Muscle Fiber Type Proportions Research Articles

Running improves muscle mass by activating autophagic flux and inhibiting ubiquitination degradation in mdx mice

BackgroundExercise therapy can improve muscle mass, strengthen muscle and cardiorespiratory function, and may be an excellent adjunctive treatment option for Duchenne muscular dystrophy. MethodsThis article investigates the effects of 10 weeks of treadmill training on skeletal muscle in control and mdx mice. Hematoxylin and eosin (H&E) staining was used to detect the morphometry of skeletal muscle; the grip strength test, suspension test, and rotarod test were used to detect limb muscle strength of mice, and Aurora Scientific Instruments were used to detect in vivo Muscle Stimulation Measuring Maximum Force of pre-fatigue and post-fatigue. The expression levels of myogenic proteins, ubiquitination markers, autophagy pathway proteins, and the proportion of different muscle fiber types were detected. ResultsThe experimental results show that running exercise can significantly improve the muscle mass of mdx mice, promote muscle strength, endurance, and anti-fatigue ability, reverse the pathological state of skeletal muscle destruction in mdx mice, and promote muscle regeneration. WB experiments showed that running inhibited the ubiquitination and degradation of muscle protein in mdx mice, inhibited AKT activation, decreased phosphorylated FoxO1 and FoxO3a, and restored the suppressed autophagic flux. Running enhances muscle strength and endurance by comprehensively promoting the expression of Myh1/2/4/7 fast and slow muscle fibers in mdx mice. ConclusionsRunning can inhibit the degradation of muscle protein in mdx mice, and promote the reuse and accumulation of proteins, thereby slowing down muscle loss. Running improves skeletal muscle mass by activating autophagic flux and inhibiting ubiquitination degradation in mdx mice.

Analysis of Muscle Fiber Type Proportions in Surface Electromyography Signals of Athletes Using Reassigned Morlet Scalogram

Analysis of Muscle Fiber Type Proportions in Surface Electromyography Signals of Athletes Using Reassigned Morlet Scalogram

Exploring the impact of temporal heat stress on skeletal muscle hypertrophy in bovine myocytes

The primary aim of this investigation was to explore the impact of different temporal stress conditions on the regulators associated with skeletal muscle hypertrophy in bovine myocytes. Bovine satellite cells (BSCs) were extracted from three-month-old Holstein bull calves and subjected to myogenic differentiation under three thermal treatments: 38 °C (control; CON), 39.5 °C (moderate heat stress; MHS), and 41 °C (extreme heat stress; EHS) for a duration of 3 or 48 h. Exposure to EHS resulted in elevated (P < 0.01) expression levels of heat shock protein (HSP)20, HSP27, HSP70, and HSP90, along with increased (P < 0.01) protein levels. Moreover, cells exposed to MHS and EHS exhibited enhanced (P < 0.01) gene expression of myoblast determination protein 1 (MyoD), while myogenin (MyoG) was overexpressed (P < 0.01) in cells exposed to EHS. These findings suggest that heat exposure can potentially induce myogenic differentiation through the modulation of myogenic regulatory factors. Furthermore, our investigations revealed that exposure to EHS upregulated (P < 0.01) myosin heavy chain (MHC) I expression, whereas MHC IIA (P < 0.01) and IIX (P < 0.01) expression were increased; P < 0.01) under MHS conditions. These observations suggest that the temperature of the muscle may alter the proportion of muscle fiber types. Additionally, our data indicated that EHS activated (P < 0.01) the expression of insulin-like growth factor 1 (IGF-1) and triggered the activation of the Akt/mTOR/S6KB1 pathway, a known anabolic pathway associated with cellular protein synthesis. Consequently, these altered signaling pathways contributed to enhanced protein synthesis and increased myotube size. Overall, the results obtained from our current study revealed that extreme heat exposure (41 °C) may promote skeletal muscle hypertrophy by regulating myogenic regulatory factors and IGF-1-mediated mTOR pathway in bovine myocytes.

Differences in Skeletal Muscle Fiber Characteristics Between Affected and Nonaffected Limbs in Individuals With Stroke: A Scoping Review.

