Background: Translational capacity (i.e. ribosomal mass) is a key determinant of protein synthesis and has been associated with skeletal muscle hypertrophy. The role of translational capacity in muscle atrophy and regrowth from disuse is largely unknown. Therefore, we investigated the effect of muscle disuse and reloading on translational capacity in middle-aged men (Study 1) and in rats (Study 2). Methods: In Study 1, 28 male participants (age 50.03 ± 3.54 years) underwent 2 weeks of knee immobilization followed by 2 weeks of ambulatory recovery and a further 2 weeks of resistance training. Muscle biopsies were obtained for measurement of total RNA and pre-ribosomal (r)RNA expression, and vastus lateralis cross-sectional area (CSA) was determined via peripheral quantitative computed tomography. In Study 2, male rats underwent hindlimb suspension (HS) for either 24 h (HS 24 h, n = 4) or 7 days (HS 7d, n = 5), HS for 7 days followed by 7 days of reloading (Rel, n = 5) or remained as ambulatory weight bearing (WB, n = 5) controls. Rats received deuterium oxide throughout the study to determine RNA synthesis and degradation, and mTORC1 signalling pathway was assessed. Results: Two weeks of immobilization reduced total RNA concentration (20%) and CSA (4%) in men (both P ≤ 0.05). Ambulatory recovery restored total RNA concentration to baseline levels and partially restored muscle CSA. Total RNA concentration and 47S pre-rRNA expression increased above basal levels after resistance training (P ≤ 0.05). In rats, RNA synthesis was 30% lower while degradation was ~400% higher in HS 7d in soleus and plantaris muscles compared with WB (P ≤ 0.05). mTORC1 signalling was lower in HS compared with WB as was 47S pre-rRNA (P ≤ 0.05). With reloading, the aforementioned parameters were restored to WB levels while RNA degradation was suppressed (P ≤ 0.05). Conclusions: Changes in RNA concentration following muscle disuse and reloading were associated with changes in ribosome biogenesis and degradation, indicating that both processes are important determinants of translational capacity. The pre-clinical data help explain the reduced translational capacity after muscle immobilization in humans and demonstrate that ribosome biogenesis and degradation might be valuable therapeutic targets to maintain muscle mass during disuse.
|Number of pages||14|
|Journal||Journal of Cachexia, Sarcopenia and Muscle|
|State||Published - Feb 2021|
Bibliographical noteFunding Information:
This work was funded by National Institute of Health//NCCIH grant AT009268 and in part by the New Zealand Primary Growth Partnership (PGP) post‐farm gate program, funded by Fonterra Co‐operative Group Ltd and the NZ Ministry for Primary Industries (MPI). The funders had no role in the data analysis or the production of the manuscript.
This work was funded by National Institute of Health//NCCIH grant AT009268 and in part by the New Zealand Primary Growth Partnership (PGP) post-farm gate program, funded by Fonterra Co-operative Group Ltd and the NZ Ministry for Primary Industries (MPI). The funders had no role in the data analysis or the production of the manuscript. We would like to thank Dr Frederick F. Peelor III for his support with GC–MS analysis. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle.68
© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders
- Resistance training
- Ribosomal RNA
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Physiology (medical)