Key Anabolic Markers in Human Soleus Muscle after 21-Day Head-Down Tilt Bed Rest

Abstract

Prolonged bed rest can have a significant negative effect on skeletal muscles, leading to muscle wasting and reduced strength. This process can take as little as 10 days in healthy individuals, with the loss of muscle mass and strength being particularly pronounced during the first week of immobilization. Head-down tilt bed rest (HDTBR) is a method used to simulate physiological changes that occur in weightlessness during spaceflight. This technique involves lying in bed with the head tilted downward. Here, we analyze the key anabolic markers of the human m. soleus during 21 days of HDTBR. Six healthy male volunteers, aged 25–35 years, were exposed to 21 days of strict bed rest at a tilt angle of –6°. A needle biopsy of the m. soleus was performed via the Bergström method before the onset of HDTBR and on day 21 after that. The biopsy material was immediately frozen in liquid nitrogen for further Western blot and PCR analysis. A study of mTORC1 substrates showed a significant decrease in p70 and 4EBP1 phosphorylation after HDTBR. We also observed a significant decrease in the phosphorylation of another ribosomal kinase, p90RSK, a significant increase in eEF2 phosphorylation, and an increase in eEF2k mRNA expression. In addition, the phosphorylation of AMPK and its substrate ACC decreased after HDTBR. The data obtained in this work support the hypothesis that a decrease in protein synthesis, together with an increase in proteolysis, contributes to the development of human m. soleus atrophy after 21 days of HDTBR.