Long-term exercise is recognized as one of the most effective means of maintaining health after aging, but the relationship between moderate exercise and health in the older population is often overlooked.

The present study was conducted to investigate the effects of excessive endurance exercise on the old mice musculoskeletal system.

The 8 weeks of normal endurance exercise significantly improved skeletal muscle mitochondrial biogenesis and increased femoral osteogenesis in young and old mice. However, the continued accumulation of total exercise volume as the exercise cycle was prolonged resulted in the younger and older mice exhibiting different exercise effects. After 8-16 weeks of moderate-intensity endurance exercise, young mice showed consistent effects of increased mitochondrial biogenesis in skeletal muscle. However, after 12-16 weeks of moderate-intensity endurance exercise, the original effects of exercise-induced mitochondrial biosynthesis were instead impaired in older mice. After 16 weeks of exercise, the aged mice showed a produces consumptive weight loss, an increase inflammation level in adipose tissue, and a decrease in femoral bone mineral density. Interestingly, with an increase in total exercise, the level of skeletal muscle inflammation in old mice did not increase significantly, while a longer exercise cycle reduced the level of skeletal muscle apoptosis, thereby maintaining the state of skeletal muscle.

Appropriate moderate-intensity endurance exercise has a significant gain in maintaining musculoskeletal health in aged mice. However, excessive endurance impairs the health of the musculoskeletal system in aged mice.

Resting-state functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity (FC) of the insula (INS) in patients with musculoskeletal pain (MSP). However, there is a lack of consistency in previous studies, which is an obstacle to understanding the underlying neuropathology of MSP.

Seven databases, including PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP, were systematically searched from inception to 15 May 2024. The meta-analysis of the aberrant INS-based FC in MSP patients was performed using the anisotropic effect-size signed differential mapping (AES-SDM).

A total of eleven neuroimaging studies with 276 patients and 253 HCs were included in the meta-analysis. The results indicate that MSP patients have increased FC between INS and the right median cingulate gyri, right inferior frontal gyrus, right paracentral lobule, and right supplementary motor area, and decreased FC between INS and the right posterior cingulate gyrus, left precuneus, and left angular gyrus. Heterogeneity and sensitivity analysis showed that most of the results of INS-based FC were highly reproducible and robust. Meta-regression analysis showed that revealed a negative association between the Visual Analog Scale (VAS) score and the reduction in FC between the INS and the left precuneus.

The meta-analysis reveals that patients with MSP show abnormal FC between the INS and multiple brain regions, which are involved in emotional, cognitive, sensory, visuospatial and motor regulation of pain. These findings provide important insights into the underlying neuropathological mechanisms of musculoskeletal disorders.

Skeletal muscle injuries are short-term, that occur in people who play sports and train. Regular exercise and sports populations undergo repetitive tearing and regeneration of skeletal muscle, in which muscle damage is a necessary component to produce an oxidative inflammatory response and tissue reconstruction. The primary goals of treating this illness are to reduce the disease process cycle and get rid of symptoms like swelling and inflammation at the site of localized injury. Berberine (BBR) has several pharmacological effects, including anti-inflammatory, anti-tumor, and anti-arrhythmic properties.

In order to treat skeletal muscle injuries, a safe and non-toxic nanogel (BBR/GelMA) was developed for efficient berberine delivery. It also investigated whether BBR/GelMA had anti-inflammatory properties via the NF-κB pathway. Microwave irradiation was added to promote the uptake of BBR in BBR/GelMA by injured skeletal muscle and to accelerate the process of injury recovery.

It turns out that the survival rates of NIH313 and L929 cells decreased to varying degrees in GelMA loaded with different concentrations of BBR, but the survival rates of the two cell lines were the highest at a concentration of 0.125 mg/mL.

