Sex-specific increases in myostatin and SMAD3 contribute to obesity-related insulin resistance in human skeletal muscle and primary human myotubes.

The purpose of the present study was to determine the effects of obesity and biological sex on myostatin expression in humans and to examine the direct effects of myostatin, SMAD2, and SMAD3 on insulin signaling in primary human skeletal muscle cells (HSkMCs). For cohort 1, 15 lean [body mass index (BMI): 22.1 ± 0.5 kg/m2; n = 8 males; n = 7 females] and 14 obese (BMI: 40.6 ± 1.4 kg/m2; n = 7 males; n = 7 females) individuals underwent skeletal muscle biopsies and an oral glucose tolerance test. For cohort 2, 14 young lean (BMI: 22.4 ± 1.9 kg/m2; n = 6 males; n = 8 females) and 14 obese (BMI: 39.3 ± 7.9 kg/m2; n = 6 males; n = 8 females) individuals underwent muscle biopsies for primary HSkMC experiments. Plasma mature myostatin (P = 0.041), skeletal muscle precursor myostatin (P = 0.048), and skeletal muscle SMAD3 (P = 0.029) were elevated in obese females compared to lean females, and plasma mature myostatin (r = 0.58, P = 0.029) and skeletal muscle SMAD3 (r = 0.56, P = 0.037) were associated with insulin resistance in females but not males. Twenty-four hours of myostatin treatment impaired insulin signaling in primary HSkMCs derived from females (P < 0.024) but not males. Overexpression of SMAD3, but not SMAD2, impaired insulin-stimulated AS160 phosphorylation in HSkMCs derived from lean females (-27%, P = 0.040), whereas silencing SMAD3 improved insulin-stimulated AS160 phosphorylation and insulin-stimulated glucose uptake (25%, P < 0.014) in HSkMCs derived from obese females. These results suggest for the first time that myostatin-induced impairments in skeletal muscle insulin signaling are sex specific and that increased body fat in females is associated with detrimental elevations in myostatin and SMAD3, which contribute to obesity-related insulin resistance.NEW & NOTEWORTHY Obesity is considered a main risk factor for the development of insulin resistance and type 2 diabetes. The present study utilizes in vivo and in vitro experiments in human skeletal muscle to demonstrate for the first time that females are inherently more susceptible to myostatin-induced insulin resistance, which is further enhanced with obesity due to increased myostatin and SMAD3 expression.

Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans.

Elevated circulating lactate has been associated with obesity and insulin resistance. The aim of the current study was to determine if lactate-induced lysine lactylation (kla), a post-translational modification, was present in human skeletal muscle and related to insulin resistance. Fifteen lean (Body Mass Index: 22.1 ± 0.5 kg/m2) and fourteen obese (40.6 ± 1.4 kg/m2) adults underwent a muscle biopsy and 2-h oral glucose tolerance test. Skeletal muscle lactylation was increased in obese compared to lean females (19%, p < 0.05) and associated with insulin resistance (r = 0.37, p < 0.05) in the whole group. Skeletal muscle lactylation levels were significantly associated with markers of anaerobic metabolism (plasma lactate and skeletal muscle lactate dehydrogenase [LDH], p < 0.05) and negatively associated with markers of oxidative metabolism (skeletal muscle cytochrome c oxidase subunit 4 and Complex I [pyruvate] OXPHOS capacity, p < 0.05). Treatment of primary human skeletal muscle cells (HSkMC) with sodium lactate for 24 h increased protein lactylation and IRS-1 serine 636 phosphorylation in a similar dose-dependent manner (p < 0.05). Inhibition of glycolysis (with 2-deoxy-d-glucose) or LDH-A (with sodium oxamate or LDH-A siRNA) for 24 h reduced HSkMC lactylation which paralleled reductions in culture media lactate accumulation. This study identified the existence of a lactate-derived post-translational modification in human skeletal muscle and suggests skeletal muscle lactylation could provide additional insight into the regulation of skeletal muscle metabolism, including insulin resistance.

