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

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 pre-clinical 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 post-exercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest additional mechanisms that feed into or are independent of these processes are also involved. This review will first provide a historical account as to 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 will be proposed.