Skeletal Muscle Transcript Profiles in Trained or Sedentary Young and Old Subjects
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9103 | GEO | 2007/11/01
SECONDARY ACCESSION(S): PRJNA102631
REPOSITORIES: GEO
Similar Datasets
Project description:Aging is associated with mitochondrial dysfunction and insulin resistance. We conducted a study to determine the role of long-term vigorous endurance exercise on age-related changes in insulin sensitivity and various indices of mitochondrial functions. Experiment Overall Design: Skeletal muscle transcript profiling was done using Vastus Lateralis muscle biopsy samples from 10 young sedentary (YS), 10 older sedentary (OS), 10 young trained (YT) and 10 older trained (OT) men and women. Note that YT2, YS1, and OT1 didn't pass the Quality Control Step of dChip (high array/single outliers). Sedentary subjects exercised less than 30 min/day, twice per week. Trained subjects performed ⥠1 hour cycling or running 6 days/week over the past 4 years.
2008-06-16 | E-GEOD-9103 | biostudies-arrayexpress
Project description:We used gene microarray analysis to compare the global expression profile of genes involved in adaptation to exercise training in skeletal muscle from chronically strength/resistance trained (ST), endurance trained (ET) and untrained control subjects (Con). Resting skeletal muscle samples (~100mg) were obtained from the vastus lateralis of 20 subjects (Con n=7, ET n=7, ST n=6; trained groups >8 years specific training). Total RNA was extracted from tissue and microarrays completed, with test samples compared with standard human reference RNA. Subjects were characterised by performance measures of maximal oxygen uptake (VO2max) on a cycle ergometer and maximal concentric and eccentric leg strength on an isokinetic dynamometer. 263 genes were differentially expressed in trained (TR collectively ET + ST) subjects compared with Con (P<0.05) while 21 genes were different between ST and ET (P<0.05). Manual cluster analyses revealed significant regulation of genes involved in muscle structure and development in TR subjects compared with Con (P<0.05), and expression of these correlated significantly with measures of performance (P<0.05). ET had increased and ST decreased expression of gene clusters related to mitochondrial/oxidative capacity (P<0.05), and these mitochondrial gene clusters correlated significantly with VO2max (P<0.05). VO2max also correlated with expression of gene clusters that regulate fat and carbohydrate oxidation (P<0.05). We have demonstrated that chronic training has marked effects on basal gene expression by regulating levels of multiple mRNAs that transcribe genes for important functional groups in human skeletal muscle. Some specific gene clusters are expressed regardless of the training stimulus, whereas others exhibit divergent expression patterns as a result of specific training stimuli. Keywords: Comparative, cluster analysis, endurance training, strength training, muscle phenotype This was a crossectional study examining basal gene expression profiles of the human vastus lateralis. Twenty healthy males volunteered for this investigation. Seven were endurance trained cyclists (ET), who had been participating in endurance training for 8 yr. These subjects had no history of resistance training. Six subjects were strength trained power-lifters (ST) who had been participating exclusively in strength/resistance training for 9 yr. The final seven subjects were healthy controls (CON) that did not participate in any formal exercise. The study was approved by the Human Research Ethics Committee of RMIT University and Monash University Standing Committee on Ethics Research on Humans. After RNA extraction, amplification and indirect labelling, a dual colour micro-array analysis was conducted by hybridizing a test (muscle RNA; Cy5) sample and a reference (Universal human RNA; Cy3) sample on the AGRF glass slide human 8K micro-array. After data capture with the Genepix scanner and associated software data was normalised and the three populations compared using GeneSpring and simplified cluster analysis.