Recurrence of Hallux Valgus After Modified Lapidus Procedure With Successful Fusion of the Intermetatarsal and Intercuneiform Joints.

Background The Lapidus procedure has become a popular procedure in correcting hallux valgus deformities and has undergone several modifications in an effort to improve the efficacy of the procedure. The senior author modifies this procedure with the addition of an intermetatarsal and intercuneiform fusion. Our hypothesis is that this will improve the procedure outcomes and decrease deformity recurrence. Methods We reviewed patient charts who underwent the procedure between 2014 and 2017 performed by the senior author. This yielded 47 reviewable cases, with 34 meeting study criteria. The cases were analyzed for standard hallux valgus measurements (intermetatarsal angle [IMA], hallux valgus angle [HVA]) and fusion on X-ray. Results The results of the study showed partial intermetatarsal and intercuneiform fusion failure in seven (20%) cases, and one case where the great toe fell into varus. These cases were excluded. In the remaining cases, there was a statistically significant improvement in the HVA and IMA between the preoperative X-ray and first postoperative X-ray. Additionally, there was no significant difference between HVA and IMA between first and final postoperative radiographs. There was a significant increase in IMA for the fusion failure cases (p=0.001). Conclusion Clinically, our findings demonstrate that successful union is possible with low recurrence and complication rates when using this modification of the Lapidus procedure in patients with hallux valgus deformity.

Heterogeneity of the strength response to progressive resistance exercise training in older adults: Contributions of muscle contractility.

BACKGROUND: Older adults display wide individual variability (heterogeneity) in the effects of resistance exercise training on muscle strength. The mechanisms driving this heterogeneity are poorly understood. Understanding of these mechanisms could permit development of more targeted interventions and/or improved identification of individuals likely to respond to resistance training interventions. Thus, this study assessed potential physiological factors that may contribute to strength response heterogeneity in older adults: neural activation, muscle hypertrophy, and muscle contractility. METHODS: In 24 older adults (72.3 ± 6.8 years), we measured the following parameters before and after 12 weeks of progressive resistance exercise training: i) isometric leg extensor strength; ii) isokinetic (60°/sec) leg extensor strength; iii) voluntary (neural) activation by comparing voluntary and electrically-stimulated muscle forces (i.e., superimposed doublet technique); iv) muscle hypertrophy via dual-energy x-ray absorptiometry (DXA) estimates of regional lean tissue mass; and v) intrinsic contractility by electrically-elicited twitch and doublet torques. We examined associations between physiological factors (baseline values and relative change) and the relative change in isometric and isokinetic muscle strength. RESULTS: Notably, changes in quadriceps contractility were positively associated with the relative improvement in isokinetic (r = 0.37-0.46, p ≤ 0.05), but not isometric strength (r = 0.09-0.21). Change in voluntary activation did not exhibit a significant association with the relative improvements in either isometric or isokinetic strength (r = 0.35 and 0.33, respectively; p > 0.05). Additionally, change in thigh lean mass was not significantly associated with relative improvement in isometric or isokinetic strength (r = 0.09 and -0.02, respectively; p > 0.05). Somewhat surprising was the lack of association between exercise-induced changes in isometric and isokinetic strength (r = 0.07). CONCLUSIONS: The strength response to resistance exercise in older adults appears to be contraction-type dependent. Therefore, future investigations should consider obtaining multiple measures of muscle strength to ensure that strength adaptations are comprehensively assessed. Changes in lean mass did not explain the heterogeneity in strength response for either contraction type, and the data regarding the influence of voluntary activation was inconclusive. For isokinetic contraction, the strength response was moderately explained by between-subject variance in the resistance-exercise induced changes in muscle contractility.

Multiple measures of muscle function influence Sorensen Test performance in individuals with recurrent low back pain.

