Needless to say, resistance training induced hypertrophy is inextricably linked to its participating variables, such as frequency, load, rest intervals, and the number of sets. As is true for adaptations like endurance and strength, the severity of the response is dependent on the manipulation of these variables. Although the role of these variables has been extensively studied and well documented, the optimum ”value” of these variables for maximum hypertrophy is still under considerate debate.
Among these variables, load seems to be the most dominant variable dictating these muscular adaptations, and hence will assume the lead role in this article. Load, typically advertised in terms of repetition maximum (RM), can be equated to the number of repetitions performed in a set. The generally accepted repetition bracket for hypertrophy is 67 – 85% 1RM, which can be equated to 6–12 repetitions, and 85-100% 1RM (1-6 repetition) for strength (7, 21).
Though the load recommendations for strength and hypertrophy seem to differ, except for existential evidence, there is hardly any scientific data to support this differential rep continuum. Interestingly, in contrast to the above said guidelines, the couple of studies which directly compared low rep and high rep protocols demonstrated similar hypertrophic responses (10, 29). Influenced by the above said discrepancies, this article will look into the factors implicated in skeletal muscle hypertrophy and examine how they are impacted by the manipulation of load.
Before we continue, I will give an introduction to the well orchestrated events leading to skeletal muscle hypertrophy. Studies, both in vivo and in vitro have repeatedly demonstrated the involvement of two fundamental events in the hypertrophy of muscle fibers. The first and foremost is an increase in protein synthesis, mainly attributed to increased mRNA activity (translational capacity). The unstable relationship between protein synthesis and protein degradation represents the basis for hypertrophy. Muscle growth follows when a positive protein balance is established and maintained by an increase in protein synthesis that exceeds the rate of protein breakdown (24).
The second facet of hypertrophy involves an increase in mRNA abundance (transcriptional capacity) via differentiation and proliferation of satellite cells, which is critical for donating additional myonuclei to the enlarging myofibers. Unlike most other cells, mammalian skeletal muscle is multinucleated. Each and every nucleus is responsible for a particular volume of the cell, known as a nuclear domain (16). This domain is tightly regulated and any increase in the fiber cross-sectional area requires a concomitant increase in the number of myonuclei (6). Conversely, if the cell experiences serious atrophy as seen in immobilization, space flight, malnutrition, or tenotomy, the number of myonuclei decreases by a process of programmed cell death (20, 26). This indicates that the tight regulation of the domain is preserved in either direction.
The concept of a finite relationship between fiber size and myonuclei number predicts that the hypertrophying fibers must increase their myonuclear number proportionally. However, shortly after birth, mammalian myofibers are permanently differentiated, and thus cannot undergo mitotic division or directly increase their myonuclear number by means of the usual myonuclear division process (11). Therefore, hypertrophying fibers require an external source of new nuclei to maintain a relatively constant nucleus-to-fiber size ratio. A significant body of evidence blames satellite (stem) cells as the probable source of the new myonuclei (8, 28).The role of satellite cells in hypertrophy has been further corroborated by studies using radiation to prevent satellite cell activity, thereby negating any potential hypertrophic response (5, 25).
In short, with utter disregard for the set tone, satellite cell activity is required for you to get big while protein synthesis is necessary for you to stay big. Frankly, at first, I thought of painting a scientific tone to the article, but soon realized that the complexity of the topic at hand would undermine the message. Perhaps, ignoring my mom’s words, there was never a scientist in me to begin with. Without further delay and resuming a laid back tone, let us cruise towards our next topic: how satellite cells are triggered and how load can have any bearing on this.
Mechanical Factors
Staying true to the principle of specificity, the cellular level changes discussed above are specific to the muscle that is experiencing functional changes. That is, the factors that confine for example almost exclusively the growth of the biceps when the biceps are exercised alone are largely mediated by things that are intrinsic or local to the exercised muscle (19). As it turns out, mounting evidence has revealed growth factors to be responsible for these localized changes.
Among these growth factors, insulin like growth factor (IGF-1) is known to stimulate satellite cell activity as well as protein synthesis, and has received increasing attention in the studies of hypertrophy. This increasing attention to IGF-1 is understandable, given its ability to stimulate both proliferation and differentiation, making it unique within the ranks of growth factors. Lest you get confused, this locally expressed IGF-1 acts independently of any change in the serum growth hormone or the serum IGF-1.
More importantly, IGF-1 is sensitive to mechanical load, as observed in a number of in vivo activity models, such as increased loading, stretch, and eccentric contraction (recently discovered, a specific isoform of IGF-1 called mechano growth factor is exclusively regulated by mechanical loading and/stretch) (1, 2, 3). To further seal IGF-1’s fate, infusion of local IGF-1 directly to skeletal muscles has shown increased muscle mass (4). Looking at all the studies (and the studies which I have omitted for the fear of turning this article into an IGF-1 review paper), I cannot help but conclude that locally expressed IGF-1 is the CHIEF player in mediating muscle growth.
Just when you thought it was over, I’d like to share what Bamman and his crew discovered when investigating IGF-1’s role in resistance training (9). Not surprisingly, they found that eccentric exercise showed the greatest muscle damage and muscle soreness. As suspected, they found significant increases in IGF-1 mRNA concentration for eccentric than concentric exercises (p<0.05). Based on the soreness and the creatine kinase (CK) data, the researchers concluded myofibrillar disruption and/or sarcolemma damage most likely to play a role in activating the IGF-1 system, and in turn activating the satellite cells.