Inducible deletion of raptor and mTOR from adult skeletal muscle impairs muscle contractility and relaxation.
Level 5 - mechanism / opinion, no new human data
Animal model study with no human data.
PubMed 36255030 · doi:10.1113/JP283686
What was done
Researchers investigated the functional role of mTOR signaling in skeletal muscle contractility using an inducible adult mouse model with muscle-specific double knockout of mTOR and the mTORC1 scaffold protein raptor, comparing them to single-knockout animals. They evaluated muscle force, post-tetanic relaxation, fiber denervation, fiber typing, in vivo post-tetanus calcium decay kinetics, and transcriptomic changes via RNA sequencing.
What was found
Double knockout in adult mice produced a more severe phenotype than deletion of raptor or mTOR alone. The animals developed muscle weakness, increased fiber denervation, delayed muscle relaxation following tetanic stimulation, and a shift toward slow-twitch fibers. Double knockout mice also exhibited reduced post-tetanic calcium decay kinetics in vivo and altered expression of calcium-handling genes (Serca1, Casq1) alongside downregulation of sarcomere-organization genes (Tcap, Fhod3). The abstract reported no numerical values or effect sizes.
Why it matters
This study shows that baseline mTOR signaling is required for normal skeletal muscle relaxation kinetics and calcium handling, clarifying downstream mechanisms involved in muscle weakness phenotypes.
Limits
The study is restricted to an animal model, limiting direct translation to human muscle pathologies. The abstract does not report animal sample sizes, specific quantitative measurements, kinetic rates, or statistical significance values.
Cited by
- supports Absence of mTORC1 in skeletal muscle causes muscle withering and wasting.