Myeloid Cell Responses to Contraction-induced Injury Differ in Muscles of Young and Old Mice.

Myeloid cells play a critical role in regulating muscle degeneration and regeneration. Thus, alterations with aging in the myeloid cell response to muscle damage may affect the progression of the injury in old animals. We hypothesized that neutrophil levels remain elevated and that macrophage accumulation is reduced or delayed in injured muscles of old compared with young animals. Muscles of young and old mice were injured with lengthening contractions and analyzed 2 or 5 days later. Regardless of age, neutrophil (Gr-1+) and macrophage (CD68+) content increased dramatically by Day 2. Between 2 and 5 days, macrophages increased further, whereas neutrophils declined to a level that in old muscles was not different from uninjured controls. M2 macrophages (CD163+) also increased between 2 and 5 days, reaching higher levels in muscles of old mice than in young mice. Although no evidence of persisting neutrophils or reduced M2 accumulation in old muscle was found, total macrophage accumulation was lower in old mice. Furthermore, messenger RNA levels showed age-related changes in macrophage-associated genes that may indicate alterations in myeloid cell function. Overall, differences between muscles of old and young mice in the inflammatory response through the early stages of injury may contribute to defects in muscle regeneration.