Antioxidant Apigenin Relieves Age-Related Muscle Atrophy by Inhibiting Oxidative Stress and Hyperactive Mitophagy and Apoptosis in Skeletal Muscle of Mice
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Skeletal muscle atrophy in the aged causes loss in muscle mass and functions. Naturally occurring antioxidant flavonoid apigenin is able to ameliorate obesity- and denervation-induced muscle atrophies, but its effects on age-related muscle atrophy remain unknown. We hypothesized that apigenin can relieve muscle atrophy in aged mice, probably through special effects on reactive oxygen species and enzymes with antioxidant functions. For the male mice of the study, apigenin showed significant dose-dependent effects in relieving aging-related muscle atrophy according to results of frailty index as indicator of frailty associated with aging, grip strength, and running distance. Apigenin also improved myofiber size and morphological features and increased mitochondria number and volume, as manifested by succinate dehydrogenase staining and transmission electron microscopy. Our tests also suggested that apigenin promoted activities of enzymes such as superoxide dismutase and glutathione peroxidase for antioxidation and those for aerobic respiration such as mitochondrial respiratory enzyme complexes I, II, and IV, increased ATP, and enhanced expression of genes such as peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A, nuclear respiratory factor-1, and ATP5B involved in mitochondrial biogenesis. The data also suggested that apigenin inhibited Bcl-2/adenovirus E1B 19kD-interacting protein 3 and DNA fragmentation as indicators of mitophagy and apoptosis in aged mice with skeletal muscle atrophy. Together, the results suggest that apigenin relieves age-related skeletal muscle atrophy through reducing oxidative stress and inhibiting hyperactive autophagy and apoptosis.
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- Authors
- Wang, D., Yang, Y., Zou, X., Zhang, J., Zheng, Z., & Wang, Z.
- Affiliations
- Southern Medical University Shenzhen Hospital (CN)
- Guangdong Medical College (CN)
- Corresponding author
- Wang, Dongtao
- Venue
- The Journals of Gerontology Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-08-28
- Volume
- 75
- Issue
- 11
- Pages
- 2081-2088
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC7566467
- OpenAlex
- W3081708729
- Cited by
- 87
- References
- 52
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 19 · 2023: 22 · 2022: 12 · 2021: 6
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journals of Gerontology Series A (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81874394)
- Science and Technology Planning Project of Shenzhen Municipality (JCYJ20180306174037820)
- Science and Technology Planning Project of Guangdong Province (2016A020226032, 2017A020213008)
- Guangdong Basic and Applied Basic Research Foundation (2020A1515010058)
- Administration of Traditional Chinese Medicine of Guangdong Province (20180326103756, 20190405225223)
- Shenzhen Key Medical Discipline Construction Fund (SZXK074)
- Innovation and Practice Base for Postdoctoral Researchers of Guangxi International Zhuang Medicine Hospital
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- apigenin, age-related muscle loss, skeletal muscle aging, oxidative stress, mitophagy, apoptosis, mitochondrial biogenesis, superoxide dismutase, glutathione peroxidase, mitochondrial function, frailty, grip strength, Bcl-2/Bax, PGC-1α, TFAM, NRF1, ATP5B
- MeSH terms
- Frailty, Animals, Male, Membrane Potentials, Mice, Inbred C57BL, Mitochondria, Muscular Atrophy, Oxygen Consumption, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Apigenin, Mice, DNA Copy Number Variations, Mitophagy
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