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Investigation of Normal Age-Related Decline

Why do we forget things as we age?

The influence of age on cognitive performance represents a fundamental quality-of-life concern. Although research of age-related cognitive loss is often solely discussed in the context of neurodegenerative disease, loss of executive function, learning, and memory can be observed in the “normal” aging process as well. Unfortunately, little is known about the mechanisms that regulate normal age-related cognitive decline. Pre-clinical rodent studies are used to model human age-related cognitive decline. Prior studies have found that immune dysregulation in the brain increases with age and correlates with reduced cognitive performance in old animals. Immune activation creates an inflammatory milieu that can ultimately lead to neuronal dysfunction. Identifying the precise mechanism(s) by which immune cells impact neuronal function—thereby altering cognitive function in the aging brain—is the focus of this project. It is important to note that a large majority of preclinical studies of aging have focused solely on male rodents, leaving large gaps in cellular understanding of female age-related cognitive changes. Sex-dimorphic cognitive decline has been reported with age in humans and rodents. Furthermore, sex-dependent differences in immune cells have been identified. Whether these sex-dimorphic responses relate to normal age-related cognitive decline is a secondary focus of this project.

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