Christopher W. Sundberg

Muscle fatigue from the perspective of a single crossbridge

The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process. This seems to be due, in part, to their direct effect on muscles molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosins ability to move actin. Indeed, recent work using a single molecule laser trap assay has revealed the specific steps in the crossbridge cycle affected by these ions. In addition to their direct effects, these ions also indirectly affect myosin by decreasing the sensitivity of the myofilaments to calcium, primarily by altering the ability of the muscle regulatory proteins, troponin and tropomyosin, to govern myosin binding to actin. This effect seems to be partially due to fatigue-dependent alterations in the structure and function of specific subunits of troponin. Parallel efforts to understand the molecular basis of muscle contraction are providing new technological approaches that will allow us to gain unprecedented molecular detail of the fatigue process. This will be crucial to fully understand this ubiquitous phenomenon and develop appropriately targeted therapies to attenuate the debilitating effects of fatigue in clinical populations.

Rates of performance loss and neuromuscular activity in men and women during cycling: evidence for a common metabolic basis of muscle fatigue

The durations that muscular force and power outputs can be sustained until failure fall predictably on an exponential decline between an individuals 3-s burst maximum to the maximum performance they can sustain aerobically. The exponential time constants describing these rates of performance loss are similar across individuals, suggesting that a common metabolically based mechanism governs muscle fatigue; however, these conclusions come from studies mainly on men. To test whether the same physiological understanding can be applied to women, we compared the performance-duration relationships and neuromuscular activity between seven men [23.3 ± 1.9 (SD) yr] and seven women (21.7 ± 1.8 yr) from multiple exhaustive bouts of cycle ergometry. Each subject performed trials to obtain the peak 3-s power output (Pmax), the mechanical power at the aerobic maximum (Paer), and 11-14 constant-load bouts eliciting failure between 3 and 300 s. Collectively, men and women performed 180 exhaustive bouts spanning an ~6-fold range of power outputs (118-1116 W) and an ~35-fold range of trial durations (8-283 s). Men generated 66% greater Pmax (956 ± 109 W vs. 632 ± 74 W) and 68% greater Paer (310 ± 47 W vs. 212 ± 15 W) than women. However, the metabolically based time constants describing the time course of performance loss were similar between men (0.020 ± 0.003/s) and women (0.021 ± 0.003/s). Additionally, the fatigue-induced increases in neuromuscular activity did not differ between the sexes when compared relative to the pedal forces at Paer These data suggest that muscle fatigue during short-duration dynamic exercise has a common metabolically based mechanism determined by the extent that ATP is resynthesized by anaerobic metabolism. NEW & NOTEWORTHY Although men and women differed considerably in their absolute cycling performances, there was no sex difference in the metabolically based exponential time constant that described the performance-duration relationship. Similarly, the fatigue-induced increases in neuromuscular activity were not different between the sexes when compared from a metabolic perspective. These data suggest that men and women have similar rate-limiting mechanisms for short-duration dynamic exercise that are determined by the extent the exercise is supported by anaerobic metabolism.

Physical activity modulates corticospinal excitability of the lower limb in young and old adults

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (>10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (<10,000 steps/day, low-PA; n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P < 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P > 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability.NEW & NOTEWORTHY Transcranial magnetic stimulation was used to determine whether achieving the recommended 10,000 steps/day for optimal health influenced the excitability of the corticospinal tract projecting to the knee extensor muscles. Irrespective of age and sex, individuals who achieved >10,000 steps/day had lower corticospinal excitability than those who performed <10,000 steps/day, possibly representing greater control of inhibitory and excitatory networks. Physical activity involving >10,000 steps/day may mediate its effects on the nervous system by decreasing corticospinal excitability.

