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) signal-ing, 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2679-2757 |
| Number of pages | 79 |
| Journal | Physiological Reviews |
| Volume | 103 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2023 |
Bibliographical note
Publisher Copyright:© 2023 The Authors.
Funding
The authors extend gratitude to Dr. Sue Bodine (University of Iowa) for critiques and assistance in the publication process.T.A.H. is supported by the National Institutes of Health (NIH) (R01AR074932). S.M.P. is supported by the Canada Research Chairs Programme, National Science and Engineering Research Council (NSERC) of Canada, and the Canadian Institutes for Health Research (CIHR). S.M.P. also reports grants or research contracts, current or recent, from the US National Dairy Council, Dairy Farmers of Canada, Roquette Freres, Nestle Health Sciences, Myos, NSERC, and NIH during the execution of stud-ies; and personal fees from the US National Dairy Council and nonfinancial support from Enhanced Recovery outside the sub-mitted work. G.A.N. is supported by NIH (AR-078430). M.D.B. is supported by NIH (R01AR072735). P.T.R. is supported by Miami University College of Education, Health and Society Summer Research Funding. R.O. is supported by Japan Society for the Promotion of Science (no. 22H03465). C.A.L. is supported by the São Paulo Research Foundation (no. 2020/13613-4) and the National Council for Scientific and Technological Development (no. 311387/2021-7). Article processing charges were provided in full by Auburn University’s School of Kinesiology. 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. contracts, current or recent, from the US National Dairy Council, Dairy Farmers of Canada, Roquette Freres, Nestle Health Sciences, Myos, NSERC, and NIH during the execution of studies; and personal fees from the US National Dairy Council and nonfinancial support from Enhanced Recovery outside the submitted work. G.A.N. is supported by NIH (AR-078430). M.D.B. is supported by NIH (R01AR072735). P.T.R. is supported by Miami University College of Education, Health and Society Summer Research Funding. R.O. is supported by Japan Society for the Promotion of Science (no. 22H03465). C.A.L. is supported by the São Paulo Research Foundation (no. 2020/13613-4) and the National Council for Scientific and Technological Development (no. 311387/2021-7). Article processing charges were provided in full by Auburn University’s School of Kinesiology. T.A.H. is supported by the National Institutes of Health (NIH) (R01AR074932). S.M.P. is supported by the Canada Research Chairs Programme, National Science and Engineering Research Council (NSERC) of Canada, and the Canadian Institutes for Health Research (CIHR). S.M.P. also reports grants or research
| Funders | Funder number |
|---|---|
| Dairy Farmers of Canada | |
| US National Dairy Council | |
| Auburn University | |
| Natural Sciences and Engineering Research Council of Canada | |
| Miami Clinical and Translational Science Institute, University of Miami | |
| Canada Excellence Research Chairs, Government of Canada | |
| Iowa Environmental Mesonet at Iowa State University | |
| Canadian Institutes of Health Research | |
| Auburn University’s School of Kinesiology | |
| Peanut Institute | |
| Fundação de Amparo à Pesquisa do Estado de São Paulo | 2020/13613-4 |
| Japan Society for the Promotion of Science | 22H03465 |
| Conselho Nacional de Desenvolvimento Científico e Tecnológico | 311387/2021-7 |
| National Institutes of Health (NIH) | R01AR074932 |
| National Dairy Council | R01AR072735, AR-078430 |
Keywords
- hypertrophy
- mechanical overload
- myofiber
- resistance training
- skeletal muscle
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Physiology (medical)