Whole blood transcriptomics to define adaptive biochemical pathways of exercise during aging
ABSTRACT: The aim of the current study was to characterize the genetic adaptive pathways altered by exercise in veteran athletes and age-matched untrained individuals. Two groups of 50-60 year old males: competitive cyclists and untrained, minimally active individuals were examined. All participants completed an acut bout of submaximal endurance exercise and blood samples pre- and post-exercise were analyzed for gene expression changes utilizing genome-wide DNA microarray analysis. Our results indicate distinct differences in gene expression involving energy metabolism, lipids, insuling signaling and cardiovascular function between the two groups. These findings may lead to new insights into beneficial signaling pathways of healthy aging and help identify surrogate markers for monitoring exercise and training load. Blood samples from the control and athlete groups were analyzed at three time-points: T1 (before exercise); T2 (immediately after exercise) and T3 (24 hours after exercise). There were n = 4 samples in each of control and athlete group at T1 and T3; and n = 7 for control group and n = 8 for athlete group at T2. One athlete sample (Sample # 010201) at time - point T2 had a technical replicate.
Project description:Arabian horses are believed to be one of the oldest and most influential horse breeds in the world. Blood is the main tissue involved in maintaining body homeostasis, and it is considered a marker of the processes taking place in the other tissues. Thus, the aim of our study was to identify the genetic basis of changes occurring in the blood of Arabian horses subjected to a training regimen and to compare the global gene expression profiles between different training periods (T1: after a slow canter phase that is considered a conditioning phase, T2: after an intense gallop phase, and T3: at the end of the racing season) and between trained and untrained horses (T0). RNA sequencing was performed on 37 samples with a 75-bp single-end run on a HiScanSQ platform (Illumina), and differentially expressed genes (DEGs) were identified based on DESeq2 (v1.11.25) software.An increase in the number of DEGs between subsequent training periods was observed, and the highest amount of DEGs (440) was detected between untrained horses (T0) and horses at the end of the racing season (T3). The comparisons of the T2 vs. T3 transcriptomes and the T0 vs. T3 transcriptomes showed a significant gain of up-regulated genes during long-term exercise (up-regulation of 266 and 389 DEGs in the T3 period compared to T2 and T0, respectively). Forty differentially expressed genes were detected between the T1 and T2 periods, and 296 between T2 and T3. Functional annotation showed that the most abundant genes up-regulated in exercise were involved in pathways regulating cell cycle (PI3K-Akt signalling pathway), cell communication (cAMP-dependent pathway), proliferation, differentiation and apoptosis, as well as immunity processes (Jak-STAT signalling pathway).We investigated whether training causes permanent transcriptome changes in horse blood as a reflection of adaptation to conditioning and the maintenance of fitness to compete in flat races. The present study identified the overrepresented molecular pathways and genes that are essential for maintaining body homeostasis during long-term exercise in Arabian horses. Selected DEGs should be further investigated as markers that are potentially associated with racing performance in Arabian horses.
