The modification of RNA through the N6-methyladenosine (m6A) has emerged as a growing area of research due to its regulatory role in gene expression and various biological processes regulating the expression of genes. m6A RNA methylation is a post-transcriptional modification that is dynamic and reversible and found in mRNA, tRNA, rRNA, and other non-coding RNA of most eukaryotic cells. It is executed by special proteins known as \"writers,\" which initiate methylation; \"erasers,\" which remove methylation; and \"readers,\" which recognize it and regulate the expression of the gene. Modification by m6A regulates gene expression by affecting the splicing, translation, stability, and localization of mRNA. Aging causes molecular and cellular damage, which forms the basis of most age-related diseases. The decline in skeletal muscle mass and functionality because of aging leads to metabolic disorders and morbidities. The inability of aged muscles to regenerate and repair after injury poses a great challenge to the geriatric populace. This review seeks to explore the m6A epigenetic regulation in the myogenesis and regeneration processes in skeletal muscle as well as the progress made on the m6A epigenetic regulation of aging skeletal muscles.

Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our bibliometric study examined research status, hotspots, and future trends. We utilized bibliometric techniques to search the Science Citation Index Extended Database on February 27, 2023, using the Bibliometrix package in R to create a map displaying scientific production and subject categories. Collaborative network maps between countries/regions were visualized using Scimago Graphica, while VOSviewer explored collaboration modes among individuals and institutions. We analyzed the top 25 emerging keywords, top co-occurring keyword networks, and co-occurring keyword clusters using CiteSpace. A total of 997 articles were retrieved for sarcopenia and microbiome, of which 633 papers were analyzed. Both the number of publications and total citation frequency had been continuously increasing. The United States had the highest total citation frequency, while China had the highest number of publications. Research on the impact of the microbiome on sarcopenia was in its nascent stage and spans multiple disciplines, including nutrition, microbiology, geriatrics, immunology, endocrinology and metabolism, molecular biology, and sports medicine. The University of Copenhagen contributed the most to the number of publications (n=16), with Tibbett M (n=7) and Hulver MW (n=7) among the top authors. The most published journal was \"Nutrients\" (n=24). Analysis of keywords and clusters revealed new research hotspots in microbes and sarcopenia, such as malnutrition, dietary fiber, signaling pathways, frailty, and intestinal permeability. Research on the impact of the microbiome on sarcopenia is in its infancy and spans multiple disciplines. Malnutrition, dietary fiber, signaling pathways, frailty, and intestinal microbes are currently research hotspots. Furthermore, the visual atlas analysis of research on microbes and sarcopenia helps to track the knowledge structure in research fields related to sarcopenia and microbes, providing direction for future research.

It is well known that the adaptations of muscular antioxidant system to aerobic exercise depend on the frequency, intensity, duration, type of the exercise. Nonetheless, the timing of aerobic exercise, related to circadian rhythms or biological clock, may also affect the antioxidant defense system, but its impact remains uncertain. Bain and muscle ARNT-like 1 (BMAL1) is the core orchestrator of molecular clock, which can maintain cellular redox homeostasis by directly controlling the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2). So, our research objective was to evaluate the impacts of aerobic exercise training at various time points of the day on BMAL1 and NRF2-mediated antioxidant system in skeletal muscle. C57BL/6J mice were assigned to the control group, the group exercising at Zeitgeber Time 12 (ZT12), and the group exercising at ZT24. Control mice were not intervened, while ZT12 and ZT24 mice were trained for four weeks at the early and late time point of their active phase, respectively. We observed that the skeletal muscle of ZT12 mice exhibited higher total antioxidant capacity and lower reactive oxygen species compared to ZT24 mice. Furthermore, ZT12 mice improved the colocalization of BMAL1 with nucleus, the protein expression of BMAL1, NRF2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, glutamate-cysteine ligase modifier subunit and glutathione reductase in comparison to those of ZT24 mice. In conclusion, the 4-week aerobic training performed at ZT12 is more effective for enhancing NRF2-mediated antioxidant responses of skeletal muscle, which may be attributed to the specific activation of BMAL1.

Microplastics (MPs) pose a significant threat to livestock health. Yet, the roles of polystyrene MPs (PS-MPs) on meat quality and skeletal muscle development in pigs have not been fully determined. To investigate the effect of PS-MPs on skeletal muscle, piglets were given diets supplementation with 0 mg/kg (CON group), 75 mg/kg (75 mg/kg PS-MPs group), and 150 mg/kg PS-MPs (150 mg/kg PS-MPs group), respectively. The results indicated that the average daily gain (ADG) of piglets in the 150 mg/kg PS-MPs group was significantly lower than that in the CON group. No significant differences were observed in the final body weight and ADG between the CON group and the 75 mg/kg PS-MPs group. Piglets in the 150 mg/kg PS-MPs group exhibited decreased meat redness index and type I muscle fiber density. Metabolomic analysis revealed that the contents of meat flavor compounds carnosine, beta-alanine, palmitic acid, and niacinamide in muscle were lower in the 150 mg/kg PS-MPs group than in the CON group. Additionally, piglets subjected to 150 mg/kg PS-MPs exhibited impaired muscle angiogenesis. Further analysis indicated that PS-MPs exposure up-regulated thrombospondin 1 (THBS1) expression by inhibiting THBS1 mRNA and protein degradation, thereby disrupting skeletal muscle angiogenesis. These findings indicate that PS-MPs exposure adversely affects meat quality and hinders skeletal muscle angiogenesis in pigs, providing deeper insights into the detrimental effects of PS-MPs on meat quality and skeletal muscle development.

