Aging is associated with an altered macrophage response during human skeletal muscle regeneration
Mohadeseh Ahmadi, Anders Karlsen, Jack Mehling, Casper Soendenbroe, Abigail L. Mackey, Robert D. Hyldahl
Abstract
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.