In this experiment, the inhibitory effect of BBR/GelMA on inflammation was studied. After NIH-313 and L929 cells were treated with GelMA loaded with different doses of BBR, it was found that the concentration of BBR/0.5 mg/mL had the best inhibitory effect on these two inflammation-inducing cell lines, and this inhibitory effect was related to the drug loading concentration. On the other hand, BBR/GelMA and microwave therapy can play an anti-inflammatory and repairing role in skeletal muscle through NF-κB pathway. In addition, microwave can accelerate the diffusion of BBR in BBR/GelMA within injured skeletal muscle, speeding up the healing process after skeletal muscle injury and shortening the disease cycle.

Emerging evidence suggests that gut microbiota imbalances may influence the onset of musculoskeletal disorders (MSDs), yet conclusive evidence establishing causation remains limited. This study investigates the causal relationship between gut microbiota and a range of MSDs, aiming to identify potential therapeutic targets. Using data on 211 gut microbiome taxa from a genome-wide association study (GWAS) and summary statistics for 26 MSDs from the Finnish Biobank, we employed Mendelian randomization (MR) with inverse-variance weighting (IVW) as the primary analytical approach, complemented by Bayesian model validation to ensure robust results. Our MR analyses revealed significant causal associations between gut microbiota and nine MSDs within four categories, including osteoporosis (IVW-Beta = 0.011, P = 0.025), rheumatoid arthritis (IVW-Beta = - 0.016, P < 0.001), rotator cuff syndrome (IVW-Beta = - 0.007, P = 0.022), and calcific tendonitis of the shoulder (IVW-Beta = - 0.021, P = 0.034). Bayesian validation underscored the plausibility of these relationships, supporting the potential causal role of gut microbiota in the development of these disorders. Our findings present a library of causal associations that underscore the gut microbiome's role in MSD pathogenesis, providing genetic evidence that highlights specific gut microbiota taxa as prospective therapeutic targets. This research offers novel insights into the pathogenic mechanisms underlying MSDs and points toward new directions for future investigation into microbiome-based therapies.

Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of tissue-nonspecific alkaline phosphatase (TNAP) caused by variants in the ALPL gene. Disease manifestations encompass skeletal hypomineralization with rickets and lung hypoplasia, vitamin B6-dependent seizures, craniosynostosis, and premature loss of deciduous teeth. The clinical presentation can comprise failure to thrive with muscular hypotonia, delayed motor development, and gait disturbances later in childhood. In adults, pseudofractures are a characteristic indicator of severely compromised enzyme activity, but non-canonical symptoms like generalized musculoskeletal pain, weakness, and fatigue, frequently accompanied by neuropsychiatric and gastrointestinal issues are increasingly recognized as key findings in patients with HPP. The diagnosis is based on clinical manifestations in combination with persistently low alkaline phosphatase (ALP) activity, elevated levels of ALP substrates, specifically inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), and genetic confirmation of a causative ALPL variant. Considering the wide range of manifestations, treatment must be multimodal and tailored to individual needs. The multidisciplinary team for comprehensive management of HPP patients should include expertise to ensure disease state metabolic and musculoskeletal treatment, dental care, neurological and neurosurgical surveillance, pain management, physical therapy, and psychological care. Asfotase alfa as first-in-class enzyme replacement therapy (ERT) for HPP has been shown to improve survival, rickets, and functional outcomes in severely affected children, but further research is needed to refine how enzyme replacement can also address emerging manifestations of the disease. Prospectively, further elucidating the pathophysiology behind the diverse clinical manifestations of HPP is instrumental for improving diagnostic concepts, establishing novel means for substituting enzyme activity, and developing integrative, multimodal care.

There is a dearth of knowledge regarding the relationship between engaging in moderate and vigorous physical activity and long-term sickness absence (LTSA), particularly among various population subgroups such as individuals of different ages or body mass indices. We aimed to evaluate the prospective associations of moderate and vigorous leisure-time physical activity with the risk of LTSA in the general working population.