2010-05-25 | E-GEOD-9405 | biostudies-arrayexpress
Project description:We used gene microarray analysis to compare the global expression profile of genes involved in adaptation to exercise training in skeletal muscle from chronically strength/resistance trained (ST), endurance trained (ET) and untrained control subjects (Con). Resting skeletal muscle samples (~100mg) were obtained from the vastus lateralis of 20 subjects (Con n=7, ET n=7, ST n=6; trained groups >8 years specific training). Total RNA was extracted from tissue and microarrays completed, with test samples compared with standard human reference RNA. Subjects were characterised by performance measures of maximal oxygen uptake (VO2max) on a cycle ergometer and maximal concentric and eccentric leg strength on an isokinetic dynamometer. 263 genes were differentially expressed in trained (TR collectively ET + ST) subjects compared with Con (P<0.05) while 21 genes were different between ST and ET (P<0.05). Manual cluster analyses revealed significant regulation of genes involved in muscle structure and development in TR subjects compared with Con (P<0.05), and expression of these correlated significantly with measures of performance (P<0.05). ET had increased and ST decreased expression of gene clusters related to mitochondrial/oxidative capacity (P<0.05), and these mitochondrial gene clusters correlated significantly with VO2max (P<0.05). VO2max also correlated with expression of gene clusters that regulate fat and carbohydrate oxidation (P<0.05). We have demonstrated that chronic training has marked effects on basal gene expression by regulating levels of multiple mRNAs that transcribe genes for important functional groups in human skeletal muscle. Some specific gene clusters are expressed regardless of the training stimulus, whereas others exhibit divergent expression patterns as a result of specific training stimuli. Keywords: Comparative, cluster analysis, endurance training, strength training, muscle phenotype
2007-10-24 | GSE9405 | GEO
Project description:Endurance-trained athletes have high oxidative capacity, enhanced insulin sensitivity, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. We used microarrays to detect gene expression profile in endurance-trained athlete skeletal muscle.
2020-07-31 | GSE155271 | GEO
Project description:Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high- and low running capacity (HCR and LCR, respectively) over 16 generations. HCR were born with an athletic phenotype, whereas LCR exhibited features of the metabolic syndrome. Left ventricle gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Western immunoblots and immunohistochemistry were used to validate the results at protein level. Out of 28.0000 screened genes, 1540 were differentially expressed between HCR and LCR. HCR expressed higher amounts of genes involved in lipid metabolism, whereas LCR expressed higher amounts of the genes involved in glucose metabolism and transport. By simply selecting for running capacity, we created a difference in cardiac energy substrate utilisation from normal mitochondrial fatty acid ï¢-oxidation in HCR to carbohydrate metabolism in LCR. This event often occurs in diseased hearts. Differential expression of genes involved in cardiomyocyte growth was also found. LCR rats were associated with fetal gene expression, indicating the presence of pathological remodelling signaling. In addition, different expression of genes associated with cardiac contractility and cellular stress were detected. Also, hypoxia triggered transcription seemed to be involved in several of the functional differences between HCR and LCR. In conclusion, high- versus low aerobic capacity was associated with differences in genes regulating cardiac energy substrate, growth signalling, contractility and cellular stress. Experiment Overall Design: Animals Experiment Overall Design: The experimental rats in this study are the result of artificial selection for high and low aerobic capacity, starting from the N: NIH stock obtained from the National Institutes of Health (USA). The generation of the model has been previously described. Briefly, the rats in each generation were tested for exercise capacity by treadmill running at about 11 weeks of age. The individuals with the highest and lowest aerobic capacity were selected and each group served as the mating population for the next generation of high- and low-capacity runners; HCR and LCR, respectively. Rats from generation 16 were used in this study. The study includes four groups; LCR trained (n=4), LCR sedentary (n=4), HCR trained (n=4) and HCR sedentary (n=4). Experiment Overall Design: Endurance training Experiment Overall Design: The animals in the training groups were submitted to an aerobic interval training program previously described by Høydal et al. Briefly, after 10 minutes of warm-up, rats ran uphill (25°) on a treadmill for 1.5 hours, alternating between 8 minutes at an exercise intensity corresponding to 85-90% of maximal oxygen uptake (VO2max), and 2 minutes active recovery at 50 - 60%. Exercise was performed 5 days per week over 8 week; controls were age-matched rats that remained sedentary. In the exercising animals VO2max was measured every week to adjust band speed in order to maintain the intended intensity throughout the experimental period. The VO2max-measurements consisted of a 20 minutes warm-up at 50-60% of VO2max, whereupon treadmill