Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise

Wackerhage, Henning; Schoenfeld, Brad J.; Hamilton, D. Lee; Lehti, Maarit; Hulmi, Juha J.

doi:10.1152/japplphysiol.00685.2018

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

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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Mechanical loading is the primary upstream driver of ribosome biogenesis.
“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]
Load intensity probably matters indirectly through its effects on mechanical tension, motor-unit recruitment, and the feasibility of accumulating productive volume.
“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]
The ribosomal literature provides almost no direct basis for claiming that one of these broad categories is inherently superior for stimulating ribosome biogenesis.
“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]
mTORC1 is activated by mechanical stimuli such as resistance training.
“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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Glycolytic atp production estimated from31p magnetic resonance spectroscopy measurements during ischemic exercisein vivo
Wackerhage, H., Mueller, K., Hoffmann, U., Leyk, D., Eßfeld, D., & Zange, J. (1996) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/bf01772002 · Cited by 15 · see citing works

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The COVID-19 pandemic and physical activity
Woods, J. A., Hutchinson, N. T., Powers, S. K., Roberts, W. O., Gómez‐Cabrera, M. C., Radak, Z. O., Berkes, I., Boros, A., Boldogh, I. R., Leeuwenburgh, C., et al. (2020) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2020.05.006 · Cited by 647 · see citing works
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 331 · see citing works
Molecular Responses to Acute Exercise and Their Relevance for Adaptations in Skeletal Muscle to Exercise Training
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
The molecular athlete: exercise physiology from mechanisms to medals
Furrer, R., Hawley, J. A., & Handschin, C. (2023) · Physiological Reviews · doi:10.1152/physrev.00017.2022 · Cited by 232 · see citing works
Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions
Roberts, M. D., McCarthy, J. J., Hornberger, T. A., Phillips, S. M., Mackey, A. L., Nader, G. A., Boppart, M. D., Kavazis, A. N., Reidy, P. T., Ogasawara, R., et al. (2023) · Physiological Reviews · doi:10.1152/physrev.00039.2022 · Cited by 214 · see citing works
Exercise adaptations: molecular mechanisms and potential targets for therapeutic benefit
McGee, S. L., & Hargreaves, M. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0377-1 · Cited by 221 · see citing works
Interactions between Muscle and Bone—Where Physics Meets Biology
Herrmann, M., Engelke, K., Ebert, R., Müller-Deubert, S., Rudert, M., Ziouti, F., Jundt, F., Felsenberg, D., & Jakob, F. (2020) · Biomolecules · doi:10.3390/biom10030432 · Cited by 197 · see citing works
Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies
Nunes, E. A., Stokes, T., McKendry, J., Currier, B. S., & Phillips, S. M. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00425.2021 · Cited by 183 · see citing works
Molecular Mechanisms of Skeletal Muscle Hypertrophy
Schiaffino, S., Reggiani, C., Akimoto, T., & Blaauw, B. (2020) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-200568 · Cited by 169 · see citing works
Molecular mechanisms of exercise contributing to tissue regeneration
Chen, J., Zhou, R. J., Ye, F., & Cheng, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01233-2 · Cited by 173 · see citing works
Pathophysiology of exercise-induced muscle damage and its structural, functional, metabolic, and clinical consequences.
Stožer, A., Vodopivc, P., & Bombek, L. K. (2020) · Physiological Research · doi:10.33549/physiolres.934371 · Cited by 168 · see citing works
An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise–Induced Human Skeletal Muscle Hypertrophy
LIM, C., NUNES, E. A., CURRIER, B. S., MCLEOD, J. C., THOMAS, A. C. Q., & PHILLIPS, S. M. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002929 · Cited by 142 · see citing works
Exercise Induces Tissue-Specific Adaptations to Enhance Cardiometabolic Health
Ashcroft, S. P., Stocks, B., Egan, B., & Zierath, J. R. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.008 · Cited by 149 · see citing works
Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass
Goodman, C. A. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01011.2018 · Cited by 133 · see citing works
Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits
BISHOP, N. C., Burton, J. O., Graham-Brown, M. P. M., Stensel, D. J., Viana, J. L., & Watson, E. L. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00675-9 · Cited by 130 · see citing works
Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta‐analysis of randomized controlled trials
Prokopidis, K., Giannos, P., Kirwan, R., Ispoglou, T., Galli, F., Witard, O. C., Triantafyllidis, K. K., Kechagias, K. S., Morwani‐Mangnani, J., Ticinesi, A., et al. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13132 · Cited by 111 · see citing works
Anabolic Resistance in the Pathogenesis of Sarcopenia in the Elderly: Role of Nutrition and Exercise in Young and Old People
Tezze, C., Sandri, M., & Tessari, P. (2023) · Nutrients · doi:10.3390/nu15184073 · Cited by 103 · see citing works
A systematic review of the effects of different resistance training volumes on muscle hypertrophy.
