An intricate balance of muscle damage and protein synthesis: the key players in skeletal muscle hypertrophy following resistance training

The benefits of resistance training for skeletal muscle mass and strength are well characterised. Early adaptations to unaccustomed resistance exercise include increased muscle strength, whereas later adaptations include muscle hypertrophy and further improvements in muscle strength (Schoenfeld, 2010). Although these strength and hypertrophy gains following resistance training are well documented in healthy and clinical populations, the mechanisms surrounding these phenomena are less implicit. The skeletal muscle microenvironment is tightly regulated and responds rapidly to resistance exercise. A single bout of unaccustomed resistance exercise can cause damage to skeletal muscle, where the structural integrity of the myofibres is compromised. This was theorised to be a significant event which stimulates hypertrophic responses within the muscle microenvironment (Schoenfeld, 2010). However, progression through a resistance training programme is marked by an attenuation in muscle damage which is termed the ‘repeated bout effect’. These findings have lead researchers to question the role of muscle damage in muscle hypertrophy following resistance training. One key factor which has an important yet poorly understood association with muscle damage and hypertrophy following resistance exercise is muscle protein synthesis.

Previous work by Damas and colleagues has demonstrated that resistance exercise is a potent stimulator of skeletal muscle protein synthesis (Damas et al. 2015). In the hours following an unaccustomed bout of resistance exercise, an increase in myofibrillar muscle protein synthesis (MyoPS) can be detected. Repeated bouts of resistance exercise cause cumulative periods of increased MyoPS where net protein synthesis is greater than protein degradation, thus favouring muscle hypertrophy (Damas et al. 2015). However, the MyoPS response to resistance exercise is not equivocal as the resistance training programme progresses. Attenuation of the MyoPS response to resistance exercise can be observed as early as 3 weeks into a training programme (Brook et al. 2015). Interestingly, the MyoPS response to initial resistance exercise bouts is not correlated with muscle hypertrophy that occurs later in the training programme (Damas et al. 2015). However, the MyoPS response to later bouts of the resistance training programme correlates strongly with muscle hypertrophy (Brook et al. 2015). The authors noted that initial bouts of unaccustomed resistance exercise cause pronounced muscle damage, which stimulates growth mechanisms and increases protein synthesis to support tissue repair. Damas therefore proposed that the lack of correlation between the MyoPS response to initial exercise bouts and subsequent muscle hypertrophy could be due to exercise‐induced muscle damage, and that the early MyoPS response is focused on repairing damaged muscle. However, following resistance training the MyoPS response is a more dedicated driver of muscle hypertrophy. Continuing on from previous research, Damas et al. therefore investigated the modulation of muscle hypertrophy during resistance training by measuring MyoPS and muscle damage throughout a resistance training intervention. The study is described in a recent article published in The Journal of Physiology (Damas et al. 2016). The authors hypothesised that the MyoPS response to the initial bout of resistance exercise would not be related to muscle hypertrophy at the end of the training programme, but that MyoPS responses at weeks 3 and 10 would be related to hypertrophy. This hypothesis would imply that the acute MyoPS response to initial bouts of resistance training cannot be used to predict subsequent muscle hypertrophy.

Using a robust study design, Damas et al. (2016 a) conducted a 10 week resistance training intervention in healthy young men to assess skeletal muscle damage, MyoPS and hypertrophic responses. Ten participants were recruited to perform high intensity lower body resistance training twice weekly. Participants were assessed at three key time points throughout the study: the initial training session, in week 3 and in the final training session of week 10. At each time point, muscle biopsy samples of the vastus lateralis were collected for analysis prior to, and 24 and 48 h following, the exercise bout. Investigators examined integrated muscle protein fractional synthesis rates through administration of deuterated water (D₂O). Muscle damage was measured directly and indirectly by Z‐band streaming and systemic creatine kinase, respectively. Muscle hypertrophy was quantified through fibre cross sectional area analysis of frozen vastus lateralis sections. Key statistical analyses included multiple regression analysis and Pearson's correlation coefficient.

The 10 week resistance training intervention successfully increased knee extension maximum voluntary contraction (MVC), and increased vastus lateralis muscle mass by 14%. As expected, 24 h after the initial resistance training bout, direct and indirect measures of muscle damage were markedly elevated. Large elevations in MyoPS were observed 24 h after the initial exercise bout, followed by a significant diminution at 48 h. In the 48 h following training in week 3, both muscle damage and MyoPS responses were attenuated compared to the initial exercise bout. No marker of muscle damage was elevated above baseline in the 48 h following the final training session in week 10; however, the MyoPS response was not further attenuated. Interestingly, when the MyoPS response to training was normalised to the area of Z‐banding (the direct measure of muscle damage), there was no difference in MyoPS response at any time point. Together, these findings support the authors’ hypothesis that the large MyoPS response to the initial resistance exercise bout is partly due to exercise‐induced muscle damage.

Due to the attenuation of muscle damage that occurs following repeated bouts of exercise, the authors also hypothesised that only during the later stages of the training intervention would MyoPS be correlated with muscle hypertrophy. As expected, MyoPS following the initial resistance exercise bout was not correlated with subsequent muscle fibre hypertrophy at week 10. However, both the week 3 and week 10 MyoPS responses were significantly correlated with the subsequent change in vastus lateralis cross sectional area, as measured by ultrasound. More convincingly, the MyoPS response in week 10 was strongly correlated with muscle fibre hypertrophy, which was quantified from laminin‐stained sections. Together, these findings lead the authors to conclude that the larger MyoPS response following the initial unaccustomed exercise bout was directed toward the repair of damaged muscle, rather than muscle hypertrophy. The authors suggest that the attenuation of muscle damage (repeated bout effect) can potentially explain the attenuated MyoPS response, and that the MyoPS at week 10 was directed toward muscle hypertrophy and not the repair of muscle damage.

In summary, the MyoPS response to resistance exercise was largest following the initial exercise bout, but was not correlated with subsequent muscle hypertrophy. The large MyoPS response to the initial exercise bout was associated with the largest muscle damage. When normalising MyoPS to muscle damage, there were no differences in MyoPS between the three exercise bouts, suggesting that the increased MyoPS response to the initial exercise bout was potentially directed toward the repair of damaged muscle. Only after the attenuation of muscle damage at week 10 of training was MyoPS strongly correlated with vastus lateralis muscle fibre hypertrophy. These findings suggest that the muscle damage following the initial exercise bout was partly responsible for the large MyoPS response. These data further confirm that the MyoPS response to initial resistance exercise bouts cannot be used as a predictor of subsequent muscle hypertrophy. The findings from this study could also be valuable for understanding muscle growth responses in populations with excessive muscle damage responses to physical activity and resistance training. To further disseminate the regulation of muscle hypertrophy following resistance training, populations such as the elderly, who display impaired MyoPS responses, could also be considered. Overall, the authors should be commended for the use of robust study parameters to investigate the relationship between protein synthesis, muscle damage and muscle hypertrophy following resistance training. The findings of Damas et al. (2016) highlight the fact that only after the attenuation of muscle damage does the protein synthesis response to resistance training correlate with skeletal muscle hypertrophy.

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Competing interests

None declared.