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Elife. 2019 Apr 23;8. pii: e44876. doi: 10.7554/eLife.44876.

Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle.

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Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati College of Medicine, Cincinnati, United States.
The Jackson Laboratory, Farmington, United States.
Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, United States.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, United States.


Skeletal muscle adapts to external stimuli such as increased work. Muscle progenitors (MPs) control muscle repair due to severe damage, but the role of MP fusion and associated myonuclear accretion during exercise are unclear. While we previously demonstrated that MP fusion is required for growth using a supra-physiological model (Goh and Millay, 2017), questions remained about the need for myonuclear accrual during muscle adaptation in a physiological setting. Here, we developed an 8 week high-intensity interval training (HIIT) protocol and assessed the importance of MP fusion. In 8 month-old mice, HIIT led to progressive myonuclear accretion throughout the protocol, and functional muscle hypertrophy. Abrogation of MP fusion at the onset of HIIT resulted in exercise intolerance and fibrosis. In contrast, ablation of MP fusion 4 weeks into HIIT, preserved exercise tolerance but attenuated hypertrophy. We conclude that myonuclear accretion is required for different facets of exercise-induced adaptive responses, impacting both muscle repair and hypertrophic growth.


cell fusion; developmental biology; exercise; mouse; muscle hypertrophy; myomaker; myonuclear accretion; regenerative medicine; stem cells

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