The objective of this scoping review was to characterize and identify knowledge gaps about the changes in skeletal muscle fiber type proportion and cross-sectional area (CSA) after stroke. This scoping review followed previously proposed frameworks. A systematic search was conducted for articles examining muscle fiber type proportion and CSA in individuals with stroke in EMBASE, MEDLINE, PsycINFO, CINAHL, SPORTDiscus, and Web of Science databases from inception to December 20, 2022. Two independent authors screened and extracted the data. Results were discussed using theories proposed by the authors of the included studies. Of 13 studies (115 participants), 6 (46%) were case studies or case series, 6 (46%) were cross-sectional studies, and 1 (8%) was an experimental study. Studies had small sample sizes (1-23 participants) and various muscle sampling sites (6 different muscles). All 13 studies examined muscle fiber type distributions, and 6 (46%) examined CSA. Ten (77%) studies examined differences between paretic and nonparetic muscles, and 5 (38%) compared people with stroke to people without stroke. Results from 9 of 13 studies (69%) supported a greater proportion of type II muscle fibers in the paretic limb. Of those, 4 studies (42 participants), 3 studies (17 participants), and 1 study (1 participant) saw no differences, preferential type II and type I CSA loss between limbs, respectively. Of the limited available evidence, stroke appears to result in a shift to a higher proportion of type II muscle fibers in the paretic muscles. There are mixed results for effects on muscle fiber CSA, but there is some evidence of specific atrophy of type II muscle fibers. Changes in paretic skeletal muscle fibers of individuals with stroke may explain, in part, the substantial losses in strength and power in this population. Interventions to restore type II muscle fiber size may benefit people with stroke.

Specification of skeletal muscle fiber-type is determined by the calcineurin/NFATc1 signaling pathway during muscle regeneration

Skeletal muscle fiber type specification is changeable during muscle regeneration following cardiotoxin (CTX) injection; however, the mechanism of muscle fiber shift in regenerating muscle fibers remains unclear. Furthermore, it is unclear as to which factors determine skeletal muscle fiber types in regenerating muscle fibers. Previous studies showed that CTX-induced muscle damage resulted in a temporary hypoxic condition, indicating that hypoxia-inducible factor (HIF)-1α may be involved in muscle fiber type transition. Stabilization of HIF-1α has been shown to result in muscle fiber type transition toward slow-twitch phenotype through the calcineurin/nuclear factor activated T cell 1 (NFATc1) signaling pathway. Therefore, the aim of the present study was to determine whether the calcineurin/NFATc1 pathway is a key mediator of skeletal muscle fiber type transition during muscle regeneration. We found that CTX-induced muscle damage resulted in transient ischemia and HIF-1α expression in skeletal muscle. Additionally, it shifted the muscle fiber type proportion toward a slow-twitch phenotype in the soleus muscle (37.5% in the control muscle vs. 61.3% in the damaged muscle; p < 0.01) three weeks after muscle damage. Moreover, the NFATc1 protein levels increased in damaged muscle, and blockage of the calcineurin/NFATc1 signaling pathway by tacrolimus (FK-506) treatment substantially decreased the number of slow-twitch muscle fibers in the soleus muscle. This study demonstrated that CTX-induced muscle injury results in transient ischemia in hind limb muscle and stabilizes HIF-1α. Moreover, muscle damage increased oxidative phenotype muscle fibers through the calcineurin/NFATc1 signaling pathway during muscle regeneration.

Generation and analysis of synthetic surface electromyography signals under varied muscle fiber type proportions and validation using recorded signals.

The magnitude and duration of muscle force production are influenced by the fiber type proportion. In this work, surface electromyography (sEMG) signals of muscles with varied fiber type proportions, are generated. For this, relevant components of existing models reported in various literature have been adopted. Also, a method to calculate the motor unit size factor is proposed. sEMG signals of adductor pollicis (AP) and triceps brachii (TB) muscles are simulated from the onset of force production to muscle fatigue state at various percentages of maximal voluntary contraction (MVC) values. The model is validated using signals recorded from these muscles using well-defined isometric exercise protocols. Root mean square and mean power spectral density values extracted from the simulated and recorded signals are found to increase for TB and decrease for AP with time. A linear variation of the features with %MVC values is obtained for simulated and experimental results. The Bland-Altman plot is used to analyze the agreement between simulated and experimental feature values. Good agreement is obtained for the feature values at various %MVCs. The mean endurance time calculated using the model is found to be comparable to that of the experimental value. This method can be used to generate sEMG signals of different muscles with varying fiber type ratios under various neuromuscular conditions.