Baz-Valle, E., Balsalobre-Fernández, C., Alix-Fages, C., & Santos-Concejero, J. (2022) · Journal of Human Kinetics · doi:10.2478/hukin-2022-0017 · Cited by 83 · see citing works
Effects of range of motion on muscle development during resistance training interventions: A systematic review
Schoenfeld, B. J., & Grgić, J. (2020) · SAGE Open Medicine · doi:10.1177/2050312120901559 · Cited by 87 · see citing works
Effects of plyometric vs. resistance training on skeletal muscle hypertrophy: A review
Grgić, J., Schoenfeld, B. J., & Mikulić, P. (2020) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2020.06.010 · Cited by 83 · see citing works
The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations
Leuchtmann, A. B., Adak, V., Dilbaz, S., & Handschin, C. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.709807 · Cited by 84 · see citing works
Is an Energy Surplus Required to Maximize Skeletal Muscle Hypertrophy Associated With Resistance Training
Slater, G. J., Dieter, B. P., Marsh, D. J., Helms, E. R., Shaw, G., & Iraki, J. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00131 · Cited by 88 · see citing works
Perceived Barriers to Blood Flow Restriction Training
Rolnick, N. D., Kimbrell, K., Cerqueira, M. S., Weatherford, B., & Brandner, C. R. (2021) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2021.697082 · Cited by 77 · see citing works
UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy
Seaborne, R. A. E., Hughes, D. C., Turner, D. C., Owens, D. J., Baehr, L. M., Gorski, P. P., Semenova, E. A., Borisov, O., Larin, A. K., Викторович, П. Д., et al. (2019) · The Journal of Physiology · doi:10.1113/jp278073 · Cited by 72 · see citing works
The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
Rybalka, E., Timpani, C. A., Debruin, D. A., Bagaric, R. M., Campelj, D. G., & Hayes, A. (2020) · Cells · doi:10.3390/cells9122657 · Cited by 65 · see citing works
Exploring the dose–response relationship between estimated resistance training proximity to failure, strength gain, and muscle hypertrophy: a series of meta-regressions.
Robinson, Z. P., Pelland, J. C., Remmert, J. F., Refalo, M. C., Jukic, I., Steele, J., & Zourdos, M. C. (2024) · Sports Medicine · doi:10.1007/s40279-024-02069-2 · Cited by 63 · see citing works
Acute sprint exercise transcriptome in human skeletal muscle
Rundqvist, H., Montelius, A., Österlund, T., Norman, B., Esbjörnsson, M., & Jansson, E. (2019) · PLoS ONE · doi:10.1371/journal.pone.0223024 · Cited by 62 · see citing works
Influence of resistance training proximity-to-failure on skeletal muscle hypertrophy: a systematic review with meta-analysis.
