National Institute on Aging 5K00AG079813-05

Reversing age-related epigenetic changes and characterizing microglia heterogeneity in obesity and aging

This award funds research on reversing age-related epigenetic changes in microglia and characterizing their heterogeneity in obesity and aging, using advanced omics and single-cell technologies, with training goals to develop expertise in anti-aging and obesity models and bioinformatics.

Description

Neuroinflammation is a hallmark of brain aging that may contribute to declines in function and neurodegenerative diseases. As the resident macrophage of the brain, microglia are crucial to brain maintenance but have been demonstrated to take on pro-inflammatory phenotypes with aging. The proposed research will examine the role of microglia-specific epigenetic mechanisms in aging and determine the effects of obesity and aging interactions on microglia phenotypic heterogeneity. We will determine whether aberrant age-related microglia-specific epigenetic patterns can be reversed by heterochronic plasma approaches. Additionally, we will determine how microglia subpopulations differ with age and obesity at a single-cell level with special interests in lipid-droplet-accumulating microglia (LDAM). The goals of the training are to: 1) obtain a strong knowledge and foundation in animal and nutritional models of anti-aging and obesity 2) gain hands-on experience in technologies and bioinformatic skills needed for various omics approaches in specific hippocampal cells and at a single-cell level 3) apply these skills to achieve the research aims outlined in this proposal and 4) improve oral and presentation skills, manuscript and grant writing to enable a transition to independence.

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