Bioenergetic basis for the increased fatigability with ageing

Abstract

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 (H2PO4−), 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. Abstract 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, [Pi], (young = 22.7 ± 4.8 mm, old = 32.3 ± 3.6 mm) and diprotonated phosphate, [H2PO4−], (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), [Pi] (r = 0.917) and [H2PO4−] (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.

Inorganic phosphate, protons and diprotonated phosphate may contribute to the exacerbated muscle fatigue in older adults

“…Third, the time course data show temporal associations between the increases of [P i ] and [H 2 PO 4 − ], a decrease of intracellular pH, and the loss of power during fatiguing exercise (Sundberg et al . ; their Figs 3 B and 5). Closer inspection reveals more detailed information associating these inorganic ions and mechanical performance but occurring with different time courses.…”

“…Their study involved simultaneous in vivo measurement of mechanical power, high‐energy phosphates and pH (using phosphorus nuclear magnetic resonance spectroscopy) of the knee extensors during exercise in young (23 years) and older adults (76 years) (Sundberg et al . ). The exercise consisted of maximal velocity contractions once every 2 s for a duration of 4 min.…”

“…Indeed, higher levels of P i , H + and H 2 PO 4 − in older adults during exercise would likely aggravate the above muscle processes to exacerbate fatigue. Thus, Sundberg and colleagues () have made a notable advancement to explain mechanisms for the greater fatigability in older adults where the key players may include a faster accumulation and greater elevation of intramuscular P i , H + and H 2 PO 4 − during exercise.…”

“…The well-performed study by Sundberg and colleagues in this issue of The Journal of Physiology sheds further valuable light on the cellular mechanisms underpinning the increased fatigability with ageing. Their study involved simultaneous in vivo measurement of mechanical power, high-energy phosphates and pH (using phosphorus nuclear magnetic resonance spectroscopy) of the knee extensors during exercise in young (23 years) and older adults (76 years) (Sundberg et al 2019). The exercise consisted of maximal velocity contractions once every 2 s for a duration of 4 min.…”

“…Because the increased fatigability with ageing is not explained by a differential effect on the muscle action potential (Sundberg et al 2018a,b), the exacerbated fatigue in older adults observed by Sundberg et al (2019) appears to predominantly involve impairment of myofilament function (rate of cross-bridge cycling) with possible contributions from impaired Ca 2+ release from the sarcoplasmic reticulum. Indeed, higher levels of P i , H + and H 2 PO 4 − in older adults during exercise would likely aggravate the above muscle processes to exacerbate fatigue.…”