Bioenergetic basis for the increased fatigability with ageing

The mechanisms for the age-related increase in fatigability during dynamic exercise remain elusive. We tested whether age-related impairments in muscle oxidative capacity would result in a greater accumulation of fatigue causing metabolites, inorganic phosphate (P_i ), hydrogen (H⁺ ) and diprotonated phosphate (H₂ PO₄^- ), in the muscle of old compared to young adults during a dynamic knee extension exercise. The age-related increase in fatigability (reduction in mechanical power) of the knee extensors was closely associated with a greater accumulation of metabolites within the working muscle but could not be explained by age-related differences in muscle oxidative capacity. These data suggest that the increased fatigability in old adults during dynamic exercise is primarily determined by age-related impairments in skeletal muscle bioenergetics that result in a greater accumulation of metabolites.

The present study aimed to determine whether the increased fatigability in old adults during dynamic exercise is associated with age-related differences in skeletal muscle bioenergetics. Phosphorus nuclear magnetic resonance spectroscopy was used to quantify concentrations of high-energy phosphates and pH in the knee extensors of seven young (22.7 ± 1.2 years; six women) and eight old adults (76.4 ± 6.0 years; seven women). Muscle oxidative capacity was measured from the phosphocreatine (PCr) recovery kinetics following a 24 s maximal voluntary isometric contraction. The fatiguing exercise consisted of 120 maximal velocity contractions (one contraction per 2 s) against a load equivalent to 20% of the maximal voluntary isometric contraction. The PCr recovery kinetics did not differ between young and old adults (0.023 ± 0.007 s^-1  vs. 0.019 ± 0.004 s^-1 , respectively). Fatigability (reductions in mechanical power) of the knee extensors was ∼1.8-fold greater with age and was accompanied by a greater decrease in pH (young = 6.73 ± 0.09, old = 6.61 ± 0.04) and increases in concentrations of inorganic phosphate, [P_i ], (young = 22.7 ± 4.8 mm, old = 32.3 ± 3.6 mm) and diprotonated phosphate, [H₂ PO₄^- ], (young = 11.7 ± 3.6 mm, old = 18.6 ± 2.1 mm) at the end of the exercise in old compared to young adults. The age-related increase in power loss during the fatiguing exercise was strongly associated with intracellular pH (r = -0.837), [P_i ] (r = 0.917) and [H₂ PO₄^- ] (r = 0.930) at the end of the exercise. These data suggest that the age-related increase in fatigability during dynamic exercise has a bioenergetic basis and is explained by an increased accumulation of metabolites within the muscle.