During aging, there is an increase in neurodegenerative diseases and a decrease in cognitive performance. Postmenopausal women are more vulnerable as their estrogen levels decline, but most hormone replacement therapies do not prevent cognitive decline. One potential reason is that the timing of hormone replacement is critical and changes in the estrogen receptor expression may over-ride hormonal intervention. In rodents, estrogen receptor β (ERβ) mRNA decreases in the cortex with age. One mechanism by which ERβ mRNA could be regulated is by epigenetic modification of ERβ promoter. Here, we show an increase in methylation of ERβ promoter corresponding to decrease in ERβ mRNA in the cortex of an aging female.