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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  Mir146b  as a microRNA whose expression progressively and unidirectionally declined with age in thioglycollate-elicited murine macrophages.  Mir146b  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  Mir146b- deficient macrophages. Identification of  Mir146b  as a potential regulator of macrophage aging provides novel insights into immune dysfunction associated with aging.

Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages