Minimizing sedentary behavior (without increasing medium-to-vigorous exercise) associated functional improvement in older women is somewhat dependent on a measurable increase in muscle size.

The optimal pattern of sedentarism displacement and mechanisms underlying its health effects are poorly understood. Therefore, the aim of this study was to quantify muscle-tendon adaptation in response to two different sedentarism displacement interventions and relate any adaptations to functional outcomes. Thirty-four older women (73±5yrs) underwent skeletal muscle-tendon size and functional assessments. Participants were randomly allocated to: Sedentary behavior fragmentation (SBF), Light intensity physical activity (LIPA), or Control groups. Measures were taken at weeks 0 and 8. Gait speed significantly increased (p=0.003), in both experimental groups (SBF: 0.06 ± 0.08m/s, 6±10%, LIPA: 0.06 ± 0.07m/s, 6±6%), but not control (-0.02 ± 0.12m/s, -2±9%). Accordingly, the relative change in Vastus Lateralis muscle volume, accounted for 30% (p=0.027), and 45% (p=0.0006) of the explained variance in the relative change in gait speed, for SBF and LIPA respectively. Gastrocnemius Medialis fascicle length changes were positively associated with gait speed changes, following LIPA exclusively (R2= 0.50, p=0.009). This is the first study to show SBF and LIPA are adequate loading in older women, with related muscle adaptation and clinically relevant gait speed improvements. Such adaptations appear similar irrespective of whether sedentarism displacement is prescribed in a single bout (LIPA) or in frequent micro-bouts (SBF).

Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults.

Evidence from clinical trials and observational studies suggests that both progressive resistance exercise training (PRT) and metformin delay a variety of age-related morbidities. Previously, we completed a clinical trial testing the effects of 14 weeks of PRT + metformin (metPRT) compared to PRT with placebo (plaPRT) on muscle hypertrophy in older adults. We found that metformin blunted PRT-induced muscle hypertrophic response. To understand potential mechanisms underlying the inhibitory effect of metformin on PRT, we analyzed the muscle transcriptome in 23 metPRT and 24 plaPRT participants. PRT significantly increased expression of genes involved in extracellular matrix remodeling pathways, and downregulated RNA processing pathways in both groups, however, metformin attenuated the number of differentially expressed genes within these pathways compared to plaPRT. Pathway analysis showed that genes unique to metPRT modulated aging-relevant pathways, such as cellular senescence and autophagy. Differentially expressed genes from baseline biopsies in older adults compared to resting muscle from young volunteers were reduced following PRT in plaPRT and were further reduced in metPRT. We suggest that although metformin may blunt pathways induced by PRT to promote muscle hypertrophy, adjunctive metformin during PRT may have beneficial effects on aging-associated pathways in muscle from older adults.

Automated assessment of regional muscle volume and hypertrophy using MRI.

This study aimed to validate a fully automatic method to quantify knee-extensor muscle volume and exercise-induced hypertrophy. By using a magnetic resonance imaging-based fat-water separated two-point Dixon sequence, the agreement between automated and manual segmentation of a specific ~15-cm region (partial volume) of the quadriceps muscle was assessed. We then explored the sensitivity of the automated technique to detect changes in both complete and partial quadriceps volume in response to 8 weeks of resistance training in 26 healthy men and women. There was a very strong correlation (r = 0.98, P < 0.0001) between the manual and automated method for assessing partial quadriceps volume, yet the volume was 9.6% greater with automated compared with manual analysis (P < 0.0001, 95% limits of agreement -93.3 ± 137.8 cm3). Partial muscle volume showed a 6.0 ± 5.0% (manual) and 4.8 ± 8.3% (automated) increase with training (P < 0.0001). Similarly, the complete quadriceps increased 5.1 ± 5.5% with training (P < 0.0001). The intramuscular fat proportion decreased (P < 0.001) from 4.1% to 3.9% after training. In conclusion, the automated method showed excellent correlation with manual segmentation and could detect clinically relevant magnitudes of exercise-induced muscle hypertrophy. This method could have broad application to accurately measure muscle mass in sports or to monitor clinical conditions associated with muscle wasting and fat infiltration.

