The DOI matches its Crossref record; 164 of the 164 references it cites were found in a registry or an index.
Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise
Open accessAbstract
One of the most striking adaptations to exercise is the skeletal muscle hypertrophy that occurs in response to resistance exercise. A large body of work shows that a mammalian target of rapamycin complex 1 (mTORC1)-mediated increase of muscle protein synthesis is the key, but not sole, mechanism by which resistance exercise causes muscle hypertrophy. While much of the hypertrophy signaling cascade has been identified, the initiating, resistance exercise-induced and hypertrophy-stimulating stimuli have remained elusive. For the purpose of this review, we define an initiating, resistance exercise-induced and hypertrophy-stimulating signal as "hypertrophy stimulus," and the sensor of such a signal as "hypertrophy sensor." In this review we discuss our current knowledge of specific mechanical stimuli, damage/injury-associated and metabolic stress-associated triggers, as potential hypertrophy stimuli. Mechanical signals are the prime hypertrophy stimuli candidates, and a filamin-C-BAG3-dependent regulation of mTORC1, Hippo, and autophagy signaling is a plausible albeit still incompletely characterized hypertrophy sensor. Other candidate mechanosensing mechanisms are nuclear deformation-initiated signaling or several mechanisms related to costameres, which are the functional equivalents of focal adhesions in other cells. While exercise-induced muscle damage is probably not essential for hypertrophy, it is still unclear whether and how such muscle damage could augment a hypertrophic response. Interventions that combine blood flow restriction and especially low load resistance exercise suggest that resistance exercise-regulated metabolites could be hypertrophy stimuli, but this is based on indirect evidence and metabolite candidates are poorly characterized.
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“Understanding this mechanobiological connection confirms mechanical loading as the primary upstream driver of ribosome biogenesis”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [45]
In the citing paper
“The most defensible interpretation is that load intensity probably matters indirectly through its effects on mechanical tension, motor-unit recruitment, and the feasibility of accumulating productive volume [45,145].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [45]
In the citing paper
“The ribosomal literature provides almost no direct basis for claiming that one of these broad categories is inherently superior for stimulating ribosome biogenesis [45].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [45]
In the citing paper
“mTORC1 is also activated by mechanical stimuli, e.g., induced through resistance training [173]”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [173]
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1 retracted
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Sarcopenia during COVID-19 lockdown restrictions: long-term health effects of short-term muscle loss
Kirwan, R., McCullough, D., Butler, T., de Heredia, F. P., Davies, I. G., & Stewart, C. E. (2020) · GeroScience · doi:10.1007/s11357-020-00272-3 · Cited by 344
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The molecular athlete: exercise physiology from mechanisms to medals
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Metadata
- Authors
- Wackerhage, H., Schoenfeld, B. J., Hamilton, D. L., Lehti, M., & Hulmi, J. J.
- Affiliations
- Technical University of Munich (DE)
- Lehman College (US)
- Deakin University (AU)
- LIKES – Foundation for Sport and Health Sciences (FI)
- University of Jyväskylä (FI)
- Corresponding author
- Wackerhage, Henning
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2019-01-01
- Volume
- 126
- Issue
- 1
- Pages
- 30-43
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2897539462
- Cited by
- 357
- References
- 163
- Citations by year
- 2026: 46 · 2025: 48 · 2024: 41 · 2023: 57 · 2022: 73 · 2021: 43 · 2020: 33 · 2019: 16
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- green
- urn.fi
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Jyväskylä University Digital Archive (University of Jyväskylä) (submittedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- Funders
- Foundation for Public Health and Physical Activity LIKES
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Keywords
- skeletal muscle hypertrophy, resistance training, mTORC1 signaling, muscle protein synthesis, mechanical stress, exercise-induced muscle damage, metabolic stress, mechanosensing, filamin C, BAG3, Hippo signaling pathway, autophagy, costameres, blood flow restriction, low-load resistance training
- MeSH terms
- Animals, Humans, Hypertrophy, Stress, Physiological, Weight-Bearing, Muscle, Skeletal, Mechanotransduction, Cellular, Resistance Training
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