Refalo, M. C., Helms, E. R., Trexler, E. T., Hamilton, D. L., & Fyfe, J. J. (2023) · Sports Medicine · doi:10.1007/s40279-022-01784-y · Cited by 61 · see citing works
Self-citation
Training Programs Designed for Muscle Hypertrophy in Bodybuilders: A Narrative Review
Alves, R. C., Prestes, J., Enes, A. A. N., de Moraes, W. M. A. M., Trindade, T. B., de Salles, B. F., Aragon, A. A., & de Souza, T. P. (2020) · Sports · doi:10.3390/sports8110149 · Cited by 61 · see citing works
Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved
Castillo, Í. M. P., Argilés, J. M. A., Rueda, R., Ramírez, M., & Pedrosa, J. M. L. (2025) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-025-09954-9 · Cited by 66 · see citing works
Redox modulation of muscle mass and function
Gómez‐Cabrera, M. C., Arc‐Chagnaud, C., Salvador‐Pascual, A., Brioche, T., Chopard, A., González, G. O., & Viña, J. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101531 · Cited by 59 · see citing works
Effects of Resistance Training Performed with Different Loads in Untrained and Trained Male Adult Individuals on Maximal Strength and Muscle Hypertrophy: A Systematic Review
de Lacio, M. L., Vieira, J. G., Trybulski, R., Campos, Y., Santana, D., Filho, J. E., Novaes, J. D. S., Vianna, J. M., & Wilk, M. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182111237 · Cited by 57 · see citing works
Alterations in Body Composition, Resting Metabolic Rate, Muscular Strength, and Eating Behavior in Response to Natural Bodybuilding Competition Preparation: A Case Study
Schoenfeld, B. J., Alto, A., Grgić, J., Tinsley, G. M., Haun, C. T., Campbell, B. I., Escalante, G., Sönmez, G., Cote, G., Francis, A., et al. (2020) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003816 · Cited by 56 · see citing works
Does stretch training induce muscle hypertrophy in humans? A review of the literature
Nunes, J. P., Schoenfeld, B. J., Nakamura, M., Ribeiro, A. S., Cunha, P. M., & Cyrino, E. S. (2020) · Clinical Physiology and Functional Imaging · doi:10.1111/cpf.12622 · Cited by 55 · see citing works
Self-citation
A cross-talk between sestrins, chronic inflammation and cellular senescence governs the development of age-associated sarcopenia and obesity
Livshits, G., & Kalinkovich, A. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101852 · Cited by 55 · see citing works
The role of the neural stimulus in regulating skeletal muscle hypertrophy
Alix‐Fages, C., Vecchio, A. D., Baz-Valle, E., Santos‐Concejero, J., & Balsalobre‐Fernández, C. (2022) · European Journal of Applied Physiology · doi:10.1007/s00421-022-04906-6 · Cited by 54 · see citing works
Resistance Exercise, Aging, Disuse, and Muscle Protein Metabolism
McKendry, J., Stokes, T., Mcleod, J. C., & Phillips, S. M. (2021) · Comprehensive physiology · doi:10.1002/cphy.c200029 · Cited by 71 · see citing works
High-Intensity Functional Training: Molecular Mechanisms and Benefits
Ben-Zeev, T., & Okun, E. (2021) · NeuroMolecular Medicine · doi:10.1007/s12017-020-08638-8 · Cited by 52 · see citing works
Effect of resistance training on bioelectrical phase angle in older adults: a systematic review with Meta-analysis of randomized controlled trials
Campa, F., Colognesi, L. A., Moro, T., Paoli, A., Casolo, A., Santos, L., Correia, R. R., Lemes, Í. R., Milanez, V. F., Christófaro, D. G. D., et al. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-022-09747-4 · Cited by 52 · see citing works
Mapping of the contraction-induced phosphoproteome identifies TRIM28 as a significant regulator of skeletal muscle size and function
Steinert, N. D., Potts, G. K., Wilson, G. M., Klamen, A. M., Lin, K., Hermanson, J. B., McNally, R. M., Coon, J. J., & Hornberger, T. A. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108796 · Cited by 52 · see citing works
Effects of Training with Different Modes of Strength Intervention on Psychosocial Disorders in Adolescents: A Systematic Review and Meta-Analysis
Barahona-Fuentes, G. D. F., Ojeda, Á. H., & Ríos, L. J. C. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18189477 · Cited by 51 · see citing works
Acute cellular and molecular responses and chronic adaptations to low-load blood flow restriction and high-load resistance exercise in trained individuals
Davids, C. J., Næss, T. C., Moen, M., Cumming, K. T., Horwath, O., Psilander, N., Ekblom, B. T., Coombes, J. S., Peake, J. M., Raastad, T., et al. (2021) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00464.2021 · Cited by 49 · see citing works
Towards an improved understanding of proximity-to-failure in resistance training and its influence on skeletal muscle hypertrophy, neuromuscular fatigue, muscle damage, and perceived discomfort: A scoping review
Refalo, M. C., Helms, E. R., Hamilton, D. L., & Fyfe, J. J. (2022) · Journal of Sports Sciences · doi:10.1080/02640414.2022.2080165 · Cited by 48 · see citing works
The effect of low‐load resistance training with blood flow restriction on chronic patellar tendinopathy — A case series
Skovlund, S. V., Aagaard, P., Larsen, P., Svensson, R. B., Kjær, M., Magnusson, S. P., & Couppé, C. (2020) · Translational Sports Medicine · doi:10.1002/tsm2.151 · Cited by 46 · see citing works
Does Training to Failure Maximize Muscle Hypertrophy?
