Wackerhage · Journal of applied physiology (Bethesda, Md. : 1985) 2019 · narrative review · n=?

Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise.

Cited 351 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of mechanistic pathways without systematic search or original data

PubMed 30335577 · doi:10.1152/japplphysiol.00685.2018 · record verified 2026-08-29

What was done

This narrative review evaluated existing mechanistic literature regarding the initiating triggers ("hypertrophy stimuli") and upstream sensing mechanisms ("hypertrophy sensors") that drive resistance exercise-induced skeletal muscle hypertrophy. The authors synthesized candidate mechanisms across mechanical stimuli (including filamin-C-BAG3 signaling, nuclear deformation, and costameres), exercise-induced muscle damage, and metabolic stress-associated triggers.

What was found

The abstract reports no numerical data or effect sizes. Mechanical tension was identified as the primary candidate stimulus for muscle hypertrophy, with filamin-C-BAG3-dependent regulation of mTORC1, Hippo, and autophagy signaling highlighted as a plausible, though incompletely characterized, sensor alongside costameres and nuclear deformation. Exercise-induced muscle damage was evaluated as likely not essential for hypertrophy, and metabolic stress candidates were noted to rest on indirect evidence from blood flow restriction protocols with poorly characterized specific metabolites.

Why it matters

This review distinguishes primary upstream mechanical triggers and sensors from downstream signaling and secondary factors, providing a conceptual framework for how muscle tissue senses and converts loading into hypertrophy.

Limits

As a narrative review, it presents theoretical and mechanistic synthesis rather than original human trial data or a systematic search. Most discussed sensors and metabolites remain incompletely characterized and rely on indirect evidence.

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