BACKGROUND: Sorensen Test time-to-task-failure (TTF) predicts several low back pain (LBP) clinical outcomes, including recurrence. Because the test is described as a measure of trunk extensor (TE) muscle endurance, LBP rehabilitation programs often emphasize endurance training, but the direct role of TE muscle function on Sorensen Test-TTF remains unclear. OBJECTIVE: To assess the discriminative and associative properties of multiple markers of isolated TE performance with regard to Sorensen Test-TTF in individuals with recurrent LBP. METHOD: Secondary analysis of baseline measures from participants in a registered (NCT02308189) trial (10 men; 20 women) was performed. Participants were classified by Sorensen Test-TTF as high, moderate or low risk for subsequent LBP episodes, and compared to determine if classification could discriminate differences in TE function. Correlations between Sorensen Test-TTF and isolated TE performance, anthropometrics and disability were investigated. RESULTS: Individuals at risk of subsequent LBP episodes had greater perceived disability and fat mass/TE strength ratios (P⩽ 0.05) than those not at risk. Modest, significant (r= 0.36-0.42, P⩽ 0.05) associations were found between Sorensen Test-TTF, TE endurance and fat mass/TE strength. Exploratory analyses suggested possible sex-specific differences related to Sorensen Test-TTF. CONCLUSIONS: Isolated TE muscle endurance is only one of several factors with similar influence on Sorensen Test-TFF, thus LBP rehabilitation strategies should consider other factors, including TE strength, anthropometrics and perceived disability.

Regional Nerve Block Complication Analysis Following Peripheral Nerve Block During Foot and Ankle Surgical Procedures.

Background Foot and ankle surgeries are frequently accompanied by a peripheral nerve block in order to reduce postoperative pain. Higher than expected complication rates with peripheral nerve blocks have led to increased concern among surgeons and patients. To our knowledge, no study conducted by the treating surgeon has identified risk factors that may predispose a patient to complications. Our goal was to attempt to identify those risk factors. Methods We reviewed patient charts of those who underwent an orthopedic foot and ankle procedure between 2013 and 2018, as performed by the senior author. This yielded 992 procedures performed across four surgical locations. Of these procedures, 137 procedures were removed because no block was used. The remaining cases were analyzed for nerve complications, defined as sensory or motor deficits along the distribution of a nerve. The patients were divided into those with and without complications and were evaluated for differences. Statistical analysis was performed using the SAS® software (SAS Institute Inc., Cary, North Carolina, USA). Results The overall short-term complication rate was 10.1% and the long-term complication rate was 4.3%, with a total of 855 blocks given. Electromyographies (EMGs) were performed on 24.4% of the patients with a complication. Of the EMGs, 95.2% confirmed nerve complications in the distribution of the blocked nerve. The significant factors associated with complications were age, BMI, location, and smoking status. A regression analysis was performed to determine the odds ratio for individual factors. Those with significantly higher odds ratio were between 40 and 65 years of age, had normal or underweight BMI, underwent surgery at an outpatient surgery center, and were current smokers. Conclusions Our study suggests that there are significant epidemiological factors in predicting postoperative complications related to a peripheral nerve block. The study also shows a similar short-term complication rate but a higher long-term complication rate than other studies. This data are important because it allows for an informed decision to be made between a surgeon, anesthesiologist, and the patient regarding the safety and necessity of delivering a preoperative peripheral nerve block based on patient risk factors.

Clinical Implications of a One-hand Versus Two-hand Technique in the Silfverskiöld Test for Gastrocnemius Equinus.

