mTORC1 signalling is not essential for the maintenance of muscle mass and function in adult sedentary mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal laboratory experiment (Oxford CEBM Level 5).
PubMed 31697050 · doi:10.1002/jcsm.12505
What was done
The authors investigated whether mTORC1 signaling is required to maintain adult muscle mass and function. They generated an inducible muscle-specific raptor knockout (iRAmKO) mouse model to conditionally ablate raptor (an essential mTORC1 component) in adult skeletal muscle fibers. They compared iRAmKO mice to developmental muscle-specific raptor knockouts (RAmKO) and controls, performing phenotypic, morphological, and biochemical analyses (including polysome profiling, proteomics, and ex vivo muscle force measurement) for up to 5 months post-depletion.
What was found
The abstract reports no exact quantitative values. Qualitatively, iRAmKO mice exhibited a decrease in the proportion of oxidative fibers and an increase in slow-type fibers. Inducible raptor depletion significantly reduced translation machinery components and overall translation rates. However, no significant decrease in body mass, muscle mass, muscle fiber cross-sectional area, or ex vivo muscle force was observed up to 5 months after raptor depletion.
Why it matters
These findings demonstrate that unlike in developing muscle, mTORC1 signaling is dispensable for preserving muscle mass and strength in fully grown sedentary mice. This suggests that systemic mTORC1 inhibition (such as with rapamycin for longevity) may not inherently trigger skeletal muscle atrophy in adults.
Limits
This was an animal study conducted exclusively in sedentary mice; human relevance remains unproven. The abstract does not provide sample sizes, effect sizes, or quantitative confidence intervals. Furthermore, the findings are restricted to sedentary conditions and do not address whether mTORC1 remains essential during muscle loading, hypertrophy, exercise, aging, or recovery from injury.
Cited by
- context Absence of mTORC1 in skeletal muscle causes muscle withering and wasting.