Mechanisms for the age-related increase in fatigability of the knee extensors in old and very old adults

The mechanisms for the age-related increase in fatigability during high-velocity contractions in old and very old adults (≥80 yr) are unresolved. Moreover, whether the increased fatigability with advancing age and the underlying mechanisms differ between men and women is not known. The purpose of this study was to quantify the fatigability of knee extensor muscles and identify the mechanisms of fatigue in 30 young (22.6 ± 0.4 yr; 15 men), 62 old (70.5 ± 0.7 yr; 33 men), and 12 very old (86.0 ± 1.3 yr; 6 men) men and women elicited by high-velocity concentric contractions. Participants performed 80 maximal velocity contractions (1 contraction per 3 s) with a load equivalent to 20% of the maximum voluntary isometric contraction. Voluntary activation and contractile properties were quantified before and immediately following exercise (<10 s) using transcranial magnetic stimulation and electrical stimulation. Absolute mechanical power output was 97 and 217% higher in the young compared with old and very old adults, respectively. Fatigability (reductions in power) progressively increased across age groups, with a power loss of 17% in young, 31% in old, and 44% in very old adults. There were no sex differences in fatigability among any of the age groups. The age-related increase in power loss was strongly associated with changes in the involuntary twitch amplitude ( r = 0.75, P < 0.001). These data suggest that the age-related increased power loss during high-velocity fatiguing exercise is unaffected by biological sex and determined primarily by mechanisms that disrupt excitation contraction coupling and/or cross-bridge function. NEW & NOTEWORTHY We show that aging of the neuromuscular system results in an increase in fatigability of the knee extensors during high-velocity exercise that is more pronounced in very old adults (≥80 yr) and occurs similarly in men and women. Importantly, the age-related increase in power loss was strongly associated with the changes in the electrically evoked contractile properties suggesting that the increased fatigability with aging is determined primarily by mechanisms within the muscle for both sexes.

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

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.

Predicting human ageing with Masters athletics: ‘one size doesn't fit all’

Scientific understanding of human ageing is confounded by lifelong differences in physical activity, exercise training, disease, nutrition and a myriad of other environmental and physiological factors. This article is protected by copyright. All rights reserved

Increased Fatigability Of Older Women Performing High-velocity Contractions Is Explained By Mechanisms Within The Muscle: 1805 Board #7 June 2, 1: 00 PM - 3: 00 PM.

METHODS: Twelve women volunteered to perform isometric leg extension muscle actions at 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100% of maximal voluntary contraction (MVC) on a HUMAC NORM isokinetic dynamometer. The women were classified into lower strength (n = 6; 23.2 ± 1.7 y, 165.6 ± 7.6 cm, 59.3 ± 10.1 kg) and higher strength (n = 6; 22.8 ± 2.0 y, 164.6 ± 4.8 cm, 72.7 ± 12.2 kg) groups on the basis of their isometric MVC values (lower strength women MVC = 98.0 ± 20.6 Nm, higher strength women MVC = 169.2 ± 27.5 Nm). An accelerometer (EGAS S704 10_Rev C) was placed over the vastus lateralis to detect the MMG signal. The amplitude of the MMG signal was expressed as root mean square (RMS), while frequency data were expressed as mean power frequency (MPF). Torque (Nm) was recorded by the dynamometer. RESULTS: Polynomial regression analyses indicated that the relationships for MMG amplitude versus isometric MVC were quadratic for both the lower strength (R^2 = 0.987) and higher strength (R^2 = 0.964) women. However, for the lower strength women, MMG amplitude increased most between 60 and 100% isometric MVC, while for the higher strength women, MMG amplitude increased most between 10 and 60% MVC, then began to plateau. For MMG MPF, the relationships were cubic for the lower strength women (R^2 = 0.861) and linear for the higher strength women (R^2 = 0.902). CONCLUSIONS: The different torque-related responses for MMG amplitude and MPF may reflect differences in the motor control strategies that modulate torque production for lower vs. higher strength women. These results also suggest that isometric torque production is controlled by a combination of recruitment and firing rate, but that the reliance on each mechanism differed throughout the entire range of torque production between lower strength and higher strength women. Lastly, the torque-related patterns for MMG amplitude and frequency may also have been affected by differences in absolute torque, and thus muscle stiffness, between the lower strength and higher strength women.