Cited by 357Muscle Physiology and DisordersMuscle metabolism and nutritionCardiovascular and exercise physiology

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Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise

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Wackerhage, Henning, Schoenfeld, Brad J., Hamilton, D. Lee, Lehti, Maarit, Hulmi, Juha J.·2019·Journal of Applied Physiology

DOI 10.1152/japplphysiol.00685.2018

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Abstract

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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BackgroundInfluential
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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
ORCID: Wackerhage, Henning
Schoenfeld, Brad J.
Hamilton, D. Lee
Lehti, Maarit
Hulmi, Juha J.
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
DOI: 10.1152/japplphysiol.00685.2018
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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Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise

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