Association of mitochondrial oxidative capacity with physical fitness in ageing: the Baltimore longitudinal study of ageing

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Abstract

Background: In younger individuals, fitness is mostly influenced by muscle mitochondrial oxidative phosphorylation (OxPhos) and cardiac output. However, compared with younger individuals, various impairments may also negatively affect fitness in older adults. Objective: To investigate the relationship of OxPhos with cardiorespiratory fitness, the energetic cost of walking and aerobic resilience with respect to age. Design: Cross-sectional. Setting: Population. Subjects: Six hundred and forty-nine Baltimore longitudinal study of ageing participants (mean age 64.5 years, 56.9% females). Methods: Muscle mitochondrial OxPhos was measured as phosphocreatine recovery rate (kPCr) through 31P magnetic resonance spectroscopy. Based on age- and sex-specific kPCr z-scores, we classified individuals with low (≤ −0.5 standard deviations [SD]), average (−0.5 to 0.5SD) and high (>0.5SD) OxPhos. Cardiorespiratory fitness was measured as peak oxygen consumption (MVO2 peak) during a treadmill testing. The energetic cost of usual pace walking was expressed as the average oxygen consumption per 100 metres. Aerobic resilience was the ratio between MVO2 peak and average VO2 during usual pace walking. Results: Participants with higher kPCr had 4.07 (95%CI: 2.88, 5.26) ml/kg/min higher MVO2 peak and 0.19 (95%CI: 0.06, 0.32) higher aerobic resilience than those with lower kPCr. The energetic cost of walking was greater by 0.84 (95% CI: 0.21, 1.47) ml/kg/100 m in those with high than low kPCr. A multiplicative interaction between age and kPCr was identified in the regressions predicting MVO2 peak and aerobic resilience (pinteraction = 0.01), with differences between OxPhos groups attenuating after age 70. Conclusion: Muscle mitochondrial OxPhos contributes to interindividual variability in cardiorespiratory fitness, especially in young and middle adulthood.

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Trevisan, C., Tian, Q., Fishbein, K. W., Church, S., Simonsick, E. M., Egan, J. M., … Ferrucci, L. (2026). Association of mitochondrial oxidative capacity with physical fitness in ageing: the Baltimore longitudinal study of ageing. Age and Ageing, 55(2). https://doi.org/10.1093/ageing/afag022

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