Impact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca2+ handling across the adult lifespan in men

Abstract

Aging-related muscle atrophy and weakness contribute to loss of mobility, falls, and disability. Mitochondrial dysfunction is widely considered a key contributing mechanism to muscle aging. However, mounting evidence positions physical activity as a confounding factor, making unclear whether muscle mitochondria accumulate bona fide defects with aging. To disentangle aging from physical activity-related mitochondrial adaptations, we functionally profiled skeletal muscle mitochondria in 51 inactive and 88 active men aged 20–93. Physical activity status confers partial protection against age-related decline in physical performance. Mitochondrial respiration remains unaltered in active participants, indicating that aging per se does not alter mitochondrial respiratory capacity. Mitochondrial reactive oxygen species (ROS) production is unaffected by aging and higher in active participants. In contrast, mitochondrial calcium retention capacity decreases with aging regardless of physical activity and correlates with muscle mass, performance, and the stress-responsive metabokine/mitokine growth differentiation factor 15 (GDF15). Targeting mitochondrial calcium handling may hold promise for treating aging-related muscle impairments. • Physical activity helps protect against age-related decline in physical performance • Physical activity boosts mitochondrial energetics while aging per se has no impact • Mitochondrial ROS production is unaffected by aging in both active and inactive men • Mitochondrial calcium handling declines with age and is linked to muscle performance Cefis et al. show that mitochondrial respiration and ROS production are not affected during healthy muscle aging but identify altered mitochondrial calcium handling as a potential key driving mechanism. They also highlight physical activity as a powerful stimulus to enhance physical performance and mitochondrial energetics throughout the human adult lifespan.