The effect of rapamycin on muscle growth and strength

Although it’s well known that mTORC1 activation stimulates protein synthesis and is necessary for muscle growth, too much mTORC1 for too long may have opposite effects.

The study below shows that mutant mice with chronically activated mTORC1 have skeletal muscle atrophy and reduced muscle strength. Administration of rapamycin to such mutant mice in old age results in increased autophagy and partial reversal of the skeletal muscle atrophy and strength, as seen in the following study:

Older animals may also suffer from chronically elevated mTORC1 similar to the mutant mice, although to a smaller extent. When atrophy due to muscle disuse is induced in old rats, they were found to have limited recovery of muscle mass in response to reuse, despite having higher myofibrillar protein synthesis than young adult rats. They also had higher rates of protein degradation. The authors speculated that the higher rate of protein synthesis in the older rats contributed to increased rates of protein misfolding and aggregation and that this was a result of chronically elevated mTORC1. See the study below:

I think this may be one of the reasons why rapamycin use does not appear to make it harder for people to gain or maintain muscle mass even in those taking pretty high doses.