Aging is associated with an altered macrophage response during human skeletal muscle regeneration

Skeletal muscle injury in aged rodents is characterized by an asynchronous infiltration of pro- and anti-inflammatory macrophage waves, leading to improper and incomplete regeneration. It is unclear whether this aberration also occurs in aged human muscle. In this study, we quantified the macrophage responses in a human model of muscle damage and regeneration induced by electrical stimulation in 7 young and 21 older adults. At baseline, total resident macrophage (CD68⁺/DAPI⁺) content was not different between young and old subjects, but pro-inflammatory (CD206^-/CD68⁺/DAPI⁺) macrophage content was lower in the old. Following damage, muscle Infiltration of CD206^-/CD68⁺/DAPI⁺ macrophages was lower in old relative to young subjects. Further, only the increase in CD206^-/CD68⁺ macrophages correlated with the change in muscle satellite cell content. Our data show that older individuals have a compromised macrophage response during muscle regeneration, pointing to an altered inflammatory response as a potential mechanism for reduced muscle regenerative efficacy in aged humans.