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 individual’s 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

Mechanisms of Fatigue with Aging: Evidence from the Whole-Limb to the Single Cell in Humans

Aging is accompanied by a loss of muscle mass and increased fatigability of limb muscles making it difficult for old adults to generate the force and power necessary to perform daily activities, such as ascending a flight of stairs. The mechanisms for the age-related increase in fatigability in old and very old adults (≥80 yrs) and whether there are differences between men and women are unknown. The purpose of this dissertation was to determine the mechanisms for the age-related increase in fatigability in men and women by studying fatigue at the level of the whole-limb and within the muscle cells. Study one compared the fatigability of the knee extensor muscles and determined the mechanisms of fatigue in young, old, and very old men and women elicited by high-velocity exercise. Fatigability of the whole-limb increased across age groups, with no sex differences observed in any age cohort. The age-related increase in power loss was strongly associated with changes in involuntary muscle contractile properties, with minimal contribution from age differences in neural drive. These data suggest the increased fatigability with aging is determined primarily by mechanisms within the muscle for both sexes. To test whether cross-bridge mechanisms could explain the age-related losses in whole-muscle power and increased fatigability, muscle cells from vastus lateralis biopsies were exposed to conditions mimicking quiescent muscle and fatiguing levels of hydrogen (H+) and phosphate (Pi). The fatigue-mimicking conditions revealed that H+ and Pi act synergistically to cause marked reductions in human cross-bridge function. However, other than severe atrophy of fast fibers in old men and women, the effects of the fatigue conditions on cross-bridge function with either severe (study 2) or a range of elevated H+ and Pi (study 3) did not differ with age. These data suggest that age-related losses in whole-muscle power are due primarily to atrophy of fast fibers, but the age-related increase in fatigability cannot be explained by an increased sensitivity of the cross-bridge to H+ and Pi. Combined, these studies suggest that interventions targeting the muscle are necessary to mitigate age-related declines in power and increased fatigability in men and women

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 ({greater than or equal to}80 yrs) are unresolved. Moreover, whether the increased fatigability with advancing age and the underlying mechanisms differ between men and women are 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 {plus minus} 0.4 yrs; 15 men), 62 old (70.5 {plus minus} 0.7 yrs; 33 men), and 12 very old (86.0 {plus minus} 1.3 yrs; 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 (\u3c10 \u3es) using transcranial magnetic stimulation and electrical stimulation. Absolute mechanical power output was 97% and 217% higher in the young compared to 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,

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 (\u3e10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P \u3c 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P \u3e 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

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 muscle’s molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosin’s 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

Symposium on scientific literacy: Introduction

This is the publisher's version, also available electronically from http://www.amjbot.org.Not applicabl

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 (\u3e10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P \u3c 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P \u3e 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

Effects of Elevated H\u3csup\u3e+\u3c/sup\u3e And P\u3csub\u3ei\u3c/sub\u3e on The Contractile Mechanics of Skeletal Muscle Fibres From Young and Old Men: Implications for Muscle Fatigue in Humans

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

Single Muscle Fibre Contractile Function With Ageing

Ageing is accompanied by decrements in the size and function of skeletal muscle that compromise independence and quality of life in older adults. Developing therapeutic strategies to ameliorate these changes is critical but requires an in-depth mechanistic understanding of the underlying physiology. Over the past 25 years, studies on the contractile mechanics of isolated human muscle fibres have been instrumental in facilitating our understanding of the cellular mechanisms contributing to age-related skeletal muscle dysfunction. The purpose of this review is to characterize the changes that occur in single muscle fibre size and contractile function with ageing and identify key areas for future research. Surprisingly, most studies observe that the size and contractile function of fibres expressing slow myosin heavy chain (MHC) I are well-preserved with ageing. In contrast, there are profound age-related decrements in the size and contractile function of the fibres expressing the MHC II isoforms. Notably, lifelong aerobic exercise training is unable to prevent most of the decrements in fast fibre contractile function, which have been implicated as a primary mechanism for the age-related loss in whole-muscle power output. These findings reveal a critical need to investigate the effectiveness of other nutritional, pharmaceutical or exercise strategies, such as lifelong resistance training, to preserve fast fibre size and function with ageing. Moreover, integrating single fibre contractile mechanics with the molecular profile and other parameters important to contractile function (e.g. phosphorylation of regulatory proteins, innervation status, mitochondrial function, fibre economy) is necessary to comprehensively understand the ageing skeletal muscle phenotype