Project description:Microgravity has a dramatic impact on human physiology, illustrated in particular with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for the definition of efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n=8), and the potential beneficial impact of protein supplementation (BRN group, n=8) and of a combined resistance and aerobic training (BRE group, n=8). Gene expression profiles were obtained using an in-house made microarray containing 6681 muscles-relevant genes. A two-class statistical analysis was applied on the 2103 genes with consolidated expression. We identified 472 and 207 modified genes, respectively for SOL and VL in BRC group. Further clustering approaches, identifying relevant biological mechanisms or pathways, underlined five main subclusters. Three are composed almost of upregulated genes involved mainly in nucleic acid and protein metabolism, and two composed almost of downregulated genes involved in energy metabolism. Exercise countermeasure demonstrated a drastic compensatory effect, decreasing the number of differentially-expressed genes by 89 and 96% in SOL and VL. In contrast, nutrition countermeasure had a moderate effect and decreased the number of differentially-expressed genes by 40 and 25% in SOL and VL. Our results allowed reporting a systematic, global and comprehensive view of long-term woman muscle atrophy and brought new lights and insights for space environment and for women who undergo a long-term clinical bed rest. Biological samples were collected from Pre- and Post- bed rest (BR) soleus and vastus lateralis biopsies of each subject from the three groups (bed rest only: BRC; Exercise: BRE; Nutrition: BRN). six technical replicate values (2 duplicate hybridizations âa et bâ to chips with triplicate spots âxxxâ) were obtained for each skeletal muscle sample. Thus for each subject, 12 expression measurements (6 before BR and 6 after BR) were obtained for each muscle.
Project description:Muscle atrophy is one of the main deleterious consequences of physical inactivity. Bed rest represents a unique model of physical inactivity and results in main changes in muscle metabolic function. However, our knowledge on the detrimental effects of bed rest still needs clarification. The aim of this study was to decipher the mechanisms involved in disuse muscle atrophy and the effects of different countermeasures in healthy men. A cross-over trial was designed, with each trial consisting in a 7-day ambulatory control period for baseline data collection, followed by 21 days head-down tilt bed rest with or without resistive vibration exercise only or combined with nutritional (protein) supplement as countermeasures. The changes in the Vastus lateralis muscle proteome collected in the eight volunteers were characterized using mass spectrometry-based label-free quantitative proteomics.
Project description:Microgravity has a dramatic impact on human physiology, illustrated in particular with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for the definition of efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n=8), and the potential beneficial impact of protein supplementation (BRN group, n=8) and of a combined resistance and aerobic training (BRE group, n=8). Gene expression profiles were obtained using an in-house made microarray containing 6681 muscles-relevant genes. A two-class statistical analysis was applied on the 2103 genes with consolidated expression. We identified 472 and 207 modified genes, respectively for SOL and VL in BRC group. Further clustering approaches, identifying relevant biological mechanisms or pathways, underlined five main subclusters. Three are composed almost of upregulated genes involved mainly in nucleic acid and protein metabolism, and two composed almost of downregulated genes involved in energy metabolism. Exercise countermeasure demonstrated a drastic compensatory effect, decreasing the number of differentially-expressed genes by 89 and 96% in SOL and VL. In contrast, nutrition countermeasure had a moderate effect and decreased the number of differentially-expressed genes by 40 and 25% in SOL and VL. Our results allowed reporting a systematic, global and comprehensive view of long-term woman muscle atrophy and brought new lights and insights for space environment and for women who undergo a long-term clinical bed rest.
Project description:Short-term bed rest is used to simulate muscle disuse in humans. In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects. Identifying muscle transcriptional events in response to bed rest and age-related differences will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations. Skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aide in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse. Short-term muscle disuse is also characterized by skeletal muscle insulin resistance, though this response is divergent across subjects. The mechanisms regulating inactivity-induced insulin resistance between populations that are more or less susceptible to disuse-induced insulin resistance are not known, and delineated by age. High Susceptibility participants were uniquely characterized with muscle gene responses described by a decrease in pathways responsible for lipid uptake and oxidation, decreased capacity for triglyceride export (APOB), increased lipogenesis (i.e., PFKFB3, FASN), and increased amino acid export (SLC43A1).
Project description:The purpose of this study was to characterize the vastus lateralis (VL) gene and microRNA responses to 70 day bed rest with and without exercise countermeasures to mitigate the negative consequences of weightlessness.
Project description:The purpose of this study was to characterize the vastus lateralis (VL) gene and microRNA responses to 70 day bed rest with and without exercise countermeasures to mitigate the negative consequences of weightlessness.
Project description:Inactivity and unloading. induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. We used mass spectrometry-based proteomics to measure the abundance changes of proteins circulating in the blood plasma of young healthy subject undergoing ten days of continuous bed rest. Several plasma components, such as the complement cascade and lipid carriers, and proteins derived from the extracellular matrix and tissue leakage, such as lumican and teneurin-4, changed their abundance at different loading states of the body. Searching for potential plasma biomarkers relaying changes in muscle trophism, we identify common proteomic signatures distinguishing the majority of subjects undergoing extensive unloading-mediated muscle atrophy from those largely maintaining their initial muscle mass at the end of bed rest. Some of these plasma proteins also have different abundance in the serum proteome of cancer patients developing cachexia compared to that of healthy controls. Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions.
Project description:Human skeletal muscle disuse-atrophy is one of the main problems associated with spaceflight, bed rest, lower limb unloading, or immobilization. This study investigates the effects of 10-day unilateral lower limb suspension (ULLS) followed by 21 days of active recovery (AR) in young healthy men.
Project description:Spaceflight causes loss of muscle mass and strength, metabolic remodeling and insulin resistance, contributing to severe challenges for astronaut health. We used highly sensitive proteomics to detail single fiber type-specific molecular remodeling caused by muscle unloading in subjects undergoing prolonged bed rest. We then measured the muscle proteome of astronauts before and after a mission on the ISS. Our combined datasets show downregulation of complexes involved in fiber-matrix interaction, force transmission and insulin receptor stabilization on the sarcolemma. Unloading upregulated anti-oxidant responses in slow but not in fast fibers, markers of neuromuscular damage and the hypusination pathway that uniquely modifies translation initiation factor 5A. These muscle intrinsic changes in adhesion, protein turnover and redox balance may contribute to the whole-body detrimental effects caused by prolonged unloading. We conclude that single muscle fiber analysis by proteomics can support the development of advanced countermeasures targeting the mechano-metabolic molecular axis.
Project description:Older individuals subjected to complete bed rest for 10 days were randomized to a complete nutritional supplement with or without hydroxymethyl butyrate (HMB). Muscle biopsies from the vastus lateralis were obtained immediately prior and at the conclusion of the bed rest. RNA-sequencing was performed to determine the gene expression changes associated with bed rest. Marked decrease in the expression of genes associated with mitochondrial energy metabolism including fatty acid oxidation, TCA cycle and the electron transport chain was observed with bed rest. These effects were partly mitigated in the subjects provided the nutritional supplement with HMB.