velocity was increased by 0.03 m/s every 2 minute until VO2 plateau despite of increased workload. The apparatus and method were previously described and validated. Experiment Overall Design: Tissue collection Experiment Overall Design: At approximately 7 months of age the animals were sacrificed. A section of the left ventricle was formalin fixated for immunohistochemistry and morphological studies, whereas the rest was snap frozen in liquid nitrogen and stored at -80oC for later genetic screening and protein analysis. Experimental protocols were approved by the respective Institutional Animal Research Ethics Councils. Experiment Overall Design: Ribonuclease (RNA) isolation Experiment Overall Design: Tissue samples (20 mg) were homogenized in 100 µL TRIzol (Life Technologies, Gaithersburg, MD) using a Mixer Mill MM301 at 20-25 Hz. RNA clean-up was performed using RNA Mini kit (Qiagen, Germantown, MD). Total RNA was isolated and RNA clean-up was performed according to the manufacturer's instructions. Experiment Overall Design: RNA integrity, purity and quantity were assessed by Bioanalyzer (Agilent Technologies, Santa Clara, CA) and Nanodrop (NanoDrop Technologies, Baltimore, MD). The concentration of total RNA was measured by Nanodrop with ultraviolet spectrophotometry at 260/280 nm. RNA quality was assessed by electrophoresis on Bioanalyzer chips (Agilent Technologies). Experiment Overall Design: Experiment Overall Design: High quality RNA was classified as a 260/280 ratio above 1.8. Only samples with a 260/280 ratio between 1.8-2.2 and no signs of degradation were used for analysis. Experiment Overall Design: Processing of Affymetrix data Experiment Overall Design: Gene expression were analyzed on whole-genome RAE 230 2.0 chip from Affymetrix GeneChip (Affymetrix, Santa Clara, CA) comprised of 31,042 probe sets, analyzing over 30,000 transcripts and variants from over 28,000 substantiated rat genes. On the Affymetrix GeneChip arrays, each gene is represented by a set of 11-20 probe pairs consisting of a perfect match (PM) and a mismatch (MM) probe. The statistical analysis is based on summary expression measures for each probe set. Experiment Overall Design: Computing summary measures (RMA) Experiment Overall Design: The summary measure for each probeset is computed based on a linear statistical model for background-corrected, normalized and log-transformed PM values for each probe pair by use of the robust multiarray average (RMA) method. The PM values are normalized using the quantile normalization method, normalizing the arrays such that the empirical distribution of the expression measures is equal across arrays. Experiment Overall Design: Statistical analysis for finding differentially expressed genes Experiment Overall Design: For each gene (probeset), a linear regression model, including parameters representing the effect of aerobe capacity is specified. Based on the estimated effects, tests for significant differential expression are performed using moderated T-tests. Experiment Overall Design: To account for multiple testing, we calculate adjusted p-values controlling the False Discovery Rate (FDR), with the use of the Benjamini-Hochberg step-up procedure. Consequently, selecting differentially expressed genes based on a threshold of 0.05 on the adjusted FDR p-values means that the expected proportion of genes falsely classified as differential expressed should be below 0.05. Experiment Overall Design: All statistical analyses on the gene expression data are performed using the R language (R Development Core Team, 2004) and packages affy, affyPLM and limma from the Bioconductor project.
2008-06-16 | E-GEOD-9445 | biostudies-arrayexpress
Project description:Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between aerobic capacity and cardiac gene expression we examined genome-wide gene expression in hearts of rats artificially selected for high- and low running capacity (HCR and LCR, respectively) over 16 generations. HCR were born with an athletic phenotype, whereas LCR exhibited features of the metabolic syndrome. Left ventricle gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Western immunoblots and immunohistochemistry were used to validate the results at protein level. Out of 28.0000 screened genes, 1540 were differentially expressed between HCR and LCR. HCR expressed higher amounts of genes involved in lipid metabolism, whereas LCR expressed higher amounts of the genes involved in glucose metabolism and transport. By simply selecting for running capacity, we created a difference in cardiac energy substrate utilisation from normal mitochondrial fatty acid betaoxidation in HCR to carbohydrate metabolism in LCR. This event often occurs in diseased hearts. Differential expression of genes involved in cardiomyocyte growth was also found. LCR rats were associated with fetal gene expression, indicating the presence of pathological remodelling signaling. In addition, different expression of genes associated with cardiac contractility and cellular stress were detected. Also, hypoxia triggered transcription seemed to be involved in several of the functional differences between HCR and LCR. In conclusion, high- versus low aerobic capacity was associated with differences in genes regulating cardiac energy substrate, growth signalling, contractility and cellular stress. Keywords: metabolic syndrome analysis
2008-01-04 | GSE9445 | GEO