A prospective cohort study with a 2-year register follow-up was conducted, where 68,222 representative workers from Denmark completed a questionnaire about work environment, lifestyle, and health. Data on LTSA (≥6 consecutive weeks of sickness absence) were obtained from the Danish Register for Evaluation of Marginalization. We used Cox regression for the statistical analysis, adjusting for relevant confounding factors. We also performed age- and BMI-stratified analyses.

In the fully adjusted model, 2 to 4 hours per week of moderate activity (hazard ratios [HR] = 0.87; 95% CI, 0.77 to 0.99) and ≥2 hours per week of vigorous activity reduced LTSA risk compared with no physical activity. However, 2 to 4 hours per week of vigorous activity (HR = 0.84; 95% CI, 0.76 to 0.91) provided the greatest risk reduction. In the total sample, the complete absence of vigorous activity was associated with increased risk of LTSA (HR = 1.13; 95% CI, 1.05 to 1.22). In stratified analyses, the results were consistent for workers <50 years (HR = 1.14; 95% CI, 1.03 to 1.26), ≥50 years (HR = 1.13; 95% CI, 1.02 to 1.26), and those with a BMI ≥ 25 (HR = 1.16; 95% CI, 1.06 to 1.28). The complete absence of moderate activity was not associated with LTSA.

Vigorous leisure-time physical activity appears to be more important than moderate activity to prevent LTSA.

Musculoskeletal disorders (MSD) comprise a great variety of medical conditions, and the economic and sanitary burdens they cause are a major concern for the sanitary systems worldwide. Conventional rehabilitation is effective; however, with the rise of new technologies, it can be further improved. Anti-gravity treadmills are starting to enter the clinical rehabilitation practice of MSD due to their characteristics, which allow weight support while performing walking and running exercises. Thus, this systematic review aims to explore the effects and use of anti-gravity treadmills in MSD. A systematic search of literature was performed by collecting articles from PubMed, Scopus, and Web of Science on the use of anti-gravity treadmills in MSD management. The PEDro scale tool and the Joanna Briggs Institute checklist were used to assess the methodological quality of the included studies. Relevant data were collected in tables, and the primary outcomes were discussed narratively. Of the 185 articles screened, 11 were included in the qualitative synthesis. The findings of the selected articles encourage the use of anti-gravity treadmills in MSD rehabilitation to improve gait functionality, balance, pain relief rct, range of motion, and fracture healing. The protocols and outcomes evaluated showed high heterogeneity, and quantitative synthesis could not be performed. In conclusion, the anti-gravity treadmill proved feasible, safe, and well tolerated by individuals with different MSD, and greater improvements were seen in participants who performed anti-gravity exercises than in those who performed only conventional rehabilitation.

Chronic pain impacts approximately 18% of the Spanish population, with low levels of vitamin D prevalent in over 80% of individuals over 65. Given vitamin D's critical role in pain modulation, its deficiency may be significantly linked to chronic musculoskeletal pain, though existing research offers mixed results.

This systematic review followed PRISMA guidelines, examining studies from PubMed, Cochrane, and PEDRO databases from 1990 onwards that investigated the relationship between vitamin D levels and chronic musculoskeletal pain.

A total of 30 studies met the inclusion criteria set by the NHLBI's quality standards. The results are inconclusive regarding the direct relationship between vitamin D levels and chronic musculoskeletal pain due to evidence heterogeneity. However, there appears to be an inverse relationship between vitamin D levels and the intensity of pain.

While the association between vitamin D levels and chronic musculoskeletal pain remains uncertain, the inverse correlation with pain intensity suggests a potential therapeutic role of vitamin D supplementation in pain management. Further research is needed to substantiate these findings and refine intervention strategies.

