Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss of muscle mass are highly debated. In particular, the extent to which disuse triggers decreases in protein synthesis or increases in protein degradation, and whether these changes are uniform across muscles or influenced by age is unclear. We aimed to determine the impact of disuse on protein synthesis and protein degradation in lower limb muscles of varied function and fiber type in adult and old rats. Alterations in protein synthesis and degradation were measured in the soleus, medial gastrocnemius (MG), and tibialis anterior (TA) muscles of adult and old rats subjected to hindlimb unloading (HU) for 3, 7 or 14 days. Loss of muscle mass was progressive during the unloading period, but highly variable (-9 to -38%) across muscle types and between ages. Protein synthesis decreased significantly in all muscles except for the old TA. MuRF1, MAFbx, and FOXO1 expression significantly increased in all muscles, but increases in proteasome and cathepsin L activity were only observed in the adult soleus. These results show that in response to unloading, a decrease in protein synthesis was apparent in all muscles, but varied in amount between muscles. Increases in protein degradation occurred primarily in predominantly slow-twitch extensor muscles, resulting in greater loss of muscle mass. Additionally, atrophy-associated gene expression showed only sporadic correlation with protein degradation; thus increased expression of so-called atrogenes is not a reliable surrogate for dynamic measures of protein degradation.
- muscle atrophy
- Copyright © 2016, Journal of Applied Physiology