Adult Muscle Research Articles

Islr regulates satellite cells asymmetric division through the SPARC/p-ERK1/2 signaling pathway.

Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.

Relationship of endogenous plasma concentrations of β-hydroxy β-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus

BackgroundSupplementation with β-hydroxy β-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. ObjectivesThe purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). MethodsData were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. Results255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. ConclusionsCross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle.

Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P=0.028, N=3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100nM) for 7days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3weeks after operation (N=3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20months of age, N=5) for 3months to investigate whether vitamin D deficiency causes IMAT formation. Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P=0.0031) and C/EBPα (P=0.0027), whereas VDR-deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P=0.0044, Oil-Red O+ area). In consistency with in-vitro findings, VdrMPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P=0.0311) and aged (P=0.0216) skeletal muscle, respectively. Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Functional outcomes following surgery for spastic hip adductor muscles in ambulatory and non-ambulatory adults.

To evaluate functional outcomes of surgery of spastic hip adductor muscles (obturator neurotomy with or without adductor longus tenotomy) in ambulatory and non-ambulatory patients, using preoperatively defined personalized goals. Retrospective observational descriptive study. Twenty-three patients with adductor spasticity who underwent obturator neurotomy between May 2016 and May 2021 at the Clinique des Cèdres, Cornebarrieu, France, were included. Postoperative functional results were evaluated in accordance with the Goal Attainment Scaling method. Patients were considered "responders" if their score was ≥ 0. Secondary outcomes included spasticity, strength, hip range of motion and change in ambulatory capacity. When data were available, a comparison of pre- and postoperative 3-dimensional instrumented gait analysis was also performed. Among the 23 patients only 3 were non-walkers. Seventeen/22 patients achieved their main goal and 14/23 patients achieved all their goals. Results were broadly similar for both walking goals (inter-knee contact, inter-feet contact, fluidity, walking perimeter, toe drag) and non-walking goals (intimacy, transfer, pain, posture, dressing). Surgery of spastic hip adductor muscles results in functional improvement in ambulation, hygiene, dressing and posture and can be offered to patients with troublesome adductor overactivity. The use of a motor nerve block is recommended to define relevant goals before the surgery.

The interplay of maternal and offspring obesogenic diets: the impact on offspring metabolism and muscle mitochondria in an outbred mouse model.

Consumption of obesogenic (OB) diets increases the prevalence of maternal obesity worldwide, causing major psychological and social burdens in women. Obesity not only impacts the mother's health and fertility but also elevates the risk of obesity and metabolic disorders in the offspring. Family lifestyle is mostly persistent through generations, possibly contributing to the growing prevalence of obesity. We hypothesized that offspring metabolic health is dependent on both maternal and offspring diet and their interaction. We also hypothesized that the sensitivity of the offspring to the diet may be influenced by the match or mismatch between offspring and maternal diets. To test these hypotheses, outbred Swiss mice were fed a control (C, 10% fat, 7% sugar, and n = 14) or OB diet (60% fat, 20% sugar, and n = 15) for 7 weeks and then mated with the same control males. Mice were maintained on the same corresponding diet during pregnancy and lactation, and the offspring were kept with their mothers until weaning. The study focused only on female offspring, which were equally distributed at weaning and fed C or OB diets for 7 weeks, resulting in four treatment groups: C-born offspring fed C or OB diets (C » C and C » OB) and OB-born offspring fed C or OB diets (OB » C and OB » OB). Adult offspring's systemic blood profile (lipid and glucose metabolism) and muscle mitochondrial features were assessed. We confirmed that the offspring's OB diet majorly impacted the offspring's health by impairing the offspring's serum glucose and lipid profiles, which are associated with abnormal muscle mitochondrial ultrastructure. Contrarily, maternal OB diet was associated with increased expression of mitochondrial complex markers and mitochondrial morphology in offspring muscle, but no additive effects of (increased sensitivity to) an offspring OB diet were observed in pups born to obese mothers. In contrast, their metabolic profile appeared to be healthier compared to those born to lean mothers and fed an OB diet. These results are in line with the thrifty phenotype hypothesis, suggesting that OB-born offspring are better adapted to an environment with high energy availability later in life. Thus, using a murine outbred model, we could not confirm that maternal obesogenic diets contribute to female familial obesity in the following generations.

