Respiratory chain failure in adult muscle fibres: relationship with ageing and possible implications for the neuronal pool.

A histochemical analysis of mitochondrial enzyme activity was carried out in 103 human diaphragmatic skeletal muscles from 49 subjects of different ages, obtained either at the time of abdominal surgery or at necropsy. Evidence of respiratory failure (cytochrome oxidase negativity) was seen in occasional fibres from the fourth decade on with an approximate 10-fold increase between the fourth and ninth decade (0.16% to 2.85%). A similar incidence of mitochondrial failure in CNS neurones to that documented in skeletal muscle could easily account for attrition of 25% of neurones over a 50-year period as reported in the literature. Possible theoretical relationships between morphological markers of mitochondrial failure and cell attrition are explored. While the projections from muscle to neurone are somewhat speculative, it is clear that if a similar extent of mitochondrial pathology exists in the brain to that documented in skeletal muscle, this could easily account for neuronal loss in the ageing brain.