Muscle growth
mTORC1-dependent process of skeletal muscle fiber enlargement (hypertrophy); driven by growth factors and exercise, blocked by rapamycin.
Muscles getting bigger. The process by which muscle fibers get bigger (hypertrophy), driven by exercise and growth signals and requiring mTORC1 activity. Blocking mTORC1 blocks this growth response.
Raptor-null muscle is dystrophic and rapamycin blocks overload hypertrophy; but constitutive mTORC1 activation alone is not sufficient for healthy hypertrophy.
TL;DR. Muscle growth appears in 6 curated studies in Oliver's mTOR Atlas: 2 in people (2 human studies); 2 in animal models; 1 at the molecular level (cells, biochemistry, structure); 1 review. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| Protein synthesis activates Muscle growth mechanism: functional-consequence · this link in full · on the map table | Ongoing protein-building is what physically builds muscle; in mice, the signals that drive it are needed for muscle growth and are enough to cause it. In people, blocking mTOR blunts the rise in muscle protein-building after a single bout of exercise, but how much muscle is gained over months under the drug was not measured. Holds under: Mouse (BOD2001) and cultured myotubes (ROM2001). The human study DRU2009 is cited on the step before this one (LOAD-MTORC1): rapamycin blocked the rise in muscle protein synthesis 1-2 h after one bout of contractions (and also blocked ERK1/2). It did not measure muscle growth, so it is not evidence for this arrow. Requires mechanical load. mTORC1 activation without loading does not reproduce healthy hypertrophy, and constitutive activation alone is not sufficient. plausible in people, not shown directly · settled in the literature | A | BOD2001, ROM2001 conflicting: LAP2026 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| H | Human study | 2 |
| A | Animal model | 2 |
| M | Molecular — cells, biochemistry, structure | 1 |
| R | Review — secondary literature, not a new result | 1 |
Studies
| Year | Evidence | Study |
|---|---|---|
| 2025 | H | Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results MOE2025 The authors describe PEARL as the longest trial of rapamycin for healthy ageing so far: 48 weeks, once a week, ages 50 to 85, 114 people finished (40 on 5 mg, 35 on 10 mg, 39 on placebo). The question the trial was built to answer was visceral fat on a DXA scan, and that did not change. Most of what gets quoted comes from secondary results. Lean mass rose in women on 10 mg, and these women also reported less pain, but pain came from a questionnaire the authors did not list as an endpoint, and only eight women were in the 10 mg group, hence the very wide interval (odds ratio 28, 95% CI 2.4 to 324). Side effects were similar to placebo, with more stomach complaints on rapamycin. Bone density was the one signal pointing the wrong way: in the 5 mg group the odds of an improvement in bone mineral density were lower than on placebo (odds ratio 0.24, 95% CI 0.06 to 0.93, p = 0.04), but 10 mg showed no change (odds ratio 1.00) and the comparisons between groups were not significant. Boundary: the capsules were compounded, and the authors found they reached about a third of the blood level of the commercial drug, so 10 mg here is closer to 3 mg of generic sirolimus. Dosing was self-reported, and the group was about two thirds men and health-conscious. |
| 2009 | H | Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis DRU2009 Rapamycin given before resistance exercise blocked the early (1–2 h) post-exercise rise in human muscle protein synthesis, which was about 40% in the control group. Rapamycin also blocked the rise in ERK1/2 phosphorylation and blunted MNK1, so the authors conclude that mTORC1 drives the response only in part. The study measured acute protein synthesis, not muscle growth. |
| 2026 | A | D-Amino Acid Prodrug DLMEH Activates mTORC1 via Sestrin2 to Restore Muscle Protein Synthesis in Sarcopenia. SHIM2026 DLMEH, a D-leucine ester prodrug, binds Sestrin2 with leucine-like potency (Kd 28.3 uM, equivalent to L-leucine) and activates mTORC1 in a Sestrin2-dependent way. It restored protein synthesis in human myotubes and preserved muscle mass, grip strength and endurance in a rat dexamethasone-induced atrophy model (not an ageing sarcopenia model). |
| 2026 | A | Feeding-Induced Muscle mTORC1 Signaling Regulates Postprandial Protein Synthesis and Endurance but Not Muscle Size LAP2026 Using a mouse model expressing an AKT-nonphosphorylatable TSC2 mutant specifically in skeletal muscle, the Manning lab genetically separated feeding-induced from contraction-induced mTORC1 activation. AKT-mediated TSC2 phosphorylation is required for feeding (but not contraction) to activate muscle mTORC1 and drive postprandial protein synthesis — yet mice lacking this feeding-induced signal have normal muscle mass and myofiber size, and instead show improved maximal endurance capacity with a modest rise in mitochondrial content. The finding dissociates mTORC1's role in postprandial anabolism from its role in maintaining steady-state muscle mass, and is a directly relevant data point for whether the pattern/source of mTORC1 activation (feeding vs. mechanical) — not just its average level — shapes downstream outcomes. |
| 2026 | R | Strengthening Muscle for Healthy Ageing: Innovative Treatments for Sarcopenia ANC2026 A major pharma-facing review (Blau lab, Stanford/Sanford Burnham) surveying emerging drug strategies for sarcopenia — the age-related loss of muscle mass/strength with no approved therapy. Among the pleiotropic mechanisms discussed, mTORC1 inhibitors are highlighted specifically for their ability to restore impaired autophagy in aging muscle, alongside NAD-related molecules, urolithin A, myostatin inhibitors, SARMs, and 15-PGDH ('gerozyme') inhibitors. Useful high-level context for where mTORC1 modulation sits among competing anti-sarcopenia strategies, though it does not itself address dynamic/temporal mTOR activity. |
| 2001 | M | Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways ROM2001 Shows IGF-1 drives muscle fiber hypertrophy through Akt, via both the mTOR and GSK3 branches, in cultured myotubes, establishing mTOR as a central node for muscle growth signaling. |
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