The exon junction complex is required for DMD gene splicing fidelity and myogenic differentiation

Deposition of the exon junction complex (EJC) upstream of exon-exon junctions helps maintain transcriptome integrity by preventing spurious re-splicing events in already spliced mRNAs. Here we investigate the importance of EJC for the correct splicing of the 2.2-megabase-long human DMD pre-mRNA, which encodes dystrophin, an essential protein involved in cytoskeletal organization and cell signaling. Using targeted RNA-seq, we show that knock-down of the eIF4A3 and Y14 core components of EJC in a human muscle cell line causes an accumulation of mis-splicing events clustered towards the 3′ end of the DMD transcript (Dp427m). This deregulation is conserved in the short Dp71 isoform expressed ubiquitously except in adult skeletal muscle and is rescued with wild-type eIF4A3 and Y14 proteins but not with an EJC assembly-defective mutant eIF4A3. MLN51 protein and EJC-associated ASAP/PSAP complexes independently modulate the inclusion of the regulated exons 71 and 78. Our data confirm the protective role of EJC in maintaining splicing fidelity, which in the DMD gene is necessary to preserve the function of the critical C-terminal protein–protein interaction domain of dystrophin present in all tissue-specific isoforms. Given the role of the EJC in maintaining the integrity of dystrophin, we asked whether the EJC could also be involved in the regulation of a mechanism as complex as skeletal muscle differentiation. We found that eIF4A3 knockdown impairs myogenic differentiation by blocking myotube formation. Collectively, our data provide new insights into the functional roles of EJC in human skeletal muscle.

Chromatin profiling reveals TFAP4 as a critical transcriptional regulator of bovine satellite cell differentiation

BackgroundSatellite cells are myogenic precursor cells in adult skeletal muscle and play a crucial role in skeletal muscle regeneration, maintenance, and growth. Like embryonic myoblasts, satellite cells have the ability to proliferate, differentiate, and fuse to form multinucleated myofibers. In this study, we aimed to identify additional transcription factors that control gene expression during bovine satellite cell proliferation and differentiation.ResultsUsing chromatin immunoprecipitation followed by sequencing, we identified 56,973 and 54,470 genomic regions marked with both the histone modifications H3K4me1 and H3K27ac, which were considered active enhancers, and 50,956 and 59,174 genomic regions marked with H3K27me3, which were considered repressed enhancers, in proliferating and differentiating bovine satellite cells, respectively. In addition, we identified 1,216 and 1,171 super-enhancers in proliferating and differentiating bovine satellite cells, respectively. Analyzing these enhancers showed that in proliferating bovine satellite cells, active enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation whereas repressed enhancers were associated with genes essential for myoblast differentiation, and that in differentiating satellite cells, active enhancers were associated with genes essential for myoblast differentiation or muscle contraction whereas repressed enhancers were associated with genes stimulating cell proliferation or inhibiting myoblast differentiation. Active enhancers in proliferating bovine satellite cells were enriched with binding sites for many transcription factors such as MYF5 and the AP-1 family transcription factors; active enhancers in differentiating bovine satellite cells were enriched with binding sites for many transcription factors such as MYOG and TFAP4; and repressed enhancers in both proliferating and differentiating bovine satellite cells were enriched with binding sites for NF-kB, ZEB-1, and several other transcription factors. The role of TFAP4 in satellite cell or myoblast differentiation was previously unknown, and through gene knockdown and overexpression, we experimentally validated a critical role for TFAP4 in the differentiation and fusion of bovine satellite cells into myofibers.ConclusionsSatellite cell proliferation and differentiation are controlled by many transcription factors such as AP-1, TFAP4, NF-kB, and ZEB-1 whose roles in these processes were previously unknown in addition to those transcription factors such as MYF5 and MYOG whose roles in these processes are widely known.

Profiling and functional analysis of circular RNAs in yaks intramuscular fat.

Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression. However, the regulatory mechanisms of lipid metabolism in yaks involved in circRNAs remain poorly understood. The IMF plays a crucial role in the quality of yak meat, to greatly improve the meat quality. In this study, the fatty acid profiles of yak IMF were determined and circRNAs were sequenced. The results showed that the total of polyunsaturated fatty acid (PUFA) content of adult yak muscle was significantly higher than that in yak calves (p < 0.05). A total of 29,021 circRNAs were identified in IMF tissue, notably, 99 differentially expressed (DE) circRNAs were identified, to be associated with fat deposition, the most significant of which were circ_12686, circ_6918, circ_3582, ci_106and ci_123 (A circRNA composed of exons is labelled 'circRNA'and a circRNA composed of introns is labelled 'ciRNA'). KEGG pathway enrichment analysis showed that the differential circRNAs were enriched in four pathways associated with fat deposition (e.g., the peroxisome proliferator-activated receptor signalling, fatty acid degradation, sphingolipid metabolismand sphingolipid signalling pathways). We also constructed co-expression networks of DE circRNA-miRNA using high-throughput sequencing in IMF deposition, from which revealed that ci_106 target binding of bta-miR-130b, bta-miR-148a, bta-miR-15a, bta-miR-34a, bta-miR-130a, bta-miR-17-5pand ci_123 target binding of bta-miR-150 were involved in adipogenesis. The study revealed the role of the circRNAs in the IMF deposition in yak and its influence on meat quality the findings demonstrated the circRNA differences in the development of IMF with the increase of age, thus providing a theoretical basis for further research on the molecular mechanism of IMF deposition in yaks.

Effect of probiotics or synbiotics on skeletal muscle in older adults: a systematic review and meta-analysis of randomized controlled trials

Effect of probiotics or synbiotics on skeletal muscle in older adults: a systematic review and meta-analysis of randomized controlled trials

Reorganization of mitochondria-organelle interactions during postnatal development in skeletal muscle.

Skeletal muscle cellular development requires the integrated assembly of mitochondria and other organelles adjacent to the sarcomere in support of muscle contractile performance. However, it remains unclear how interactions among organelles and with the sarcomere relates to the development of muscle cell function. Here, we combine 3D volume electron microscopy, proteomic analyses, and live cell functional imaging to investigate the postnatal reorganization of mitochondria-organelle interactions in skeletal muscle. We show that while mitochondrial networks are disorganized and loosely associated with the contractile apparatus at birth, contact sites among mitochondria, lipid droplets and the sarcoplasmic reticulum are highly abundant in neonatal muscles. The maturation process is characterized by a transition to highly organized mitochondrial networks wrapped tightly around the muscle sarcomere but also to less frequent interactions with both lipid droplets and the sarcoplasmic reticulum. Concomitantly, expression of proteins involved in mitochondria-organelle membrane contact sites decreases during postnatal development in tandem with a decrease in abundance of proteins associated with sarcomere assembly despite an overall increase in contractile protein abundance. Functionally, parallel measures of mitochondrial membrane potential, NADH redox status, and NADH flux within intact cells revealed that mitochondria in adult skeletal muscle fibres maintain a more activated electron transport chain compared with neonatal muscle mitochondria. These data demonstrate a developmental redesign reflecting a shift from muscle cell assembly and frequent inter-organelle communication toward a muscle fibre with mitochondrial structure, interactions, composition and function specialized to support contractile function. KEY POINTS: Mitochondrial network organization is remodelled during skeletal muscle postnatal development. The mitochondrial outer membrane is in frequent contact with other organelles at birth and transitions to more close associations with the contractile apparatus in mature muscles. Mitochondrial energy metabolism becomes more activated during postnatal development. Understanding the developmental redesign process within skeletal muscle cells may help pinpoint specific areas of deficit in muscles with developmental disorders.

Bisphenol-A Abrogates Proliferation and Differentiation of C2C12 Mouse Myoblasts via Downregulation of Phospho-P65 NF-κB Signaling Pathway.

Previous studies showed that bisphenol-A (BPA), a monomer of polycarbonate plastic, is leached out and contaminated in foods and beverages. This study aimed to investigate the effects of BPA on the myogenesis of adult muscle stem cells. C2C12 myoblasts were treated with BPA in both proliferation and differentiation conditions. Cytotoxicity, cell proliferation and differentiation, antioxidant activity, apoptosis, myogenic regulatory factors (MRFs) gene expression, and mechanism of BPA on myogenesis were examined. C2C12 myoblasts exposed to 25-50 µM BPA showed abnormal morphology, expressing numerous and long cytoplasmic extensions. Cell proliferation was inhibited and was accumulated in subG1 and S phases of the cell cycle, subsequently leading to apoptosis confirmed by nuclear condensation and the expression of apoptosis markers, cleaved caspase-9 and caspase-3. In addition, the activity of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase was significantly decreased. Meanwhile, BPA suppressed myoblast differentiation by decreasing the number and size of multinucleated myotubes via the modulation of MRF gene expression. Moreover, BPA significantly inhibited the phosphorylation of P65 NF-κB in both proliferation and differentiation conditions. Altogether, the results revealed the adverse effects of BPA on myogenesis leading to abnormal growth and development via the inhibition of phospho-P65 NF-κB.

