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Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, Akt/mTOR and Akt/FOXO3a signaling in aged rats
Abstract
Resistance exercise training (RET) remains the most effective treatment for the loss of muscle mass and strength in elderly people. However, the underlying cellular and molecular mechanisms are not well understood. Recent evidence suggests that autophagic signaling is altered in aged skeletal muscles. This study aimed to investigate if RET affects IGF-1 and its receptors, the Akt/mTOR, and Akt/FOXO3a signaling pathways and regulates autophagy and apoptosis in the gastrocnemius muscles of 18-20 month old rats. The results showed that 9 weeks of RET prevented the loss of muscle mass and improved muscle strength, accompanied by reduced LC3-II/LC3-I ratio, reduced p62 protein levels, and increased levels of autophagy regulatory proteins, including Beclin 1, Atg5/12, Atg7, and the lysosomal enzyme cathepsin L. RET also reduced cytochrome c level in the cytosol but increased its level in mitochondrial fraction, and inhibited cleaved caspase 3 production and apoptosis. Furthermore, RET upregulated the expression of IGF-1 and its receptors but downregulated the phosphorylation of Akt and mTOR. In addition, RET upregulated the expression of total AMPK, phosphorylated AMPK, and FOXO3a. Taken together, these results suggest that the benefits of RET are associated with increased autophagy activity and reduced apoptosis of muscle cells by modulating IGF-1 and its receptors, the Akt/mTOR and Akt/FOXO3a signaling pathways in aged skeletal muscles.
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“Resistance exercise (ladder-climbing training, 3 days/week for 9 weeks) has been shown to enhance autophagy and reduce apoptosis in the skeletal muscle of older rats by modulating insulin-like growth factor-1 (IGF-1) and its receptors, as well as the downregulation of Akt/mTOR and Akt/FOXO3a signaling pathways [41].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [41]
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Metadata
- Authors
- Luo, L., Lu, A.-M., Wang, Y., Hong, A., Chen, Y., Hu, J., Li, X., & Qin, Z.-H.
- Affiliations
- Soochow University (CN)
- Suzhou Vocational Health College (CN)
- Corresponding author
- Qin, Zheng-Hong
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 48
- Issue
- 4
- Pages
- 427-436
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W1985127050
- Cited by
- 192
- References
- 69
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 12 · 2023: 9 · 2022: 15 · 2021: 26 · 2020: 14 · 2019: 11 · 2018: 16 · 2017: 16 · 2016: 13 · 2015: 20 · 2014: 12 · 2013: 5
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- resistance training, autophagy, apoptosis, skeletal muscle aging, insulin-like growth factor I, IGF-1 receptor, Akt/mTOR signaling, AMPK, gastrocnemius, sarcopenia, muscle mass and strength, LC3, p62, Beclin-1, cathepsin L, cytochrome c, caspase-3, aged rats
- MeSH terms
- Forkhead Box Protein O3, Aging, Animals, Autophagy, Insulin-Like Growth Factor I, Signal Transduction, Rats, Sprague-Dawley, Apoptosis, Receptor, IGF Type 1, Muscle Fibers, Skeletal, Models, Animal, Proto-Oncogene Proteins c-akt, Rats, Forkhead Transcription Factors, Metabolic Networks and Pathways, Resistance Training, TOR Serine-Threonine Kinases
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