Asymmetrical thigh creases or isolated thigh crease may be a false positive sign with low predictive value in the diagnosis of developmental dysplasia of the hip in infants: a prospective cohort study of 117 patients.

BACKGROUND: The clinical importance of asymmetrical thigh creases in the diagnosis of developmental dysplasia of the hip (DDH) in infants remains controversial. The aim of this study is to investigate the association of asymmetrical skinfolds of the thigh as the only clinical finding with the DDH in infants. METHODS: One hundred and thirty-four infants between January 2010 and December 2015 were referred to our clinics for DDH with the only clinical sign being asymmetrical or isolated thigh creases and met the inclusion criteria of the study. Patients with another clinical sign for DDH in our initial evaluation, those infants suspicious for syndrome and those older than 6 months were excluded. Finally, 117 patients had undergone clinical and ultrasound evaluation and were included to statistical analysis. RESULTS: There were 82 females and 35 males, with mean age of 2.2 months old. In 96 of the 117 infants (82.1%), there were provocative skin creases in the opposite thigh after a little pressure of the thigh by the examiner during the evaluation. Three of the babies (3.1%) with provocative skin creases and 1 (4.8%) with true isolated thigh crease had immature hips in ultrasonography. Positive predictive value for DDH of an isolated or asymmetrical thigh crease was 4.55% (95% CI 0.83-21.36%), and negative predictive value was 96.97% (95% CI 94.75-98.27%). Sensitivity of skinfold asymmetry found to be 25% (95% CI 0.63-80.59%), and specificity was 82.05% (95% CI 73.88-88.53%) for DDH. CONCLUSION: The positive predictive value of asymmetrical or isolated thigh creases for DDH in infants was found to be low, as the majority of hips with normal clinical examination and asymmetry in thigh skinfolds seemed to be normal. Moreover, in-depth evaluation of the patients could highlight new provocative thigh creases in the opposite thigh, which could limit the referrals to expert physicians to exclude DDH. LEVEL OF EVIDENCE: Level III.

Relationship between regional neuromuscular regulation within human rectus femoris muscle and lower extremity kinematics during gait in elderly men.

Biomechanical and neurophysiological mechanisms of age-related gait dysfunction have not been fully understood. We aimed to investigate the relationship between region-specific electromyography (EMG) response of the rectus femoris (RF) muscle and lower extremity kinematics during swing phase of gait for the elderly. For thirteen elderly men (age: mean 71.3 years, standard deviation 5.7 years), multi-channel surface EMG from the proximal to distal regions of the RF muscle and lower extremity kinematics were measured during normal gait on a treadmill. At minimum foot clearance during swing phase, relationship between central locus activation (CLA), which is indicator of spatial distribution of surface EMG along the RF muscle and lower joint kinematics were calculated. No significant correlations were found between CLA and any joint angle (p > 0.05). The results of our study suggested that regional neuromuscular activation of the RF muscle is not associated to lower extremity joint movements and toe clearance strategy during gait in the elderly.

High-Frequency Neuromuscular Electrical Stimulation Increases Anabolic Signaling.

PURPOSE: Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation settings to increase muscle mass and strength. However, the effects of NMES on muscle growth are not clear and no human studies have compared anabolic signaling between low-frequency (LF) and high-frequency (HF) NMES. The purpose of this study was to determine the skeletal muscle anabolic signaling response to an acute bout of LF- and HF-NMES. METHODS: Eleven young healthy volunteers (6 men, 5 women) received an acute bout of LF-NMES (20 Hz) and HF-NMES (60 Hz). Muscle biopsies were obtained from the vastus lateralis muscle before the first NMES treatment and 30 min after each NMES treatment. Phosphorylation of the following key anabolic signaling proteins was measured by Western blot, and proteins are expressed as a ratio of phosphorylated to total: mammalian target of rapamycin, p70-S6 kinase 1, and eukaryotic initiation factor 4E binding protein 1. RESULTS: Compared with pre-NMES, phosphorylation of mammalian target of rapamycin was upregulated 40.2% for LF-NMES (P = 0.018) and 68.4% for HF-NMES (P < 0.0001), and HF-NMES was 29.3% greater than LF-NMES (P = 0.026). Phosphorylation of p70-S6 kinase 1 after HF-NMES was 96.6% higher than pre-NMES (P = 0.001) and was not different between pre-NMES and LF-NMES (although it was 50.4% higher after LF-NMES) or LF- and HF-NMES (P > 0.05). There were no differences between treatment conditions for eukaryotic initiation factor 4E binding protein 1 phosphorylation (P > 0.05). CONCLUSIONS: An acute bout of LF- and HF-NMES upregulated anabolic signaling with HF-NMES producing a greater anabolic response compared with LF-NMES, suggesting that HF stimulation may provide a stronger stimulus for processes that initiate muscle hypertrophy. In addition, the stimulation frequency parameter should be considered by clinicians in the design of optimal NMES treatment protocols.

