Ambient air pollution exposure and the risk of probable sarcopenia: A prospective cohort study.

BACKGROUND: Sarcopenia is characterized by decreased muscle mass and strength, posing threat to quality of life. Air pollutants are increasingly recognized as risk factors for diseases, while the relationship between the two remains to be elucidated. This study investigated whether exposure to ambient air pollution contributes to the development of sarcopenia. METHODS: We employed the data from the UK Biobank with 303,031 eligible participants. Concentrations of PM2·5, NO2, and NOx were estimated. Cox proportional hazard regression models were applied to investigate the associations between pollutants and sarcopenia. RESULTS: 30,766 probable sarcopenia cases was identified during the follow-up. We observed that exposure to PM2.5 (HR, 1.232; 95% CI, 1.053-1.440), NO2 (HR, 1.055; 95% CI, 1.032-1.078) and NOx (HR, 1.016; 95% CI, 1.007-1.026) were all significantly associated with increased risk for probable sarcopenia for each 10 µg/m3 increase in pollutant concentration. In comparison with individuals in the lowest quartiles of exposure, those in the upper quartiles had significantly increased risk of probable sarcopenia. Sarcopenia-related factors, e.g., reduced lean muscle mass, diminished walking pace, and elevated muscle fat infiltration ratio, also exhibited positive associations with exposure to ambient air pollution. On the contrary, high level physical activity significantly mitigated the influence of air pollutants on the development of probable sarcopenia. CONCLUSIONS: Air pollution exposure elevated the risk of developing sarcopenia and related manifestations in a dose-dependent manner, while physical activity maintained protective under this circumstance. Efforts should be made to control air pollution and emphasize the importance of physical activity for skeletal muscle health under this circumstance.

Ageing of skeletal muscle extracellular matrix and mitochondria: finding a potential link.

Aim: To discuss the progress of extracellular matrix (ECM) characteristics, mitochondrial homeostasis, and their potential crosstalk in the pathogenesis of sarcopenia, a geriatric syndrome characterized by a generalized and progressive reduction in muscle mass, strength, and physical performance.Methods: This review focuses on the anatomy and physiology of skeletal muscle, alterations of ECM and mitochondria during ageing, and the role of the interplay between ECM and mitochondria in the pathogenesis of sarcopenia.Results: Emerging evidence points to a clear interplay between mitochondria and ECM in various tissues and organs. Under the ageing process, the ECM undergoes changes in composition and physical properties that may mediate mitochondrial changes via the systematic metabolism, ROS, SPARC pathway, and AMPK/PGC-1α signalling, which in turn exacerbate muscle degeneration. However, the precise effects of such crosstalk on the pathobiology of ageing, particularly in skeletal muscle, have not yet been fully understood.Conclusion: The changes in skeletal muscle ECM and mitochondria are partially responsible for the worsened muscle function during the ageing process. A deeper understanding of their alterations and interactions in sarcopenic patients can help prevent sarcopenia and improve its prognoses.

Sarcopenia is a senile syndrome featured by a progressive and generalized decline of muscle mass, strength, and physical performance. Given the complexity and importance of the extracellular matrix (ECM) and mitochondria of skeletal muscle, we, in this review, summarized current progress in the alterations of ECM properties and mitochondrial homeostasis in aged skeletal muscle, and have found several potential links between them. And we believe that this work could provide new insight into the prevention and treatment of age-related sarcopenia.

Pharmacological Validation of ASIC1a as a Druggable Target for Neuroprotection in Cerebral Ischemia Using an Intravenously Available Small Molecule Inhibitor.

Acidosis is a hallmark of ischemic stroke and a promising neuroprotective target for preventing neuronal injury. Previously, genetic manipulations showed that blockade of acid-sensing ion channel 1a (ASIC1a)-mediated acidotoxicity could dramatically alleviate the volume of brain infarct and restore neurological function after cerebral ischemia. However, few pharmacological candidates have been identified to exhibit efficacy on ischemic stroke through inhibition of ASIC1a. In this work, we examined the ability of a toxin-inspired compound 5b (C5b), previously found to effectively inhibit ASIC1a in vitro, to exert protective effects in animal models of ischemic stroke in vivo. We found that C5b exerts significant neuroprotective effects not only in acid-induced neuronal death in vitro but also ischemic brain injury in vivo, suggesting that ASIC1a is a druggable target for therapeutic development. More importantly, C5b is able to cross the blood brain barrier and significantly reduce brain infarct volume when administered intravenously in the ischemic animal model, highlighting its systemic availability for therapies against neurodegeneration due to acidotoxicity. Together, our data demonstrate that C5b is a promising lead compound for neuroprotection through inhibiting ASIC1a, which warrants further translational studies.

Identification and validation of a muscle failure index to predict prognosis and immunotherapy in lung adenocarcinoma through integrated analysis of bulk and single-cell RNA sequencing data.

Background: It was previously reported that the production of exerkines is positively associated with the beneficial effects of exercise in lung adenocarcinoma (LUAD) patients. This study proposes a novel scoring system based on muscle failure-related genes, to assist in clinical decision making. Methods: A comprehensive analysis of bulk and single cell RNA sequencing (scRNA-seq) of early, advanced and brain metastatic LUAD tissues and normal lung tissues was performed to identify muscle failure-related genes in LUAD and to determine the distribution of muscle failure-related genes in different cell populations. A novel scoring system, named MFI (Muscle failure index), was developed and validated. The differences in biological functions, immune infiltration, genomic alterations, and clinical significance of different subtypes were also investigated. Results: First, we conducted single cell analysis on the dataset GSE131907 and identified eight cell subpopulations. We found that four muscle failure-related genes (BDNF, FNDC5, IL15, MSTN) were significantly increased in tumor cells. In addition, IL15 was widely distributed in the immune cell population. And we have validated it in our own clinical cohort. Then we created the MFI model based on 10 muscle failure-related genes using the LASSO algorithm, and MFI remained an independent prognostic factor of OS in both the training and validation cohorts. Moreover, we generated MFI in the single-cell dataset, in which cells with high MFI received and sent more signals compared to those with low MFI. Biological function analysis of both subtypes revealed stronger anti-tumor immune activity in the low MFI group, while tumor cells with high MFI had stronger metabolic and proliferative activity. Finally, we systematically assessed the immune cell activity and immunotherapy responses in LUAD patients, finding that the low MFI group was more sensitive to immunotherapy. Conclusion: Overall, our study can improve the understanding of the role of muscle failure-related genes in tumorigenesis and we constructed a reliable MFI model for predicting prognosis and guiding future clinical decision making.