The RU486-dependent activation of the GeneSwitch system in adult muscles leads to severe adverse effects in Drosophila.

Robust genetic systems to control the expression of transgenes in a spatial and temporal manner are a valuable asset for researchers. The GeneSwitch system induced by the drug RU486 has gained widespread use in the Drosophila community. However, some concerns were raised as negative effects were seen depending on the stock, transgene, stage, and tissue under study. Here, we characterized the adverse effects triggered by activating the GeneSwitch system in adult muscles using the MHC-GS-GAL4 driver. When a control, mock UAS-RNAi transgene was induced by feeding adult flies with RU486, we found that the overall muscle structure, including myofibrils and mitochondrial shape, was significantly disrupted and led to a significant reduction in the lifespan. Remarkably, lifespan was even shorter when 2 copies of the driver were used even without the mock UAS-RNAi transgene. Thus, researchers should be cautious when interpreting the results given the adverse effects we found when inducing RU486-dependent MHC-GS-GAL4 in adult muscles. To account for the impact of these effects we recommend adjusting the dose of RU486, setting up additional control groups, such as a mock UAS-RNAi transgene, as comparing the phenotypes between RU486-treated and untreated animals could be insufficient.

Ciliary muscle and anterior segment characteristics in pre-presbyopic adults with Down syndrome.

Previous research has shown that accommodation deficits are common in individuals with Down syndrome (DS), but the origin and mechanisms behind these deficits are still unknown. The aim of this study was to investigate the characteristics of different ocular structures involved in accommodation, in particular the ciliary muscle (CM), in a population of individuals with DS to further understand this deficit and its mechanisms. Thirty-two volunteer participants of pre-presbyopic age with (n = 16) and without DS (n = 16) were recruited. Temporal and nasal images of the CM were acquired using anterior segment optical coherence tomography (AS-OCT) while participants fixated an eccentrically located target. Analysis of CM parameters was undertaken using validated semi-automated software. Axial length, anterior chamber depth, lens thickness and corneal curvature were obtained with the Topcon Aladdin Optical Biometer and Corneal Topographer. Non-cycloplegic refractive error and accommodative ability were obtained with an open-field autorefractor and dynamic retinoscopy, respectively. Independent t-tests were conducted to determine differences in CM and other anterior segment parameters between participants with and without DS. No significant differences were found in the CM parameters studied between participants with and without DS (p > 0.05). In contrast, significant differences were found in visual acuity (p < 0.001), accommodative response (p < 0.001) and corneal curvature (K1 p = 0.003 and K2 p < 0.001) between participants with and without DS. Despite having poorer accommodation, pre-presbyopic adults with DS do not have a different CM morphology to that found in typically developing adults. These findings suggest that the accommodative deficit found in this population is not due to a mechanical deficit of the CM.

Percutaneous biopsies of skeletal muscle and adipose tissue in individuals older than 70: methods and outcomes in the Study of Muscle, Mobility and Aging (SOMMA).

Biopsies of muscle and adipose tissue (AT) are useful tools to gain insights into the aging processes in these tissues. However, they are invasive procedures and their risk/benefit profile in older adults can be altered by sarcopenia, frailty, poor healing, and multimorbidity. Their success rates, safety, and tolerability in a geriatric population have not been reported in detail. Investigators in the Study of Muscle, Mobility, and Aging (SOMMA) performed biopsies of muscle and AT in older adults and prospectively collected data on biopsy success rates, safety, and tolerability. We report here the methods and outcomes of these two procedures. In total, 861 participants (aged 70-94) underwent percutaneous biopsies of the Vastus lateralis muscle with a Bergstrom needle. A subset (n = 241) also underwent percutaneous biopsies of the abdominal subcutaneous AT with the tumescent liposuction technique. Success rate was assessed by the percentage of biopsies yielding adequate specimens for analyses; tolerability by pain scores; and safety by frequency of adverse events. All data were prospectively collected. The overall muscle biopsy success rate was 97.1% and was modestly lower in women. The AT biopsy success rate was 95.9% and slightly lower in men. Minimal or no pain was reported in 68% of muscle biopsies and in 83% of AT biopsies. Adverse events occurred in 2.67% of muscle biopsies and 4.15% of AT biopsies. None was serious. In older adults, percutaneous muscle biopsies and abdominal subcutaneous AT biopsies have an excellent safety profile, often achieve adequate tissue yields for analyses, and are well tolerated.

