Loss of <i>Mir146b</i> with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages.

Abstract

Macrophages undergo programmatic changes with age, leading to altered cytokine polarization and immune dysfunction, shifting these critical immune cells from protective sentinels to disease promoters. The molecular mechanisms underlying macrophage inflammaging are poorly understood. Using an unbiased RNA sequencing (RNA-seq) approach, we identified <i>Mir146b</i> as a microRNA whose expression progressively and unidirectionally declined with age in thioglycollate-elicited murine macrophages. <i>Mir146b</i> deficiency led to altered macrophage cytokine expression and reduced mitochondrial metabolic activity, two hallmarks of cellular aging. Single-cell RNA-seq identified patterns of altered inflammation and interferon gamma signaling in <i>Mir146b-</i>deficient macrophages. Identification of <i>Mir146b</i> as a potential regulator of macrophage aging provides novel insights into immune dysfunction associated with aging.