Effect of aging on microRNAs and regulation of pathogen recognition receptors

Abstract

Immunosenescence is the multifactorial age-associated immune deteriorization that leads to increased susceptibility to infections and decreased responses to vaccines. Recent studies have shown a fundamental role for microRNAs (miRNAs) in regulating immune responses, and nearly all the miRNAs involved in immune regulation show modulation during aging. Aging-associated miRNAs are largely negative regulators of the immune innate response and target central nodes of aging-associated networks, in particular, NF-κB, the downstream effector of TLR signals that leads to induction of proinflammatory responses. Multiple miRNAs have been reported to share similar regulatory activity. Here we review miRNA regulation of human innate immune recognition in aging, including both activation and resolution of inflammation, critical issues in detection, and areas of active investigation into our understanding of immunosenescence.

miR-206 modulates lipopolysaccharide-mediated inflammatory cytokine production in human astrocytes

“…Astrocytes are the most abundant cell type in the central nervous system, where they play important roles in promoting localized inflammation [3]. Multiple miRNAs regulate human innate immune signaling pathways and result in inflammatory responses [31,32], but the roles of miRNAs in astrocyte-derived inflammatory responses are not fully understood. In this study, we showed that astrocytes express high levels of miR-206 in LPS-treated U251 cells.…”

The Experimental Pathology at Ancona: 50 Years of Exciting and Pioneering Research on Human Pathology

“…Based on these hypotheses and the integrated and complementary expertise of the General Pathology team, an integrated series of studies was conducted to test the ability of miRNA/cf-DNA signatures and their shuttles to be robust predictive/prognostic biomarkers of the most common ARDs, i.e. type 2 diabetes (T2DM), cardiovascular disease (CVD), tumors and neurodegenerative diseases [46]. We analysed existing sample collections from a number of case-control studies nested in cohort studies and longitudinal studies, including healthy individuals of different ages ranging from healthy young subjects to centenarians and their offspring, and non-healthy individuals ranging from obese adults to patients affected by CVD [47,49,50], T2DM [45,58], and neurodegenerative diseases (AD, NAD).…”

Paradoxical changes in innate immunity in aging: recent progress and new directions

“…Aging-associated miRNAs are largely negative regulators of the immune innate response and target, in particular, NF-kB, a downstream effector of TLR signals that leads to induction of proinflammatory responses. In innate immune cells, miR-146, whose expression is increased in aging, represses endothelial cell and macrophage activation and cytokine production by inhibiting NF-kB proinflammatory pathways [60][61][62][63]. The age-related up-regulation of certain miRNAs with potential anti-inflammatory activity, such as miR-21, miR-146, miR-223, and miR-29, may be a compensatory mechanism enacted by senescent and/or activated immune cells to restrain the excessive proinflammatory activity associated with normal aging [64,65].…”