Native collagen VI delays early muscle stem cell differentiation.

Adult muscle stem cells (MuSCs) are critical for muscle homeostasis and regeneration, and their behavior relies on a finely regulated niche made of specific extracellular matrix (ECM) components and soluble factors. Among ECM proteins, collagen VI (Col6) influences the mechanical properties of the niche and, in turn, MuSC self-renewal capabilities. Here, we investigated whether Col6 can exert a direct function as a biochemical signal for regulating the stemness and differentiation of murine MuSCs and myoblasts. Native Col6, but not its pepsin-resistant fragment, counteracts the early differentiation of myogenic cells by reducing the expression of differentiation marker genes and preserving stemness features, with inhibition of the canonical Wnt pathway. Our data indicate that extracellular Col6 acts as a soluble ligand in delaying early myogenic differentiation by regulating intracellular signals involved in adult myogenesis.

Association between bilateral condylar resorption and reduced volumes of the craniofacial skeleton and masticatory muscles in adult patients: A retrospective study

ObjectivesThis retrospective cohort study aimed to analyze volumes of craniomaxillofacial bone and masticatory muscles of young adults with bilateral idiopathic condylar resorption. MethodsThis was a retrospective cohort study of 84 adults with bilateral idiopathic condylar resorption (BCR) and 48 adults with normal temporal-mandibular joint (TMJ) matched for age and sex (mean age, 23.2 ± 3.6 years). The volumes of craniomaxillofacial bone and masticatory muscles, as well as intercondylar angle were measured. Unpaired t-tests and Pearson correlation tests were applied to analyze the data. Multivariable linear regression models were used to estimate the association between bilateral condylar volume and volumes of craniomaxillofacial bone and masticatory muscles adjusted for age, sex, and disc status. ResultsCompared to the control group, the BCR group displayed significant decreased volumes of craniomaxillofacial bone (p < 0.001), craniomaxillofacial bone without mandible (p < 0.001), mandible (p < 0.001), mandible without mandibular condylar process (p < 0.001), bilateral masseter muscle (p < 0.001) and bilateral temporalis muscle (p < 0.001), as well as the intercondylar angle (p < 0.001). These variables were significantly correlated to the volume of mandibular condylar process (0.5< r < 0.8; p < 0.001). By linear regression analyses, significant associations were found for the bilateral condylar volume with craniomaxillofacial bone volume and mandible bone volume. ConclusionsYoung adults with BCR displayed smaller volumes of craniomaxillofacial skeleton and masticatory muscles, and smaller intercondylar angle than the normal patients. The craniofacial musculoskeletal volume and intercondylar angle are associated with mandibular condylar process volume.

Intra- and inter-rater reliability of muscle and fat thickness measurements obtained using portable ultrasonography in older adults

