David W. Russ

Older adults exhibit more intracortical inhibition and less intracortical facilitation than young adults.

BACKGROUND Aging results in decreased neuromuscular function, which is likely associated with neurologic alterations. At present little is known regarding age-related changes in intracortical properties. METHODS In this study we used transcranial magnetic stimulation (TMS) to measure intracortical facilitation (ICF), short- and long-interval intracortical inhibition (SICI and LICI), motor evoked potential amplitude, and silent period duration in young and older adults (21.4+/-0.8years and 70.9+/-1.8years). These variables were assessed from the flexor carpi radialis muscle of the non-dominant arm under resting conditions, and during a submaximal contraction (intensity 15% maximum strength). RESULTS Older adults exhibited increased SICI and LICI in comparison to young adults (SICI: 29.0+/-9.2% vs. 46.2+/-4.8% of unconditioned pulse; LICI: 6.5+/-1.7% vs. 15.8+/-3.3% of unconditioned pulse; P=0.04), and less ICF under resting conditions (74.6+/-8.7% vs. 104.9+/-6.9% of unconditioned pulse; P=0.02). These age-related differences disappeared during contraction, although the older adults did exhibit a longer silent period during contraction (112.5+/-6.5 vs. 84.0+/-3.9ms; P<0.01). CONCLUSIONS Collectively, these findings suggest increased GABA mediated intracortical inhibition with age.

Effects of activation pattern on human skeletal muscle fatigue

Variable‐frequency stimulation trains (VFTs) that take advantage of the catchlike property of skeletal muscle have been shown to augment the force production of fatigued muscles compared with constant‐frequency trains (CFTs). The present study is the first to report the force augmentation produced by VFTs after fatiguing the muscle with VFTs versus fatiguing the muscle with CFTs. Data were obtained from the human quadriceps femoris muscles of 12 healthy subjects. Each subject participated in three experimental sessions. Each session fatigued the muscle with one of three protocols: CFTs with 70‐ms interpulse intervals (CFT70); CFTs with 55.5‐ms interpulse intervals (CFT55.5); or VFTs. Following each fatiguing protocol the muscles were tested with all three stimulation patterns (i.e., CFT55.5, CFT70, and VFT). At the end of the fatiguing protocol the VFT produced force–time integrals and peak forces ∼18% and 32% greater than the CFT70, respectively. The testing trains showed that the VFT produced ∼25–35% greater force–time integrals than either CFT and ∼35–47% greater peak forces than the CFT70. For each testing train, ∼10–15% greater force–time integrals were seen when the muscles were fatigued with the CFTs than when fatigued with the VFTs. These results support suggestions that VFTs may be useful during clinical applications of electrical stimulation.

Sex differences in glycolysis during brief, intense isometric contractions

We have previously observed less muscle fatigue in women than men under conditions of intact circulation, but similar fatigue across the sexes during local ischemia. Thus, we hypothesized that women utilize their aerobic metabolic pathways to a greater extent than do men. To test this hypothesis, we examined the extent to which different pathways of intramuscular adenosine triphosphate (ATP) production were utilized by men and women during maximal voluntary isometric contractions. Force production during 15‐s and 60‐s contractions were recorded in parallel sessions. In one session, central activation was assessed with electrical stimulation. In the other, phosphorus magnetic resonance spectroscopy was used to quantify muscle oxidative capacity, and the contributions of glycolysis and oxidative phosphorylation to ATP synthesis during the 60‐s contraction. Fatigue and central activation were similar in men and women during both the 15‐s and 60‐s contractions. The rate constants of phosphocreatine recovery following the 15‐s contraction were similar in men and women, indicating similar oxidative capacities. Men exhibited greater acidosis and peak glycolytic rates compared with women during the 60‐s contraction, with no differences observed in creatine kinase flux or the percent of oxidative capacity utilized. We conclude that men exhibit greater in vivo glycolysis during brief, intense isometric contractions. Although this metabolic difference did not contribute to any observable differences in fatigue in the present study, these results highlight a potentially important mechanism to explain sex‐related differences in muscle function. Muscle Nerve, 2005

Ageing, but not yet senescent, rats exhibit reduced muscle quality and sarcoplasmic reticulum function.

