Exercise preconditioning confers skeletal muscle myometaplasticity
- 1University of Missouri
Abstract
Previously exercise trained skeletal muscle is more growth-responsive to retraining. Using a murine training-detraining-retraining approach and multi-omics, we find that Pecam1 gene expression is lower, but capillarization is appreciably higher in previously trained (preconditioned) relative to naive trained control muscle. Greater capillarity could be permissive for accelerated hypertrophic adaptation. Exercise preconditioned myonuclei feature differential promoter CpG regulation in genes related to Wnt signaling. These epigenetic alterations with retraining align with our prior observations of methylation changes within the same pathway after a longer period of chronic training, suggesting a more rapid response due to preconditioning. Methylome-transcriptome integration and single myonucleus RNA-sequencing expose the polyamine metabolism enzyme Smox as a target that relates to heightened hypertrophic adaptability with retraining. Smox induction is sufficient to cause hypertrophy in aligned myotubes cultured on a stiffness-tuned substrate along with a growth-supportive transcriptional program. Integration of our multi-omics data suggests that Smox regulates repression of Ddit4/Redd1 (an inhibitor of mTORC1 signaling) after retraining. Smox may govern a favorable muscle fiber growth environment in previously trained muscle by sensitizing anabolic potential through polyamine metabolism. A lower adaptive threshold mediated by Smox could contribute to myometaplasticity, or a change to how subsequent muscle adaptations are made.
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BibTeX
@misc{chambers2026exercise,
title = {{Exercise preconditioning confers skeletal muscle myometaplasticity}},
author = {T. L. Chambers and A. R. Cabrera and R. G. Jones and P. J. Koopmans and F. Morena and N. Serrano and A. Parhizkar and C. S. Peterson and A. L. Stokes and Z. B. Malik and K. Papanikolaou and F. von Walden and D. A. Englund and C. Dungan and C. E. Nelson and Y. Wen and K. A. Murach},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.753020},
url = {https://www.biorxiv.org/content/10.64898/2026.09.20.753020v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Exercise preconditioning confers skeletal muscle myometaplasticity
AU - T. L. Chambers
AU - A. R. Cabrera
AU - R. G. Jones
AU - P. J. Koopmans
AU - F. Morena
AU - N. Serrano
AU - A. Parhizkar
AU - C. S. Peterson
AU - A. L. Stokes
AU - Z. B. Malik
AU - K. Papanikolaou
AU - F. von Walden
AU - D. A. Englund
AU - C. Dungan
AU - C. E. Nelson
AU - Y. Wen
AU - K. A. Murach
PY - 2026
DA - 2026/09/20
PB - bioRxiv
DO - 10.64898/2026.09.20.753020
UR - https://www.biorxiv.org/content/10.64898/2026.09.20.753020v1
AB - Previously exercise trained skeletal muscle is more growth-responsive to retraining. Using a murine training-detraining-retraining approach and multi-omics, we find that Pecam1 gene expression is lower, but capillarization is appreciably higher in previously trained (preconditioned) relative to naive trained control muscle. Greater capillarity could be permissive for accelerated hypertrophic adaptation. Exercise preconditioned myonuclei feature differential promoter CpG regulation in genes related to Wnt signaling. These epigenetic alterations with retraining align with our prior observations of methylation changes within the same pathway after a longer period of chronic training, suggesting a more rapid response due to preconditioning. Methylome-transcriptome integration and single myonucleus RNA-sequencing expose the polyamine metabolism enzyme Smox as a target that relates to heightened hypertrophic adaptability with retraining. Smox induction is sufficient to cause hypertrophy in aligned myotubes cultured on a stiffness-tuned substrate along with a growth-supportive transcriptional program. Integration of our multi-omics data suggests that Smox regulates repression of Ddit4/Redd1 (an inhibitor of mTORC1 signaling) after retraining. Smox may govern a favorable muscle fiber growth environment in previously trained muscle by sensitizing anabolic potential through polyamine metabolism. A lower adaptive threshold mediated by Smox could contribute to myometaplasticity, or a change to how subsequent muscle adaptations are made.
ER -