Mitochondrial DNA mutation associated with aging and degenerative disease.
P Nagley, IR Mackay, A Baumer, RJ Maxwell, F Vaillant, ZX Wang, C Zhang, AW Linnane
Ann N Y Acad Sci | Published : 1992
Previous theories of aging based on somatic mutation neglected mtDNA, which has a high propensity for mutational error. Knowledge of yeast mtDNA mutations and their functional effects, and of human mtDNA mutations identified in the mitochondrial cytopathies, provides for a concept of aging based on the cumulative effect of mutations affecting human mtDNA. An essential feature of this concept is heteroplasmy, representing mixtures of normal and mutant mtDNA at the cellular and mitochondrial level, resulting in a "tissue mosaic" of focal bioenergetic deficits. Direct evidence for the concept is provided by (i) focal loss of staining for mitochondrially encoded enzymes, such as cytochrome c oxi..View full abstract