Bioenergetic basis for the increased fatigability with ageing.

KEY POINTS: 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 with 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.

ABSTRACT: The purpose of this study was 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 (31 P-MRS) was used to quantify concentrations of high-energy phosphates and pH in the knee extensors of 7 young (22.7 ± 1.2 years, 6 women) and 8 old adults (76.4 ± 6.0 years, 7 women). Muscle oxidative capacity was measured from the phosphocreatine (PCr) recovery kinetics (kPCr ) following a 24-s maximal voluntary isometric contraction (MVC). The fatiguing exercise consisted of 120 maximal velocity contractions (1 contraction per 2-s) against a load equivalent to 20% of the MVC. 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 ([Pi ], 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 with 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. This article is protected by copyright. All rights reserved.