Repetitions to failure versus not to failure during concurrent training in healthy elderly men: A randomized clinical trial.

This randomized clinical trial compared the neuromuscular adaptations induced by concurrent training (CT) performed with repetitions to concentric failure and not to failure in elderly men. Fifty-two individuals (66.2 ±â€¯5.2 years) completed the pre- and post-measurements and were divided into three groups: repetitions to failure (RFG, n = 17); repetitions not to failure (NFG, n = 20); and repetitions not to failure with total volume equalized to RFG (ENFG, n = 15). Participants were assessed in isometric knee extension peak torque (PTiso), maximal strength (1RM) in the leg press (LP) and knee extension (KE) exercises, quadriceps femoris muscle thickness (QF MT), specific tension, rate of torque development (RTD) at 50, 100 and 250 ms, countermovement jump (CMJ) and squat jump (SJ) performance, as well as maximal neuromuscular activity (EMGmax) of the vastus lateralis (VL) and rectus femoris (RF) muscles. CT was performed over 12 weeks, twice weekly. Along with each specific strength training program, each group also underwent an endurance training in the same session. After training, all groups improved similarly and significantly in LP and KE 1RM, PTiso, CMJ and SJ performance, RTD variables, specific tension, and VL EMGmax, (P < 0.05-0.001). QF MT improved only in RFG and ENFG (P < 0.01). These results suggest that repetitions until concentric failure does not provide further neuromuscular performance gains and muscle hypertrophy, and that even a low number of repetitions relative to the maximal possible (i.e., 50%) optimizes neuromuscular performance in elderly men. Moreover, training volume appears to be more important for muscle hypertrophy than training using maximal repetitions.

Strength Training Effects on Muscular Regeneration after ACL Reconstruction.

PURPOSE: Protracted quadriceps muscle atrophy is observed after anterior cruciate ligament reconstruction (ACL-R). The aim of this study was to assess if quadriceps strength training with eccentric overload (CON/ECC) is more efficient to induce muscle regeneration after ACL-R than conventional concentric/eccentric (CON/ECC) strength training. METHODS: Biopsies from the vastus lateralis muscle were obtained from 37 recreational athletes after 12 wk of regular rehabilitation after ACL-R and again after 12 wk with twice a week of either conventional CON/ECC (n = 16) or CON/ECC (n = 21) one-legged supervised leg-press training. Immunohistochemical analyses were used to determine satellite cell (SC) number (Pax7); activated SC number (Pax7/MyoD); fibers expressing myosin heavy-chain (MHC) I and II, MHC neonatal, and fiber cross-sectional area. Magnetic resonance imaging was performed to measure quadriceps cross-sectional area and isokinetic testing for the measurement of quadriceps strength. RESULTS: CON/ECC induced a significantly (P = 0.002) greater increase in quadriceps cross-sectional area than did CON/ECC. There also was a significant increase in the fiber cross-sectional areas of all fiber types and in quadriceps strength, but without significant difference between training groups. Only CON/ECC training led to a significant (P < 0.05) increase in percent type I fibers. After training, the number of MHC I/MHCneo fibers was significantly (P < 0.05) greater in the CON/ECC than after in the CON/ECC group. The proportion of hybrid fibers tended to decrease in both groups; percent type II fibers, SC number, and activated SC number remained unchanged. CONCLUSIONS: CON/ECC leads to significantly greater muscle hypertrophy compared with CON/ECC, but without the hypothesized enhancing effect on SC activation. At the same time, CON/ECC+ induces a less favorable slower muscle phenotype for strong and fast movements.

