The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

Sebastian Edman; Ronald G Jones Iii; Paulo R Jannig; Rodrigo Fernandez-Gonzalo; Jessica Norrbom; Nicholas T Thomas; Sabin Khadgi; Pieter J Koopmans; Francielly Morena; Toby L Chambers; Calvin S Peterson; Logan N Scott; Nicholas P Greene; Vandre C Figueiredo; Christopher S Fry; Liu Zhengye; Johanna T Lanner; Yuan Wen; Björn Alkner; Kevin A Murach; Ferdinand von Walden

doi:10.1038/s44319-024-00299-z

The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

EMBO Rep. 2024 Oct 31. doi: 10.1038/s44319-024-00299-z. Online ahead of print.

Authors

Sebastian Edman^#¹, Ronald G Jones Iii^#², Paulo R Jannig¹, Rodrigo Fernandez-Gonzalo^{3

4}, Jessica Norrbom⁵, Nicholas T Thomas^{6

7}, Sabin Khadgi², Pieter J Koopmans^{2

8}, Francielly Morena², Toby L Chambers², Calvin S Peterson², Logan N Scott^{6

9

10}, Nicholas P Greene², Vandre C Figueiredo^{6

11}, Christopher S Fry^{6

7}, Liu Zhengye¹², Johanna T Lanner¹², Yuan Wen^{6

9

10}, Björn Alkner^{13

14}, Kevin A Murach^#^{15

16}, Ferdinand von Walden^#¹⁷

Affiliations

¹ Division of Pediatric Neurology, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
² Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA.
³ Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
⁴ Unit of Clinical Physiology, Karolinska University Hospital, Huddinge, Sweden.
⁵ Molecular Exercise Physiology Group, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
⁶ Center for Muscle Biology, University of Kentucky, Lexington, KY, USA.
⁷ Department of Athletic Training and Clinical Nutrition, University of Kentucky, Lexington, KY, USA.
⁸ Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, AR, USA.
⁹ Department of Physiology, University of Kentucky, Lexington, KY, USA.
¹⁰ Division of Biomedical Informatics, Department of Internal Medicine, University of Kentucky, Lexington, KY, USA.
¹¹ Department of Biological Sciences, Oakland University, Rochester Hills, MI, USA.
¹² Molecular Muscle Physiology & Pathophysiology Group, Department of Physiology & Pharmacology, Karolinska Institute, Stockholm, Sweden.
¹³ Department of Orthopaedic Surgery, Region Jönköping County, Eksjö, Sweden.
¹⁴ Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
¹⁵ Exercise Science Research Center, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR, USA. [email protected].
¹⁶ Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, AR, USA. [email protected].
¹⁷ Division of Pediatric Neurology, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden. [email protected].

^# Contributed equally.

PMID: 39482487
DOI: 10.1038/s44319-024-00299-z

Abstract

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.

Keywords: Biopsy; Methylome; Time Course; Transcription Factors; Transcriptome.

Abstract

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