Schoenfeld, B. J., & Grgić, J. (2019) · Strength and conditioning journal · doi:10.1519/ssc.0000000000000473 · Cited by 46 · see citing works
Exercise-specific adaptations in human skeletal muscle: Molecular mechanisms of making muscles fit and mighty
Thomas, A. C. Q., Stead, C. A., Burniston, J. G., & Phillips, S. M. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.08.010 · Cited by 52 · see citing works
Cellular and molecular pathways controlling muscle size in response to exercise
Attwaters, M., & Hughes, S. M. (2021) · FEBS Journal · doi:10.1111/febs.15820 · Cited by 45 · see citing works
Physiology of Stretch-Mediated Hypertrophy and Strength Increases: A Narrative Review
Warneke, K., Lohmann, L. H., Lima, C. D., Hollander, K., Konrad, A., Zech, A., Nakamura, M., WIRTH, K. J., Keiner, M., & Behm, D. G. (2023) · Sports Medicine · doi:10.1007/s40279-023-01898-x · Cited by 51 · see citing works
Skeletal muscle hypertrophy rewires glucose metabolism: An experimental investigation and systematic review
Baumert, P., Mäntyselkä, S., Schönfelder, M., Heiber, M., Jacobs, M. J., Swaminathan, A., Minderis, P., Dirmontas, M., Kleigrewe, K., Meng, C., et al. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13468 · Cited by 43 · see citing works
Exercise attenuates angiotensinⅡ-induced muscle atrophy by targeting PPARγ/miR-29b
Liu, Q., Chen, L., Liang, X., Cao, Y., Zhu, X., Wang, S., Li, J., Gao, J., & Xiao, J. (2021) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2021.06.002 · Cited by 44 · see citing works
The Effect of Load and Volume Autoregulation on Muscular Strength and Hypertrophy: A Systematic Review and Meta-Analysis
Hickmott, L. M., Chilibeck, P. D., Shaw, K. A., & Butcher, S. J. (2022) · Sports Medicine - Open · doi:10.1186/s40798-021-00404-9 · Cited by 48 · see citing works
Greater Gastrocnemius Muscle Hypertrophy After Partial Range of Motion Training Performed at Long Muscle Lengths
Kassiano, W., Costa, B. D. D. V., Kunevaliki, G., Soares, D., Zacarias, G., Manske, I., Takaki, Y., Ruggiero, M. F., Stavinski, N. G. D. L., Francsuel, J., et al. (2023) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000004460 · Cited by 43 · see citing works
Training, Supplementation, and Pharmacological Practices of Competitive Male Bodybuilders Across Training Phases
Hackett, D. A. (2021) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003989 · Cited by 43 · see citing works
Supervised Physical Training Enhances Muscle Strength but Not Muscle Mass in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis
Chen, Z., Zhang, Y., Lu, C., Zeng, H., Schumann, M., & Cheng, S. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00843 · Cited by 42 · see citing works
Postnatal skeletal muscle myogenesis governed by signal transduction networks: MAPKs and PI3K–Akt control multiple steps
Endo, T. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.09.048 · Cited by 42 · see citing works
Sex differences in absolute and relative changes in muscle size following resistance training in healthy adults: a systematic review with Bayesian meta-analysis
Refalo, M. C., Nuckols, G., Galpin, A. J., Gallagher, I. J., Hamilton, D. L., & Fyfe, J. J. (2025) · PeerJ · doi:10.7717/peerj.19042 · Cited by 40 · see citing works
Associations Between Handgrip Strength and Disease-Specific Mortality Including Cancer, Cardiovascular, and Respiratory Diseases in Older Adults: A Meta-Analysis
Lee, J. (2019) · Journal of Aging and Physical Activity · doi:10.1123/japa.2018-0348 · Cited by 40 · see citing works
Aerobic Adaptations to Resistance Training: The Role of Time under Tension
Mang, Z. A., Ducharme, J. B., Mermier, C. M., Kravitz, L. R., Magalhães, F. D. C., & Amorim, F. T. (2022) · International Journal of Sports Medicine · doi:10.1055/a-1664-8701 · Cited by 40 · see citing works
Ketogenic Diet and Skeletal Muscle Hypertrophy: a Frenemy Relationship?
