The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth
A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle ( http://data.myoanalytics.com ) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape.
Authors
- Nicholas P. Greene (ORCID: https://orcid.org/0000-0001-9621-2005)
- Johanna T. Lanner (ORCID: https://orcid.org/0000-0002-1222-9473)
- Nicholas T. Thomas (ORCID: https://orcid.org/0000-0003-4578-8463)
- Björn Alkner (ORCID: https://orcid.org/0000-0001-9332-9363)
- Pieter J Koopmans
- Rodrigo Fernandez‐Gonzalo (ORCID: https://orcid.org/0000-0003-2816-9855)
- Jessica Norrbom
- Kevin A. Murach (ORCID: https://orcid.org/0000-0003-2783-7137)
- Toby L. Chambers (ORCID: https://orcid.org/0000-0001-7567-1819)
- Ferdinand von Walden (ORCID: https://orcid.org/0000-0003-1134-2252)
- Francielly Morena da Silva (ORCID: https://orcid.org/0000-0001-5019-2125)
- Zhengye Liu (ORCID: https://orcid.org/0000-0002-7054-6151)
- Christopher S. Fry (ORCID: https://orcid.org/0000-0002-4207-6594)
- Ronald G. Jones
- Vandré C. Figueiredo (ORCID: https://orcid.org/0000-0002-3012-7905)
- Paulo R. Jannig
- Sebastian Edman (ORCID: https://orcid.org/0000-0003-2921-833X)
- Sabin Khadgi (ORCID: https://orcid.org/0009-0002-8394-624X)
- Yuan Wen (ORCID: https://orcid.org/0000-0002-3210-1629)
- Calvin Peterson
- Logan N Scott
Institutions
- Linköping University (SE)
- Karolinska University Hospital (SE)
- University of Kentucky (US)
- Oakland University (US)
- Karolinska Institutet (SE)
- Region Jönköpings län (SE)
- University of Arkansas at Fayetteville (US)
Publication Details
- Journal
- EMBO Reports
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1038/s44319-024-00299-z
- Citations
- 20
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 4.68
Funders
- Glenn Foundation for Medical Research
- University of Southern California
- University of Arkansas
- Fondation pour la Recherche Médicale
- Karolinska Institutet
- Vetenskapsrådet
- Centrum för idrottsforskning
- Sveriges Läkarförbund
- National Institutes of Health