genes are altered, oxidative modification of proteins are increased and their turnover are decreased in tissues of old human subjects and animals. Accumulating evidence has suggested that mtDNA mutations, oxidative stress, defective disposal of dysfunctional proteins and a slower turnover of mitochondria are associated with aging.