Paoli, A., Cancellara, P., Pompei, P., & Moro, T. (2019) · Journal of Human Kinetics · doi:10.2478/hukin-2019-0071 · Cited by 39 · see citing works
PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle
Verbrugge, S. A. J., Gehlert, S., Stadhouders, L. E. M., Jacko, D., Aussieker, T., de Wit, G. M. J., Vogel, I. S. P., Offringa, C., Schönfelder, M., Jaspers, R. T., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197062 · Cited by 39 · see citing works
Which ROMs Lead to Rome? A Systematic Review of the Effects of Range of Motion on Muscle Hypertrophy
Kassiano, W., Costa, B. D. D. V., Nunes, J. P., Ribeiro, A. S., Schoenfeld, B. J., & Cyrino, E. S. (2023) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000004415 · Cited by 36 · see citing works
Low-Load vs. High-Load Resistance Training to Failure on One Repetition Maximum Strength and Body Composition in Untrained Women
Dinyer, T. K., Byrd, M. T., Garver, M. J., Rickard, A. J., Miller, W. M., Burns, S. P., Clasey, J. L., & Bergstrom, H. C. (2019) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003194 · Cited by 36 · see citing works
Calculating Set-Volume for the Limb Muscles with the Performance of Multi-Joint Exercises: Implications for Resistance Training Prescription
Schoenfeld, B. J., Grgić, J., Haun, C. T., Itagaki, T., & Helms, E. R. (2019) · Sports · doi:10.3390/sports7070177 · Cited by 36 · see citing works
Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials
Fairman, C. M., Lønbro, S., Cardaci, T. D., VanderVeen, B. N., Nilsen, T. S., & Murphy, A. E. (2021) · JCSM Rapid Communications · doi:10.1002/rco2.56 · Cited by 36 · see citing works
Protein Intake and Exercise-Induced Skeletal Muscle Hypertrophy: An Update
Deldicque, L. (2020) · Nutrients · doi:10.3390/nu12072023 · Cited by 34 · see citing works
Comparison of the effects of long-lasting static stretching and hypertrophy training on maximal strength, muscle thickness and flexibility in the plantar flexors
Warneke, K., WIRTH, K. J., Keiner, M., Lohmann, L. H., Hillebrecht, M., Brinkmann, A., Wohlann, T., & Schiemann, S. (2023) · European Journal of Applied Physiology · doi:10.1007/s00421-023-05184-6 · Cited by 35 · see citing works
Effect of Plyometric Jump Training on Skeletal Muscle Hypertrophy in Healthy Individuals: A Systematic Review With Multilevel Meta-Analysis
Arntz, F., Mkaouer, B., Markov, A., Schoenfeld, B. J., Moran, J., Ramírez‐Campillo, R., Behrens, M., Baumert, P., Erskine, R. M., Hauser, L., et al. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.888464 · Cited by 33 · see citing works
The role of exercise selection in regional Muscle Hypertrophy: A randomized controlled trial
Zabaleta-Korta, A., Fernández-Peña, E., Torres‐Unda, J., Garbisu-Hualde, A., & Santos‐Concejero, J. (2021) · Journal of Sports Sciences · doi:10.1080/02640414.2021.1929736 · Cited by 33 · see citing works
Moderate vs high-load resistance training on muscular adaptations in rats
Padilha, C. S., Cella, P. S., Ribeiro, A. S., Voltarelli, F. A., Testa, M. T. J., Marinello, P. C., Iarosz, K. C., Guirro, P. B., & Deminice, R. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116964 · Cited by 32 · see citing works
Effects of Acute and Chronic Resistance Exercise on the Skeletal Muscle Metabolome
