**1. Introduction**

Skeletal muscle comprises approximately 40% of body mass and plays a critical role in posture, breathing, motion, and metabolic regulation [1]. As we age, the occurrence of age-related diseases, such as the loss of muscle mass (i.e., sarcopenia), are expected to become more prevalent [2]. For instance, between the ages of 25–80 years, the average individual will lose approximately 25% of their muscle mass [3,4]. This age-associated loss of muscle mass leads to an increased risk of fall-related injury, institutionalization, loss of independence, and disease [5–7]. Indeed, in the United States alone, the healthcare costs for muscle wasting related illnesses were estimated to be \$18.5 billion in 2000 [8]. Based on this figure, reducing the rate of muscle wasting related diseases by even 10% could save a striking \$1.1 billion in annual healthcare costs. The number of people over the age of 60 is expected to double by 2050, and thus, the costs associated with sarcopenia will only continue to increase [9]. Accordingly, the development of therapies that can restore, maintain, and/or increase muscle mass will be of great clinical and fiscal significance. However, to develop such therapies, we will first need to establish a comprehensive understanding of the mechanisms that regulate the size of this vital tissue.

Mechanical load-induced signals are one of the most widely recognized regulators of skeletal muscle mass. Indeed, historical evidence suggests that the growth-promoting effects of mechanical loading has been recognized since at least the 7th century BC [10]. During the last century, a variety of human and animal models have been used to further establish this point. For instance, in humans, resistance exercise is the most commonly used model of mechanical load-induced growth and it typically induces a 5–20% increase in skeletal muscle volume/mass within 8–16 weeks [11–17]. Similar changes in muscle mass have also been observed in animal models that are intended to mimic human resistance exercise [18–20]. Furthermore, animal models that use extreme forms of mechanical loading, such as synergist ablation, can promote a doubling of muscle mass within as little as 2 weeks [21–23]. Collectively, these models have provided extensive insight into the macroscopic and microscopic changes that contribute to the mechanical load-induced growth response, but surprisingly, the ultrastructural changes that drive these changes remain poorly understood. In this review, we will thoroughly summarize what is currently known about the structural adaptations that drive mechanical load-induced growth and highlight the critical gaps in knowledge that need to be filled.