Introduction Isolated gastrocnemius equinus contracture has been associated with several foot and ankle pathologies within the literature. The Silfverskiöld test is commonly used to identify isolated gastrocnemius contracture, however, the proper technique for performing the test has been scrutinized. The purpose of this study was to determine if there is a clinical significance in the ankle dorsiflexion that is obtained when the examination is performed incorrectly with a single hand versus the correct two-hand technique. Methods Thirty consecutive new patients with conditions associated with gastrocnemius equinus were included in the study. The Silfverskiöld test was performed with a two-hand technique and a single-hand technique. The amount of dorsiflexion obtained with the knee in full extension was measured and recorded using an extendable goniometer for each technique, with the arms aligned with the fifth metatarsal and fibular head. Results The average amount of dorsiflexion that was obtained with the two-hand technique with the knee in full extension was 76.3°±4.2°. When the one-hand technique was utilized the average amount of dorsiflexion obtained with the knee in full extension was 88.4°±4.2°. This was found to be statistically significant (p<0.01). Conclusion This study demonstrates that if the Silfverskiöld test is not performed correctly, the diagnosis of an isolated gastrocnemius contracture could be underappreciated. Accordingly, it may be important to perform the test with two hands in order to neutralize the hindfoot, midfoot, and forefoot, so that the dorsiflexion motion is through the tibiotalar joint alone.

A Randomized Clinical Trial Comparing Three Different Exercise Strategies for Optimizing Aerobic Capacity and Skeletal Muscle Performance in Older Adults: Protocol for the DART Study.

Background: Age-related declines in physical function lead to decreased independence and higher healthcare costs. Individuals who meet the endurance and resistance exercise recommendations can improve their physical function and overall fitness, even into their ninth decade. However, most older adults do not exercise regularly, and the majority of those who do only perform one type of exercise, and in doing so are not getting the benefits of endurance or resistance exercise. Herein we present the study protocol for a randomized clinical trial that will investigate the potential for high-intensity interval training (HIIT) to improve maximal oxygen consumption, muscular power, and muscle volume (primary outcomes), as well as body composition, 6-min walk distance, and muscular strength and endurance (secondary outcomes). Methods and Analysis: This is a single-site, single-blinded, randomized clinical trial. A minimum of 24 and maximum of 30 subjects aged 60-75 that are generally healthy but insufficiently active will be randomized. After completion of baseline assessments, participants will be randomized in a 1:1:1 ratio to participate in one of three 12-week exercise programs: stationary bicycle HIIT, stationary bicycle moderate-intensity continuous training (MICT), or resistance training. Repeat assessments will be taken immediately post intervention. Discussion: This study will examine the potential for stationary bicycle HIIT to result in both cardiorespiratory and muscular adaptations in older adults. The results will provide important insights into the effectiveness of interval training, and potentially support a shift from volume-driven to intensity-driven exercise strategies for older adults. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (registration number: NCT03978572, date of registration June 7, 2019).

Changes in DXA-derived lean mass and MRI-derived cross-sectional area of the thigh are modestly associated.

Dual-energy X-ray absorptiometry (DXA) derived measures of lean mass demonstrate strong associations with magnetic resonance imaging (MRI) derived measures of muscle volume (MV) in cross-sectional studies, however, few studies have compared changes in response to an intervention. The purpose of this study was to determine the accuracy of DXA at detecting changes in lean mass, using MRI-derived MV as a reference standard. 10 male and 16 female subjects (29.2 ± 9.5 years) underwent DXA and MRI scans before and after a 10-week resistance training intervention. DXA thigh lean mass was compared to MRI mid-thigh MV, and percent change in size was compared between MRI and DXA. There was a strong correlation between measures cross-sectionally (r = 0.89) in agreement with previous investigations. However, there was a modest correlation of percentage change over time between methods (r = 0.49). Bland-Altman plots revealed that the amount of random error increased as the magnitude of the change from baseline increased. DXA measures of change in lean mass were modestly associated with MRI measures of change in MV. While there are several advantages to using DXA for the measurement of lean mass, the inability to accurately detect changes over time calls into question its use in clinical trials.

Blood Flow-restricted Exercise Does Not Induce a Cross-Transfer of Effect: A Randomized Controlled Trial.

