Mechanisms underlying age-related changes in the human skeletal muscle bioenergetic system

Purpose: To determine which age-related alterations in muscle bioenergetic system parameters could explain variability between different experimental studies concerning changes in muscle fatigability and bioenergetics comparing young and old groups during all-out (AOE) knee-extension (KE) exercise. Methods: A computer model of the skeletal muscle bioenergetic system involving the each-step activation (ESA) mechanism of oxidative phosphorylation (OXPHOS) regulation during work transitions and the Pi_peak-P_i-distance mechanism of muscle fatigue in AOE was used. Results: Differences between young and old individuals can be explained by changes in only three parameter values: a reduction in the maximal ATP usage activity (A_UTref, proportional to the maximal power), a fall in OXPHOS activity (k_OX), and changes in Pi_peak, the peak P_i at which task failure occurs in constant power-exercise (CPE) and which is approached asymptotically by P_i in AOE. Fatigability decreases with ageing when k_OX declines less than A_UTref, whereas fatigability increases when k_OX declines more than A_UTref and/or Pi_peak increases. The model also demonstrates that phosphocreatine (PCr) recovery kinetics are not only influenced by k_OX, but also more strongly by the ESA decay kinetics after exercise termination. Conclusions: These findings provide a mechanistic framework within which to interpret the often inconsistent findings in the literature concerning ageing and skeletal muscle fatigability using only a few parameter values, although the contribution of other factors cannot be excluded. Older muscle behaves to a large extent like significantly detrained muscle, highlighting the role of physical activity and training in improving muscle performance and delaying fatigue with ageing.