Project description:Purpose: Next-generation sequencing (NGS) was used to select genes potentially associated with exercise adaptation in Arabian horses. Methods: Whole transcriptome profiling of blood was performed for untrained horses and horses from which samples were collected during at 3 different periods of training procedure (T1-during intense training period - March, T2- before starts - May and T3 -after flat racing season - October). The muscle transcriptome sequencing was performed for 37 blood samples using Illumina HiScan SQ in 75 single-end cycles. The quantifying transcript abundances was made using the RSEM supported by STAR aligner. The raw reads were aligned to the Equus caballus reference genome. Differentially expressed genes in blood tissue were detected by DESeq2. The RNA-seq results were validated using by qPCR. Results: The increase of the number of DEGs between subsequent training periods has been observed and the highest amount of DEGs was detected between untrained horses (T0) and horses at the end of the racing season (T3) – 440. The comparison of transcriptome of T2 vs T3 and T0 vs T3 showed a significant advantage of up-regulated genes during long-term exercise (up-regulation of 266 and 389 DEGs in T3 period compared T2 and T0; respectively). Our results showed that the largest number of identified genes encoded transcription factors, nucleic acid binding proteins and G-protein modulators, which mainly were transcriptional activated at the last training phase (T3) . Moreover, in the T3 period the identified DEGs represented genes coded for cytoskeletal proteins including actin cytoskeletal proteins and kinases. The most abundant exercise-upregulated genes were involved in pathways important in regulating the cell cycle (PI3K-Akt signaling pathway), cell communication (cAMP-dependent pathway), proliferation, differentiation and apoptosis as well as immunity processes (Jak-STAT signaling pathway). We also observed exercise induced expression of genes related in regulation of actin cytoskeleton, gluconeogenesis (FoxO signaling pathway; Insulin signaling pathway), glycerophospholipid metabolism and calcium signaling. Conclusions: TOur results allow to identify changes in genes expression profile following training schedule in Arabian horses. Based on comparison analysis of blood transcriptomes, several exercise-regulated pathways and genes most affected by exercise were detected. We pinpointed overrepresented molecular pathways and genes essential for exercise adaptive response via maintaining of body homeostasis. The observed transcriptional activation of such gene as LPGAT1, AGPAT5, PIK3CG, GPD2, FOXN2, FOXO3, ACVR1B and ACVR2A can be a base for further research in order to identify genes potentially associated with race performance in Arabian horses. Such markers will be essential to choice the training type, and could result in differences in racing performance specific to various breeds. The blood transcriptome sequencing was performed for 37 samples collected form Arabian horses using Illumina HiScan SQ in75 single-end cycles and in 3-4 technical repetitions.repetitions.
Project description:Years of training in competitive sports leads to human body adaptation to a specific type of exercise. In judo bouts, maintaining hand grip on an opponent's clothes and postural balance is essential for the effective technical and tactical actions. This study compares changes after maximal anaerobic exercise among judo athletes and untrained subjects regarding 1) maximum isometric handgrip strength (HGSmax) and accuracy at the perceived 50% maximum handgrip force (1/2HGSmax) and 2) the balance of 13 judo athletes at national (n = 8) and international (n = 5) competitive levels and 19 untrained university students. The groups did not differ in age, body height, and weight. Body mass index (BMI) and body composition (JAWON) were evaluated. The Wingate Anaerobic Test (WAnT, Monark 875E) measured recommended anaerobic capacity indices. Hand grip strength (Takei dynamometer) and balance (biplate balance platform) were measured before warm-up (T1), before the WAnT test (T2), and after (T3). Parametric or non-parametric tests were performed after verifying the variable distribution assumption. Judoists had higher BMI and fat-free mass index (FFMI) than the students. The athletes also showed higher relative total work and relative peak power and lower levels of lactic acid. The difference in judoists between HGSmax at T1 and HGSmax at T3 was statistically significant. Before warm-up (T1), athletes showed higher strength (more divergent from the calculated ½HGSmax value) compared to students. Substantial fatigue after the WAnT test significantly deteriorated the body stability indices, which were significantly better in judo athletes at all time points. The findings suggest specific body adaptations in judoists, especially for body composition, anaerobic energy system efficiency, and postural balance. These characteristics could be trained for specifically by judo athletes to meet the time-motion and anaerobic demands of contemporary bouts.