Temporomandibular disorders (TMDs) are musculoskeletal disorders characterised by jaw pain and typically temporomandibular joint limitations. Resistance training (RT) has been shown to be effective at reducing pain and improving function for different musculoskeletal conditions (eg, neck pain, low back pain); however, the effectiveness of RT for patients with TMDs remains unclear. This systematic review will evaluate the effectiveness of RT on pain and temporomandibular joint range of motion in people with TMDs.

The report of this protocol aligns with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. The search strategy will be conducted from 1 March 2024 to 31 March 2024 via the following electronic databases: MEDLINE (OVID interface), EMBASE (OVID interface), SCOPUS, Web of Science, PubMed and Cochrane Central Register of Controlled Trials. Any randomised controlled trials or non-randomised studies of interventions in adults with TMD that examine RT targeting the masticatory muscles, compared to other interventions not including RT, will be included. Primary outcomes will be jaw pain intensity and maximal mouth opening. Secondary outcomes will include measures of neuromuscular performance and pressure pain thresholds. Two independent reviewers will conduct the screening of articles for inclusion, data extraction, risk-of-bias assessment using the revised Cochrane risk-of-bias tool for included studies and will evaluate the overall quality of evidence following the Grading of Recommendations Assessment, Development and Evaluation framework. A meta-analysis will be performed where applicable. Alternately, a narrative synthesis will be performed by adhering to the synthesis without meta-analysis guidelines. Data will be summarised according to the outcome measures or, when this is not possible, according to other pertinent variables such as TMD type (ie, temporomandibular joint disorders, masticatory muscle disorders and mixed disorders).

Ethical approval is not necessary, since this study does not involve the collection of primary data. The results will be disseminated through presentations at scientific conferences and publication in a peer-reviewed journal.

CRD42023476269.

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation and demyelination in the central nervous system (CNS) with subsequent axonal and neuronal degeneration. These changes are associated with a broad range of symptoms including skeletal muscle dysfunction. Importantly, musculoskeletal impairments manifest in various ways, compromise the quality of life and often precede the later development of mobility disability. As current standard disease modifying therapies for MS predominantly act on neuroinflammation, practitioners and patients face an unmet medical need for adjunct therapies specifically targeting skeletal muscle function. This review is intended to detail the nature of the skeletal muscle dysfunctions common in people with MS (pwMS), describe underlying intramuscular alterations and outline evidence-based therapeutic approaches. Particularly, we discuss the emerging role of aerobic and resistance exercise for reducing the perception of fatigue and increasing muscle strength in pwMS. By integrating the most recent literature, we conclude that both exercise interventions should ideally be implemented as early as possible as they can address MS-specific muscle impairments. Aerobic exercise is particularly beneficial for pwMS suffering from fatigue and metabolic impairments, while resistance training efficiently counters muscle weakness and improves the perception of fatigue. Thus, these lifestyle interventions or possible pharmacological mimetics have the potential for improving the general well-being and delaying the functional declines that are relevant to mobility.

Aging is a multifaceted process influenced by hereditary factors, lifestyle, and environmental elements. As time progresses, the human body experiences degenerative changes in major functions. The external and internal signs of aging manifest in various ways, including skin dryness, wrinkles, musculoskeletal disorders, cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer. Additionally, cancer, like aging, is a complex disease that arises from the accumulation of various genetic and epigenetic alterations. Circadian clock dysregulation has recently been identified as an important risk factor for aging and cancer development. Natural compounds and herbal medicines have gained significant attention for their potential in preventing age-related diseases and inhibiting cancer progression. These compounds demonstrate antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic effects as well as circadian clock regulation. This review explores age-related diseases, cancers, and the potential of specific natural compounds in targeting the key features of these conditions.

The present review will highlight recent reports supporting the relevance of extracellular vesicles to the musculoskeletal system in health and disease.

