Muscle-specific cellular and molecular adaptations to late-life voluntary concurrent exercise in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE197045 | GEO | 2022/09/24
REPOSITORIES: GEO
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Project description:Aged mice (22-24 mo) underwent Progressive weighted wheel running (PoWeR) for 8 weeks. RNA-seq on soleus and plantaris muscles was conducted on untrained and PoWeR trained mice. RNA from soleus and plantaris of young mice (4-6 months old) was used as a comparator (Englund et al. 2021 Function)
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Project description:Murine exercise models can provide information on factors that influence muscle adaptability with aging, but few translatable solutions exist. Progressive weighted wheel running (PoWeR) is a simple, voluntary, low-cost, high-volume endurance/resistance exercise approach for training young mice. In the current investigation, aged mice (22-mo-old) underwent a modified version of PoWeR for 8 wk. Muscle functional, cellular, biochemical, transcriptional, and myonuclear DNA methylation analyses provide an encompassing picture of how muscle from aged mice responds to high-volume combined training. Mice run 6-8 km/d, and relative to sedentary mice, PoWeR increases plantarflexor muscle strength. The oxidative soleus of aged mice responds to PoWeR similarly to young mice in every parameter measured in previous work; this includes muscle mass, glycolytic-to-oxidative fiber type transitioning, fiber size, satellite cell frequency, and myonuclear number. The oxidative/glycolytic plantaris adapts according to fiber type, but with modest overall changes in muscle mass. Capillarity increases markedly with PoWeR in both muscles, which may be permissive for adaptability in advanced age. Comparison to published PoWeR RNA-sequencing data in young mice identified conserved regulators of adaptability across age and muscles; this includes Aldh1l1 which associates with muscle vasculature. Agrn and Samd1 gene expression is upregulated after PoWeR simultaneous with a hypomethylated promoter CpG in myonuclear DNA, which could have implications for innervation and capillarization. A promoter CpG in Rbm10 is hypomethylated by late-life exercise in myonuclei, consistent with findings in muscle tissue. PoWeR and the data herein are a resource for uncovering cellular and molecular regulators of muscle adaptation with aging.
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Project description:Exercise training improves whole body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues including adipose tissue. To determine if exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, nine days post-transplantation, mice receiving trained scWAT had improved glucose tolerance and enhanced insulin sensitivity compared to mice transplanted with sedentary scWAT or sham-treated mice. Mice transplanted with trained scWAT had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat fed recipient mice were transplanted with trained scWAT. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT including increased expression of ∼1550 genes involved in numerous cellular functions, including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis. Microarray analysis of scWAT obtained from a cohort of mice that were housed in wheel cages for 11 days compared to sedentary control mice.
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Project description:Exercise training improves whole body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, training also affects other tissues including adipose tissue. To determine if exercise-induced adaptations to adipose tissue contribute to training-induced improvements in glucose homeostasis, subcutaneous white adipose tissue (scWAT) from trained or sedentary donor mice was transplanted into the visceral cavity of sedentary recipients. Remarkably, nine days post-transplantation, mice receiving trained scWAT had improved glucose tolerance and enhanced insulin sensitivity compared to mice transplanted with sedentary scWAT or sham-treated mice. Mice transplanted with trained scWAT had increased insulin-stimulated glucose uptake in tibialis anterior and soleus muscles and brown adipose tissue, suggesting that the transplanted scWAT exerted endocrine effects. Furthermore, the deleterious effects of high-fat feeding on glucose tolerance and insulin sensitivity were completely reversed if high-fat fed recipient mice were transplanted with trained scWAT. In additional experiments, voluntary exercise training by wheel running for only 11 days resulted in profound changes in scWAT including increased expression of ∼1550 genes involved in numerous cellular functions, including metabolism. Exercise training causes adaptations to scWAT that elicit metabolic improvements in other tissues, demonstrating a previously unrecognized role for adipose tissue in the beneficial effects of exercise on systemic glucose homeostasis.
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Project description:To determine the influence of a previous physcial activity period (e.g., exercise) on global gene expression, we compared differential expression in sedentary (SED) and detrained (DETR) rats relative to trained (TR) rats with regular access to physcial activity. TR and DETR rats had voluntary access to caged running wheels for 8 and 4 weeks, respectively. DETR rats were moved to sedentary conditions (normal cage activity) for another 4 weeks. SED rats experienced 8 weeks of normal caged activity; n=8 per group. At the end of each group's respective 8 weeks, all rats underwent 1 hr of moderate of acute exercise stress (e.g., forced wheel running at a speed of 20 m/min). Soleus muscles were harvested 24h post-running.
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Project description:Muscle-specific cellular and molecular adaptations to late-life voluntary concurrent exercise in mice
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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.
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