Oxidative energy failure in post-mitotic cells: a major factor in senescence.

A significant decline with age in state III respiration rates has been documented in man and experimental animals in several tissues. Focal areas of cytochrome oxidase negativity, resembling those in skeletal muscle fibres in patients with chronic progressive external ophthalmoplegia (CPEO) syndromes, appear in old age. The mitochondrial genome is susceptible to mutation because of a high turnover rate, ineffective DNA repair mechanisms and a hostile environment rich in free radicals. The available data supports the development of mitochondrial failure in old age in fixed post-mitotic tissues suggesting that mitochondrial failure may be central to the senescent process.