Late-life exercise mitigates skeletal muscle epigenetic aging

Kevin A. Murach, Andrea L. Dimet-Wiley, Yuan Wen, Camille R. Brightwell, Christine M. Latham, Cory M. Dungan, Christopher S. Fry, Stanley J. Watowich

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere13527
JournalAging Cell
Volume21
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
The authors wish to thank Drs. Keith Booher and Kai Chang of Zymo Research and Drs. John McCarthy and Charlotte Peterson of the University of Kentucky Center for Muscle Biology for their support and encouragement, as well as their grant funding (National Institutes of Health AR060701 and DK119619). The graphical abstract was generated using BioRender. We apologize to all the authors whose work could not be included due to the brief nature of this article.

Funding Information:
Research was conceived by KAM, CSF, and SJW. Experiments were carried out by CRB, CML, and CMD. Data were analyzed by KAM, ALD‐W, and YW. Manuscript was written and figures were generated by KAM, ALD‐W, and YW. Funding support was provided by KAM, CSF, and SJW. All authors reviewed, edited, and approved of the final manuscript.

Funding Information:
This work was supported by the National Institutes of Health under grant R00 AG063994 to KAM and R21 AG063056 to SJW The authors wish to thank Drs. Keith Booher and Kai Chang of Zymo Research and Drs. John McCarthy and Charlotte Peterson of the University of Kentucky Center for Muscle Biology for their support and encouragement, as well as their grant funding (National Institutes of Health AR060701 and DK119619). The graphical abstract was generated using BioRender. We apologize to all the authors whose work could not be included due to the brief nature of this article.

Publisher Copyright:
© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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