Defects of the respiratory chain in various tissues of old monkeys: a cytochemical-immunocytochemical study

The aim of the present study was to evaluate if defects of the respiratory chain known to occur in humans, also exist in lower primates. Cytochemical-immunocytochemical studies of the respiratory chain enzymes in five monkeys (10-25 years of age) showed defects of ubiquinone cytochrome-c-oxidoreductase (complex III), of cytochrome-c-oxidase (complex IV) and of ATP-synthase (complex V) in the limb muscles, diaphragm, heart muscle and extraocular muscles of three old animals (about 25 years) and also in the heart muscle of two younger animals (10 and 15 years). Characteristically, the defects were randomly distributed and there was no loss of succinate-dehydrogenase (complex II) in the fibres. Ultracytochemistry-immunocytochemistry of complex IV disclosed that in an involved fibre segment all the mitochondria exhibited the defect. The highest number of defects was observed in the extraocular muscle (up to 340/cm2) while the lowest defect density was present in the limb muscles (2-5/cm2). Defects of complex IV occurred two to three times more often than defects of complex III and besides isolated defects of complex III and IV, combined defects of both complexes were also observed. Defects of complex V occurred exclusively in combination and were rarely seen. Using subunit specific antisera against complex IV, it could be demonstrated at light and electron microscopic level that loss of activity of cytochrome-c-oxidase was associated with a loss both of mitochondrially and nuclearly coded subunits of the enzyme. In summary, aging in lower primates and humans is characterised by a highly similar defect expression of the respiratory chain enzymes, with intercellular and interorgan differences of the aging process, underlining the universal nature of the involved pathogenetic mechanisms.