Search Results (1,528)

The increasing prevalence of chronic metabolic diseases poses a significant challenge in the modern world, impacting healthcare systems and individual life expectancy. The World Health Organization (WHO) recommends that older adults (65+ years) engage in 150–300 min of moderate-intensity or 75–150 min of vigorous-intensity physical activity, alongside muscle-strengthening and balance-training exercises at least twice a week. However, nearly one-third of the adult population (31%) is physically inactive, which increases the risk of developing obesity, type 2 diabetes, cardiovascular diseases, hypertension, and psychological issues. Physical activity in the form of aerobic exercise, resistance training, or a combination of both is effective in preventing and managing these metabolic diseases. In this review, we explored the effects of exercise training, especially on respiratory and pulmonary factors, including oxygen consumption, pulmonary ventilation, and blood gas analyses among adults. During exercise, oxygen consumption can increase up to 15-fold (from a resting rate of ~250 mL/min) to meet heightened metabolic demands, enhancing tidal volume and pulmonary efficiency. During exercise, the increased energy demand of skeletal muscle leads to increases in tidal volume and pulmonary function, while blood gases play a key role in maintaining the pH of the blood. In this review, we explored the influence of age, body composition (BMI and obesity), lifestyle factors (smoking and alcohol use), and comorbidities (diabetes, hypertension, neurodegenerative disorders) in the modulation of these physiological responses. We underscored exercise as a potent non-pharmacological intervention for improving cardiopulmonary health and mitigating the progression of metabolic diseases in aging populations. Full article

Circadian rhythms are intrinsic 24 h cycles that regulate metabolic processes across multiple tissues, with skeletal muscle emerging as a central node in this temporal network. Muscle clocks govern gene expression, fuel utilisation, mitochondrial function, and insulin sensitivity, thereby maintaining systemic energy homeostasis. However, circadian misalignment, whether due to behavioural disruption, nutrient excess, or metabolic disease, impairs these rhythms and contributes to insulin resistance, and the development of obesity, and type 2 diabetes mellitus. Notably, the muscle clock remains responsive to non-photic cues, particularly exercise, which can reset and amplify circadian rhythms even in metabolically impaired states. This work synthesises multi-level evidence from rodent models, human trials, and in vitro studies to elucidate the role of skeletal muscle clocks in circadian metabolic health. It explores how exercise entrains the muscle clock via molecular pathways involving AMPK, SIRT1, and PGC-1α, and highlights the time-of-day dependency of these effects. Emerging data demonstrate that optimally timed exercise enhances glucose uptake, mitochondrial biogenesis, and circadian gene expression more effectively than time-agnostic training, especially in individuals with metabolic dysfunction. Finally, findings are integrated from multi-omic approaches that have uncovered dynamic, time-dependent molecular signatures that underpin circadian regulation and its disruption in obesity. These technologies are uncovering biomarkers and signalling nodes that may inform personalised, temporally targeted interventions. By combining mechanistic insights with translational implications, this review positions skeletal muscle clocks as both regulators and therapeutic targets in metabolic disease. It offers a conceptual framework for chrono-exercise strategies and highlights the promise of multi-omics in developing precision chrono-medicine approaches aimed at restoring circadian alignment and improving metabolic health outcomes. Full article

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

Insulin-regulated glucose uptake is a central mechanism in maintaining systemic glucose homeostasis, primarily occurring in skeletal muscle and adipose tissue. This process relies on the insulin-stimulated translocation of the glucose transporter, GLUT4, from specialized intracellular compartments, known as GLUT4 storage vesicles (GSVs), to the plasma membrane. Disruption of this pathway is a hallmark of insulin resistance and a key contributor to the pathogenesis of type 2 diabetes. Recent advances have provided critical insights into both the insulin signalling cascades and the complex biogenesis, as well as the trafficking and fusion dynamics of GSVs. This review synthesizes the current understanding of the molecular mechanisms governing GSV mobilization and membrane fusion, highlighting key regulatory nodes that may become dysfunctional in metabolic disease. By elucidating these pathways, we propose new therapeutic avenues targeting GSV trafficking to improve insulin sensitivity and combat type 2 diabetes. Full article

Background: Menopause increases the risk of cardiovascular diseases (CVD) accompanied by a decline in muscle function. Myokines, released by skeletal muscle, could play a significant role in cardiovascular health. Objectives and Methods: This study aimed to investigate the changes induced by a 16-week resistance training (RT) program and/or the docosahexaenoic acid (DHA)-rich n-3 PUFA supplementation on myokine and cytokine circulating levels and to study their associations with parameters of body composition, muscle function, and glucose and lipid serum markers in postmenopausal women with overweight/obesity. Results: At baseline, interleukin-6 (IL-6) levels were positively correlated with body fat and with tumor necrosis factor-alpha (TNF-α) levels and negatively associated with meterorin-like (METRNL) levels. Moreover, METRNL was inversely associated with insulin levels and with HOMA-IR. After the intervention, muscle quality improved with either treatment but more notably in response to RT. N-3 supplementation caused significant improvements in cardiometabolic health markers. TNF-α decreased in all experimental groups. Myostatin levels decreased in the RT and in the n-3 groups, and IL-6 increased in the n-3+RT group. Lastly, no interactions between treatments were observed. Conclusions: In postmenopausal women with overweight or obesity, RT could help improve skeletal muscle function, while DHA-rich n-3 supplementation might decrease CVD risk and might potentially improve muscle function. The modulation of myokine levels could be underlying some of the effects of DHA or RT; however, further research is necessary. Full article

