Jane A. Kent

Human skeletal muscle metabolic economy in vivo: effects of contraction intensity, age, and mobility impairment

We tested the hypothesis that older muscle has greater metabolic economy (ME) in vivo than young, in a manner dependent, in part, on contraction intensity. Twenty young (Y; 24±1 yr, 10 women), 18 older healthy (O; 73±2, 9 women) and 9 older individuals with mild-to-moderate mobility impairment (OI; 74±1, 7 women) received stimulated twitches (2 Hz, 3 min) and performed nonfatiguing voluntary (20, 50, and 100% maximal; 12 s each) isometric dorsiflexion contractions. Torque-time integrals (TTI; Nm·s) were calculated and expressed relative to maximal fat-free muscle cross-sectional area (cm2), and torque variability during voluntary contractions was calculated as the coefficient of variation. Total ATP cost of contraction (mM) was determined from flux through the creatine kinase reaction, nonoxidative glycolysis and oxidative phosphorylation, and used to calculate ME (Nm·s·cm(-2)·mM ATP(-1)). While twitch torque relaxation was slower in O and OI compared with Y (P≤0.001), twitch TTI, ATP cost, and economy were similar across groups (P≥0.15), indicating comparable intrinsic muscle economy during electrically induced isometric contractions in vivo. During voluntary contractions, normalized TTI and total ATP cost did not differ significantly across groups (P≥0.20). However, ME was lower in OI than Y or O at 20% and 50% MVC (P≤0.02), and torque variability was greater in OI than Y or O at 20% MVC (P≤0.05). These results refute the hypothesis of greater muscle ME in old age, and provide support for lower ME in impaired older adults as a potential mechanism or consequence of age-related reductions in functional mobility.

Mechanisms of in vivo muscle fatigue in humans: investigating age‐related fatigue resistance with a computational model

Muscle fatigue can be defined as the transient decrease in maximal force that occurs in response to muscle use. Fatigue develops because of a complex set of changes within the neuromuscular system that are difficult to evaluate simultaneously in humans. The skeletal muscle of older adults fatigues less than that of young adults during static contractions. The potential sources of this difference are multiple and intertwined. To evaluate the individual mechanisms of fatigue, we developed an integrative computational model based on neural, biochemical, morphological and physiological properties of human skeletal muscle. Our results indicate first that the model provides accurate predictions of fatigue and second that the age‐related resistance to fatigue is due largely to a lower reliance on glycolytic metabolism during contraction. This model should prove useful for generating hypotheses for future experimental studies into the mechanisms of muscle fatigue.

High-intensity interval training alters ATP pathway flux during maximal muscle contractions in humans

High‐intensity interval training (HIT) results in potent metabolic adaptations in skeletal muscle; however, little is known about the influence of these adaptations on energetics in vivo. We used magnetic resonance spectroscopy to examine the effects of HIT on ATP synthesis from net PCr breakdown (ATPCK), oxidative phosphorylation (ATPOX) and non‐oxidative glycolysis (ATPGLY) in vivo in vastus lateralis during a 24‐s maximal voluntary contraction (MVC).

In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use

Because of the fundamental dependence of mammalian life on adequate mitochondrial function, the question of how and why mitochondria change in old age is the target of intense study. Given the importance of skeletal muscle for the support of mobility and health, this question extends to the need to understand mitochondrial changes in the muscle of older adults, as well. We and others have focused on clarifying the age-related changes in human skeletal muscle mitochondrial function in vivo. These changes include both the maximal capacity for oxidative production of energy (ATP), as well as the relative use of mitochondrial ATP production for powering muscular activity. It has been known for nearly 50 yr that muscle mitochondrial content is highly plastic; exercise training can induce an ∼2-fold increase in mitochondrial content, while disuse has the opposite effect. Here, we suggest that a portion of the age-related changes in mitochondrial function that have been reported are likely the result of behavioral effects, as physical activity influences have not always been accounted for. Further, there is emerging evidence that various muscles may be affected differently by age-related changes in physical activity and movement patterns. In this review, we will focus on age-related changes in oxidative capacity and flux measured in vivo in human skeletal muscle.

