Muscle-Specific Cellular and Molecular Adaptations to Late-Life Voluntary Concurrent Exercise.

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.

Senolytic treatment rescues blunted muscle hypertrophy in old mice.

With aging, skeletal muscle plasticity is attenuated in response to exercise. Here, we report that senescent cells, identified using senescence-associated β-galactosidase (SA β-Gal) activity and p21 immunohistochemistry, are very infrequent in resting muscle, but emerge approximately 2 weeks after a bout of resistance exercise in humans. We hypothesized that these cells contribute to blunted hypertrophic potential in old age.

Deletion of SA β-Gal+ cells using senolytics improves muscle regeneration in old mice.

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months.

Exercise-mediated alteration of hippocampal Dicer mRNA and miRNAs is associated with lower BACE1 gene expression and Aβ in female 3xTg-AD mice.

Changes to cerebral miRNA expression have been implicated in the progression of Alzheimer's disease (AD), as miRNAs that regulate the expression of gene products involved in amyloid beta (Aβ) processing, such as BACE1, are dysregulated in those that suffer from AD. Exercise training improves cognition and reduces BACE1 and Aβ-plaque burden; however, the mechanisms are not fully understood. Using our progressive weighted wheel running (PoWeR) exercise program, we assessed the effect of 20 wk of exercise training on changes in hippocampal miRNA expression in female 3xTg-AD (3xTg) mice.

Muscle memory: myonuclear accretion, maintenance, morphology, and miRNA levels with training and detraining in adult mice.

Background: In the context of mass regulation, 'muscle memory' can be defined as long-lasting cellular adaptations to hypertrophic exercise training that persist during detraining-induced atrophy and may facilitate future adaptation. The cellular basis of muscle memory is not clearly defined but may be related to myonuclear number and/or epigenetic changes within muscle fibres.

Methods: Utilizing progressive weighted wheel running (PoWeR), a novel murine exercise training model, we explored myonuclear dynamics and skeletal muscle miRNA levels with training and detraining utilizing immunohistochemistry, single fibre myonuclear analysis, and quantitative analysis of miRNAs.