It has been proposed that ageing results from the accumulation of mitochondrial DNA mutations with age which interfere with respiratory chain ATP production. Insufficient ATP production impairs cell function, and tissue dysfunction ensues, leading to morbidity, decline and eventually death. Supporting this theory, mitochondrial DNA mutations accumulate with age and respiratory chain function declines dramatically in human skeletal muscle. However, the extent of decline in respiratory chain function is greater (50%) than anticipated from the low levels of mitochondrial DNA mutations (< 1 %) observed in aged muscle. We hypothesized that an age-related reduction in physical activity could be an important factor in this decline and thus studied the influence of chronological age on muscle mitochondria in subjects matched for levels of physical activity. In this carefully selected group, there was little correlation between oxidative metabolism and age. However, several parameters of respiratory chain function did correlate with markers of physical activity (activity score and handgrip strength). Our results suggest that reduced physical activity is a major contribution to the decline in mitochondrial oxidations during ageing. Physical activity ameliorates and may even mask mitochondrial ‘ageing’ in muscle.