PURPOSE: The goal of this trial was to determine whether low-load blood flow-restricted (BFR) exercise of appendicular muscles induces a cross-transfer of effect to the trunk extensor (TE) muscles, such that low-load TE exercise would enhance TE size and function to a greater extent than standard low-load exercise in people with recurrent low back pain (LBP). We also investigated the direct effects of BFR exercise in the appendicular muscles. METHODS: Thirty-two adults with recurrent, nonspecific LBP were randomized into two groups: Appendicular BFR exercise (BFR exercise) or control exercise (CON exercise). All participants trained (two times per week) for 10 wk, with a 12-wk follow-up. Participants performed three sets of leg extension (LE), plantar flexion (PF), and elbow flexion (EF) exercises followed by low-load TE exercise without BFR. Outcome measures included magnetic resonance imaging-derived muscle size (quadriceps and TE), strength (LE, PF, EF, and TE), and endurance (LE and TE). RESULTS: There was no evidence for a cross-transfer of effect to the TE. There was also no statistically significant enhancement of limb skeletal muscle size or function of BFR relative to CON exercise at any time point; though, moderate effect sizes for BFR exercise were observed for enhanced muscle size and strength in the leg extensors. CONCLUSIONS: Low-load BFR exercise of the appendicular muscles did not result in a cross-transfer of effect to the TE musculature. There was also no significant benefit of low-load BFR exercise on the appendicular muscle size and function, suggesting no benefit from low-load BFR exercise in adults with recurrent, nonspecific LBP.

A randomized control trial to determine the effectiveness and physiological effects of spinal manipulation and spinal mobilization compared to each other and a sham condition in patients with chronic low back pain: Study protocol for The RELIEF Study.

BACKGROUND: Low back pain (LBP) is one of the most common reasons for seeking medical care. Manipulative therapies are a common treatment for LBP. Few studies have compared the effectiveness of different types of manipulative therapies. Moreover, the physiologic mechanisms underlying these treatments are not fully understood. Herein, we present the study protocol for The Researching the Effectiveness of Lumbar Interventions for Enhancing Function Study (The RELIEF Study). METHODS AND STUDY DESIGN: The RELIEF Study is a Phase II RCT with a nested mechanistic design. It is a single-blinded, sham-controlled study to test the mechanisms and effectiveness of two manual therapy techniques applied to individuals (n = 162; 18-45 years of age) with chronic LBP. The clinical outcome data from the mechanistic component will be pooled across experiments to permit an exploratory Phase II RCT investigating the effectiveness. Participants will be randomized into one of three separate experiments that constitute the mechanistic component to determine the muscular, spinal, and cortical effects of manual therapies. Within each of these experimental groups study participants will be randomly assigned to one of the three treatment arms: 1) spinal manipulation, 2) spinal mobilization, or 3) sham laser therapy. Treatments will be delivered twice per week for 3-weeks. DISCUSSION: This data from this will shed light on the mechanisms underlying popular treatments for LBP. Additionally, the coupling of this basic science work in the context of a clinical trial will also permit examination of the clinical efficacy of two different types of manipulative therapies.

Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia.

For well over twenty centuries the muscle wasting (sarcopenia) and weakness (dynapenia) that occurs with old age has been a predominant concern of mankind. Exercise has long been suggested as a treatment to combat sarcopenia and dynapenia, as it exerts effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations (e.g., enhanced muscle strength). For more than two decades scientists have recognized the profound role that progressive resistance exercise training can have on increasing muscle strength, muscle size and functional capacity in older adults. In this review article we discuss how resistance exercise training can be used in the management and prevention of sarcopenia and dynapenia. We first provide an overview of the evidence for this notion and highlight certain critical factors- namely exercise intensity, volume and progression- that are key to optimizing the resistance exercise prescription. We then highlight how many, if not most, of the commonly prescribed exercise programs for seniors are not the 'best practices', and subsequently present easy-to-read guidelines for a well-rounded resistance exercise training program designed for the management and prevention of sarcopenia and dynapenia, including example training programs for the beginner through the advanced senior resistance exerciser. These guidelines have been written for the academician as well as the student and health care provider across a variety of disciplines, including those in the long term care industry, such as wellness instructors or activity directors.