Increase in echo intensity and extracellular-to-intracellular water ratio is independently associated with muscle weakness in elderly women.

PURPOSE: The changes in muscle composition and its heterogeneity during aging are associated with muscle weakness in elderly persons independent of decreases in muscle mass or muscle thickness (MT). Both the assessment of echo intensity (EI) with ultrasound imaging and the evaluation of the extracellular water/intracellular water (ECW/ICW) ratio with segmental bioelectrical impedance spectroscopy (BIS) are non-invasive and convenient methods and seem valuable for muscle quality determination. However, no previous study has evaluated both EI and the ECW/ICW ratio simultaneously to investigate their relationship to muscle strength. The purpose of the present study was to investigate whether both EI and the ECW/ICW ratio are independently associated with muscle strength in elderly women. METHODS: A total of 179 elderly women with a mean age of 74.1 ± 4.9 years, living independently in the community, were enrolled. The MT and EI of the quadriceps femoris were measured using transverse ultrasound imaging. The ECW/ICW ratio in the upper thigh was calculated from segmental BIS. The maximum knee extensor strength and the presence of knee pain were also assessed. RESULTS: Knee extensor strength showed a significant positive correlation with MT, and significant negative correlations with EI, the ECW/ICW ratio, and age. Stepwise regression analysis revealed that knee extensor strength in elderly women was predicted by MT, EI, and the ECW/ICW ratio. CONCLUSIONS: This study suggests that the simultaneous application of EI and the ECW/ICW ratio is useful in assessing muscle strength, and accurately estimates the changes in muscle quality related to muscle weakness.

The effect of age and knee osteoarthritis on muscle activation patterns and knee joint biomechanics during dual belt treadmill gait.

PURPOSE: To compare a group of individuals with moderate medial compartment knee osteoarthritis (OA) to both an age-matched asymptomatic group of older adults and younger adults to determine whether differences in knee joint muscle activation patterns and joint biomechanics exist during gait between these three groups. SCOPE: 20 young adults, 20 older adults, and 40 individuals with moderate knee OA were recruited. Using standardized procedures, surface electromyograms were recorded from the vastus lateralis and medialis, rectus femoris and the medial and lateral hamstrings. All individuals walked on a dual belt instrumented treadmill while segment motions and ground reaction forces were recorded. Sagittal plane motion and net external sagittal and frontal plane moments were calculated. Discrete measures and principal component analyses extracted amplitude and temporal waveform features. Analysis of Variance models using Bonferroni corrections determined between and within group differences in these gait features (α=0.05). CONCLUSIONS: Individuals with knee OA have distinct biomechanics and muscle activation patterns when compared to age-matched asymptomatic adults and younger adults whereas differences between the young and older adults were few and included only measures of muscle activation amplitude.

Effects of blood-flow restriction on biomarkers of myogenesis in response to resistance exercise.

We investigated the acute myogenic response to resistance exercise with and without blood-flow restriction (BFR). Six men and women (age, 22 ± 1 years) performed unilateral knee extensions at 40% of 1-repetition maximum with or without (CNTRL) BFR applied via pressure cuff inflated to 220 mm Hg. Muscle biopsies were collected at 4 h and 24 h postexercise. Addition of BFR increased myoD and c-Met messenger RNA expression relative to CNTRL. Expression of hepatocyte growth factor protein was significantly higher following CNTRL.

Effects of morning versus evening combined strength and endurance training on physical performance, muscle hypertrophy, and serum hormone concentrations.

