Age-Associated Changes in MicroRNA Expression in Bone Marrow Derived Dendritic Cells

Abstract

MiRNAs have shown to regulate aging process at the level of cellular senescence, tissue aging, and lifespan of whole organism. Given that many miRNAs also function as important regulators of hematopoietic system as well as aging process, it is highly likely that miRNAs would be involved in the changes of myeloid function and differentiation during aging. Therefore, here we examine differential expression of miRNAs in aged myeloid lineage cells and assess if altered miRNA expression pattern would reflect the change of miRNA targets and related function. We demonstrated that the expressions of myelogenic miRNAs such as miR-155, miR-223, miR-146a, miR-146b, miR-132, miR-142-5p, and miR-142-3p were increased in aged bone marrow derived dendritic cells (BMDC) under normal and activated conditions. We also observed that the expressions of IRAK1 and TRAF6, the targets of miR-146a, and DC-SIGN, a target of miR-155 were diminished while miR-146a and miR-155 were augmented during aging. In addition, we found that the production of pro-inflammatory cytokines, which is mediated by the activation of NFkB pathway via IRAK1 and TRAF6, was greatly reduced in aged BMDC. Taken together, our data reveal that age-associated changes occur in miRNA expression in BMDC, and this altered miRNA expression affects miRNA target expression and compromises BMDC function such as cytokine production during aging.