Loss of Mir146b 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-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 sequencing 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.

Regulatory RNAs in immunosenescence

“…93 A recent mice study clarified that the expression levels of miR-146b in thioglycolate-elicited macrophages were reduced during aging and that may contribute to age-associated inflammation and cellular dysfunction. 94…”

“…The regulatory role of MiRNAs in sequential stages of T cell development is well documented. [94][95][96][97] MiR-181a plays a major role in both positive and negative selection of double positive cells during thymic development of immature T cells. Indeed, miR-181a is involved in the clonal deletion of autoreactive T cells via modulating the TCR signaling threshold and survival of low-affinity peptide-specific T cells.…”

“…It has been indicated that miR‐150 is upregulated in aged murine peritoneal, splenic and BM‐derived macrophages and induces differentiation of aged macrophages toward disease‐prone phenotype 93 . A recent mice study clarified that the expression levels of miR‐146b in thioglycolate‐elicited macrophages were reduced during aging and that may contribute to age‐associated inflammation and cellular dysfunction 94 …”

“…The regulatory role of MiRNAs in sequential stages of T cell development is well documented 94–97 . MiR‐181a plays a major role in both positive and negative selection of double positive cells during thymic development of immature T cells.…”

Hypertrophic cardiomyopathy in MYBPC3 carriers in aging

“…Upregulated during senescence [274] ; lower expression levels in bronchial tissues of elderly [275] and aged macrophages [276] ; downregulated in perivascular adipose tissue of aged mice with cold stimulus [277] ; upregulated in aging heart [278] 4 miR-208b…”