FHL3 promotes the formation of fast glycolytic muscle fibers by interacting with YY1 and muscle glycolytic metabolism.

The proportions of the various muscle fiber types are important in the regulation of skeletal muscle metabolism, as well as animal meat production. Four-and-a-half LIM domain protein 3 (FHL3) is highly expressed in fast glycolytic muscle fibers and differentially regulates the expression of myosin heavy chain (MyHC) isoforms at the cellular level. Whether FHL3 regulates the transformation of muscle fiber types in vivo and the regulatory mechanism is unclear. In this study, muscle-specific FHL3 transgenic mice were generated by random integration, and lentivirus-mediated gene knockdown or overexpression in muscles of mice or pigs was conducted. Functional analysis showed that overexpression of FHL3 in muscles significantly increased the proportion of fast-twitch myofibers and muscle mass but decreased muscle succinate dehydrogenase (SDH) activity and whole-body oxygen consumption. Lentivirus-mediated FHL3 knockdown in muscles significantly decreased muscle mass and the proportion of fast-twitch myofibers. Mechanistically, FHL3 directly interacted with the Yin yang 1 (YY1) DNA-binding domain, repressed the binding of YY1 to the fast glycolytic MyHC2b gene regulatory region, and thereby promoted MyHC2b expression. FHL3 also competed with EZH2 to bind the repression domain of YY1 and reduced H3K27me3 enrichment in the MyHC2b regulatory region. Moreover, FHL3 overexpression reduced glucose tolerance by affecting muscle glycolytic metabolism, and its mRNA expression in muscle was positively associated with hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Therefore, FHL3 is a novel potential target gene for the treatment of muscle metabolism-related diseases and improvement of animal meat production.

Morphological and histochemical characterization of the pectoral fin muscle of batoids.

Batoids differ from other elasmobranch fishes in that they possess dorsoventrally flattened bodies with enlarged muscled pectoral fins. Most batoids also swim using either of two modes of locomotion: undulation or oscillation of the pectoral fins. In other elasmobranchs (e.g., sharks), the main locomotory muscle is located in the axial myotome; in contrast, the main locomotory muscle in batoids is found in the enlarged pectoral fins. The pectoral fin muscles of sharks have a simple structure, confined to the base of the fin; however, little to no data are available on the more complex musculature within the pectoral fins of batoids. Understanding the types of fibers and their arrangement within the pectoral fins may elucidate how batoid fishes are able to utilize such unique swimming modes. In the present study, histochemical methods including succinate dehydrogenase (SDH) and immunofluoresence were used to determine the different fiber types comprising these muscles in three batoid species: Atlantic stingray (Dasyatis sabina), ocellate river stingray (Potamotrygon motoro) and cownose ray (Rhinoptera bonasus). All three species had muscles comprised of two muscle fiber types (slow-red and fast-white). The undulatory species, D. sabina and P. motoro, had a larger proportion of fast-white muscle fibers compared to the oscillatory species, R. bonasus. The muscle fiber sizes were similar between each species, though generally smaller compared to the axial musculature in other elasmobranch fishes. These results suggest that batoid locomotion can be distinguished using muscle fiber type proportions. Undulatory species are more benthic with fast-white fibers allowing them to contract their muscles quickly, as a possible means of escape from potential predators. Oscillatory species are pelagic and are known to migrate long distances with muscles using slow-red fibers to aid in sustained swimming.

The electrophysiological properties of hindlimb motoneurons do not differ between male and female rats.

Several studies have reported differences in the morphological characteristics of motoneurons and the contractile properties of motor units of male and female rats. However, differences in spinal motoneuron activity between the sexes are not well understood. This study investigates the electrophysiological properties of spinal α‐motoneurons in male and female Wistar rats under pentobarbital anaesthesia. Fast and slow types of tibial motoneurons were recorded intracellularly in 15 male and 15 female rats, and the measured parameters were compared statistically using two‐way ANOVA and Tukey post hoc tests. The membrane properties, action potential parameters and firing characteristics were not different between sexes, though significant differences were observed in the properties of fast and slow motoneuron types within both sex groups. We conclude that the sex‐related differences observed in motor performance between male and female rats are largely due to differences in muscle mass, the proportion of muscle fibre types and the related motor unit contractile properties, while the mechanisms of motor control dependent on the electrophysiological activity of motoneurons are similar between the sexes. These findings are significant, as they indicate that results of experiments investigating electrophysiological properties can be reliably compared between sexes.

Association of muscle fiber type with measures of obesity: A systematic review.

Obesity derives from an extended period of positive energy imbalance due to a complex interplay of environmental and biological factors. Muscle fiber type and physiology have been hypothesized to affect metabolism and energy expenditure and thus to affect an individual's propensity to gain weight. However, there have been conflicting reports regarding a relationship between muscle fiber type and obesity. Here, we systematically reviewed literature investigating this topic from PubMed, Web of Science, and EMBASE. Of these, 32 articles were included in our final review and analysis. Most studies (22/32) reported a significant relationship between muscle fiber-type proportion and a measure of obesity. Overall, there was a significant negative relationship between the proportion of type I fibers and body mass index (BMI) and a significant positive relationship between the proportion of type IIX fibers and BMI. Moreover, between-group comparisons indicated a greater prevalence of type IIX fibers and a lower prevalence of type I fibers in patients living with obesity relative to lean individuals. These significant relationships were confirmed in a meta-analysis of these data. The causal nature of these associations remains to be evaluated.

Are muscle fiber types different between normal and dark-cutting beef?

Muscle fiber (MF) characteristics of longissimus thoracis (LT) muscles from heifer (n = 11) and steer (n = 12) carcasses graded Canada AA (AA, normal, n = 4 per sex) or dark-cutting (Canada B4) were examined and related to beef quality. Atypical (AB4, pH &lt; 5.9, n = 4 per sex) and typical (TB4, pH &gt; 5.9, n = 3 and 4 for heifers and steers, respectively) dark-cutting carcasses were represented. Muscle fiber type proportions did not differ between AA, AB4, and TB4 muscles, although type I and IIB muscle fiber diameters were greater in TB4 than in AA LT. That AB4 muscle fiber proportions were not different from AA and TB4 muscles suggests that the increased MF diameter of TB4 muscle was due to water retained by muscle proteins at high ultimate pH, as evidenced by decreased cooking loss. Dark-cutting was therefore unrelated to muscle fiber proportions, and increased type I and IIB diameters in dark cutting LT were likely driven by elevated intramuscular ultimate pH.

Skeletal muscle phenotyping of Hippo gene-mutated mice reveals that Lats1 deletion increases the percentage of type I muscle fibers

The Hippo signal transduction network regulates transcription through Yap/Taz-Tead1-4 in many tissues including skeletal muscle. Whilst transgenic mice have been generated for many Hippo genes, the resultant skeletal muscle phenotypes were not always characterized. Here, we aimed to phenotype the hindlimb muscles of Hippo gene-mutated Lats1−/−, Mst2−/−, Vgll3−/−, and Vgll4+/− mice. This analysis revealed that Lats1−/− mice have 11% more slow type I fibers than age and sex-matched wild-type controls. Moreover, the mRNA expression of slow Myh7 increased by 50%, and the concentration of type I myosin heavy chain is 80% higher in Lats1−/− mice than in age and sex-matched wild-type controls. Second, to find out whether exercise-related stimuli affect Lats1, we stimulated C2C12 myotubes with the hypertrophy agent clenbuterol or the energy stress agent AICAR. We found that both stimulated Lats1 expression by 1.2 and 1.3 fold respectively. Third, we re-analyzed published datasets and found that Lats1 mRNA in muscle is 63% higher in muscular dystrophy, increases by 17–77% after cardiotoxin-induced muscle injury, by 41–71% in muscles during overload-induced hypertrophy, and by 19–21% after endurance exercise when compared to respective controls. To conclude, Lats1 contributes to the regulation of muscle fiber type proportions, and its expression is regulated by physiological and pathological situations in skeletal muscle.

A highly prevalent SINE mutation in the myostatin (MSTN) gene promoter is associated with low circulating myostatin concentration in Thoroughbred racehorses

Horse racing is a popular and financially important industry worldwide and researchers and horse owners are interested in genetic and training influences that maximise athletic performance. An association has been found between the presence of a short interspersed nuclear element (SINE) mutation in the myostatin (MSTN) gene promoter and optimal race distance in Thoroughbred horses. There is previous laboratory evidence that this mutation reduces MSTN expression in a cell culture model and influences skeletal muscle fibre type proportions in horses. Manipulating MSTN expression has been proposed for illicit gene doping in human and equine athletes and already, researchers have generated homozygous and heterozygous MSTN-null horse embryos following CRISPR/Cas9 editing at the equine MSTN locus and nuclear transfer, aiming artificially to enhance performance. To date however, the role of the naturally-occurring equine MSTN SINE mutation in vivo has remained unclear; here we hypothesised that it reduces, but does not ablate circulating myostatin expression. Following validation of an ELISA for detection of myostatin in equine serum and using residual whole blood and serum samples from 176 Thoroughbred racehorses under identical management, horses were genotyped for the SINE mutation by PCR and their serum myostatin concentrations measured. In our population, the proportions of SINE homozygotes, heterozygotes and normal horses were 27%, 46% and 27% respectively. Results indicated that horses that are homozygous for the SINE mutation have detectable, but significantly lower (p < 0.0001) serum myostatin concentrations (226.8 pg/ml; 69.3–895.4 pg/ml; median; minimum–maximum) than heterozygous (766 pg/ml; 64.6–1182 pg/ml) and normal horses (1099 pg/ml; 187.8–1743 pg/ml). Heterozygotes have significantly lower (p < 0.0001) myostatin concentrations than normal horses. Variation in serum myostatin concentrations across horses was not influenced by age or sex. This is the first study to reveal the direct functional effect of a highly prevalent mutation in the equine MSTN gene associated with exercise performance. Determining the reason for variation in expression of myostatin within SINE-genotyped groups might identify additional performance-associated environmental or genetic influences in Thoroughbreds. Understanding the mechanism by which altered myostatin expression influences skeletal muscle fibre type remains to be determined.

Skeletal Muscle Development in Postnatal Beef Cattle Resulting from Maternal Protein Restriction during Mid-Gestation.

Simple SummaryThe intrauterine period plays a major role in skeletal muscle development and metabolism, including the formation of muscle fibers and adipose and connective tissue. Since the embryo and fetus depend on maternal nutrition to develop and grow, understanding the effects and finding potential strategies of skeletal muscle manipulation may be a valuable alternative to enhance beef cattle performance postnatally. In the present study, we evaluated the effects of maternal protein restriction during mid-gestation on the short and long -term skeletal muscle composition of the offspring. Our results suggest that the detrimental effects of maternal protein restriction during mid-gestation were associated with decrease in muscle fibers formation and may have contributed to the increase in collagen content in the skeletal muscle of the offspring. Although the changes in muscle fiber metabolism were not persistent, maternal protein restriction may contribute to such a short-term alteration. Our findings highlight the importance of an adequate nutritional plane for pregnant beef cows, to improve offspring’s performance, and consequently, the meat quality.We aimed to investigate the effects of maternal protein restriction during mid-gestation on the skeletal muscle composition of the offspring. In the restriction treatment (RES, n = 9), cows were fed a basal diet, while in the control (CON, n = 9) group cows received the same RES diet plus the protein supplement during mid-gestation (100–200d). Samples of Longissimus dorsi muscle were collected from the offspring at 30d and 450d postnatal. Muscle fiber number was found to be decreased as a result of maternal protein restriction and persisted throughout the offspring’s life (p < 0.01). The collagen content was enhanced (p < 0.05) due to maternal protein restriction at 30d. MHC2X mRNA expression tended to be higher (p = 0.08) in RES 30d offspring, however, no difference (p > 0.05) was found among treatments at 450d. Taken together, our results suggest that maternal protein restriction during mid-gestation has major and persistent effects by reducing muscle fiber formation and may slightly increase collagen accumulation in the skeletal muscle of the offspring. Although maternal protein restriction may alter the muscle fiber metabolism by favoring the establishment of a predominant glycolytic metabolism, the postnatal environment may be a determinant factor that establishes the different proportion of muscle fiber types.

Torque Production at Different Velocities as a Predictor of the Proportion of Fast-twitch Muscle Fibers in Skeletal Muscles of Athletes

The aim of the study was to evaluate the possibility to predict the muscle fiber-type proportion in men of different sports specialization by testing the maximal torque production by knee extensors at different velocities. For this reason the proportion of fast- and slow-twitch muscle fibers (MFs) in m. vastus lateralis of 23 athletes (11 endurance and 12 power athletes), as well the maximal torque production of knee extensors at various angular velocities in isokinetic mode were determined. The group of strength trained athletes significantly exceeded the group of endurance trained athletes in body mass, body mass index, volume of the m. quadriceps femoris, maximum torque production, and specific force at angular velocities 30, 180 and 300 degrees per second. In contrast to cross-sectional area (CSA) of slow-twitch MFs, the average CSA of fast-twitch MFs and the proportion of fast-twitch MFs in the group of power athletes significantly exceeded those in the group of endurance athletes. In the combined group of volunteers (n = 23), the proportion of fast-twitch MFs significantly correlated with the torque production at high angular velocities (r = 0.51 and p = 0.01 at 180 deg/s; r = 0.47 and p = 0.02 at 300 deg/s). We did not find any correlation between these parameters in the separate groups of power and endurance athletes. The results indicate a low accuracy in predicting the proportion of fast-twitch MF in m. vastus lateralis in athletes using the maximal torque production of knee extensors at different angular velocities. Significant correlation between the proportion of fast-twitch MF and maximal torque at high angular velocities in the general group (n = 23) was due to the presence of two significantly different subgroups.

Functional correlations of axial muscle fiber type proportions in the waterfall-climbing Hawaiian stream fish Sicyopterus stimpsoni.

Assessing the factors that contribute to successful locomotor performance can provide critical insight into how animals survive in challenging habitats. Locomotion is powered by muscles, so that differences in the relative proportions of red (slow-oxidative) vs. white (fast-glycolytic) fibers can have significant implications for locomotor performance. We compared the relative proportions of axial red muscle fibers between groups of juveniles of the amphidromous gobiid fish, Sicyopterus stimpsoni, from the Hawaiian Islands. Juveniles of this species migrate from the ocean into freshwater streams, navigating through a gauntlet of predators that require rapid escape responses, before reaching waterfalls which must be climbed (using a slow, inching behavior) to reach adult breeding habitats. We found that fish from Kaua'i have a smaller proportion of red fibers in their tail muscles than fish from Hawai'i, matching expectations based on the longer pre-waterfall stream reaches of Kaua'i that could increase exposure to predators, making reduction of red muscle and increases in white muscle advantageous. However, no difference in red muscle proportions was identified between fish that were either successful or unsuccessful in scaling model waterfalls during laboratory climbing trials, suggesting that proportions of red muscle are near a localized fitness peak among Hawaiian individuals.

Masticatory muscle function affects the pathological conditions of dentofacial deformities.

SummaryThe causes of dentofacial deformities include various known syndromes, genetics, environmental and neuromuscular factors, trauma, and tumors. Above all, the functional effects of muscles are important, and deformation of the mandible is often associated with a mechanical imbalance of the masticatory muscles.With the vertical position of the face, weakness of the sling of the masseter muscle and medial pterygoid muscle causes dilatation of the mandibular angle. In patients with a deep bite, excessive function of the masticatory muscles is reported.Myosin heavy chain (MyHC) properties also affect jawbone morphology. In short-face patients, the proportion of type II fibers, which are fast muscles, is high. The proportions of muscle fiber types are genetically determined but can be altered by postnatal environmental factors. Orthognathic surgery may results in the transition of MyHC to type II (fast) fibers, but excessive stretching enhances the release of inflammatory mediators and causes a shift toward a greater proportion of slow muscle fibers. This feature can be related to postoperative relapse.Bones and muscles are in close crosstalk, and it may be possible to use biochemical approaches as well as biomechanical considerations for the treatment of jaw deformities.

