The accumulation rate of ribosomes predicts muscle training‐induced hypertrophy

Muscle training-induced hypertrophy is secondary to an improved balance between protein synthesis and degradation although it could also involve the fusion of and myogenesis of satellite cells. The rate of muscle protein synthesis is to a large extent dependent upon the translational capacity of skeletal muscle which can be equalled to the amount of ribosomes per unit tissue. Therefore the biogenesis of ribosomes has a key role for the increase in muscle mass following resistance training.1, 2 Total RNA is considered to be a valid proxy marker of ribosomal density.3 In the current issue of Acta Physiologica, Hammarström, Øfsteng and colleagues from the Inland Norway University of Applied Sciences present very interesting new information about ribosome accumulation during the early phase of resistance training and how this impacts on muscle training-induced hypertrophy.4 They studied eleven men and women, 18-35 years of age, with a low previous history of resistance training. The subjects performed resistance training involving 12 sessions of resistance exercise (RE, 3-4 sessions per week) of unilateral knee extension with alternating legs. With one leg, subjects trained with constant volume (each session being 6 sets of 10 RM, ie 10 repetition maximum), whereas the volume was varied for the contralateral leg (sessions 1-4:6 sets of 10 RM; sessions 5-8:3 sets of 10 RM; sessions 9-12:9 sets of 10 RM. Ribosome density and accumulation were measured by total RNA, ribosomal RNA and rpS6 protein in vastus lateralis biopsies obtained at baseline, 48 h after sessions 1, 4, 5, 8, 9, and 12, and after 8 days of de-training. The control subjects were biopsied at relevant time points. Muscle thickness was measured before and after the intervention by ultrasound. The central finding of the manuscript is that skeletal muscle in the untrained state is highly responsive with respect to ribosome biogenesis following acute RE. The time-course analysis revealed that the greatest increase in total RNA occurred during the first four sessions, with a 35%–40% increase from pretraining. This equals a 9% increase in total RNA per RE training session. After that only a minor further increase was noted, with a plateau reached at 50% above pretraining values following the 8th training session. The initial rapid induction of ribosomes is therefore only to a minor extent further stimulated by continued training, the importance of which seems to secure that the elevated RNA pool is maintained. In addition, this pool is balanced towards the accompanying training-induced muscle hypertrophy so that the RNA amount per weight of muscle does not to decrease. Although several previous studies have shown that total RNA content in skeletal muscle is altered by resistance training,5 the detailed time-course analysis is a novelty of the present Manuscript. Apart from this, there are several other intriguing findings in this paper. One is that training led to muscle growth (on average 3.9% over baseline with the 12 training sessions), with an individual variation that was mirrored by a similar variation in the individual increase in the RNA content. This means that individual rates of increases in total RNA abundance predicted the magnitude of muscle growth, confirming the link between ribosomal biogenesis and muscle protein accretion3 and muscle hypertrophy.1, 2 Another novel and intriguing finding was that if individual rates of increases in total RNA abundance was substituted by the individual variation in total RNA content, the link between ribosomes and muscle growth vanished. In fact, higher levels of total RNA were instead associated with a tendency towards lowered muscle growth. This suggests a quality over quantity factor when it comes to the effect of RNA abundance on translational capacity in skeletal muscle, highlighting the importance of making new ribosomes in contrast to having a lot of ribosomes. This is interpreted to suggest that newly synthesized ribosomes would be more beneficial for muscle growth in response to a new stimuli as novel ribosomes are potentially specialized for growth rather than cellular status quo. However, ribosomal accumulation is unlikely to be the only ribosome-derived trait that is important for training responsiveness. Evidence suggests that mechanical loading may lead to changes in ribosome characteristics6 potentially leading to heterogeneous tissue-specific ribosome populations.7 This is suggested by the sustained elevation of pre-rRNA transcripts, coinciding with peak values of UBF (Upstream binding factor) protein levels, which may also play a role in regulation of rRNA transcription in response to resistance training. Total RNA increases were not affected by weekly fluctuations in training volume in the present study. However, since the clever protocol in this study, comparing constant or varying training volumes in the contralateral legs, coincided with identical training volumes in both legs during the first four resistance training sessions, that is, when most of the RNA increases took place, this conclusion remains tentative. With 8 days of detraining, around 20% of total RNA was lost, indicating the importance of actively maintaining translational capacity in order not to lose it and suggesting that training cessation halts ribosome biogenesis. Although UBF levels were related to RNA accumulation over the course of the intervention, it was noted that levels of UBF were maintained at the detraining time-point, when total RNA was decreasing. Together, these results and perspectives emphasizes the potentially crucial role of RT-induced ribosomal synthesis for adaptations to training, making ribosomal responses to RT an interesting biomarker in relation to manipulation of training loads for specific populations. There is no conflict of interest to declare.