Project description:substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1α and AMPKα2. The muscle transcriptome of the non-responders is further characterized by an activation of TGFβ and TGFβ target genes, which is associated with increases in inflammatory and macrophage markers. TGFβ1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGFβ1 signaling down-regulates the abundance of PGC1α, AMPKα2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGFβ activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity. We performed gene expression microarray analysis on muscle biopsies from humans before and after an eight weeks endurance training intervention
2016-06-29 | E-GEOD-72462 | biostudies-arrayexpress
Project description:Mitochondrial dysfunction is implicated in aging and aging-related disorders, such as neurodegenerative diseases and stroke. To study the effects of progressive mitochondrial dysfunction, a homozygous knock-in mouse expressing a proof-reading deficient version of the nucleus-encoded catalytic subunit of mitochondrial DNA (mtDNA) polymerase (PolgA) has been developed. In the mtDNA mutator mouse the proofreading activity of PolgA has been abolished by a single amino acid change. PolgA is the catalytic subunit of the polymerase gamma, which is involved in replicating and proofreading the mitochondrial DNA. As a result, mtDNA mutator mice develop high levels of point mutations and linear deletions, which lead to several human-like phenotypes associated with aging, including reduced lifespan (42-44 weeks), weight loss, alopecia, anemia, kyphosis, osteoporosis, sarcopenia, loss of subcutaneous fat, and reduced fertility. We investigate the molecular mechanism through which exercise may improve the phenotype of the mtDNA mutator mouse, which is a model of premature aging induced by mitochondrial dysfunction. Remarkably, forced endurance exercise has been shown to rescue the progeroid aging phenotypes of the mtDNA mutator mice, and to induce systemic mitochondrial rejuvenation. Here, using voluntary, rather than forced exercise, we investigate the molecular mechanisms underlying such a dramatic improvement, and also assess the effect of exercise on brain tissues, such as cortex and striatum in our model. The complete proteome of key tissues (muscle, brain cortex, brain striatum) from exercising and sedentary mtDNA mutator mice as well as exercising and sedentary wild type mice is quantified using peptide high-resolution isoelectric focusing (HiRIEF) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) with an isobaric tag (TMT10plex) strategy.
2019-08-05 | PXD011741 | Pride
Project description:Age-related declines in cardiorespiratory fitness and physical function are mitigated by regular endurance exercise in older adults. This may be due, in part, to changes in the transcriptional program of skeletal muscle following repeated bouts of exercise. However, the impact of chronic exercise training on the transcriptional response to an acute bout of endurance exercise has not been clearly determined. Here, we characterized baseline differences in muscle transcriptome and exercise-induced response in older adults who were active/endurance trained or sedentary. RNA-sequencing was performed on vastus lateralis biopsy specimens obtained before, immediately after, and 3 h following a bout of endurance exercise (40 min of cycling at 60%–70% of heart rate reserve). Using a recently developed bioinformatics approach, we found that transcript signatures related to type I myofibers, mitochondria, and endothelial cells were higher in active/endurance-trained adults and were associated with key phenotypic features including V̇o2peak, ATPmax, and muscle fiber proportion. Immune cell signatures were elevated in the sedentary group and linked to visceral and intermuscular adipose tissue mass. Following acute exercise, we observed distinct temporal transcriptional signatures that were largely similar among groups. Enrichment analysis revealed catabolic processes were uniquely enriched in the sedentary group at the 3-h postexercise timepoint. In summary, this study revealed key transcriptional signatures that distinguished active and sedentary adults, which were associated with difference in oxidative capacity and depot-specific adiposity. The acute response signatures were consistent with beneficial effects of endurance exercise to improve muscle health in older adults irrespective of exercise history and adiposity.
2022-03-01 | GSE151066 | GEO
Project description:Time course of mRNA after 30 minutes of endurance exercise at simulated altitude of 4000 m in an untrained or six weeks trained state of six subjects. Time course of mRNA after 30 minutes of endurance exercise at simulated altitude of 4000 m in an untrained (1) or six weeks trained state (2) of six subjects (Hoxxx) Ho981: (1) GSM343213, GSM343214, GSM343215, GSM343216; (2) GSM343217, GSM343218, GSM343219, GSM343220 Ho982: (1) GSM343221, GSM343222, GSM343223, GSM343224; (2) GSM343225, GSM343226, GSM343227, GSM343228 Ho984: (1) GSM343229, GSM343230, GSM343231, GSM343232; (2) GSM343233, GSM343234, GSM343235, GSM343236 Ho994: (1) GSM343237, GSM343238, GSM343239, GSM343240; (2) GSM343241, GSM343242, GSM343243, GSM343244 Ho998: (1) GSM343245, GSM343246, GSM343247, GSM343248; (2) GSM343249, GSM343250, GSM343251, GSM343252 Ho996: (1) GSM343253, GSM343254, GSM343255, GSM343256 Keywords: time-course
2009-11-15 | E-GEOD-13623 | biostudies-arrayexpress