Project description:Impact of antibiotics (T2) or antibiotics in combination with stress (T3) in early life on intestinal functioning in pigs on 8, 55, 176 days in jejunum and ileum (blood only day 8) and control pigs (T1) 4 pools consisting of 16 animals were generated per time-point (day 8, 55, 176 after birth) per treatment (T1;control, T2; antibiotics, T3; antibiotics+stress)
Project description:to examine the effect of a 4-day NO3- loading protocol on the submaximal oxygen cost of both low fit and high fit participants at five different exercise intensities.participants were initially assigned to a placebo (PL; negligible NO3-) or inorganic nitrate-rich (NR; 6.2 mmol nitrate/day) group; double-blind, placebo-controlled, crossover. Participants completed three trials (T1, T2 and T3). T1 included a maximal aerobic capacity (VO2max) treadmill test. A 6-day washout, minimizing nitrate consumption, preceded T2. Each of the four days prior to T2 and T3, participants consumed either PL or NR; final dose 2.5 hours prior to exercise. A 14-day washout followed T2. T2 and T3 consisted of 5-minute submaximal treadmill bouts (45, 60, 70, 80 and 85% VO2max) determined during T1.Low fit nitrate-supplemented participants consumed less oxygen (p<0.05) at lower workloads (45% and 60% VO2max) compared to placebo trials; changes not observed in high fit participants. The two lowest intensity workloads of 45 and 60% VO2max revealed the greatest correlation (r=0.54, p=0.09 and r=0.79, p<0.05; respectively). No differences were found between conditions for heart rate, respiratory exchange ratio or rating of perceived exertion for either fitness group.Nitrate consumption promotes reduced oxygen consumption at lower exercise intensities in low fit, but not high fit males. Lesser fit individuals may receive greater benefit than higher fit participants exercising at intensities <60% VO2max.
Project description:CONTEXT:Episodic breathlessness is common and debilitating in cancer patients. OBJECTIVES:In this pilot study, we examined the effect of prophylactic fentanyl pectin nasal spray (FPNS) on exercise-induced dyspnea, physiologic function, and adverse events. METHODS:In this parallel, double-blind randomized placebo-controlled trial, opioid-tolerant patients performed three six-minute walk tests (6MWTs) to induce dyspnea. They were randomized to receive either FPNS (15%-25% of total daily opioid dose each time) or placebo 20 minutes before the second and third 6MWTs. We compared dyspnea Numeric Rating Scale (NRS, 0-10, primary outcome), walk distance, vital signs, neurocognitive function, and adverse events between the first and second 6MWTs (T2-T1) and between the first and third 6MWTs (T3-T1). RESULTS:Twenty-four patients enrolled, with 96% completion. FPNS was associated with significant within-arm reduction in dyspnea NRS at rest (T2-T1: -0.9 [95% CI -1.7, -0.1]; T3-T1: -1.3 [95% CI -2.0, -0.5]) and at the end of a 6MWT (T2-T1: -2.0 [95% CI -3.5, -0.6]; T3-T1: -2.3 [95% CI -4.0, -0.7]), and longer walk distance (T2-T1 +23.8 m [95% CI +1.3, +46.2 m]; T3-T1: +23.3 m [95% CI -1.7, +48.2]). In the placebo arm, we observed no significant change in walk distance nor dyspnea NRS at rest, but significant reduction in dyspnea NRS at six minutes (T2-T1: -1.7 [95% CI -3.3, -0.1]; T3-T1: -2.5 [95% CI -4.2, -0.9]). Vital signs, neurocognitive function, and adverse effects did not differ significantly. CONCLUSION:FPNS was safe, reduced dyspnea at rest, and increased walk distance in before-after comparison. The placebo effect was substantial, which needs to be factored in future study designs. TRIAL REGISTRATION:ClinicalTrials.govNCT01832402.
