Our neurobiology of aging research is focused on both the positive and negative changes to the brain with aging and understanding how these contribute to or prevent age-related cognitive decline and susceptibility to neurodegenerative diseases.
Our scientific premise is that changes in genomic patterns of DNA modifications – methylation (mC) and hydroxymethylation hmC – are central regulators of altered genome function and gene expression with aging. Our studies are determining changes in mC and hmC patterns with aging in specific hippocampal cell populations (neurons, microglia, and astrocytes) across the lifespan in both female and male mice, testing whether a ‘youthful’ modification pattern can be retained through caloric restriction, and identifying how altered DNA modification patterns regulate gene expression. The long-term goal of this research is to prevent or reverse age-related changes in DNA modification patterns to maintain healthy brain function and prevent neurodegenerative diseases such as Alzheimer’s.
Contrary to common assumptions, the brain does not lose a significant number of neurons with aging. Our research is investigating activation of microglial and astrocyte cell populations in the brain with aging as a mechanism of synapse loss. Intriguingly, neuroinflammatory processes demonstrate some of the largest sex divergences with aging and could underlie differences between males and females in Alzheimer's disease.