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

C. M. Dungan, C. R. Brightwell, Y. Wen, C. J. Zdunek, C. M. Latham, N. T. Thomas, A. M. Zagzoog, B. D. Brightwell, G. L. VonLehmden, A. R. Keeble, S. J. Watowich, K. A. Murach, C. S. Fry

Research output: Contribution to journalArticlepeer-review


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.
Original languageAmerican English
Pages (from-to)zqac027
Issue number4
StatePublished - 2022

Bibliographical note

Dungan, Cory M Brightwell, Camille R Wen, Yuan Zdunek, Christopher J Latham, Christine M Thomas, Nicholas T Zagzoog, Alyaa M Brightwell, Benjamin D VonLehmden, Georgia L Keeble, Alexander R Watowich, Stanley J Murach, Kevin A Fry, Christopher S eng R00 AG063994/AG/NIA NIH HHS/ R01 AG069909/AG/NIA NIH HHS/ R01 DK119619/DK/NIDDK NIH HHS/ England 2022/07/02 Function (Oxf). 2022 May 23;3(4):zqac027. doi: 10.1093/function/zqac027. eCollection 2022.


  • DNA methylation capillarization concurrent training hypertrophy sarcopenia skeletal muscle


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