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

Sebastian Edman; Ronald G. Jones; 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

Sebastian Edman
, Ronald G. Jones
, 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

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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.

Original language	English
Pages (from-to)	5810-5837
Number of pages	28
Journal	EMBO Reports
Volume	25
Issue number	12
DOIs	https://doi.org/10.1038/s44319-024-00299-z https://doi.org/10.1038/s44319-024-00299-z
State	Published - Dec 6 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

Thank you to the volunteers for their willingness to participate in this research and contribute their tissue and time. Thank you to Kate Mamiseishvili, PhD, Dean of the College of Education at the University of Arkansas for resources that enabled the rapid completion of the histology for this project. Thank you to Charlotte Peterson, PhD, and John McCarthy, PhD, of the University of Kentucky for their support of this work. Thank you to Andrew P. McMahon, PhD, of the University of Southern California who provided the “tet-o” Myc mice as a generous gift. Thank you to Stefan Reitzner, PhD, Eric Emanulesson, and Carl-Johan Sundberg, PhD, of the Karolinska Institute for kindly providing data to enable fiber type interpolation. This work was supported by National Institutes of Health R00 AG063994, R01 AG080047, and funds from the University of Arkansas Vice Chancellor for Research and Innovation as well as the College of Education and Health Professions to KAM. This research was conducted while KAM was a Glenn Foundation for Medical Research and AFAR Grant for Junior Faculty awardee. This work was also supported by the Arkansas Integrated Metabolic Research Center – AIMRC (P20GM139768). YW was supported by funding from the National Institute of Health K99 AR081367. SE was supported by Centrum för Idrottsforskning (P2024-0166). FVW was supported by Vetenskapsrådet (2022-01392), AFM-Telethon (23137), Åke WibergStiftelse, Sveriges Läkarförbund, and Centrum för Idrottsforskning (P2023-0137, P2024-0102).

Funders	Funder number
Arkansas Integrated Metabolic Research Center
Glenn Foundation for Medical Research/American Federation for Aging Research
University of Southern California
Åke WibergStiftelse
University of Kentucky
College of Education and Health Professions
University of Arkansas Vice Chancellor for Research and Innovation
Karolinska Institutet
Glenn Foundation for Medical Research
National Institutes of Health (NIH)	R00 AG063994, R01 AG080047, K99 AR081367
Sveriges Läkarförbund	P2023-0137, P2024-0102
AFM-Telethon	23137
Vetenskapsrådet	2022-01392
Centrum för idrottsforskning	P2024-0166
AIMRC	P20GM139768

Keywords

Humans
Muscle, Skeletal/metabolism
Proto-Oncogene Proteins c-myc/genetics
Animals
Mice
Exercise/physiology
Male
Adult
DNA Methylation
Gene Expression Regulation
Muscle Development/genetics

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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Edman, S., Jones, R. G., Jannig, P. R., Fernandez-Gonzalo, R., Norrbom, J., Thomas, N. T., Khadgi, S., Koopmans, P. J., Morena, F., Chambers, T. L., Peterson, C. S., Scott, L. N., Greene, N. P., Figueiredo, V. C., Fry, C. S., Zhengye, L., Lanner, J. T., Wen, Y., Alkner, B., ... von Walden, F. (2024). The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth. EMBO Reports, 25(12), 5810-5837. https://doi.org/10.1038/s44319-024-00299-z, https://doi.org/10.1038/s44319-024-00299-z

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

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.",

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note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

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doi = "10.1038/s44319-024-00299-z",

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Edman, S, Jones, RG, Jannig, PR, Fernandez-Gonzalo, R, Norrbom, J, Thomas, NT, Khadgi, S, Koopmans, PJ, Morena, F, Chambers, TL, Peterson, CS, Scott, LN, Greene, NP, Figueiredo, VC, Fry, CS, Zhengye, L, Lanner, JT, Wen, Y, Alkner, B, Murach, KA & von Walden, F 2024, 'The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth', EMBO Reports, vol. 25, no. 12, pp. 5810-5837. https://doi.org/10.1038/s44319-024-00299-z, https://doi.org/10.1038/s44319-024-00299-z

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T1 - The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

AU - Edman, Sebastian

AU - Jones, Ronald G.

AU - Jannig, Paulo R.

AU - Fernandez-Gonzalo, Rodrigo

AU - Norrbom, Jessica

AU - Thomas, Nicholas T.

AU - Khadgi, Sabin

AU - Koopmans, Pieter J.

AU - Morena, Francielly

AU - Chambers, Toby L.

AU - Peterson, Calvin S.

AU - Scott, Logan N.

AU - Greene, Nicholas P.

AU - Figueiredo, Vandre C.

AU - Fry, Christopher S.

AU - Zhengye, Liu

AU - Lanner, Johanna T.

AU - Wen, Yuan

AU - Alkner, Björn

AU - Murach, Kevin A.

AU - von Walden, Ferdinand

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/12/6

Y1 - 2024/12/6

N2 - 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.

AB - 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.

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KW - Muscle, Skeletal/metabolism

KW - Proto-Oncogene Proteins c-myc/genetics

KW - Animals

KW - Mice

KW - Exercise/physiology

KW - Male

KW - Adult

KW - DNA Methylation

KW - Gene Expression Regulation

KW - Muscle Development/genetics

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UR - https://www.scopus.com/pages/publications/85208055332#tab=citedBy

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C2 - 39482487

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EP - 5837

JO - EMBO Reports

JF - EMBO Reports

IS - 12

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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