mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle
Abstract
Resistance training-induced muscle anabolism and subsequent hypertrophy occur most rapidly during the early phase of training and become progressively slower over time. Currently, little is known about the intracellular signaling mechanisms underlying changes in the sensitivity of muscles to training stimuli. We investigated the changes in the exercise-induced phosphorylation of hypertrophic signaling proteins during chronic resistance training and subsequent detraining. Male rats were divided into four groups: 1 bout (1B), 12 bouts (12B), 18 bouts (18B), and detraining (DT). In the DT group, rats were subjected to 12 exercise sessions, detrained for 12 days, and then were subjected to 1 exercise session before being killed. Isometric training consisted of maximum isometric contraction, which was produced by percutaneous electrical stimulation of the gastrocnemius muscle every other day. Muscles were removed 24 h after the final exercise session. Levels of total and phosphorylated p70S6K, 4E-BP1, rpS6, and p90RSK levels were measured, and phosphorylation of p70S6K, rpS6, and p90RSK was elevated in the 1B group compared with control muscle (CON) after acute resistance exercise, whereas repeated bouts of exercise suppressed those phosphorylation in both 12B and 18B groups. Interestingly, these phosphorylation levels were restored after 12 days of detraining in the DT group. On the contrary, phosphorylation of 4E-BP1 was not altered with chronic training and detraining, indicating that, with chronic resistance training, anabolic signaling becomes less sensitive to resistance exercise stimuli but is restored after a short detraining period.
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In trained individuals, repeated exposure to similar stimuli may attenuate the transcriptional response associated with ribosome biogenesis, making further increases in capacity more difficult to achieve.
“In trained individuals, repeated exposure to similar stimuli may attenuate the transcriptional response associated with ribosome biogenesis, making further increases in capacity more difficult to achieve”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [65]
Initial massive spikes in ribosomal gene transcription in untrained individuals following a novel mechanical stimulus are severely blunted after several weeks of continuous training.
“Ogasawara et al. observed that the initial, massive spikes in ribosomal gene transcription seen in untrained individuals following a novel mechanical stimulus are severely blunted after several weeks of continuous training [65].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [65]
As the muscle fiber adapts and the initial structural bottleneck widens, an identical mechanical load relative to the new 1RM fails to elicit the same magnitude of 45S pre-rRNA expression.
“As the muscle fiber adapts and the initial structural bottleneck widens, an identical mechanical load (relative to the new 1RM) fails to elicit the same magnitude of 45S pre-rRNA expression [65,89].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [65]
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“As the muscle fiber adapts and the initial structural bottleneck widens, an identical mechanical load (relative to the new 1RM) fails to elicit the same magnitude of 45S pre-rRNA expression [65,89].”
- Authors
- Ogasawara, R., Kobayashi, K., Tsutaki, A., Lee, K., Abe, T., Fujita, S., Nakazato, K., & Ishii, N.
- Affiliations
- Ritsumeikan University (JP)
- Graduate School of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan; and
- Nippon Sport Science University (JP)
- University of Mississippi (US)
- The University of Tokyo (JP)
- Corresponding author
- Ogasawara, Riki
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2013-04-01
- Volume
- 114
- Issue
- 7
- Pages
- 934-940
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2115471419
- Cited by
- 138
- References
- 45
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 9 · 2023: 8 · 2022: 14 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 16 · 2015: 16 · 2014: 9 · 2013: 5
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22300210, 22680050)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Keywords
- mTOR signaling, resistance training, detraining, skeletal muscle hypertrophy, muscle anabolism, p70S6K, 4E-BP1, ribosomal protein S6, p90RSK, protein phosphorylation, acute resistance exercise, gastrocnemius, electrical stimulation
- MeSH terms
- Animals, Physical Exertion, Isometric Contraction, Male, Muscle Proteins, Phosphorylation, Physical Endurance, Rats, Sprague-Dawley, MAP Kinase Signaling System, Rats, Resistance Training, TOR Serine-Threonine Kinases
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