Our work and that of others suggest that interactions between genetic and modifiable dietary factors are key determinants of cognitive aging trajectory (i.e., cognitive longevity) that has significant implications for human brain aging and dementia. Our recent research suggests that caloric restriction, one of the most robust and reproducible dietary interventions for extending lifespan, can cause severe memory deficits in some individuals. This proposal uses a mouse-to-human approach specifically designed to identify how caloric restriction differentially affects cognitive aging in mice and humans using state-of-the-art approaches. This project discovers and leverages genetic factors that protect the brain in response to caloric restriction to point to new therapeutic strategies for managing or delaying age-related cognitive decline in the context of resilience to AD.
