Mitochondrial DNA mutations associated with aging and degenerative diseases.

Accumulating evidence has emphasized the role of genetic factors in the development of aging and degenerative diseases. Mitochondrial DNA (mtDNA), that codes for protein subunits essential for the maintenance of mitochondrial ATP synthesis, acquires mutations at a much higher rate than that of nuclear DNA. Recent studies have shown that somatically acquired mutations such as deletions in mtDNA are caused by oxygen damage during the life of an individual. Accumulation of these somatic mutations in postmitotic neuromuscular cells causes bioenergetic deficiency leading to age-associated dysfunction of cells and organs. The base sequencing of the entire mtDNA from individuals revealed that inherited germ-line point mutations accelerate the somatic oxygen damage, and the fragmentation in mtDNA leads to phenotypic expression such as premature aging and degenerative diseases. This article reviews the concept, molecular genetics, pathology, clinical symptoms, diagnosis, and therapy of mitochondrial aging and related diseases.