Exercise-Induced MYC as an Epigenetic Reprogramming Factor That Combats Skeletal Muscle Aging

Abstract

Of the "Yamanaka factors" Oct3/4 , Sox2 , Klf4 , and c-Myc (OSKM), the transcription factor c-Myc ( Myc ) is the most responsive to exercise in skeletal muscle and is enriched within the muscle fiber. We hypothesize that the pulsatile induction of MYC protein after bouts of exercise can serve to epigenetically reprogram skeletal muscle toward a more resilient and functional state.

Figure

Summary of hypotheses about Myc in muscle with exercise and aging. Myc gene and protein increases acutely after exercise, and particularly hypertrophic resistance exercise, in young healthy skeletal muscle. MYC performs a variety of key functions in skeletal muscle cells and influences DNA methylation. With aging, skeletal muscle becomes smaller and weaker (i.e., sarcopenia), and exercise adaptive potential declines concomitant with reduced Myc responsiveness to exercise. Pulses of Myc/MYC throughout the lifespan and late in life may attenuate sarcopenia and/or restore skeletal muscle adaptability to training. The benefits of MYC pulses in muscle may be related to partial epigenetic reprogramming (The figure was generated using BioRender).