Benefits of higher resistance-training volume are related to ribosome biogenesis
Open accessAbstract
Key points For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross‐sectional area, strength and type II fibre‐type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Out of 34 participants, thirteen displayed clear benefit of MOD on muscle hypertrophy and sixteen showed clear benefit of MOD on muscle strength gains. This coincided with greater total RNA accumulation in the early phase of the training period, suggesting that ribosomal biogenesis regulates the dose–response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose‐dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis. Abstract Resistance‐exercise volume is a determinant of training outcomes. However not all individuals respond in a dose‐dependent fashion. In this study, 34 healthy individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3) years) performed moderate‐ (3 sets per exercise, MOD) and low‐volume (1 set, LOW) resistance training in a contralateral fashion for 12 weeks (2–3 sessions per week). Muscle cross‐sectional area (CSA) and strength were assessed at Weeks 0 and 12, along with biopsy sampling (m. vastus lateralis). Muscle biopsies were also sampled before and 1 h after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4–7.7% difference, all P < 0.05. This coincided with greater reductions in type IIX fibres from Week 0 to Week 12 (MOD, −4.6 percentage points; LOW −3.2 percentage points), greater phosphorylation of S6‐kinase 1 (p85 S6K1 Thr412 , 19%; p70 S6K1 Thr389 , 58%) and ribosomal protein S6 Ser235/236 (37%), greater rested‐state total RNA (8.8%) and greater exercise‐induced c‐Myc mRNA expression (25%; Week 2, all P < 0.05). Thirteen and sixteen participants, respectively, displayed clear benefits in response to MOD on muscle hypertrophy and strength. Benefits were associated with greater accumulation of total RNA at Week 2 in the MOD leg, with every 1% difference increasing the odds of MOD benefit by 7.0% ( P = 0.005) and 9.8% ( P = 0.002). In conclusion, MOD led to greater functional and biological adaptations than LOW. Associations between dose‐dependent total RNA accumulation and increases in muscle mass and strength point to ribosome biogenesis as a determinant of dose‐dependent training responses.
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In a within-subject human trial comparing low-volume (1 set) versus high-volume (3 sets) resistance exercise, both protocols activated mTORC1 equivalently, but only the high-volume protocol elicited sustained massive upregulation of total RNA and mature rRNA species over the ensuing weeks.
“Their data revealed that while both protocols activated mTORC1 equivalently, only the high-volume protocol elicited a sustained, massive upregulation of total RNA and mature rRNA species over the ensuing weeks.”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
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Experimental — accuracy not yet measuredEarly accumulation of total RNA and mature rRNA species during the initial weeks of mechanical overload obligatorily precedes phenotypic hypertrophy.
“the early accumulation of total RNA and mature rRNA species during the initial weeks of mechanical overload obligatorily precedes phenotypic hypertrophy”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
The Results report greater total RNA and mature rRNA abundance after two weeks of higher-volume resistance training. The Discussion describes early ribosomal accumulation as a predictor of subsequent *additional* growth with higher-volume training, but does not establish that RNA accumulation obligatorily precedes all phenotypic hypertrophy. Page numbers were not provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA statistically significant accumulation of bulk total RNA after a standardized mechanical stimulus is robustly interpreted as expansion of the mature rRNA pool and widening of the translational capacity bottleneck.
“Consequently, a statistically significant accumulation of bulk total RNA following a standardized mechanical stimulus, such as exhaustive resistance exercise, is robustly interpreted as an expansion of the mature rRNA pool and, thus, a definitive widening of the translational capacity bottleneck [33,35].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
The Results section (page unavailable) reports that after two weeks of resistance training, greater total RNA abundance accompanied greater abundance of mature rRNA transcripts. The Introduction describes increased translational capacity as a suggested explanation for muscle growth, not a definitive consequence of a total-RNA increase. The paper does not establish that bulk RNA accumulation after a single standardized exercise stimulus can be robustly interpreted as mature-rRNA expansion or a definitive widening of translational capacity. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe translational capacity bottleneck possesses a high activation threshold: a minimal mechanical volume is required to sustain the Pol I transcription spark long enough to outpace the basal decay rate of existing ribosomes.
“This strongly indicates that the translational capacity bottleneck possesses a high activation threshold: a minimal mechanical volume is strictly required to sustain the Pol I transcription spark long enough to outpace the basal decay rate of existing ribosomes [35,87,88].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
The volume-dependent regulation section (page unavailable) reports greater ribosomal RNA accumulation after multiple-set than single-set training, supporting a relationship between training volume and translational capacity. It does not establish a high activation threshold, a strictly required minimum volume, sustained Pol I transcription, or a need to outpace basal ribosome decay. It also reports an increase in 45S pre-rRNA in the single-set condition. (LLM, conf=0.88)
Experimental — accuracy not yet measuredWeekly volume is the training variable with the clearest direct human support in relation to ribosome biogenesis.