UNASSIGNED: Quantitative computed tomography (CT) analysis is an important method for diagnosis and severity evaluation of lung diseases. However, the association between CT-derived biomarkers and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. We aimed to investigate its potential in predicting COPD exacerbations.
UNASSIGNED: Patients with COPD were consecutively enrolled, and their data were analyzed in this retrospective study. Body composition and thoracic abnormalities were analyzed from chest CT scans. Logistic regression analysis was performed to identify independent risk factors of exacerbation. Based on 2-year follow-up data, the deep learning system (DLS) was developed to predict future exacerbations. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance. Finally, the survival analysis was performed to further evaluate the potential of the DLS in risk stratification.
UNASSIGNED: A total of 1,150 eligible patients were included and followed up for 2 years. Multivariate analysis revealed that CT-derived high affected lung volume/total lung capacity (ALV/TLC) ratio, high visceral adipose tissue area (VAT), and low pectoralis muscle cross-sectional area (CSA) were independent risk factors causing COPD exacerbations. The DLS outperformed exacerbation history and the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, with an area under the ROC (AUC) value of 0.88 (95%CI, 0.82-0.92) in the internal cohort and 0.86 (95%CI, 0.81-0.89) in the external cohort. The DeLong test revealed significance between this system and conventional scores in the test cohorts (p < 0.05). In the survival analysis, patients with higher risk were susceptible to exacerbation events.
UNASSIGNED: The DLS could allow accurate prediction of COPD exacerbations. The newly identified CT biomarkers (ALV/TLC ratio, VAT, and pectoralis muscle CSA) could potentially enable investigation into underlying mechanisms responsible for exacerbations.

BACKGROUND: Aging negatively impacts tissue repair, particularly in skeletal muscle, where the regenerative capacity of muscle stem cells (MuSCs) diminishes with age. Although aerobic exercise is known to attenuate skeletal muscle atrophy, its specific impact on the regenerative and repair capacity of MuSCs remains unclear.
METHODS: Mice underwent moderate-intensity continuous training (MICT) from 9 months (aged + Ex-9M) or 20 months (aged + Ex-20M) to 25 months, with age-matched (aged) and adult controls. Histological examinations and MuSC transplantation assays assessed aerobic exercise effects on MuSC function and muscle regeneration. CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored.
RESULTS: Aged mice displayed significantly reduced running duration (65.33 ± 4.32 vs. 161.9 ± 1.29 min, mean ± SD, P < 0.001) and distance (659.17 ± 103.64 vs. 3058.28 ± 46.26 m, P < 0.001) compared with adults. This reduction was accompanied by skeletal muscle weight loss and decreased myofiber cross-sectional area (CSA). However, MICT initiated at 9 or 20 months led to a marked increase in running duration (142.75 ± 3.14 and 133.86 ± 20.47 min, respectively, P < 0.001 compared with aged mice) and distance (2347.58 ± 145.11 and 2263 ± 643.87 m, respectively, P < 0.001). Additionally, MICT resulted in increased skeletal muscle weight and enhanced CSA. In a muscle injury model, aged mice exhibited fewer central nuclear fibres (CNFs; 266.35 ± 68.66/mm2), while adult, aged + Ex-9M and aged + Ex-20M groups showed significantly higher CNF counts (610.82 ± 46.76, 513.42 ± 47.19 and 548.29 ± 71.82/mm2, respectively; P < 0.001 compared with aged mice). MuSCs isolated from aged mice displayed increased CCN2 expression, which was effectively suppressed by MICT. Transplantation of MuSCs overexpressing CCN2 (Lenti-CCN2, Lenti-CON as control) into injured tibialis anterior muscle compromised regeneration capacity, resulting in significantly fewer CNFs in the Lenti-CCN2 group compared with Lenti-CON (488.07 ± 27.63 vs. 173.99 ± 14.28/mm2, P < 0.001) at 7 days post-injury (dpi). Conversely, knockdown of CCN2 (Lenti-CCN2shR, Lenti-NegsiR as control) in aged MuSCs improved regeneration capacity, significantly increasing the CNF count from 254.5 ± 26.36 to 560.39 ± 48.71/mm2. Lenti-CCN2 MuSCs also increased fibroblast proliferation and exacerbated skeletal muscle fibrosis, while knockdown of CCN2 in aged MuSCs mitigated this pattern. AICAR supplementation, mimicking exercise, replicated the beneficial effects of aerobic exercise by mitigating muscle weight decline, enhancing satellite cell activity and reducing fibrosis.
CONCLUSIONS: Aerobic exercise effectively reverses the decline in endurance capacity and mitigates muscle atrophy in aged mice. It inhibits CCN2 secretion from senescent MuSCs, thereby enhancing skeletal muscle regeneration and preventing fibrosis in aged mice. AICAR supplementation mimics the beneficial effects of aerobic exercise.