Ultrasonography (US) is a promising tool for assessing body composition, offering accuracy and accessibility. However, technician skills and equipment characteristics can impact measurement reliability. We aimed to evaluate the intra- and inter-rater reliability of two evaluators using A-mode Portable Ultrasound to measure muscle and fat thickness in Brazilian older adults. Quantitative cross-sectional study carried out with 150 community-dwelling older adults of Campinas-SP-Brazil, recruited in a retirement preparation program and a geriatric outpatient care unit. Scans of nine anatomical points were performed using the portable ultrasound in A-mode (BodyMetrix Pro System BX2000; Livermore, CA), with 6 scans per location and 3 measurements taken by each evaluator. After the selection and analysis of the generated images, muscle and fat thickness were measured. Reliability estimates between measures of the same evaluator (intra-rater) and between evaluators (inter-rater) were assessed using intraclass correlation coefficients (ICC), and differences within and between technicians were assessed using one-way ANOVA. Analyses were carried out for the overall sample and stratified by sex and by nutritional status. Excellent ICC values (>0.90) were found for subcutaneous fat thickness in intra- and inter-rater reliability analyses. The lowest ICC values were observed for deep abdominal fat thickness measured by evaluator 1 (ICC=0.90) and evaluator 2 (ICC=0.87), as well as in the inter-rater analysis (ICC=0.85). Muscle thickness measurements had satisfactory ICC values for triceps, biceps, anterior thigh, and calf, ranging from moderate to good (ICC 0.50-0.90). A portable A-mode ultrasound demonstrates excellent reliability among both intra- and inter-raters for assessing fat thickness but only moderate for muscle thickness in older adults. Hence, this could prompt inquiries regarding the sole reliance on this tool for quantifying muscle mass and examining sarcopenia in older adults. To our knowledge, this study represents the first assessment of reliability for a portable A-mode ultrasound device conducted with older adults.

CircUBE3C modulates myoblast development by binding to miR-191 and upregulating the expression of p27.

Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.

Peripheral thickening of the sarcomeres and pointed end elongation of the thin filaments are both promoted by SALS and its formin interaction partners.

During striated muscle development the first periodically repeated units appear in the premyofibrils, consisting of immature sarcomeres that must undergo a substantial growth both in length and width, to reach their final size. Here we report that, beyond its well established role in sarcomere elongation, the Sarcomere length short (SALS) protein is involved in Z-disc formation and peripheral growth of the sarcomeres. Our protein localization data and loss-of-function studies in the Drosophila indirect flight muscle strongly suggest that radial growth of the sarcomeres is initiated at the Z-disc. As to thin filament elongation, we used a powerful nanoscopy approach to reveal that SALS is subject to a major conformational change during sarcomere development, which might be critical to stop pointed end elongation in the adult muscles. In addition, we demonstrate that the roles of SALS in sarcomere elongation and radial growth are both dependent on formin type of actin assembly factors. Unexpectedly, when SALS is present in excess amounts, it promotes the formation of actin aggregates highly resembling the ones described in nemaline myopathy patients. Collectively, these findings helped to shed light on the complex mechanisms of SALS during the coordinated elongation and thickening of the sarcomeres, and resulted in the discovery of a potential nemaline myopathy model, suitable for the identification of genetic and small molecule inhibitors.

Does Aerobic Exercise Increase Skeletal Muscle Mass in Female and Male Adults?

It is uncertain whether aerobic exercise in the form of walking contributes to the preservation or increase in total or regional skeletal muscle mass (SMM). This study aimed to determine the effects of aerobic exercise on total and regional (upper body verses leg SMM) in male ( n = 105) and female ( n = 133) adults with overweight and obesity. A retrospective analysis of data from four randomized controlled trials. Participants included those who completed the given trial (control, n = 63; intervention, n = 175) and with complete magnetic resonance imaging (MRI) measured adipose tissue and SMM pre- and postintervention. Macronutrient intake was assessed for a subsample of participants. Supervised exercise was performed by walking on a treadmill for durations ranging from 12 to 24 wk at intensities between 50% and 75% of V̇O 2peak . All MRI-measured adipose tissue depots were reduced, and cardiorespiratory fitness was increased by aerobic exercise compared with controls ( P < 0.001). Independent of baseline SMM, aerobic exercise was associated with a small reduction (estimated mean difference ± standard error) in whole-body SMM (-0.310 ± 0.150 kg, P = 0.039) and upper body SMM (-0.273 ± 0.121 kg, P = 0.025) compared with control. No between-group difference was observed for change in leg SMM ( P > 0.10). A negative association was observed between the relative change in body weight and change in total ( R2 = 0.37, P < 0.001), upper body ( R2 = 0.21, P < 0.001), and leg SMM ( R2 = 0.09, P = 0.701). The SMM-to-adipose tissue ratio increased in response to aerobic exercise and was positively associated with weight loss ( P < 0.001). Change in SMM was not associated with dietary protein intake ( P > 0.10). Aerobic exercise performed while walking preserves, but does not increase, SMM in exercising muscle of adults. SMM not directly targeted by aerobic exercise may not be maintained.