Muscle biopsies differ in relation to expression of fiber-type specific genes

Background: Skeletal muscle transcriptome has been analyzed to report muscle-specific biomarkers, but muscle heterogeneity has largely been overlooked in pursuit of formulating a balanced design. Given the heterogeneity of muscle tissue in terms of both function and fiber-type composition, there could be several unaccounted sources of variation affecting the gene expression profile of skeletal muscles. Categorization of muscle transcriptome according to the source of variation will not only improve the power of transcriptome comparison tests but also will help to identify unaccounted biological sources of variation. Materials and Methods: Gene expression profile of normal skeletal muscle subjects (GSE18732) were analyzed with R-statistical software and Bioconductor packages. Gene-sets were prepared by grouping Affymetrix probes according to biological processes they were annotated. Coherence score and associated P values were calculated for each gene-set. All gene-sets having P < 0.05 were selected as coherent gene-set. Results: We have analyzed gene-sets and used coherence scores to measure the degree of coregulation between genes of a gene-set. We have shown that coherent gene-sets have a better chance to classify samples into biologically relevant subgroups as compared to noncoherent gene-sets. Further, we have applied the developed method to the muscle gene expression profiles and found that muscle fiber-type proportion in collected biopsies is one of the most prominent unaccounted “source of variations” affecting gene expression measurements. Conclusion: The sample classification produced based on the expression profile of genes belonging to coherent gene-sets has a better chance to result in biologically meaningful clusters.

MiR-222 is involved in the regulation of genistein on skeletal muscle fiber type

In skeletal muscle, the composition of the fiber types has a profound impact on athletic performance, such as endurance or strength output. The proportions of muscle fiber types have also been associated with certain diseases, including dyskinesia, obesity and insulin resistance. Genistein, a natural estrogen, has been demonstrated to regulate fatty acid oxidation and insulin sensitivity in skeletal muscle. However, it is unknown whether genistein can regulate skeletal muscle fiber types. Furthermore, the mechanism of its effect on skeletal muscle energy metabolism is not entirely clear. In this study, in vivo and in vitro experiments were used to explore the effect of genistein on the muscle fiber-type transitions and muscle metabolism. The results indicated that genistein not only promotes skeletal muscle development but increases the expression of slow muscle fibers in mice as well. It was also demonstrated that genistein altered the ratios of fiber type and promoted mitochondrial biogenesis in C2C12 myoblasts. Interestingly, the expression of miR-222 was decreased by genistein, and it was demonstrated that this microRNA targets the PGC1α gene. In C2C12 myoblasts, miR-222 appears to regulate fiber type conversion and mitochondrial biogenesis. However, this function was significantly reduced following genistein treatment. These results suggest that miR-222 may be involved in the regulation of genistein on skeletal muscle fiber and muscle metabolism, and genistein may be used to improve muscle health.

EFFECTS OF MUSCLE ALTERATIONS AND REHABILITATION ON MOBILITY IN CHRONIC CONDITIONS OF AGING

Age-related changes in muscle morphology and composition are associated with the development of mobility impairments, an increased risk for institutionalization, and mortality. While primary aging may account for some of these changes, the presence of aging related co-morbid conditions such as frailty, stroke, diabetes, and Parkinson’s disease is associated with muscle fiber atrophy, increased intramuscular fat, changes in muscle fiber distribution, and vascular dysfunction that occurs in both large and small vessels. These changes ultimately result in impaired substrate delivery to the muscle, reduced capacity for muscle regeneration, and anabolic resistance leading to declines in balance, strength, and endurance. It is important to understand the biological underpinnings of the changes in muscle following each of these conditions to develop effective preventive measures and maximize restorative rehabilitation protocols. This session will discuss the changes in muscle from the fiber level (i.e., changes in innervation and muscle fiber type proportion) to the systemic level (i.e., changes in specific postural and locomotor muscles), and their relationship to mobility, balance, and function. We will describe techniques (i.e., imaging, EMG, and muscle biopsies) used to assess muscle changes and their applicability in rehabilitation research. Further, we will discuss clinical recommendations for exercise to preserve and enhance skeletal muscle in the aging adult.