Delineating the relationship between immune system aging and myogenesis in muscle repair.
Recruited immune cells play a critical role in muscle repair, in part by interacting with local stem cell populations to regulate muscle regeneration. How aging affects their communication during myogenesis is unclear. Here, we investigate how aging impacts the cellular function of these two cell types after muscle injury during normal aging or after immune rejuvenation using a young to old (Y-O) or old to old (O-O) bone marrow (BM) transplant model. We found that skeletal muscle from old mice (20 months) exhibited elevated basal inflammation and possessed fewer satellite cells compared with young mice (3 months). After cardiotoxin muscle injury (CTX), old mice exhibited a blunted inflammatory response compared with young mice and enhanced M2 macrophage recruitment and IL-10 expression. Temporal immune and cytokine responses of old mice were partially restored to a young phenotype following reconstitution with young cells (Y-O chimeras). Improved immune responses in Y-O chimeras were associated with greater satellite cell proliferation compared with O-O chimeras. To identify how immune cell aging affects myoblast function, conditioned media (CM) from activated young or old macrophages was applied to cultured C2C12 myoblasts. CM from young macrophages inhibited myogenesis while CM from old macrophages reduced proliferation. These functional differences coincided with age-related differences in macrophage cytokine expression. Together, this study examines the infiltration and proliferation of immune cells and satellite cells after injury in the context of aging and, using BM chimeras, demonstrates that young immune cells retain cell autonomy in an old host to increase satellite cell proliferation.
['Tobin|Stephanie W|SW|', 'Alibhai|Faisal J|FJ|', 'Wlodarek|Lukasz|L|', 'Yeganeh|Azadeh|A|', 'Millar|Sean|S|', 'Wu|Jun|J|', 'Li|Shu-Hong|SH|', 'Weisel|Richard D|RD|', 'Li|Ren-Ke|RK|0000-0002-2584-060X']
D000818:Animals D054715:Cardiotoxins D016922:Cellular Senescence D051379:Mice D024510:Muscle Development D032496:Satellite Cells, Skeletal Muscle
aging myogenesis inflammation satellite cells bone marrow transplant