This study investigated the effects of 24 weeks of morning versus evening same-session combined strength (S) and endurance (E) training on physical performance, muscle hypertrophy, and resting serum testosterone and cortisol diurnal concentrations. Forty-two young men were matched and assigned to a morning (m) or evening (e) E + S or S + E group (mE + S, n = 9; mS + E, n = 9; eE + S, n = 12; and eS + E, n = 12). Participants were tested for dynamic leg press 1-repetition maximum (1RM) and time to exhaustion (Texh) during an incremental cycle ergometer test both in the morning and evening, cross-sectional area (CSA) of vastus lateralis and diurnal serum testosterone and cortisol concentrations (0730 h; 0930 h; 1630 h; 1830 h). All groups similarly increased 1RM in the morning (14%-19%; p < 0.001) and evening (18%-24%; p < 0.001). CSA increased in all groups by week 24 (12%-20%, p < 0.01); however, during the training weeks 13-24 the evening groups gained more muscle mass (time-of-day main effect; p < 0.05). Texh increased in all groups in the morning (16%-28%; p < 0.01) and evening (18%-27%; p < 0.001), however, a main effect for the exercise order, in favor of E + S, was observed on both testing times (p < 0.051). Diurnal rhythms in testosterone and cortisol remained statistically unaltered by the training order or time. The present results indicate that combined strength and endurance training in the evening may lead to larger gains in muscle mass, while the E + S training order might be more beneficial for endurance performance development. However, training order and time seem to influence the magnitude of adaptations only when the training period exceeded 12 weeks.

Dystrophin-deficient dogs with reduced myostatin have unequal muscle growth and greater joint contractures.

BACKGROUND: Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition. Based partly on these results, myostatin inhibitors are in development for use in human muscular dystrophies. However, persisting concerns regarding the effects of long-term and profound myostatin inhibition will not be easily or imminently answered in clinical trials. METHODS: To address these concerns, we developed a canine (GRippet) model by crossbreeding dystrophin-deficient GRMD dogs with Mstn-heterozygous (Mstn (+/-)) whippets. A total of four GRippets (dystrophic and Mstn (+/-)), three GRMD (dystrophic and Mstn wild-type) dogs, and three non-dystrophic controls from two litters were evaluated. RESULTS: Myostatin messenger ribonucleic acid (mRNA) and protein levels were downregulated in both GRMD and GRippet dogs. GRippets had more severe postural changes and larger (more restricted) maximal joint flexion angles, apparently due to further exaggeration of disproportionate effects on muscle size. Flexors such as the cranial sartorius were more hypertrophied on magnetic resonance imaging (MRI) in the GRippets, while extensors, including the quadriceps femoris, underwent greater atrophy. Myostatin protein levels negatively correlated with relative cranial sartorius muscle cross-sectional area on MRI, supporting a role in disproportionate muscle size. Activin receptor type IIB (ActRIIB) expression was higher in dystrophic versus control dogs, consistent with physiologic feedback between myostatin and ActRIIB. However, there was no differential expression between GRMD and GRippet dogs. Satellite cell exhaustion was not observed in GRippets up to 3 years of age. CONCLUSIONS: Partial myostatin loss may exaggerate selective muscle hypertrophy or atrophy/hypoplasia in GRMD dogs and worsen contractures. While muscle imbalance is not a feature of myostatin inhibition in mdx mice, findings in a larger animal model could translate to human experience with myostatin inhibitors.

Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro.

Resistance exercise training (RT) is the most effective method for increasing skeletal muscle mass in older adults; however, the amount of RT-induced muscle growth is highly variable between individuals. Recent evidence from our laboratory and others suggests ribosome biogenesis may be an important factor regulating RT-induced hypertrophy, and we hypothesized that the extent of hypertrophy is at least partly regulated by the amount of RT-induced ribosome biogenesis. To examine this, 42 older adults underwent 4 wk of RT aimed at inducing hypertrophy of the knee extensors (e.g., 2 sets of squat, leg press, and knee extension, 10-12 repetition maximums, 3 days/wk), and vastus lateralis muscle biopsies were performed pre- and post-RT. Post hoc K-means cluster analysis revealed distinct differences in type II myofiber hypertrophy among subjects. The percent change in type II myofiber size in nonresponders (Non; n = 17) was -7%, moderate responders (Mod; n = 19) +22%, and extreme responders (Xtr; n = 6) +83%. Total muscle RNA increased only in Mod (+9%, P < 0.08) and Xtr (+26%, P < 0.01), and only Xtr increased rRNA content (+40%, P < 0.05) and myonuclei/type II fiber (+32%, P < 0.01). Additionally, Mod and Xtr had a greater increase in c-Myc protein levels compared with Non (e.g., approximately +350 and +250% vs. +50%, respectively, P < 0.05). In vitro studies showed that growth factor-induced human myotube hypertrophy is abolished when rRNA synthesis is knocked down using the Pol I-specific inhibitor CX-5461. Overall, these data implicate ribosome biogenesis as a key process regulating the extent of RT-induced myofiber hypertrophy in older adults.