“Among training variables, weekly volume remains the factor with the clearest direct human support in relation to ribosome biogenesis.”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
The Participants and study overview and Resistance-exercise training protocol sections describe a direct human comparison of one versus three sets per exercise across a repeated weekly programme. The Volume-dependent regulation of mTOR signalling and ribosomal biogenesis section reports greater early ribosomal RNA abundance with multiple sets. The paper does not compare the strength of evidence for volume with that for other training variables, so it does not establish that weekly volume has the clearest support. (LLM, conf=0.85)
Experimental — accuracy not yet measured
The ribosomal-specific literature reviewed above more directly implicates repeated mechanical loading, recoverable training volume, training continuity, blood-flow restriction under appropriate conditions, and the timing of concurrent endurance exercise as practical modulators of ribosome-related outcomes.
“the ribosomal-specific literature reviewed above more directly implicates repeated mechanical loading, recoverable training volume, training continuity, blood-flow restriction under appropriate conditions, and the timing of concurrent endurance exercise as practical modulators of ribosome-related outcomes [35,141,155,157]”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
The Abstract and the section ‘Volume-dependent regulation of mTOR signalling and ribosomal biogenesis’ (pages not supplied) link repeated resistance training and higher training volume to ribosome-related outcomes. The paper does not establish recoverable volume as a threshold or address training continuity, blood-flow restriction, or the timing of concurrent endurance exercise as modulators. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEarly-phase molecular evidence suggests that reaching higher volume may help ensure the anabolic signal exceeds the natural turnover of pre-existing ribosomes.
“Nonetheless, early-phase molecular evidence suggests that reaching this higher volume may help ensure that the anabolic signal exceeds the natural turnover of pre-existing ribosomes [35].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
The Results (section ‘Volume-dependent regulation of mTOR signalling and ribosomal biogenesis’; page unavailable) report greater total RNA and mature rRNA abundance after two weeks of multiple-set than single-set training. The Discussion links early volume-dependent ribosomal accumulation to later gains. The paper does not establish that a higher-volume anabolic signal exceeds the natural turnover of pre-existing ribosomes; that proposed mechanism is not supported by the cited evidence. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn Hammarström et al.'s unilateral resistance-training study, participants who benefited most from the higher-volume condition also showed the greatest early increases in total RNA.
“In the unilateral resistance-training study by Hammarström et al., participants who benefited most from the higher-volume condition were also those who showed the greatest early increases in total RNA”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
Ribosome accretion may help explain the superior adaptation sometimes seen with greater set volume.
“suggesting that ribosome accretion may help explain the superior adaptation sometimes seen with greater set volume [35].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
High-confidence direct effects are restricted to the mechanical-load-dependent training variables (volume, proximity to failure, blood-flow restriction) for which human ribosomal-end measurements are available.
“High-confidence direct effects are restricted to the mechanical-load-dependent training variables (volume, proximity to failure, blood-flow restriction) for which human ribosomal-end measurements are available [35,145,155]”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [35]
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Self-citationPhysiological adaptations to resistance exercise as a function of age
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Self-citationRibonucleic Acids Associated with Myofibrils*
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Andersen (2000) · doi:10.1002/1097-4598(200007)23:7
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- Authors
- Hammarström, D., Øfsteng, S., Koll, L., Hanestadhaugen, M., Hollan, I., Apró, W., Whist, J. E., Blomstrand, E., Rønnestad, B. R., & Ellefsen, S.
- Affiliations
- University of Inland Norway (NO)
- Innlandet Hospital Trust (NO)
- Brigham and Women's Hospital (US)
- Swedish School of Sport and Health Sciences (SE)
- Corresponding author
- Hammarström, Daniel
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2020-01-15
- Volume
- 598
- Issue
- 3
- Pages
- 543-565
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- OpenAlex
- W2992335857
- Cited by
- 99
- References
- 86
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 13 · 2023: 11 · 2022: 22 · 2021: 17 · 2020: 14
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Physiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Sykehuset Innlandet HF (150282)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- resistance training volume, ribosome biogenesis, muscle hypertrophy, muscle strength, dose-response relationship, S6K1 phosphorylation, ribosomal protein S6, RNA accumulation, muscle cross-sectional area, untrained individuals, vastus lateralis
- MeSH terms
- Female, Humans, Male, Ribosomes, Exercise, Muscle, Skeletal, Muscle Strength, Resistance Training
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