Review

. 2023 Oct 1;103(4):2679-2757.

doi: 10.1152/physrev.00039.2022. Epub 2023 Jun 29.

Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions

Affiliations

¹ School of Kinesiology, Auburn University, Auburn, Alabama, United States.
² Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States.
³ Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, United States.
⁴ Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
⁵ Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital-Bispebjerg and Frederiksberg, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁶ Department of Kinesiology and Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States.
⁷ Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States.
⁸ Department of Kinesiology, Nutrition and Health, Miami University, Oxford, Ohio, United States.
⁹ Healthy Food Science Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
¹⁰ MUSCULAB-Laboratory of Neuromuscular Adaptations to Resistance Training, Department of Physical Education, Federal University of São Carlos, São Carlos, Brazil.
¹¹ School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
¹² Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, United States.
¹³ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, Florida, United States.

PMID: 37382939
PMCID: PMC10625844 (available on 2024-10-01)
DOI: 10.1152/physrev.00039.2022

Review

Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions

Michael D Roberts et al. Physiol Rev. 2023.

. 2023 Oct 1;103(4):2679-2757.

doi: 10.1152/physrev.00039.2022. Epub 2023 Jun 29.

Authors

Affiliations

¹ School of Kinesiology, Auburn University, Auburn, Alabama, United States.
² Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, United States.
³ Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin, United States.
⁴ Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
⁵ Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital-Bispebjerg and Frederiksberg, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁶ Department of Kinesiology and Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States.
⁷ Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States.
⁸ Department of Kinesiology, Nutrition and Health, Miami University, Oxford, Ohio, United States.
⁹ Healthy Food Science Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
¹⁰ MUSCULAB-Laboratory of Neuromuscular Adaptations to Resistance Training, Department of Physical Education, Federal University of São Carlos, São Carlos, Brazil.
¹¹ School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
¹² Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, United States.
¹³ Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, Florida, United States.

PMID: 37382939
PMCID: PMC10625844 (available on 2024-10-01)
DOI: 10.1152/physrev.00039.2022

Abstract

Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.

Keywords: hypertrophy; mechanical overload; myofiber; resistance training; skeletal muscle.

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Conflict of interest statement

M.D.R. has received funding in the form of contracts, gifts, and grants from industry sources, Auburn University (Intramural Grants Program), and the Peanut Institute (commodities) for work in certain areas discussed in this article. S.M.P. has patent (Canadian) 3052324 assigned to Exerkine and patent (US) 20200230197 pending to Exerkine but reports no financial gains from any patent or related work. None of the other authors has any conflicts of interest, financial or otherwise, to disclose.

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Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions

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Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions

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