Preserving the health of the musculoskeletal system is important to maintain a good quality of life, and the bone-muscle crosstalk is crucial in this regard. This latter is largely mediated by extracellular vesicles released by the different cell populations residing in muscle and bone, which deliver cargoes, microRNAs, and proteins being the most relevant ones, to target cells. Extracellular vesicles could be exploited as therapeutic tools, in view of their resistance to destruction in the biological fluid and of the possibility to be functionalized according to the need. Extracellular vesicles are recognized as crucial players in the bone-muscle cross-talk. Additional studies however are required to refine their use as biomarkers of early alterations of the musculoskeletal system, and as potential therapeutic tools.

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology, entitled "Association of low muscle strength with metabolic dysfunction-associated fatty liver disease: A nationwide study". We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD), as well as the mechanisms underlying the correlation and related clinical applications. NAFLD, which is now redefined as MAFLD, is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition, which may contribute to decreased muscle strength. Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/ MAFLD, including insulin resistance, inflammation, sedentary behavior, as well as insufficient vitamin D. Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD. However, studies investigating the relationship between muscle strength and MAFLD are limited. Owing to the shortage of specific medications for NAFLD/MAFLD treatment, early detection is essential. Furthermore, the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy, as well as tailored physical activity.

With the rapid development of sports science and molecular biology technology, academia refers to molecules or microorganisms that mimic or enhance the beneficial effects of exercise on the body, called "exercise mimetics." This review aims to clarify the concept and development history of exercise mimetics, and to define the concept of exercise mimetics by summarizing its characteristics and functions. Candidate molecules and drug targets for exercise mimetics are summarized, and the relationship between exercise mimetics and exercise is explained, as well as the targeting system and function of exercise mimetics. The main targeting systems for exercise mimetics are the exercise system, circulatory system, endocrine system, endocrine system, and nervous system, while the immune system is potential targeting systems. Finally, future research directions for exercise mimetics are discussed.

Sarcopenia refers to the loss of muscle strength and mass in older individuals and is a major determinant of fall risk and impaired ability to perform activities of daily living, often leading to disability, loss of independence, and death. Owing to its impact on morbidity, mortality, and healthcare expenditure, sarcopenia in the elderly has become a major focus of research and public policy debates worldwide. Despite its clinical importance, sarcopenia remains under-recognized and poorly managed in routine clinical practice, partly owing to the lack of available diagnostic testing and uniform diagnostic criteria. Since the World Health Organization and the United States assigned a disease code for sarcopenia in 2016, countries worldwide have assigned their own disease codes for sarcopenia. However, there are currently no approved pharmacological agents for the treatment of sarcopenia; therefore, interventions for sarcopenia primarily focus on physical therapy for muscle strengthening and gait training as well as adequate protein intake. In this review, we aimed to examine the latest information on the epidemiology, molecular mechanisms, interventions, and possible treatments with new drugs for sarcopenia.

An impairment in mitochondrial homeostasis plays a crucial role in the process of aging and contributes to the incidence of age-related diseases, including sarcopenia, which is defined as an age-dependent loss of muscle mass and strength. Mitochondrial dysfunction exerts a negative impact on several cellular activities, including bioenergetics, metabolism, and apoptosis. In sarcopenia, mitochondria homeostasis is disrupted because of reduced oxidative phosphorylation and ATP generation, the enhanced production of reactive species, and impaired antioxidant defense. This review re-establishes the most recent evidence on mitochondrial defects that are thought to be relevant in the pathogenesis of sarcopenia and that may represent promising therapeutic targets for its prevention/treatment. Furthermore, we describe mechanisms of action and translational potential of promising mitochondria-targeted drug delivery systems, including molecules able to boost the metabolism and bioenergetics, counteract apoptosis, antioxidants to scavenge reactive species and decrease oxidative stress, and target mitophagy. Even though these mitochondria-delivered strategies demonstrate to be promising in preclinical models, their use needs to be promoted for clinical studies. Therefore, there is a compelling demand to further understand the mechanisms modulating mitochondrial homeostasis, to characterize powerful compounds that target muscle mitochondria to prevent sarcopenia in aged people.