biostudies-literatureUnknown6(2)Cefis MFonds de recherche du Quebec SanteNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchAging-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 rCell reports. Medicine101968https://www.ebi.ac.uk/biostudies/studies/S-EPMC11866497biostudies-literatureImpact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca<sup>2+</sup> handling across the adult lifespan in men.PMC11866497Aubertin-Leheudre MMarcangeli VGaudreau PRobitaille RGranet JHuang QGouspillou GHammad RTrumpff CBelanger MCefis MLeduc-Gaudet JPMorais JAPicard MfalseImpact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca<sup>2+</sup> handling across the adult lifespan in men.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 r2025-01-01T00:00:00Z2025 Feb2026-07-15T08:51:19.639Z2025-04-07T07:50:27.862ZS-EPMC118664973993352810.1016/j.xcrm.2025.101968