Middle age is a critical time for cognitive changes that may precede dementia onset. Interestingly, studies have shown that lifestyle factors such as exercise can reverse age-related cognitive decline and improve memory function. However, the underlying mechanisms that underpin these effects are unknown. Besides a decline in physical fitness, middle age is characterized by extensive change in gastrointestinal function, gut microbiota composition, and related metabolites.

During middle age, accumulating neuroinflammation threatens cognitive capacity and negatively affects hippocampal neurogenesis, a process important for cognitive function. Physical exercise promotes neurogenesis and may delay cognitive decline. This project investigates convergent proteomic and metabolic processes dysregulated in the hippocampus and systemic milieu during middle age and in response to exercise. Results will identify predictors of cognitive decline that are modifiable by exercise.