Aim:  Reduced muscle force greater than expected from loss of muscle mass has been reported in ageing muscles. Impaired sarcoplasmic reticulum (SR) Ca2+ release has been implicated as a possible mechanism, and attributed to several factors, including loss of ryanodine receptor (RYR) expression and protein binding. The aim of this study was to evaluate muscle quality and SR Ca2+ release in ageing rats that were not so old that major atrophy had occurred.

Is skeletal muscle oxidative capacity decreased in old age

In humans, decreases in cardiac output play an important role in the age-related decrease in whole-body oxidative capacity. What remains less clear is whether a decline in skeletal muscle oxidative capacity is also an inevitable consequence of aging, as a number of other factors that could affect oxidative capacity also change with age, including: physical activity, health status, fibre-type composition, rates of protein synthesis and muscle blood supply. Both in vitro studies using muscle biopsy tissue and in vivo studies using 31P-magnetic resonance spectroscopy are used to study muscular oxidative capacity. Using these methodologies, researchers have found age-associated reductions in the oxidative capacities of specific muscles. In most cases, however, the influence of physical activity has not been adequately controlled, making it difficult to evaluate the effects of age itself from those of lifestyle changes associated with aging.Upon critical evaluation of the existing literature, the following picture regarding the effect of age on muscle oxidative capacity appears: although the maximum level of muscular oxidative capacity attainable through training may decline with age, much of the age-associated decline in oxidative function is related to the reductions in fitness and/or habitual physical activity that typically occur in this population. Future studies in this area must account for the health and activity status of their study participants.

Contrasting influences of age and sex on muscle fatigue

PURPOSE Greater resistance to muscle fatigue has been observed in women versus men and in older versus young individuals. As suggested mechanisms for these differences include task intensity and duty cycle, the purpose of this study was to evaluate fatigue in healthy young and older men and women during maximum-effort isometric contractions with a 70% duty cycle (7 s of contraction, 3 s of rest). We hypothesized that no differences in fatigue would be observed across age or sex, in contrast to studies incorporating lower duty cycles. METHODS The protocol was carried out on ankle dorsiflexors of older (73 +/- 1 yr) and younger (25 +/- 1 yr) men and women. Volitional and stimulated force, compound muscle action potential, and muscle contractile responses were collected before, during, and immediately after the fatigue protocol. These measurements allowed for assessment of fatigue as well as central and peripheral activation. RESULTS At baseline, older subjects had longer force half-relaxation times and less twitch potentiation than younger subjects, consistent with a slower muscle phenotype. During contractions, younger subjects fatigued more than older subjects did, with no differences between men and women. Central activation decreased similarly in all groups with fatigue. There were no fatigue-related differences in peripheral excitation or contractile properties attributable to age or sex. CONCLUSIONS These data indicate that age-related differences in fatigue are observed even during intermittent MVC with a high duty cycle, and that these differences are independent of central and peripheral activation. Further, it seems that sex-based differences in both fatigue and central activation failure were abolished with this duty cycle. Overall, these results suggest that age- and sex-based differences in fatigue arise from distinct mechanisms.

Variable‐frequency trains offset low‐frequency fatigue in human skeletal muscle

Variable‐frequency trains that exploit the catchlike property of skeletal muscle can augment force production in fatigued skeletal muscle. The present study is the first to examine the effect of such trains during recovery. The quadriceps femoris muscles of 12 healthy individuals were fatigued using six‐pulse, 14.3‐Hz trains delivered at a rate of 1/s for 3 min. The force‐generating ability of the muscle was tested with several constant‐frequency trains (8.3–100 Hz) and a variable‐frequency train before and after fatigue and at 2, ∼13, and ∼38 min of recovery. The variable‐frequency train produced significant augmentation of force versus the best constant‐frequency train (12.5 Hz) in acute fatigue and during recovery. The fatiguing protocol also induced low‐frequency fatigue (LFF); the time courses of the degree of LFF and the amount of variable‐frequency train force augmentation were inversely related (r = 0.629; F = 38.024; P ≤ 0.001), suggesting a common mechanism between the two phenomena. These results suggest that clinical use of variable‐frequency trains (e.g., functional electrical stimulation) will enable the muscle to generate more force during acute fatigue and offset, at least partially, the long‐term effects of LFF.

