Effects of elevated H⁺ and P_i on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans

Abstract

The present study aimed to identify the mechanisms responsible for the loss in muscle power and increased fatigability with ageing by integrating measures of whole-muscle function with single fibre contractile mechanics. After adjusting for the 22% smaller muscle mass in old (73-89 years, n = 6) compared to young men (20-29 years, n = 6), isometric torque and power output of the knee extensors were, respectively, 38% and 53% lower with age. Fatigability was ∼2.7-fold greater with age and strongly associated with reductions in the electrically-evoked contractile properties. To test whether cross-bridge mechanisms could explain age-related decrements in knee extensor function, we exposed myofibres (n = 254) from the vastus lateralis to conditions mimicking quiescent muscle and fatiguing levels of acidosis (H ) (pH 6.2) and inorganic phosphate (P ) (30 mm). The fatigue-mimicking condition caused marked reductions in force, shortening velocity and power and inhibited the low- to high-force state of the cross-bridge cycle, confirming findings from non-human studies that these ions act synergistically to impair cross-bridge function. Other than severe age-related atrophy of fast fibres (-55%), contractile function and the depressive effects of the fatigue-mimicking condition did not differ in fibres from young and old men. The selective loss of fast myosin heavy chain II muscle was strongly associated with the age-related decrease in isometric torque (r = 0.785) and power (r = 0.861). These data suggest that the age-related loss in muscle strength and power are primarily determined by the atrophy of fast fibres, but the age-related increased fatigability cannot be explained by an increased sensitivity of the cross-bridge to H and P .

Bioenergetic basis for the increased fatigability with ageing

“…Familiarization sessions were conducted to habituate each participant to performing brief 3–5 s maximal voluntary isometric contractions (MVCs) and maximal voluntary concentric contractions with the knee extensors as described previously (Sundberg et al . ; Sundberg et al . ).…”

“…Because of the restricted range of motion that could be attained within the scanner bore (∼20 cm linear displacement and ∼30° angular displacement), the frequency of contractions was increased from the 0.33 Hz used previously (Sundberg et al . ; Sundberg et al . ) to 0.50 Hz in the present study.…”

“…Because power output increased over the first few contractions in some participants as observed previously (Sundberg et al . ; Sundberg et al . ), the baseline power output for each participant was the highest average obtained from 10 sequential contractions within the first 20 contractions.…”

“…; Sundberg et al . ). Another important factor for mobility and physical function is the fatigability of limb muscle (Foulis et al .…”

“…Our recent findings on fibres isolated from muscle biopsies of the vastus lateralis revealed that the decrements in single fibre force, velocity and power elicited by a fatigue‐mimicking condition (pH 6.2 + 30 mM P i ) did not differ in fibres from young compared to old men (Sundberg et al . ). These data suggest that the age‐related increase in fatigability during dynamic exercise is not likely attributed to an increased sensitivity of the cross‐bridge to H + and P i , at least not under saturating Ca 2+ conditions.…”