Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: an age-related alteration.

Cytochrome c oxidase (complex IV of the respiratory chain) was studied histochemically in human limb muscle (n = 109) and diaphragm (n = 115) obtained at autopsy revealing randomly distributed muscle fibres without enzyme activity. The defects were present both in normal type I and type II fibres and in ragged red like fibres with increased content of mitochondria. In both organs an age associated manifestation of the defect was observed. First defects occurred sporadically in the 3rd and 4th decade, but were present from the 6th to 9th decade in 66-83% of the limb muscles and 75-100% of the diaphragms. Also the number of defects/cm2 (defect density) increased with age from approx. 5, and 7 in limb muscle and diaphragm below the 6th decade to 54 and 60 defects in the 8th-9th decade (P = 0.000). Between both muscles no statistically significant difference in defect density (P greater than 0.15) existed. Irrespective of the defect density the defect typically affected isolated fibres showing normal histochemical reactivity for succinate dehydrogenase (complex II). The results indicate that cytochrome c oxidase deficient muscle fibres in normal skeletal muscle represent an age related phenomenon which probably results from cellular ageing and might be involved in the reduction of muscle mass and strength during senescence.