Progressive loss of cytochrome c oxidase in the human extraocular muscles in ageing--a cytochemical-immunohistochemical study.

Cytochrome c oxidase (complex IV of the respiratory chain) was studied histochemically in autoptic human extraocular muscles (n = 135), revealing randomly distributed single fibers without enzyme activity. The enzyme defect was expressed in all the mitochondria of an involved fiber as evidenced by ultracytochemistry. Succinate dehydrogenase showed normal histochemical reactivity. The defects occurred already in the second decade and were regularly seen from the third decade on. The defect density (defects/mm2) increased from approx. 1/mm2 below the fifth decade to about 4/mm2 in advanced age (P = 0.000). The highest defect density was observed in the levator palpebrae muscle. On the whole, the defect density was about 5-6 times higher in the extraocular muscles than in the limb muscle, diaphragm and heart (Müller-Höcker, 1989, 1990). Immunocytochemical detection of cytochrome c oxidase showed that loss of cytochrome c oxidase activity was due to an almost complete absence of both nuclear and mitochondria subunits of the enzyme. The results document different organ and heterogenic cellular sensitivity to the age-related loss of cytochrome c oxidase. The loss of both mitochondrial and nuclear subunits indicates that nuclear factors are most probably involved in the decline of the respiratory chain function in senescence.