Myeloid Cell-Derived Tumor Necrosis Factor-Alpha Promotes Sarcopenia and Regulates Muscle Cell Fusion with Aging Muscle Fibers
Open accessAbstract
Sarcopenia is age‐related muscle wasting that lacks effective therapeutic interventions. We found that systemic ablation of tumor necrosis factor‐α (TNF‐α) prevented sarcopenia and prevented age‐related change in muscle fiber phenotype. Furthermore,TNF‐α ablation reduced the number of satellite cells in aging muscle and promoted muscle cell fusion in vivo and in vitro. Because CD68+ macrophages are important sources of TNF‐α and the number of CD68+ macrophages increases in aging muscle, we tested whether macrophage‐derived TNF‐α affects myogenesis. Media conditioned by TNF‐α‐null macrophages increased muscle cell fusion in vitro, compared to media conditioned by wild‐type macrophages. In addition, transplantation of bone marrow cells from wild‐type mice into TNF‐α‐null recipients increased satellite cell numbers and reduced numbers of centrally nucleated myofibers, indicating that myeloid cell‐secreted TNF‐α reduces muscle cell fusion. Transplanting bone marrow cells from wild‐type mice into TNF‐α‐null recipients also increased sarcopenia, although transplantation did not restore the age‐related change in muscle fiber phenotype. Collectively, we show that myeloid cell‐derived TNF‐α contributes to muscle aging by affecting sarcopenia and muscle cell fusion with aging muscle fibers. Our findings also show that TNF‐α that is intrinsic to muscle and TNF‐α secreted by immune cells work together to influence muscle aging.
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TNF-α secreted by myeloid cells (CD68+ macrophages) inhibits myotube fusion in vivo.
“TNF-α secreted by myeloid cells (CD68+ macrophages) inhibits myotubes fusion in vivo [34]”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [34]
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Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting
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“TNF-α secreted by myeloid cells (CD68+ macrophages) inhibits myotubes fusion in vivo [34], supporting its catabolic role.”
BackgroundPharmacological blockade of TNFα prevents sarcopenia and prolongs survival in aging mice
Sciorati, C., Gamberale, R., Monno, A., Citterio, L., Lanzani, C., De Lorenzo, R., Ramirez, G. A., Esposito, A., Manunta, P., Manfredi, A. A., et al. (2020) · Aging · doi:10.18632/aging.202200 · Cited by 79 · see citing works
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Self-citation
- Authors
- Wang, Y., Welc, S. S., Wehling‐Henricks, M., & Tidball, J. G.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Tidball, James G.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2018-09-06
- Volume
- 17
- Issue
- 6
- Pages
- e12828-e12828
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC6260911
- OpenAlex
- W2891663411
- Cited by
- 80
- References
- 12
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 8 · 2023: 13 · 2022: 12 · 2021: 15 · 2020: 7 · 2019: 2
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR054451)
- National Institute on Aging (R01AR054451, RO1AG041147)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- sarcopenia, TNF-α, muscle aging, muscle cell fusion, satellite cells, myeloid cells, CD68+ macrophages, muscle fiber phenotype, myogenesis, bone marrow transplantation
- MeSH terms
- Aging, Animals, Bone Marrow Cells, Cell Fusion, Macrophages, Mice, Inbred C57BL, Mutation, Regeneration, Tumor Necrosis Factor-alpha, Bone Marrow Transplantation, Gene Deletion, Muscle Fibers, Skeletal, Myeloid Cells, Satellite Cells, Skeletal Muscle, Sarcopenia
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