Muscle-Specific Cellular and Molecular Adaptations to Late-Life Voluntary Concurrent Exercise
Cory M Dungan1, Camille R Brightwell2, Yuan Wen1
1Department of Physical Therapy, University of Kentucky, Lexington 40536, KY, USA.
Function (Oxford, England)
|July 1, 2022
Summary
Progressive weighted wheel running (PoWeR) in aged mice improved muscle strength and adaptability, mirroring responses in younger mice. This high-volume exercise offers a valuable model for studying age-related muscle changes.
Area of Science:
- Exercise physiology
- Aging research
- Muscle biology
Background:
- Aging muscle exhibits reduced adaptability, limiting functional capacity.
- Existing murine exercise models offer limited translatable solutions for age-related muscle decline.
- Progressive weighted wheel running (PoWeR) is an established high-volume exercise model for young mice.
Purpose of the Study:
- To investigate the effects of a modified PoWeR protocol on aged mice.
- To comprehensively analyze muscle functional, cellular, biochemical, transcriptional, and epigenetic changes in response to exercise in aging.
- To identify conserved molecular regulators of muscle adaptation across age groups.
Main Methods:
- Aged mice (22 months old) underwent 8 weeks of modified PoWeR (6-8 km/day).
- Muscle strength, fiber type, size, satellite cell frequency, and myonuclear number were assessed.
- Capillarity, gene expression (RNA-sequencing), and myonuclear DNA methylation were analyzed.
- Results were compared to sedentary controls and previously published data from young mice.
Main Results:
- PoWeR significantly increased plantarflexor muscle strength in aged mice.
- The oxidative soleus muscle showed adaptability similar to young mice, including increased mass and fiber size.
- Capillarity markedly increased in both soleus and plantaris muscles.
- Conserved gene expression regulators, including *Aldh1l1*, *Agrn*, and *Samd1*, were identified, with associated DNA hypomethylation in myonuclei.
- *Rbm10* promoter hypomethylation was observed, consistent with previous findings.
Conclusions:
- Modified PoWeR is effective in improving muscle strength and adaptability in aged mice.
- The aged mouse soleus muscle responds robustly to high-volume exercise, similar to young mice.
- PoWeR reveals conserved molecular pathways and epigenetic modifications that regulate muscle adaptation with aging, offering a valuable resource for future research.
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