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

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 unbiase...

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Veröffentlicht in:eLife 2021-08, Vol.10
Hauptverfasser: Santeford, Andrea, Lee, Aaron Y, Sene, Abdoulaye, Hassman, Lynn M, Sergushichev, Alexey A, Loginicheva, Ekaterina, Artyomov, Maxim N, Ruzycki, Philip A, Apte, Rajendra S
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Sprache:eng
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Zusammenfassung: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 as a microRNA whose expression progressively and unidirectionally declined with age in thioglycollate-elicited murine macrophages. 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 deficient macrophages. Identification of as a potential regulator of macrophage aging provides novel insights into immune dysfunction associated with aging.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.66703