Oxygen damage and mutations in mitochondrial DNA associated with aging and degenerative diseases

This article reviews the theory and molecular genetics of mitochondrial aging and diseases. Mitochondrial DNA (mtDNA) that codes protein subunits essential for the maintenance of the mitochondrial ATP synthesis system located in the inner membrane acquires mutations at a much higher rate than nuclear DNA. Recent study clarifies somatically acquired mutations such as deletions in mtDNA caused by oxygen damage during the life of an individual. Cumulative accumulation of these somatic mutations in postmitotic neuromuscular cells causes bionenergetic deficit leading to age-associated dysfunction of cells and organs. The base-sequencing of the entire mtDNA from individuals revealed that germ-line point mutations transmitted from the ancestor accelerate the somatic oxygen damage and the fragmentation in mtDNA leading to phenotypic expression as premature aging and degenerative diseases.