Gehlert, S., Weinisch, P., Römisch‐Margl, W., Jaspers, R. T., Artati, A., Adamski, J., Dyar, K. A., Aussieker, T., Jacko, D., Bloch, W., et al. (2022) · Metabolites · doi:10.3390/metabo12050445 · Cited by 31 · see citing works
Effects of Chronic Static Stretching on Maximal Strength and Muscle Hypertrophy: A Systematic Review and Meta-Analysis with Meta-Regression
Warneke, K., Lohmann, L. H., Behm, D. G., WIRTH, K. J., Keiner, M., Schiemann, S., & Wilke, J. (2024) · Sports Medicine - Open · doi:10.1186/s40798-024-00706-8 · Cited by 32 · see citing works
Similar muscle hypertrophy following eight weeks of resistance training to momentary muscular failure or with repetitions-in-reserve in resistance-trained individuals
Refalo, M. C., Helms, E. R., Robinson, Z. P., Hamilton, D. L., & Fyfe, J. J. (2024) · Journal of Sports Sciences · doi:10.1080/02640414.2024.2321021 · Cited by 29 · see citing works
The Connection Between Resistance Training, Climbing Performance, and Injury Prevention
Sæterbakken, A. H., Stien, N., Pedersen, H., Langer, K., Scott, S., Michailov, M. L., Grønhaug, G., Baláš, J., Solstad, T. E. J., & Andersen, V. S. (2024) · Sports Medicine - Open · doi:10.1186/s40798-024-00677-w · Cited by 30 · see citing works
Skeletal Muscle Gene Expression in Long-Term Endurance and Resistance Trained Elderly
Bolotta, A., Filardo, G., Abruzzo, P. M., Astolfi, A., Sanctis, P. D., Martino, A. D., Höfer, C., Indio, V., Kern, H., Löfler, S., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113988 · Cited by 29 · see citing works
Resistance Exercise, Aging, Disuse, and Muscle Protein Metabolism
McKendry, J., Stokes, T., Mcleod, J. C., & Phillips, S. M. (2021) · Comprehensive physiology · doi:10.1002/j.2040-4603.2021.tb00179.x · Cited by 28 · see citing works
Aging, Osteo-Sarcopenia, and Musculoskeletal Mechano-Transduction
Leser, J. M., Harriot, A. D., Buck, H., Ward, C. W., & Stains, J. P. (2021) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2021.782848 · Cited by 28 · see citing works
Effects of Neuromuscular Electrical Stimulation and Blood Flow Restriction in Rehabilitation after Anterior Cruciate Ligament Reconstruction
Kong, D.-H., Jung, W., Yang, S.-J., Kim, J. G., Park, H., & Kim, J. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192215041 · Cited by 26 · see citing works
Adaptation of the transcriptional response to resistance exercise over 4 weeks of daily training
Viggars, M. R., Sutherland, H., Lanmüller, H., Schmoll, M., Bijak, M., & Jarvis, J. C. (2022) · The FASEB Journal · doi:10.1096/fj.202201418r · Cited by 26 · see citing works
Serine synthesis pathway enzyme PHGDH is critical for muscle cell biomass, anabolic metabolism, and mTORC1 signaling
Mäntyselkä, S., Kolari, K., Baumert, P., Ylä-Outinen, L., Kuikka, L., Lahtonen, S., Permi, P., Wackerhage, H., Kalenius, E., Kivelä, R., et al. (2024) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00151.2023 · Cited by 25 · see citing works
Resistance exercise and skeletal muscle: protein synthesis, degradation, and controversies
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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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Health Sciences › Medicine › Complementary and alternative medicine › 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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