Premedical Students' Attitudes Toward Primary Care Medicine.

BACKGROUND: Expanded insurance coverage will likely increase the demand for primary care physicians in the United States. Despite this demand, the number of medical students planning to specialize in primary care is decreasing. OBJECTIVE: To explore premedical students' attitudes toward the primary care specialty. METHODS: Students enrolled in premedicine at a large Midwestern university were invited to complete the Primary Care Attitudes Survey (Cronbach α=.76). This 25-item survey measures attitudes about primary care on a 5-point Likert scale, ranging from 1, "strongly disagree" to 5, "strongly agree." Basic sociodemographic characteristics were assessed using descriptive statistics, and frequencies of individual survey responses were calculated using SPSS statistical software version 21.0. RESULTS: A total of 100 premedical students (mean [SD] age, 19.8 [1.5] years; 59 female, 82 white non-Hispanic, and 33 freshman) completed the survey. Of 100 students, 33 planned to pursue primary care; 66 thought that primary care physicians would always have a job; 25 thought that primary care may become obsolete as medicine becomes more specialized; 48 thought that physician assistants and nurse practitioners would take over many primary care duties in the future; 91 thought that primary care physicians make important contributions to medicine; and 84 agreed that primary care focuses on the whole patient. CONCLUSIONS: Premedical students held positive views about the importance of primary care; however, many expressed uncertainty about the stability of primary care careers in the future. Further, a substantial number of students believed common misconceptions about the scope and practice of primary care, such as primary care doctors are gatekeepers and mostly diagnose colds and ear infections.

Effectiveness of blood flow restricted exercise compared with standard exercise in patients with recurrent low back pain: study protocol for a randomized controlled trial.

BACKGROUND: Low back pain is a highly prevalent condition in the United States and has a staggeringly negative impact on society in terms of expenses and disability. It has previously been suggested that rehabilitation strategies for persons with recurrent low back pain should be directed to the medial back muscles as these muscles provide functional support of the lumbar region. However, many individuals with low back pain cannot safely and effectively induce trunk muscle adaptation using traditional high-load resistance exercise, and no viable low-load protocols to induce trunk extensor muscle adaptation exist. Herein, we present the study protocol for a randomized controlled trial that will investigate the "cross-transfer" of effects of a novel exercise modality, blood flow restricted exercise, on cross-sectional area (primary outcome), strength and endurance (secondary outcomes) of trunk extensor muscles, as well as the pain, disability, and rate of recurrence of low back pain (tertiary outcomes). METHODS AND STUDY DESIGN: This is a single-blinded, single-site, randomized controlled trial. A minimum of 32 (and up to 40) subjects aged 18 to 50 years with recurrent low back pain and poor trunk extensor muscle endurance will be recruited, enrolled and randomized. After completion of baseline assessments, participants will be randomized in a 1:1 ratio to receive a 10-week resistance exercise training program with blood flow restriction (BFR exercise group) or without blood flow restriction (control exercise group). Repeat assessments will be taken immediately post intervention and at 12 weeks after the completion of the exercise program. Furthermore, once every 4 weeks during a 36-week follow-up period, participants will be asked to rate their perceived disability and back pain over the past 14 days. DISCUSSION: This study will examine the potential for blood flow restricted exercise applied to appendicular muscles to result in a "cross-transfer" of therapeutic effect to the lumbar musculature in individuals with low back pain. The results of this study will provide important insights into the effectiveness of this novel exercise modality, which could potentially provide the foundation for a cost-effective and easy-to-implement rehabilitation strategy to induce muscle adaptation in the absence of high mechanical and compressive loading on the spine. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (registration number: NCT02308189, date of registration: 2 December 2014).

Weaker Seniors Exhibit Motor Cortex Hypoexcitability and Impairments in Voluntary Activation.

