Epigenomic analysis of primary immune cells from young and old animals

National Institute On Aging

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Abstract

Tissue-resident macrophages play a major role in tissue homeostasis. They have also been associated with age-related pathological inflammation. It is important to understand how macrophages are epigenetically and functionally altered during aging and in age-dependent chronic inflammation. To address this question in neuroinflammation, we analyzed the functional capacity of microglia, the brain-resident macrophages, from a mouse model of Alzheimer’s disease. We also investigated NF-κB signaling dynamics, Aβ phagocytosis, morphological features, responses to innate stimuli, and DNA compaction of microglia isolated from young or old mice of 5xFAD in the NF-κB endogenous knock-in reporter background. Microglia from 5xFAD mice had a larger proportion of c-Rel expressing cells and showed a defect in amyloid beta uptake. We are analyzing the transcriptomic changes using scRNA-seq in microglia and recruited immune cells in the brain of old WT and 5xFAD mice.