Brain aging and the molecular and cellular processes associated with it are responsible for the many neurological disorders evident with aging. The study of central nervous system aging is known as geroscience. Historically, this field has been reliant on male mice. This has left shockingly limited data on female brain aging. Understanding sex differences offers the opportunity to develop treatments tailored to women where few exist today.
My mentor Dr. Freeman and his research group have been studying sex differences and brain aging in mice. In a series of studies, they found sex divergences (i.e., sex differences that only become apparent with aging) in neuroinflammation at the level of the epigenome (DNA modifications that control genome structure) and transcriptome (mRNAs expressed in a cell or tissue). Their findings raise two important questions – what is causing these sex divergences; and what are the functional impacts on brain aging in regards to neurological disease?
My research project investigates the regulation of sex divergences with aging. Sex differences can be either organizational, hardwired during development, or activational, differentially responsive to stimuli. My hypothesis is that the sex divergences with aging are activational in nature and in large part arise from age-related differences in sex hormones. I am using the naturally occurring variations of sex hormones across the estrus cycle (menstrual cycle of a mouse) to test the responsiveness of genes to altered hormone levels. Specifically, I am examining the expression of genes identified in previous studies as sexually divergent in mouse hippocampi.
Ultimately, my hope for this research is a better understanding of women’s health with aging and a biological basis for personalizing neurological treatment to women. Comprehending the nature and regulation of heightened neuroinflammation in women with aging could point to new forms of stroke treatment targeted to women.