Project description:Exercise late in life mitigates skeletal muscle epigenetic aging, providing evidence that physical activity is a "fountain of youth".
Project description:Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training. Keywords: resistance exercise, muscle, aging
Project description:There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late-life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial-specific examination of methylation, targeted high-resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late-life PoWeR from 22-24 months of age modestly but significantly attenuates an age-associated shift toward promoter hypermethylation. The epigenetic age of muscle from old mice that PoWeR-trained for eight weeks was approximately eight weeks younger than 24-month-old sedentary counterparts, which represents ~8% of the expected murine lifespan. These data provide a molecular basis for exercise as a therapy to attenuate skeletal muscle aging.
Project description:Ribosomes are the macromolecular engines of protein synthesis. Factors mediating ribosome biogenesis in skeletal muscle that facilitate adaptation to exercise are multi-factorial, but may be related to ribosomal DNA (rDNA) dosage and/or epigenetic modifications to rDNA. To investigate these possibilities, we conducted reduced representation bisulfite sequencing (RRBS) on skeletal muscle biopsies from human subjects before and after exercise and to detect differences in methylation patterns during exercise adaptation.
Project description:The few investigations on exercise-induced global gene expression responses in human skeletal muscle haves typically focused at one specific mode of exercise and few such studies have implemented control measures. However, interpretation on distinct phenotype regulation necessitate comparison between essentially different modes of exercise and the ability to identify true exercise effects, necessitate implementation of independent non-exercise control subjects. Furthermore, muscle transkriptometranscriptome data made available through previous exercise studies can be difficult to extract and interpret by individuals that are inexperienced with bioinformatic procedures. In a comparative study, we; (1) investigated the human skeletal muscle transcriptome response to differentiated exercise and non-exercise control intervention, and; (2) aimed to develop a straightforward search tool to allow for easy extraction and interpretation of our data. We provide a simple spreadsheet containing transcriptome data allowing other investigators to see how mRNA of their interest behave in skeletal muscle following exercise, both endurance, strength and non-exercise. Our approach, allow investigators easy access to information on genuine transcriptome effects of differentiated exercise, to better aid hyporthesis-driven question in this particular field of research. 18 subjects were divided into 3 groups, performing 12 weeks of Endurance or Strength training or no training. Biopsies for microarray were take before (Pre) and 2½ and 5 hours after the last training session. Isolated RNA from these biopsies were then measured with the Affymetrix Human Gene 1.0 ST arrays.
Project description:The few investigations on exercise-induced global gene expression responses in human skeletal muscle haves typically focused at one specific mode of exercise and few such studies have implemented control measures. However, interpretation on distinct phenotype regulation necessitate comparison between essentially different modes of exercise and the ability to identify true exercise effects, necessitate implementation of independent non-exercise control subjects. Furthermore, muscle transkriptometranscriptome data made available through previous exercise studies can be difficult to extract and interpret by individuals that are inexperienced with bioinformatic procedures. In a comparative study, we; (1) investigated the human skeletal muscle transcriptome response to differentiated exercise and non-exercise control intervention, and; (2) aimed to develop a straightforward search tool to allow for easy extraction and interpretation of our data. We provide a simple spreadsheet containing transcriptome data allowing other investigators to see how mRNA of their interest behave in skeletal muscle following exercise, both endurance, strength and non-exercise. Our approach, allow investigators easy access to information on genuine transcriptome effects of differentiated exercise, to better aid hyporthesis-driven question in this particular field of research.
Project description:Unconditioned thoroughbred geldings were exercised to maximal heart rate or fatigue on an equine high-speed treadmill. Skeletal muscle biopsies were taken from the middle gluteal muscle before, immediately after and four hours after exercise. Three-condition experiment, Pre exercise (T0), Immediately post exercise (T1), 4 hours post exercise (T2). Hybridisations: T0 vs T1, T0 vs T2 Biological replicates: 8 Technical replication Dye swap
Project description:Exercise is an important strategy in the prevention and treatment of metabolic diseases, like diabetes and obesity. Alterations in the skeletal muscle proteome, including post-translational modifications, especially acetylation, regulate its metabolic adaptations to exercise. Here, we examined the effect of 6-week aerobic exercise and Scriptaid, a HDAC4/5 inhibitor, on the proteome and acetylome of skeletal muscle in mice. We find Scriptaid and exercise both induce acetylation modification changes of some proteins involved in metabolism, suggest that exercise improves metabolic health by regulating protein acetylation level.
Project description:Habitual exercise modulates the composition of the intestinal microbiota. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet-fed mice. The recipient mice that received fecal samples from trained donor mice for 1 week showed elevated levels of metabolic signalings in skeletal muscle. Glucose tolerance was improved by fecal microbiota transplantation after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvement in mice. We performed a microarray analysis to compare the metabolic gene expression profiles in the skeletal muscle from each mouse.