Identification and restoration of estradiol-mediated gene programs in the aging brain
Dr. Tuscher's laboratory investigates the complex relationship between estradiol and cognitive decline during aging. While estradiol serves as a master regulator of neural communication and memory consolidation in young adults, advancing age brings diminished hormone levels and alterations in the brain's responsiveness to estradiol's neuroprotective effects. The research team employs cutting-edge multiomic profiling techniques to examine how different cell types respond to estradiol across the lifespan, comparing young, middle-aged, and aged populations of both sexes. This single-cell resolution approach reveals complex gene expression patterns and chromatin dynamics governing estradiol signaling during aging, insights previously obscured by conventional bulk sequencing methods. To translate these findings into therapeutic strategies, the lab pairs multiomic profiling with CRISPR-based epigenetic editing to directly test whether manipulating specific estradiol-responsive gene loci can restore cognitive function in aging brains. The team also explores the brain's capacity for local estradiol synthesis by modulating aromatase, the enzyme responsible for estradiol production, in memory-critical brain regions. By investigating targeted enhancement of neuronal and glial estradiol production, this work may yield treatments to counteract age-related memory deficits. This comprehensive approach promises to illuminate novel therapeutic pathways for preserving cognitive function throughout aging.
