Impacts of Mechanistic Target of Rapamycin (mTOR) Inhibition on Aged Human Muscle (Rapamune)
Status:
Recruiting
Trial end date:
2024-05-01
Target enrollment:
Participant gender:
Summary
As people age, muscle mass and function is lost and exercise training is an important way to
reduce the effects of this and remain independent. However, not everyone can perform this
exercise and the muscle responses to exercise are often reduced in older people. So far there
has been no drug found to specifically treat or reduce this problem.
Muscle size depends on the balance of muscle protein breakdown and synthesis (building). This
balance is regulated by multiple signals within the body, but a particular molecule - the
mechanistic target of rapamycin (mTOR), is known to play an important role. For protein
synthesis to build up the muscles, this pathway is needed to start the process when triggered
by eating protein or exercise. Although this would suggest that mTOR activity is good,
excessive levels of this signalling seem to have negative impacts on muscle maintenance with
age.
In animal studies, blocking mTOR signalling has stopped the development of a number of
age-related diseases and increased health-span. Drugs that block this pathway (e.g. Rapamune)
reduce the stimulation of muscle protein synthesis, possibly through changing the immune
system, but conversely have also been shown to increase muscle size and reduce markers of
nerve supply loss. This means that drugs which block the mTOR pathway could, in older people,
help to reduce the negative impacts of excessive mTOR signalling on muscle size and function.
The investigators aim to recruit 16 healthy male volunteers over 50 years old to investigate
how the drug Rapamune (which blocks the mTOR pathway) affects aged human muscle both on its
own and when combined with resistance exercise training.