Effects of elevated H+ and Pi on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans. J Physiol 2018 Sep;596(17):3993-4015
Date
05/29/2018Pubmed ID
29806714Pubmed Central ID
PMC6117549DOI
10.1113/JP276018Scopus ID
2-s2.0-85052527500 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
KEY POINTS: The mechanisms responsible for the loss in muscle power and increased fatigability with ageing are unresolved. We show that the contractile mechanics of fibres from the vastus lateralis of old men were well-preserved compared to those of young men, but the selective loss of fast myosin heavy chain II muscle was strongly associated with age-related decrements in whole-muscle strength and power. We reveal that the combination of acidosis (H+ ) and inorganic phosphate (Pi ) is an important mediator of muscle fatigue in humans by inhibiting the low- to high-force state of the cross-bridge cycle and peak power, but the depressive effects of these ions on cross-bridge function were similar in fibres from young and old men. These findings suggest that the age-related loss in muscle power is 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 Pi .
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 (Pi ) (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 Pi .
Author List
Sundberg CW, Hunter SK, Trappe SW, Smith CS, Fitts RHAuthors
Robert Fitts PhD Professor in the Biological Sciences department at Marquette UniversityChrisopher Sundberg in the CTSI department at Medical College of Wisconsin - CTSI
MESH terms used to index this publication - Major topics in bold
AcidosisAdult
Age Factors
Aged
Aged, 80 and over
Humans
Male
Muscle Contraction
Muscle Fatigue
Muscle Fibers, Skeletal
Muscle Strength
Phosphates
Young Adult
