While you inherit your genes from your mother and father, how these genes are used is controlled, in part, by something called the epigenome. This epigenome is how your genome is organized and packaged in a cell, with some parts being ready for use and other parts stored away. The human genome in every cell is about 6.5 ft long, which means it has to be very organized in order to fit. We characterize how the brain epigenome changes with aging and the influences of sex, diet, and other environmental factors on how the epigenome changes. We use a combination of transgenic mouse approaches, next-generation sequencing, and bioinformatic methods to understand epigenetic processes within specific central nervous system cell populations, including microglia, astrocytes, and neurons. Working with other OMRF scientists, we also study the retina, ovary, muscle, and other organs to maintain health.

In combination with these studies we identified the Major Histocompatibility Complex I (MHC-I) as an unexplored aspect of neuroinflammation with aging and Alzheimer’s Disease. MHC-I presents antigens to T cells to fight infections in the periphery but we are examining how microglial MHC-I could both signal within the brain to cause the neuroinflammation found with aging and neurodegenerative diseases.

Our scientific advances over the past decade in aging research have been:

• Identifying that the majority of age-related CNS epigenomic changes are sexually divergent in mice and man
• Disproving the genomic hypomethylation with aging hypothesis
• Identifying 100s of epigenomic aging clocks in humans of similar performance to existing clocks
• Discovering new relationships between epigenomic patterns and gene expression