Metabolic disorders are highly prevalent in modern society. Exercise mimetics are defined as pharmacological compounds that can produce the beneficial effects of fitness. Recently, there has been increased interest in the role of eugenol and transient receptor potential vanilloid 1 (TRPV1) in improving metabolic health. The aim of this study was to investigate whether eugenol acts as an exercise mimetic by activating TRPV1. Here, we showed that eugenol improved endurance capacity, caused the conversion of fast-to-slow muscle fibers, and promoted white fat browning and lipolysis in mice. Mechanistically, eugenol promoted muscle fiber-type transformation by activating TRPV1-mediated CaN signaling pathway. Subsequently, we identified IL-15 as a myokine that is regulated by the CaN/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Moreover, we found that TRPV1-mediated CaN/NFATc1 signaling, activated by eugenol, controlled IL-15 levels in C2C12 myotubes. Our results suggest that eugenol may act as an exercise mimetic to improve metabolic health via activating the TRPV1-mediated CaN signaling pathway.

The composition of skeletal muscle fiber types affects the quality of livestock meat and human athletic performance and health. L-arginine (Arg), a semi-essential amino acid, has been observed to promote the formation of slow-twitch muscle fibers in animal models. However, the precise molecular mechanisms are still unclear. This study investigates the role of Arg in skeletal muscle fiber composition and mitochondrial function through the mTOR signaling pathway. In vivo, 4-week C56BL/6J male mice were divided into three treatment groups and fed a basal diet supplemented with different concentrations of Arg in their drinking water. The trial lasted 7 weeks. The results show that Arg supplementation significantly improved endurance exercise performance, along with increased SDH enzyme activity and upregulated expression of the MyHC I, MyHC IIA, PGC-1α, and NRF1 genes in the gastrocnemius (GAS) and quadriceps (QUA) muscles compared to the control group. In addition, Arg activated the mTOR signaling pathway in the skeletal muscle of mice. In vitro experiments using cultured C2C12 myotubes demonstrated that Arg elevated the expression of slow-fiber genes (MyHC I and Tnnt1) as well as mitochondrial genes (PGC-1α, TFAM, MEF2C, and NRF1), whereas the effects of Arg were inhibited by the mTOR inhibitor rapamycin. In conclusion, these findings suggest that Arg modulates skeletal muscle fiber type towards slow-twitch fibers and enhances mitochondrial functions by upregulating gene expression through the mTOR signaling pathway.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index with a value of 0.250 ± 0.000 because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes (0.031 myocytes/μm2 ± 0.004 at 60 months) and an increase in collagen with aging up to 15% ± 1.639 in the 60-month group, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a nearly 50% reduction in the number of intermyofibrillar mitochondria, 100% mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

BACKGROUND: The analysis of differentially expressed genes in muscle tissues of sheep at different ages is helpful to analyze the gene expression trends during muscle development. In this study, the longissimus dorsi muscle of pure breeding Hu sheep (H), Suffolk sheep and Hu sheep hybrid F1 generation (SH) and East Friesian and Hu sheep hybrid sheep (EHH) three strains of sheep born 2 days (B2) and 8 months (M8) was used as the research object, and transcriptome sequencing technology was used to identify the differentially expressed genes of sheep longissimus dorsi muscle in these two stages. Subsequently, GO and KEGG enrichment analysis were performed on the differential genes. Nine differentially expressed genes were randomly selected and their expression levels were verified by qRT-PCR.
RESULTS: The results showed that 842, 1301 and 1137 differentially expressed genes were identified in H group, SH group and EHH group, respectively. Among them, 191 differential genes were enriched in these three strains, including pre-folding protein subunit 6 (PFDN6), DnaJ heat shock protein family member A4 (DNAJA4), myosin heavy chain 8 (MYH8) and so on. GO and KEGG enrichment analysis was performed on 191 differentially expressed genes shared by the three strains to determine common biological pathways. The results showed that the differentially expressed genes were significantly enriched in ribosomes, unfolded protein binding, FoxO signaling pathway, glycolysis / glycogen generation and glutathione signaling pathway that regulate muscle protein synthesis and energy metabolism. The results of qRT-PCR were consistent with transcriptome sequencing, which proved that the sequencing results were reliable.
CONCLUSIONS: Overall, this study revealed the important genes and signaling pathways related to sheep skeletal muscle development, and the result laid a foundation for further understanding the mechanism of sheep skeletal muscle development.