Bioenergetic basis for the increased fatigability with ageing.

Abstract

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 (Pi ), 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±1.2years; six women) and eight old adults (76.4±6.0years; seven women). Muscle oxidative capacity was measured from the phosphocreatine (PCr) recovery kinetics following a 24s maximal voluntary isometric contraction. The fatiguing exercise consisted of 120 maximal velocity contractions (one contraction per 2s) 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±0.007s-1 vs. 0.019±0.004s-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, [Pi ], (young=22.7±4.8mm, old=32.3±3.6mm) and diprotonated phosphate, [H2 PO4- ], (young=11.7±3.6mm, old=18.6±2.1mm) 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), [Pi ] (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.