Time Course of Resistance Training-Induced Muscle Hypertrophy in the Elderly.

Extended periods of resistance training (RT) induce muscle hypertrophy. Nevertheless, to date, no study has investigated the time window necessary to observe significant changes in muscle cross-sectional area (CSA) in older adults. Therefore, this study investigated the time course of muscle hypertrophy after 10 weeks (20 sessions) of RT in the elderly. Fourteen healthy older subjects were randomly allocated in either the RT (n: 6) or control group (n: 8). The RT was composed of 4 sets × 10 repetitions (70-80% 1 repetition maximum [1RM]) in a leg press machine. The time course of vastus lateralis muscle hypertrophy (CSA) was assessed on a weekly basis by mode-B ultrasonography. Leg press muscle strength was assessed by dynamic 1RM test. Our results demonstrated that the RT group increased leg press 1RM by 42% (p ≤ 0.05) after 10 weeks of training. Significant increases in vastus lateralis muscle CSA were observed only after 18 sessions of training (9 weeks; p ≤ 0.05; 7.1%). In conclusion, our training protocol promoted muscle mass accrual in older subjects, and this was only observable after 18 sessions of RT (9 weeks).

Not all the number of skeletal muscle fibers is determined prenatally.

BACKGROUND: The investigation of skeletal muscle development is of importance in stock farming and biomedicine. It is still ambiguous that whether animals are born with the full set of skeletal muscle fibers or if the number of myofibers continues to increase postnatally. RESULTS: Here, an inducible lineage-tracing system was employed to monitor the changes of myofiber number in various skeletal muscles during development. We confirm that the total myofiber number of longissimus dorsi, gastrocnemius and rectus femoris is determined prenatally. However, tibialis anterior and extensor digitorum longus have a different development pattern, and their myofiber number still increases in the first postnatal week and then remains stable afterwards. CONCLUSIONS: Our results highlight different development time frames of anatomically distinct skeletal muscles.

Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle.

Mitochondrial health is critical to physiological function, particularly in tissues with high ATP turnover, such as striated muscle. It has been postulated that derangements in skeletal muscle mitochondrial function contribute to impaired physical function in older adults. Here, we determined mitochondrial respiratory capacity and coupling control in skeletal muscle biopsies obtained from young and older adults. Twenty-four young (28 ± 7 yr) and thirty-one older (62 ± 8 yr) adults were studied. Mitochondrial respiration was determined in permeabilized myofibers from the vastus lateralis after the addition of substrates oligomycin and CCCP. Thereafter, mitochondrial coupling control was calculated. Maximal coupled respiration (respiration linked to ATP production) was lower in muscle from older vs. young subjects (P < 0.01), as was maximal uncoupled respiration (P = 0.06). Coupling control in response to the ATP synthase inhibitor oligomycin was lower in older adults (P < 0.05), as was the mitochondria flux control ratio, coupled respiration normalized to maximal uncoupled respiration (P < 0.05). Calculation of respiratory function revealed lower respiration linked to ATP production (P < 0.001) and greater reserve respiration (P < 0.01); i.e., respiratory capacity not used for phosphorylation in muscle from older adults. We conclude that skeletal muscle mitochondrial respiratory capacity and coupling control decline with age. Lower respiratory capacity and coupling efficiency result in a reduced capacity for ATP production in skeletal muscle of older adults.

The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels.