BACKGROUND: Weakness predisposes seniors to a fourfold increase in functional limitations. The potential for age-related degradation in nervous system function to contribute to weakness and physical disability has garnered much interest of late. In this study, we tested the hypothesis that weaker seniors have impairments in voluntary (neural) activation and increased indices of GABAergic inhibition of the motor cortex, assessed using transcranial magnetic stimulation. METHODS: Young adults (N = 46; 21.2±0.5 years) and seniors (N = 42; 70.7±0.9 years) had their wrist flexion strength quantified along with voluntary activation capacity (by comparing voluntary and electrically evoked forces). Single-pulse transcranial magnetic stimulation was used to measure motor-evoked potential amplitude and silent period duration during isometric contractions at 15% and 30% of maximum strength. Paired-pulse transcranial magnetic stimulation was used to measure intracortical facilitation and short-interval and long-interval intracortical inhibition. The primary analysis compared seniors to young adults. The secondary analysis compared stronger seniors (top two tertiles) to weaker seniors (bottom tertile) based on strength relative to body weight. RESULTS: The most novel findings were that weaker seniors exhibited: (i) a 20% deficit in voluntary activation; (ii) ~20% smaller motor-evoked potentials during the 30% contraction task; and (iii) nearly twofold higher levels of long-interval intracortical inhibition under resting conditions. CONCLUSIONS: These findings indicate that weaker seniors exhibit significant impairments in voluntary activation, and that this impairment may be mechanistically associated with increased GABAergic inhibition of the motor cortex.

The effects of testosterone and insulin-like growth factor 1 on motor system form and function.

In this perspective article, we review the effects of selected anabolic hormones on the motoric system and speculate on the role these hormones may have on influencing muscle and physical function via their impact on the nervous system. Both muscle strength and anabolic hormone levels decline around middle age into old age over a similar time period, and several animal and human studies indicate that exogenously increasing anabolic hormones (e.g., testosterone and insulin-like growth factor-1 (IGF-1)) in aged subjects is positively associated with improved muscle strength. While most studies in humans have focused on the effects of anabolic hormones on muscle growth, few have considered the impact these hormones have on the motoric system. However, data from animals demonstrate that administering either testosterone or IGF-1 to cells of the central and peripheral motor system can increase cell excitability, attenuate atrophic changes, and improve regenerative capacity of motor neurons. While these studies do not directly indicate that changes in anabolic hormones contribute to reduced human performance in the elderly (e.g., muscle weakness and physical limitations), they do suggest that additional research is warranted along these lines.

The power of the mind: the cortex as a critical determinant of muscle strength/weakness.

We tested the hypothesis that the nervous system, and the cortex in particular, is a critical determinant of muscle strength/weakness and that a high level of corticospinal inhibition is an important neurophysiological factor regulating force generation. A group of healthy individuals underwent 4 wk of wrist-hand immobilization to induce weakness. Another group also underwent 4 wk of immobilization, but they also performed mental imagery of strong muscle contractions 5 days/wk. Mental imagery has been shown to activate several cortical areas that are involved with actual motor behaviors, including premotor and M1 regions. A control group, who underwent no interventions, also participated in this study. Before, immediately after, and 1 wk following immobilization, we measured wrist flexor strength, voluntary activation (VA), and the cortical silent period (SP; a measure that reflect corticospinal inhibition quantified via transcranial magnetic stimulation). Immobilization decreased strength 45.1 ± 5.0%, impaired VA 23.2 ± 5.8%, and prolonged the SP 13.5 ± 2.6%. Mental imagery training, however, attenuated the loss of strength and VA by ∼50% (23.8 ± 5.6% and 12.9 ± 3.2% reductions, respectively) and eliminated prolongation of the SP (4.8 ± 2.8% reduction). Significant associations were observed between the changes in muscle strength and VA (r = 0.56) and SP (r = -0.39). These findings suggest neurological mechanisms, most likely at the cortical level, contribute significantly to disuse-induced weakness, and that regular activation of the cortical regions via imagery attenuates weakness and VA by maintaining normal levels of inhibition.