Physical activity, sleep quality, and self-reported fatigue across the adult lifespan

Deteriorating sleep quality and increased fatigue are common complaints of old age, and poor sleep is associated with decreased quality of life and increased mortality rates. To date, little attention has been given to the potential effects of physical activity on sleep quality and fatigue in aging. The purpose of this study was to examine the relationships between activity, sleep and fatigue across the adult lifespan. Sixty community-dwelling adults were studied; 22 younger (21-29 years), 16 middle-aged (36-64 years), and 22 older (65-81 years). Physical activity was measured by accelerometer. Sleep quality was assessed using the Pittsburg Sleep Quality Index. Self-reported fatigue was evaluated with the Patient-Reported Outcomes Measurement Information System (PROMIS). Regression analysis revealed a positive relationship between activity and sleep quality in the older (r(2)=0.18, p=0.05), but not the younger (r(2) = 0.041, p = 0.35) or middle-aged (r(2) = 0.001, p = 0.93) groups. This association was mainly established by the relationship between moderate-vigorous activity and sleep quality (r(2)=0.37, p=0.003) in older adults. No association was observed between physical activity and self-reported fatigue in any of the groups (r(2) ≤ 0.14, p ≥ 0.15). However, an inverse relationship was found between sleep quality and fatigue in the older (r(2) = 0.29, p = 0.05), but not the younger or middle-aged (r(2) ≤ 0.13, p ≥ 0.10) groups. These results support the hypothesis that physical activity may be associated with sleep quality in older adults, and suggest that improved sleep may mitigate self-reported fatigue in older adults in a manner that is independent of activity.

Post-fatigue recovery of power, postural control and physical function in older women

Low muscle power, particularly at high velocities, has been linked to poor physical function in older adults. Any loss in muscle power following fatiguing exercise or daily activities could impact physical function and postural control until power has fully recovered. To test the overall hypothesis that a common task such as walking can result in prolonged power loss and decreased physical function and balance, 17 healthy older (66–81 years) women completed a 32-min walking test (32MWT) designed to induce neuromuscular fatigue, followed by 60min of recovery (60R). Fatigue and recovery of knee extensor muscle power (3 velocities) were quantified by dynamometry. Function was quantified by chair rise time and postural control by measures of center of pressure (COP) range (mm) and velocity (mm·s-1) during quiet stance. Power declined at all velocities by 8–13% 2min following the 32MWT (p≤0.02) and remained depressed by 8–26% at 60R (p≤0.04). Postural control decreased following the 32MWT, indicated by increased COP range in the anterior-posterior (AP, p<0.01) direction and a trend in the medial-lateral (ML) direction (p = 0.09), and returned to baseline by 60R (p≥0.10). COP velocity was unchanged immediately following the 32MWT, but at 60R was lower in ML (p = 0.03) and tended to be reduced in AP (p = 0.07). Changes in high-velocity power (270°·s-1) were associated with altered postural control (p = 0.02) and chair rise performance (p≤0.03). These results provide evidence of long-duration neuromuscular changes following fatigue in healthy older women that may place them at increased risk for functional deficits during everyday mobility tasks.

Energy cost of walking, symptomatic fatigue and perceived exertion in persons with multiple sclerosis

A higher energy cost of walking (Cw) is sometimes observed in MS, and could contribute to fatigue. The purpose of this study was to compare Cw at three speeds in MS and controls, and determine the effects of walking speed on fatigue and perceived exertion. We hypothesized that MS would have higher Cw, fatigue and exertion during walking than controls. Ten persons with MS and 14 controls of similar age and physical activity levels were studied. Oxygen consumption (VO2) was obtained at rest and during treadmill walking at 0.6 and 1.4ms(-1), and preferred speed. Cw was calculated as net VO2:velocity. Fatigue and exertion were assessed using the visual analog fatigue and modified Borg scales, respectively. Preferred treadmill speed was not different between groups. Cw was higher in MS than controls across walking speeds (p=0.003), with a group-by-speed interaction indicating higher Cw in MS at 0.6ms(-1) (p=0.001), but not at preferred speed or 1.4ms(-1). MS reported greater fatigue (p=0.001) and exertion (p=0.004) at all speeds. Despite similar preferred speeds, and Cw at preferred and fast speeds, MS exhibited higher fatigue and exertion at all walking speeds. These results suggest that increased energy demands in MS are most notable at low speeds such as those used in everyday activities, which may contribute to fatigue over the day.