AIM: To investigate how suppression of endogenous testosterone during an 8-week strength training period influences the activity of satellite cells and myonuclei. METHODS: Twenty-two moderately trained young men participated in this randomized, placebo-controlled, and double-blinded intervention study. The participants were randomized to treatment with a GnRH analogue, goserelin (n = 12), which suppresses testosterone or placebo (n = 10) for 12 weeks. The strength training period of 8 weeks started after 4 weeks of treatment and included exercises for all major muscles. Biopsies were obtained from the mid-portion of the vastus lateralis muscle. RESULTS: Testosterone resting level in goserelin was 10-20 times lower compared with placebo, and the training-induced increase in the level of testosterone was abolished in goserelin. Training increased satellite cells number in type II fibres by 20% in placebo and by 52% in goserelin (P < 0.01), whereas the myonuclear number significantly increased by 12% in type II fibres in placebo and remained unchanged in goserelin (P < 0.05). No changes in satellite cells and myonuclei were seen in type I fibres in either group. Data from the microarray analysis indicated that low testosterone affects the bone morphogenetic proteins signalling, which might regulate proliferation vs. differentiation of satellite cells. CONCLUSION: Eight weeks of strength training enhances the myonuclear number in type II fibres, and this is largely blocked by the suppression of testosterone. The data indicate that low testosterone levels could reduce the differentiation of satellite cells to myonuclei via the bone morphogenetic proteins signalling pathway, resulting in reduced increases in lean leg mass.

Effects of three different low-intensity exercise interventions on physical performance, muscle CSA and activities of daily living: a randomized controlled trial.

OBJECTIVES: To evaluate the short-term effects of three different resistance training programs, conducted at low intensity, on physical performance, muscle cross-sectional area (CSA) and the capacity to perform daily tasks in older adults living in a geriatric nursing home. DESIGN: Randomized controlled trial, with a 4-month intervention period. SETTING: A geriatric nursing home in Valencia, Spain. PARTICIPANTS: Eighty-nine adults aged 75 to 96 who were independent in their daily activities. INTERVENTION: After a baseline assessment, the participants were randomly assigned to the control group or one of the three intervention groups: volitional contraction (VC; n=22), neuromuscular electrical stimulation (NMES; n=22), or neuromuscular electrical stimulation superimposed onto voluntary contractions (NMES+; n=22). The intervention focused on knee extension exercises and its intensity was set at 40% of one-repetition maximum (1RM). MEASUREMENTS: The primary outcome measure was mobility. Secondary outcomes were rectus femoris CSA, balance, aerobic endurance, upper-body strength and the capacity to perform daily tasks. All data were collected at baseline and after the 4-month intervention period. RESULTS: The two-way ANOVA analysis showed a significant group×time interaction effect for the mobility (P=.022), rectus femoris CSA (P=.001), and the capacity to perform daily tasks (P=.05). The within-group analysis found a more prominent effect in the NMES+ group. Significant improvements were seen in rectus femoris CSA and the capacity to perform daily tasks in all intervention groups. Mobility only improved in the NMES+ group (P=.026). CONCLUSION: From a short-term perspective, NMES+ exercise training, performed at low intensity, can improve physical performance, muscle CSA, and the capacity to perform daily activities, and to partially mitigate age-related consequences in older adults.

EHD1 mediates vesicle trafficking required for normal muscle growth and transverse tubule development.

EHD proteins have been implicated in intracellular trafficking, especially endocytic recycling, where they mediate receptor and lipid recycling back to the plasma membrane. Additionally, EHDs help regulate cytoskeletal reorganization and induce tubule formation. It was previously shown that EHD proteins bind directly to the C2 domains in myoferlin, a protein that regulates myoblast fusion. Loss of myoferlin impairs normal myoblast fusion leading to smaller muscles in vivo but the intracellular pathways perturbed by loss of myoferlin function are not well known. We now characterized muscle development in EHD1-null mice. EHD1-null myoblasts display defective receptor recycling and mislocalization of key muscle proteins, including caveolin-3 and Fer1L5, a related ferlin protein homologous to myoferlin. Additionally, EHD1-null myoblast fusion is reduced. We found that loss of EHD1 leads to smaller muscles and myofibers in vivo. In wildtype skeletal muscle EHD1 localizes to the transverse tubule (T-tubule), and loss of EHD1 results in overgrowth of T-tubules with excess vesicle accumulation in skeletal muscle. We provide evidence that tubule formation in myoblasts relies on a functional EHD1 ATPase domain. Moreover, we extended our studies to show EHD1 regulates BIN1 induced tubule formation. These data, taken together and with the known interaction between EHD and ferlin proteins, suggests that the EHD proteins coordinate growth and development likely through mediating vesicle recycling and the ability to reorganize the cytoskeleton.