Project description:BackgroundThe gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under-investigated, and the molecular mechanism remains unclear.MethodsTo investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi-ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model.ResultsThe study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non-sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non-sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P < 0.001). The LPC mice had significantly longer wire and grid hanging time (P < 0.02), longer time on rotor (P = 0.0001) and larger grip strength (P < 0.0001), indicating better muscle function. The weight of gastrocnemius mass and rectus femoris mass (P < 0.05) was higher in LPC mice. The micro-computed tomography showed a larger leg area (P = 0.0031), and a small animal analyser showed a higher lean mass ratio in LPC mice (P = 0.0157), indicating higher muscle mass.ConclusionsThe results indicated that there were lower levels of both P. copri and BCAA in sarcopenia individuals. In vivo experiments, gavage with LPC could attenuate muscle mass and function decline, indicating alleviating sarcopenia. This suggested that P. copri may play a therapeutic potential role in the management of sarcopenia.

Project description:BackgroundThe quadriceps muscle is one of the human body's largest and most clinically important muscles and is evaluated using mid-thigh computed tomography (CT); however, its relationship with motor function and sarcopenia remains unclear. Herein, we investigated the relationship between the cross-sectional area (CSA) of the quadriceps muscle, CT attenuation value (CTV), dual-energy X-ray absorptiometry muscle mass measurements, and muscle strength and motor function to evaluate the relationship between muscle mass loss and motor function decline, determine the diagnostic ability for sarcopenia, and confirm the usefulness of quadriceps muscle CT evaluation.MethodsA total of 472 middle-aged and older community dwellers (254 men and 218 women) aged ≥40 years (mean age: 62.3 years) were included in this study. The quantity and quality of the quadriceps muscle were assessed using CSA and CTV (CSA×CTV) as a composite index multiplied by quality and quantity. Age-adjusted partial correlations by sex with eight motor functions (knee extension muscle strength, power, normal walking speed, fast walking speed, grip strength, sit-up ability, balance ability, and reaction time) were evaluated, including correction methods for height, weight, and body mass index (BMI). Further, the accuracy of sarcopenia diagnosis was evaluated using appendicular muscle mass with dual-energy X-ray absorptiometry measurements, grip strength, and walking speed as the gold standard, and receiver operating characteristic curves were plotted to evaluate diagnostic performance.ResultsIn men, CSA and CSA×CTV were significantly associated with seven of the eight motor functions (p<0.05), excluding only balance ability. BMI-corrected CSA was significantly correlated with all eight motor functions in men and women (p<0.05). In the diagnosis of sarcopenia based on skeletal muscle index, CSA (area under the curve (AUC) 0.935) and CSA×CTV (AUC 0.936) and their correction by height (CSA/height (AUC 0.917) and CSA×CTV/height (AUC 0.920)) were highly accurate and useful for diagnosis in men but moderately accurate in women (CSA (AUC 0.809), CSA×CTV (AUC 0.824), CSA/height (AUC 0.799), CSA×CTV/height (AUC 0.814)).ConclusionThe present results showed that a single CT image of the quadriceps muscle at the mid-thigh is useful for diagnosing sarcopenic changes, such as loss of muscle mass, muscle weakness, and muscle function.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 Î¼m and smaller than 0.5 Î¼m (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013. The PM filter samples used in the present study were PM10 and PM0.5 from the urban site - total of 4 samples from 2 sampling months; and PM0.5 from the rural site - total of 2 samples from 2 sampling months (PM10 samples from the rural site were not tested due to their very low concentration in organic compounds, and insignificant biological activity, previously measured). Sampling occurred during the cold periods of the year 2012/2013. The organic fraction of PM samples was extracted by sonication using a mixture of dichloromethane:methanol. Then, the extracts were filtered, evaporated and re-dissolved in Dimethyl sulfoxide (DMSO). Zebrafish fertilized eggs were exposed to PM organic extracts (0.2% DMSO) from the urban and rural sites from 24 to 120h post-fertilization. Total RNA was isolated from whole embryos (pools of 20 individuals), using Trizol reagent protocol (Invitrogen Life Technologies, Carlsberg, CA). The microarray study was performed using the Agilent Two-colour D. rerio Oligo Microarray v3 platform, following the Agilent Microarray â?? Based Gene Expression Analysis protocol. Three biological replicates were performed for each PM sample and controls. Biological replicates, a technical replicate and a self-to-self, were simultaneously amplified and labelled using Cyanine 3 (Cy3) and Cyanine 5 (Cy5) dye. After cRNA purification (RNeasy Kit, Quiagen GmbH, Hilden, Germany), the cRNA concentration and labelling were quantified in the NanoDrop spectrophotometer, obtaining incorporation rates in the range of 15-20pmol of cyanide dye/Âµl cRNA and yield values > 0.825ug, as recommended. cRNA was fragmented and hybridized in 4x44K arrays, for 17h at 65oC. After the hybridization the array slides were washed, and immediately scanned using Microarray Scanner Agilent G2505C system. Data was extracted using Agilent Feature Extraction Software v10.5.1.1, and the quality of microarray data was evaluated using the Quality Control report provided by Agilent Software. Based on the microarray data analysis, 22 primers were selected and designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA). Genes were quantified by real-time PCR to validate the microarray data, and a subset of 13 genes were further selected by their robust behaviour in the validation assays, allowing to differentiate the toxic potential of PM from urban and rural sources.

Dataset Information

Low muscle mass, low muscle function, and sarcopenia in the urban and rural elderly.

Publications

Low muscle mass, low muscle function, and sarcopenia in the urban and rural elderly.

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