Non-coding RNAs in the transcriptional network that differentiates skeletal muscles of sedentary from long-term endurance- and resistance-trained elderly (microarray)
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ABSTRACT: In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared, the two groups representing the two ends of a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMPK and mTOR, which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.
Project description:In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared, the two groups representing the two ends of a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMPK and mTOR, which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.
Project description:How skeletal muscle adapts to different types of exercise intensity with age is not known. Adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group’s exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear. Skeletal muscle exhibited structural and functional adaptations to exercise training, as revealed by electron microscopy, OXPHOS assays, respirometry, and muscle protein biomarkers. Transcriptomics analysis of gastrocnemius muscle combined with liver and serum metabolomics unveiled an age-dependent metabolic remodeling in response to exercise training. These results support a tailored exercise prescription approach aimed at improving health and ameliorating age-associated loss of muscle strength and function in the elderly.
Project description:This study investigates the effects of exercise and genetic predisposition on the transcriptomic profile of the pituitary gland of long-term selected marathon (DUhTP) and non-inbred (DUC) mice. In the exercise group, mice underwent treadmill training for three weeks. For the sedentary control group, mice were kept under minimal physical activities. For the 3-week training program, the mice were running five days per week (Monday to Friday) starting at age of 49 days after birth (Walz et. al. 2021). All mice used in this experiment were male and sacrificed at day 70 of life for tissue sampling.
Project description:This study investigates the effects of exercise and genetic predisposition on the transcriptomic profile of the rectus femoris muscle of long-term selected marathon (DUhTP) and non-inbred (DUC) mice. All mice used in this experiment were male. In the exercise group, mice underwent treadmill training for three weeks. For the sedentary control group, mice were kept under minimal physical activities. For the 3-week training program, the mice were running five days per week (Monday to Friday) starting at age of 49 days after birth (Walz et. al. 2021). All mice were sacrificed at day 70 of life for tissue sampling.
Project description:Consequence of physical exercise in skeletal muscle was investigated in C57BL/6 mice after 4 weeks of exercise training and compared to sedentary controls. Exercised mice received four 4 weeks of regular exercise training on a motorized treadmill and were compared to sedentary controls. 6 mice of each Treatment were used to extract RNA from the quadriceps muscle three hours after the last training bout
Project description:In order to assess the impact of treadmill exercise on traumatic brain injury outcomes, we subjected male and female swiss webster mice to a controlled cortical impact (CCI), followed by 10 days of sedentary, low-, moderate-, or high-intensity treadmill exercise. Outcome measures included neurometabolic function, cognitive recovery, oxidative stress, pathophysiology, and single nuclei RNA sequencing (snRNA seq). The snRNA seq study was conducted on both male and female mice, and included a total of 2 replicates (each was a pool of 2 tissue samples) from each of the following groups: male sham sedentary, male CCI sedentary, male CCI low, male CCI high, female sham sedentary, female CCI sedentary, female CCI low, female CCI high. Our data reveal exercise intensity- and sex-dependent effects of treadmill exercise following injury. Transcriptomic changes were largely limited to the low-intensity exercised CCI males.
Project description:Lifestyle induces long lasting effects on the brain and cognition, with some interventions like stress including transgenerational inheritance on the next generations mediated by epigenetic mechanisms. Physical exercise is one potent intervention driving robust improvements of cognition and brain health, also inducing intergenerational transmission to the litter. However, little is known about whether exercise effects may be transgenerationally transmitted. Here we analyzed the adult hippocampal neurogenesis (AHN) and the behavioral phenotype of sedentary adult male mice of the F2 generation of exercised grandfathers (F0, patrilineal design). Both F1 and F2 were sedentary, while F0 performed a moderate exercise training. We found that the F2 mice from exercised F0 acquired and recalled both spatial and non-spatial information better than F2 from sedentary F0. Contextual fear conditioning resulted not affected, together with no differences in the AHN markers. These results demonstrate that the transgenerational transmission of the effects of exercise on specific cognitive tasks persists after two generations, even though some of the cellular changes induced in F1 disappear in F2, and suggest that moderate exercise training has a longer-lasting effect than previously thought, and this aspect is worth taking into account in public health programs.
Project description:Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. However, the impact of short-term (0.5 year in this study) and long-term (25+ years in this study) regular bouts of exercise on circulating exosomal microRNAs (exomiRs) remains unknown. Our aim was to elucidate the prevention pattern of exomiRs and their targeted pathways. Therefore, in the present study we analyzed serum exomiR expression in healthy young, sedentary participants (n=14) at baseline and following a half year-long moderate-intensity regular exercise training. We also analyzed serum exomiR expression in older, healthy trained participants (seniors, n=11) who engaged in endurance activities for at least 25 years. Following the isolation and enrichment of serum exosomes their exomiR levels were determined using the amplification-free Nanostring platform.
Project description:Seventy two rats were randomized to twelve independent groups of rats (n = 6 in all groups) where half of the rats were chosen for training (treadmill exercise training 1.5 hour 5 days a week, in 1, 4, 24, 48 days and for 4 and 8 weeks) or sedentary (no training) as described in detail by Wisloff et al. (Intensity-controlled treadmill running in rats: VO(2 max) and cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1301-10.) or Kemi et al.(Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation. 2004 Jun 15;109(23):2897-904. Epub 2004 Jun 1.). The rats were scarified one hour after training (1, 4, 24 and 48 days) or 24 hours after training (4 and 8 weeks). Biopsies form left ventricle was taken form all rats and stored on -80°C for preparation of RNA. The same procedures were performed for the control/sedentary rats which were sacrificed at the same time as the exercised rats.
Project description:The goal of the endurance exercise training study in young adult rats was to perform exercise training studies in young adult (6-month-old) F344 rats, and from these rats collect multiple tissues in order to provide high quality samples for detailed analysis by chemical analysis sites. Tissues were collected from 10-12 rats sedentary control rats concurrent with the collection of the 8-week training groups. The 8-week training group and controls were from the same cohort and same age at euthanasia. For the older age group, an additional set of controls (n=5-6) were collected with the 1-2 week training group. Rats were either sedentary or underwent an exercise training program. Rats were exercised on the rodent treadmill 5 days per week using a progressive training protocol designed to exercise the rats at approximately 70% of VO2max and training was performed no earlier than 10:00 am and no later than 5:00 pm over 5 consecutive days per week. Training was initiated with the treadmill set at 70% of VO2 max and 5 degrees grade for 20 minutes. The duration of exercise was increased by one minute each day until day 31 of training (start of week 7), when a duration of 50 min was reached. Speed and grade of each training session increased in larger increments due to treadmill parameters. The highest intensity and duration of training began on day 31. This intensity was maintained for the final 10 days of the protocol to ensure steady state had been achieved. If any rats were unable to perform at least 4 days of training per week they were removed from the study and euthanized. It is important to note that the starting treadmill speed varied depending on the sex and age of the rat. The initial and maximum speeds were based on VO2max measurements obtained during the pre-training testing of the compliant rats. Rats assigned to the control group followed a schedule similar to the training group. They were placed in one lane on the treadmill for 15 minutes/day, 5 days per week. The treadmill was set at 0 m/min at an incline that corresponded to the incline being used by the training group.