| First Author | Wang Y | Year | 2018 |
| Journal | Aging Cell | Volume | 17 |
| Issue | 6 | Pages | e12828 |
| PubMed ID | 30256507 | Mgi Jnum | J:267350 |
| Mgi Id | MGI:6259009 | Doi | 10.1111/acel.12828 |
| Citation | Wang Y, et al. (2018) Myeloid cell-derived tumor necrosis factor-alpha promotes sarcopenia and regulates muscle cell fusion with aging muscle fibers. Aging Cell 17(6):e12828 |
| abstractText | Sarcopenia is age-related muscle wasting that lacks effective therapeutic interventions. We found that systemic ablation of tumor necrosis factor-alpha (TNF-alpha) prevented sarcopenia and prevented age-related change in muscle fiber phenotype. Furthermore, TNF-alpha 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-alpha and the number of CD68+ macrophages increases in aging muscle, we tested whether macrophage-derived TNF-alpha affects myogenesis. Media conditioned by TNF-alpha-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-alpha-null recipients increased satellite cell numbers and reduced numbers of centrally nucleated myofibers, indicating that myeloid cell-secreted TNF-alpha reduces muscle cell fusion. Transplanting bone marrow cells from wild-type mice into TNF-alpha-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-alpha contributes to muscle aging by affecting sarcopenia and muscle cell fusion with aging muscle fibers. Our findings also show that TNF-alpha that is intrinsic to muscle and TNF-alpha secreted by immune cells work together to influence muscle aging. |
