Co-Localization of Macrophage Inhibitory Factor and Nix in Skeletal Muscle of the Aged Male Interleukin 10 Null Mouse

Chronic inflammation is associated with muscle weakness and frailty in older adults. The antagonistic cross-talk between macrophage migration inhibitory factor (Mif), an anti-apoptotic cytokine and NIP3-like protein X (Nix), a pro-apoptotic mitochondrial protein, may play a role in mitochondrial free radical homeostasis and inflammatory myopathies. We examined Nix-Mif interaction in inflammation and aging using young and old, IL-10tm/tm (a rodent model of chronic inflammation) and C57BL/6 mice. In this study, we observed that Nix and Mif were co-localized in skeletal muscles of aged and inflamed mice. We show an inflammation- and age-related association between Nix and Mif gene expression, with the strongest positive correlation observed in old IL-10tm/tm skeletal muscles. The IL-10tm/tm skeletal muscles also had the highest levels of oxidative stress damage. These observations suggest that Nix-Mif cross-talk may play a role in the interface between chronic inflammation and oxidative stress in aging skeletal muscles.