Project description:Growing evidence points to the effectiveness of flywheel (FW) based iso-inertial resistance training in improving physical performance capacities. However, molecular adaptations induced by FW exercises are largely unknown. Eight resistance-trained men performed 5 sets of 10 maximal squats on a FW device. Muscle biopsies (fine needle aspiration technique) and blood samples were collected before (t0), and 2 h (t1) after FW exercise. Blood samples were additionally drawn after 24 h (t2) and 48 h (t3). Paired samples t-tests revealed significant increases, at t1, of mRNA expression of the genes involved in inflammation, in both muscle (MCP-1, TNF-?, IL-6) and peripheral blood mononuclear cells (IkB-?, MCP-1). Circulating extracellular vesicles (EVs) and EV-encapsulated miRNA levels (miR-206, miR-146a) significantly increased at t1 as well. Conversely, muscle mRNA level of genes associated with muscle growth/remodeling (IGF-1Ea, cyclin D1, myogenin) decreased at t1. One-way repeated measure ANOVAs, with Bonferroni corrected post-hoc pairwise comparisons, revealed significant increases in plasma concentrations of IL-6 (t1; t2; t3) and muscle creatine kinase (t1; t2), while IGF-1 significantly increased at t2 only. Our findings show that, even in experienced resistance trained individuals, a single FW training session modifies local and systemic markers involved in late structural remodeling and functional adaptation of skeletal muscle.
Project description:Tannin, an antinutritional component of plant proteins was fed to grass carp (Ctenopharyngodon idellus, 8. 18 ± 0.81 g) for 8 weeks to investigate their tolerance levels. Semi-purified diets (T0, T1, T2, and T3) with varying levels of hydrolysable tannin (0, 0.75, 1.25, and 1.75% respectively) were used. No significant difference was obtained in weight gain, while feed conversion ratio of T0 was significantly lower than T2. Muscle protein content of T0 and T3 were significantly higher than T2, while lipid content of T0 was significantly higher than other groups. Muscle and hepatic glycogen in T0 were significantly lower than other groups. Muscle saturated fatty acids in T3 were significantly higher than T0, and lowest in T1 and T2, while the poly-unsaturated fatty acids in T1 and T2 were higher than T0 and lowest in T3. Significant increases were obtained in trypsin and amylase activities as tannin levels increased, the lipase activity of T0 and T1 was significantly higher than T2 and T3. Activities of hepatic alanine aminotransferase and aspartate aminotransferase decreased with increasing tannin level. The total protein in serum of T2 was significantly higher than T0 and T1 and lowest in T3, whereas globulin of T2 was significantly higher than T0 and T3 and lowest in T1, while albumin of T1 was significantly higher than other groups. Urea nitrogen of T0 was significantly higher than other groups, triglyceride and total cholesterol significantly increased with tannin level and decreased in T3, significant decreases were obtained in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in T3. mRNA expression of intestinal TOR was significantly upregulated as dietary tannin increased. In hepatopancreas, the expression of glucokinase in T1 was significantly higher than T2, and lowest in T0 and T3, pyruvate kinase in T2 was significantly higher than T0 and T1 and lowest T3. The expression of lipoprotein lipase upregulated as tannin level and downregulated in T3, and fatty acid synthase downregulated as tannin level. In conclusion, grass carp could tolerate 1.75% dietary tannin without influencing growth. However, 1.25% tannin impaired digestion and metabolism of protein, decreased the deposition of lipid and promoted utilization of carbohydrate.
Project description:This study tested the efficacy of audio-visual reading training in nine patients with pure alexia, an acquired reading disorder caused by damage to the left ventral occipitotemporal cortex. As well as testing the therapy's impact on reading speed, we investigated the functional reorganization underlying therapy-induced behavioural changes using magnetoencephalography. Reading ability was tested twice before training (t1 and t2) and twice after completion of the 6-week training period (t3 and t4). At t3 there was a significant improvement in word reading speed and reduction of the word length effect for trained words only. Magnetoencephalography at t3 demonstrated significant differences in reading network connectivity for trained and untrained words. The training effects were supported by increased bidirectional connectivity between the left occipital and ventral occipitotemporal perilesional cortex, and increased feedback connectivity from the left inferior frontal gyrus. Conversely, connection strengths between right hemisphere regions became weaker after training.