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Skeletal muscle aging and related diseases are characterized by progressive loss of muscle mass, strength, and metabolic function. Central to these processes is mitochondrial dysfunction, which impairs energy metabolism, redox homeostasis, and proteostasis. In addition, non-mitochondrial factors such as muscle stem cell exhaustion, neuromuscular junction remodeling, and chronic inflammation also contribute significantly to muscle degeneration. This review integrates recent advances in understanding mitochondrial and non-mitochondrial mechanisms underlying muscle aging and disease. Additionally, we discuss emerging therapeutic approaches targeting these pathways to preserve muscle health and promote healthy aging. Full article

Plant-derived extracellular vesicles (PDEVs) are nanoscale, phospholipid bilayer-enclosed vesicles secreted by living cells through cytokinesis under physiological and pathological conditions. Owing to their high biocompatibility and stability, PDEVs have attracted considerable interest in regenerative medicine applications. They can exhibit the capacity to enhance cellular proliferation, migration, and multi-lineage differentiation through immunomodulation, anti-inflammation effects, antioxidative protection, and tissue regeneration mechanisms. Given their abundant availability, favorable safety profile, and low immunogenicity risks, PDEVs have been successfully employed in therapeutic interventions for skeletal muscle disorders, cardiovascular diseases, neurodegenerative conditions, and tissue regeneration applications. This review mainly provides a comprehensive overview of PDEVs, systematically examining their biological properties, standardized isolation and characterization methodologies, preservation techniques, and current applications in regenerative medicine. Furthermore, we critically discuss future research directions and clinical translation potential, aiming to facilitate the advancement of PDEV-based therapeutic strategies. Full article

Osteoporosis is a multifactorial, polygenic disease characterized by reduced bone mineral density (BMD) and increased fracture risk. Genome-wide association studies (GWASs) have identified numerous loci associated with BMD and/or bone fractures, but functional characterization of these target genes is essential to understand the biological mechanisms underlying osteoporosis. This review focuses on current methodologies and key examples of successful functional studies aimed at evaluating gene function in osteoporosis research. Functional evaluation typically follows a multi-step approach. In silico analyses using omics datasets expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and DNA methylation quantitative trait loci (mQTLs) help prioritize candidate genes and predict relevant biological pathways. In vitro models, including immortalized bone-derived cell lines and primary mesenchymal stem cells (MSCs), are used to explore gene function in osteogenesis. Advanced three-dimensional culture systems provide additional physiological relevance for studying bone-related cellular processes. In situ analyses of patient-derived bone and muscle tissues offer validation in a disease-relevant context, while in vivo studies using mouse and zebrafish models enable comprehensive assessment of gene function in skeletal development and maintenance. Integration of these complementary methodologies helps translate GWAS findings into biological insights and supports the identification of novel therapeutic targets for osteoporosis. Full article

Background: Spinal muscular atrophy (SMA) is a treatable motor neuron disease. Biomarkers for skeletal muscle atrophy are extremely important for measuring the effects of treatment and monitoring the natural course of the disease. The urinary titin N fragment (UNT) has recently been proven to be related to muscle damage. Methods: The UNT was measured in 41 patients with SMA and 41 healthy controls. Clinical data, functional tests, and laboratory findings were also recorded. Results: We found significantly higher UNT levels in the patient samples than in the healthy subjects. The UNT was not related to disease type, functional test results, or serum creatine kinase levels. Conclusions: This cross-sectional study highlights the importance of the UNT as a potential noninvasive biomarker for spinal muscular atrophy. Its role can potentially be verified through longitudinal studies. Full article

