**6. Take Home Messages**

Mechanical loads are one of the most potent regulators of muscle mass and the maintenance of muscle mass plays a critical role in health and quality of life. In Table 1 we have summarized the major structural adaptations that have been implicated in the mechanical load-induced growth of skeletal muscle. Based on our review, we have also considered whether each of these adaptations makes a substantive contribution to the overall growth process, as well as the level of evidence that is available to support that conclusion. The table also lists some of the major gaps in knowledge that we identified during our review of the literature. Importantly, this is not meant to be an exhaustive summary, and exclusion from the table does not indicate that a given adaptation or gap in knowledge is unimportant (e.g., satellite cell fusion, are satellite cells necessary for mechanical load-induced growth, etc.).


**Table 1.** The Structural Adaptations that Drive the Mechanical Load-Induced Growth of Skeletal Muscle.

As documented in this review, several of the adaptations that we consider as having weak supporting evidence have been engrained in the literature as "textbook" mechanisms (e.g., the longitudinal growth of myofibers is driven by the addition of new sarcomeres at the ends of myofibers, new myofibrils are formed via myofibril splitting, etc.). We hope that after reading this review, the reader appreciates how little we actually know about the structural adaptations that drive skeletal muscle growth, and the number of extremely fundamental gaps in knowledge that remain to be filled.

**Author Contributions:** K.W.J., S.M.P. and T.A.H.; all contributed to the writing of this manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** The research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number AR074932 to SMP and TAH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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