Project description:Background:The regular assessment of hormonal and mood state parameters in professional soccer are proposed as good indicators during periods of intense training and/or competition to avoid overtraining. Objective:The aim of this study was to analyze hormonal, psychological, workload and physical fitness parameters in elite soccer players in relation to changes in training and match exposure during a congested period of match play. Methods:Sixteen elite soccer players from a team playing in the first Tunisian soccer league were evaluated three times (T1, T2, and T3) over 12 weeks. The non-congested period of match play was from T1 to T2, when the players played 6 games over 6 weeks. The congested period was from T2 to T3, when the players played 10 games over 6 weeks. From T1 to T3, players performed the Yo-Yo intermittent recovery test level 1 (YYIR1), the repeated shuttle sprint ability test (RSSA), the countermovement jump test (CMJ), and the squat jump test (SJ). Plasma Cortisol (C), Testosterone (T), and the T/C ratio were analyzed at T1, T2, and T3. Players had their mood dimensions (tension, depression, anger, vigor, fatigue, confusion, and a Total Mood Disturbance) assessed through the Profile of Mood State questionnaire (POMS). Training session rating of perceived exertion (sRPE) was also recorded on a daily basis in order to quantify internal training load and elements of monotony and strain. Results:Significant performance declines (T1 < T2 < T3) were found for SJ performance (p = 0.04, effect size [ES] ES1 - 2 = 0.15-0.06, ES2 - 3 = 0.24) from T1 to T3. YYIR1 performance improved significantly from T1 to T2 and declined significantly from T2 to T3 (p = 0.001, ES1 - 2 = 0.24, ES2 - 3 = -2.54). Mean RSSA performance was significantly higher (p = 0.019, ES1 - 2 = -0.47, ES2 - 3 = 1.15) in T3 compared with T2 and T1. Best RSSA performance was significantly higher in T3 when compared with T2 and T1 (p = 0.006, ES2 - 3 = 0.47, ES1 - 2 = -0.56), but significantly lower in T2 when compared with to T1. T and T/C were significantly lower in T3 when compared with T2 and T1 (T: p = 0.03, ES3 - 2 = -0.51, ES3 - 1 = -0.51, T/C: p = 0.017, ES3 - 2 = -1.1, ES3 - 1 = -1.07). Significant decreases were found for the vigor scores in T3 when compared to T2 and T1 (p = 0.002, ES1 - 2 = 0.31, ES3 - 2 = -1.25). A significant increase was found in fatigue scores in T3 as compared to T1 and T2 (p = 0.002, ES1 - 2 = 0.43, ES2 - 3 = 0.81). A significant increase was found from T1 < T2 < T3 intension score (p = 0.002, ES1 - 2 = 1.1, ES2 - 3 = 0.2) and anger score (p = 0.03, ES1 - 2 = 0.47, ES2 - 3 = 0.33) over the study period. Total mood disturbance increased significantly (p = 0.02, ES1 - 2 = 0.91, ES2 - 3 = 1.1) from T1 to T3. Between T1-T2, significant relationships were observed between workload and changes in T (r = 0.66, p = 0.003), and T/C ratio (r = 0.62, p = 0.01). There were significant relationships between performance in RSSAbest and training load parameters (workload: r = 0.52, p = 0.03; monotony: r = 0.62, p = 0.01; strain: r = 0.62, p = 0.009). Between T2-T3, there was a significant relationship between ?% of total mood disturbance and ?% of YYIR1 (r = -0.54; p = 0.04), RSSAbest (r = 0.58, p = 0.01), SJ (r = -0,55, p = 0.01), T (r = 0.53; p = 0.03), and T/C (r = 0.5; p = 0.04). Conclusion:An intensive period of congested match play significantly compromised elite soccer players' physical and mental fitness. These changes were related to psychological but not hormonal parameters; even though significant alterations were detected for selected measures. Mood monitoring could be a simple and useful tool to determine the degree of preparedness for match play during a congested period in professional soccer.