Background and Objectives: Urothelial bladder carcinoma includes a spectrum of malignant lesions with heterogeneous molecular, biological, and clinical features and a variable risk of progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) and ultimately to metastatic urothelial carcinoma (mUC). Sarcopenia, a condition secondary to a catabolic state, is characterized by progressive loss of skeletal muscle mass and function and is highly prevalent across all stages of bladder cancer. This review aims to synthesize current evidence regarding the clinical impact of sarcopenia and its dynamic changes throughout the disease course. Materials and Methods: A narrative literature review was conducted using PubMed, Scopus, and Cochrane databases, incorporating the most relevant published sources. Search terms included “bladder carcinoma”, “sarcopenia”, “body composition”, “NMIBC”, and “MIBC”. Case reports and congress abstracts were excluded. Results: In NMIBC treated with intravesical Bacillus Calmette–Guérin (BCG), sarcopenia has been shown to have a negative predictive value in some studies. Among patients receiving neoadjuvant chemotherapy (NAC) for MIBC, sarcopenia has been associated with increased toxicity, dose reductions, and treatment delays. In the context of radical surgery, sarcopenia correlates with increased postoperative mortality and a higher rate of severe complications. In mUC, low muscle mass is a negative prognostic factor regardless of treatment type and is associated with chemotherapy-related hematologic toxicity, although it does not appear to predict immune-related adverse events (irAEs). Conclusions: Sarcopenia is a highly prevalent and clinically relevant phenotype of urothelial bladder cancer patients, impacting prognosis, treatment response, and chemotherapy toxicity. Incorporating sarcopenia with other relevant components of body composition (BC) and systemic inflammatory markers may facilitate the development of more robust risk scores. Current evidence is primarily limited by the retrospective design of most studies. Future prospective research is needed to clarify the prognostic role of sarcopenia and support its integration into routine clinical decision-making. Full article

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. Full article

Maternal obesity programs the fetus for increased risk of chronic disease development in early life and adulthood. We hypothesized that maternal nutrient excess leads to fetal inflammation and impairs offspring skeletal muscle mitochondrial biogenesis in non-human primates. At least 12 months before pregnancy, female baboons were fed a normal chow (CTR, 12% energy fat) or a maternal nutrient excess (MNE, 45% energy fat, and ad libitum fructose sodas) diet, with the latter to induce obesity. After 165 days of gestation (0.9 G), offspring baboons were delivered by cesarean section, and the soleus muscle was collected (CTR n = 16, MNE n = 5). At conception, MNE mothers presented increased body fat and weighed more than controls. The soleus muscle of MNE fetuses exhibited increased levels of stress signaling associated with inflammation (TLR4, TNFα, NF-kB p65, and p38), concomitant with reduced expression of key regulators of mitochondrial biogenesis, including PGC1α, both at the protein and transcript levels, as well as downregulation of PPARGC1B, PPARA, PPARB, CREB1, NOS3, SIRT1, SIRT3. Decreased transcript levels of NRF1 were observed alongside diminished mitochondrial DNA copy number, mitochondrial fusion elements (MFN1, MFN2), cytochrome C protein levels, and cytochrome C oxidase subunits I and II transcripts (cox1 and cox2). MNE coupled to MO-induced stress signaling in fetal baboon soleus muscle is associated with impaired mitochondrial biogenesis and lower mitochondrial content, resembling the changes observed in metabolic dysfunctions, such as diabetes. The observed fetal alterations may have important implications for postnatal development and metabolism, potentially increasing the risk of early-onset metabolic disorders and other non-communicable diseases. Full article

Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that IGFBP5 is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of IGFBP5 in atherosclerosis. The expression of IGFBP5 was induced in the skeletal muscle of male ApoE^−/− mice, an atherosclerosis model, using adeno-associated virus, resulting in elevated circulating IGFBP5 levels. Changes in blood lipids were detected, and pathological changes in the aorta were observed. Analysis of IGFBP5 function using RNA sequencing and validation were performed in a mouse aortic smooth muscle cell line. The results demonstrated that IGFBP5 overexpression exacerbated the development of aortic lesions in this murine models without any discernible alterations in lipid profile parameters; the arterial transcriptomic landscape revealed that heightened IGFBP5 levels predominantly influenced pathways governing smooth muscle cell proliferation and motility. In vitro experimentation corroborated these findings, showcasing the stimulatory effect of IGFBP5 on VSMC (vascular smooth muscle cell) proliferation and migration, provoking a transition toward a proliferative phenotype. IGFBP5 promotes atherosclerosis in ApoE^−/− mice through the phenotypic transformation of VSMCs. This finding suggests that IGFBP5 has the potential to serve as an indicator of atherosclerosis diagnosis and a target for therapeutic interventions in the future. Full article

The advantages of extra virgin olive oil (EVOO) intake as part of a varied, healthy and balanced diet were demonstrated by many epidemiological studies. In particular, several components present in EVOO, such as tocopherols, carotenoids and phenolic compounds, play an important protective role in mitigating inflammatory diseases, atherosclerosis, neurodegenerative diseases and cancer. The protective effect exerted by EVOO was proposed to be accounted for by its antioxidant, anti-inflammatory or anti-proliferative properties. The present review will focus on the interactions among EVOO’s components and pro-inflammatory cytokines, aiming to reveal the mechanisms potentially involved in the anticancer action of EVOO. Cancer patients very frequently develop a devastating syndrome known as cachexia, which negatively impinges on their outcome. The main features of cachexia include progressive body weight loss, fat and muscle wasting, and dysmetabolism, all of which partially result from the onset of systemic inflammation. In this regard, the possibility that EVOO could be beneficial to cancer patients by mitigating cachexia will be reviewed, focusing on the skeletal muscle. Full article