Restoration of voluntary muscle strength after 3 weeks of cast immobilization is suppressed in women compared with men.

OBJECTIVE To investigate sex-related differences in the loss and recovery of voluntary muscle strength after immobilization. DESIGN Longitudinal, repeated measures. SETTING Research laboratory. PARTICIPANTS Healthy men (n=5) and healthy women (n=5). INTERVENTION Three weeks of forearm immobilization. MAIN OUTCOME MEASURES Voluntary wrist flexion muscle strength was assessed at baseline and weekly during the immobilization protocol and 1 week after cast removal. Central activation was assessed before and after immobilization and after 1 week of recovery to determine what percentage of the muscle could be activated voluntarily. RESULTS Men and women lost voluntary strength at a similar rate during immobilization. However, after 1 week of recovery voluntary strength had returned to within 1% of baseline in the men, but remained approximately 30% less than baseline in the women (P=0.03). Both sexes displayed reduced central activation after immobilization (P=0.02), but the decrease was similar in both sexes (P=0.82). CONCLUSIONS These findings suggest sex-dependent adaptations to and recovery from limb immobilization, with voluntary strength recovering slower in women. As such, sex-specific rehabilitation protocols may be warranted, with women requiring additional or more intensive rehabilitation programs after periods of disuse. Future work is needed to determine the extent and mechanisms of these differences.

Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middle‐aged rats

We examined the molecular and metabolomic effects of voluntary running wheel activity in late middle‐aged male Sprague Dawley rats (16–17 months). Rats were assigned either continuous voluntary running wheel access for 8 weeks (RW+) or cage‐matched without running wheel access (RW−). The 9 RW+ rats averaged 83 m/day (range: 8–163 m), yet exhibited both 84% reduced individual body weight gain (4.3 g vs. 26.3 g, P = 0.02) and 6.5% reduced individual average daily food intake (20.6 g vs. 22.0 g, P = 0.09) over the 8 weeks. Hindlimb muscles were harvested following an overnight fast. Muscle weights and myofiber cross‐sectional area showed no difference between groups. Western blots of gastrocnemius muscle lysates with a panel of antibodies suggest that running wheel activity improved oxidative metabolism (53% increase in PGC1α, P = 0.03), increased autophagy (36% increase in LC3B‐II/‐I ratio, P = 0.03), and modulated growth signaling (26% increase in myostatin, P = 0.04). RW+ muscle also showed 43% increased glycogen phosphorylase expression (P = 0.04) and 45% increased glycogen content (P = 0.04). Metabolomic profiling of plantaris and soleus muscles indicated that even low‐volume voluntary running wheel activity is associated with decreases in many long‐chain fatty acids (e.g., palmitoleate, myristoleate, and eicosatrienoate) relative to RW− rats. Relative increases in acylcarnitines and acyl glycerophospholipids were also observed in RW+ plantaris. These data establish that even modest amounts of physical activity during late middle‐age promote extensive metabolic remodeling of skeletal muscle.

The Impact of Old Age on Skeletal Muscle Energetics: Supply and Demand

Properly functioning skeletal muscle is critical for locomotion and performance of many activities of daily living. Muscle wasting and decreased function of skeletal muscle are important factors in many age-related morbidities. There are several pathways for generating ATP in skeletal muscle that allow adequate ATP supply to meet increased demand during muscle activity. A growing body of literature provides evidence that the aging process may be accompanied by changes in metabolic supply and demand during muscle contractions. Herein, we review a body of evidence that several pathways of ATP synthesis (anaerobic glycolysis, oxidative phosphorylation) may be impaired in aging skeletal muscle as well as several underlying molecular and cellular mechanisms. However, detrimental effects of aging on muscle energy metabolism are not universally accepted, particularly when physical inactivity is accounted for. We discuss this important concept as well as several potential countermeasures that may compress the period of morbidity in old age. In the second half of this review, we discuss how energetic demand of skeletal muscle is affected by aging, with specific focus on basal and contractile ATPase activity.