REF-682 · Wackerhage, Schoenfeld, Hamilton, Lehti & Hulmi, 2019 · Journal of Applied Physiology, · Paper · PubMed
Mechanical signals are the prime candidate stimuli for resistance-exercise hypertrophy
Damage is probably not essential, and the metabolite case rests on indirect evidence
Key Findings
An mTORC1-mediated rise in muscle protein synthesis is the key, but not the sole, mechanism by which resistance exercise causes hypertrophy.
Mechanical signals are the prime hypertrophy-stimulus candidates; a filamin-C–BAG3-dependent regulation of mTORC1, Hippo and autophagy signalling is a plausible, still incompletely characterised sensor. Nuclear deformation and costamere-related mechanisms are other candidate mechanosensors.
Exercise-induced muscle damage is probably not essential for hypertrophy; whether it can augment the response is unclear.
Blood-flow-restriction and low-load studies suggest metabolites could be hypertrophy stimuli, but the evidence is indirect and the metabolite candidates are poorly characterised.
Practical Application
This mechanistic review names mechanical signals as the leading candidate trigger for muscle growth after resistance exercise, with damage probably not essential and metabolic stress only indirectly supported — so mechanical loading, not soreness or "the pump", is the lever to prioritise.
Not from this paper; the base's own practice: use challenging loads taken near failure through a full range of motion as the main hypertrophy lever, and treat pump/metabolic-stress methods as supplementary.
Limitations
Mechanistic narrative review; the sensor mechanisms are described as candidates, not established, and molecular pathways do not translate one-to-one into a training prescription.
How this entry was checked and changed
Content correction 2026-09-27
"Mechanical tension is the primary trigger" stated as fact -> the abstract calls mechanical signals the prime CANDIDATES and the sensor plausible but incompletely characterised; wording softened.
Damage "secondary/contributory" -> the abstract says probably not essential, augmenting role unclear; metabolites = indirect evidence only.
Loading/near-failure/full-ROM prescription relabelled as the base's own practice (not in the paper).
Revision 2026-10-16: cross-reference to SYNTH-89 (the occlusion and metabolite claims of static-dynamic training) added. Content and level unchanged. (SYNTH-89)