RBAP48 AS A POTENTIAL MEMORY GENE

Aging individuals tend to experience cognitive decline, which provide an opportunity to investigate why some individuals age successfully while others do not. Our study investigates RbAp48, a gene related to cognitive function, to determine if the expression of this “memory gene” declines with age. Our data suggests that RbAp48 does decrease with age, and future studies will test whether steroid hormones, which have known influences on cognitive function, play a role in regulating RbAp48 gene expression. Purpose (a): With aging, there is a tendency for humans to experience cognitive decline. These variations in cognitive functioning provide an opportunity to investigate the reasons why some individuals age successfully versus those that do not. In a comprehensive analysis of gene regulation in the normal aging processes, it was recently shown that the histone binding protein, RbAp48, is implicated in age-related memory loss. Given the suggested role of RbAp48 in cognitive function, we sought to determine if, in animal models of aging currently being used in our laboratory, RbAp48 declines with age. Methods (b): We evaluated the expression of RbAp48 in the hippocampus of female C57Bl/6 mice that were 7.5 months and 25.5 months of age, representing young adult and old mice. RbAp48 mRNA was assessed using reverse transcriptase (rt) conversion of RNA to cDNA, followed by real time polymerase chain reaction (PCR). In parallel, the levels of GAPDH, a “housekeeping” gene, was measured to take into consideration variation in starting material. Differences in expression of RbAp48 were based on the delta-delta CT methodology published by Livak and Schmittgen (2001). Statistical evaluation of differences between experimental groups was determined using a two-tailed t-test. Results (c): Our data revealed an approximate 21% reduction in the levels of RbAp48 mRNA in the 25.5 month mice, compared to the 7.5 month mice. While not statistically significant (n=3, p=0.0791), we anticipate that these data warrant further analysis and expansion of our sample size to more reliably ascertain differences as a function of chronological age. Conclusions (d): These studies suggest that the expression of RbAp48, a presumptive “memory gene”, declines with age. Our future studies will determine if the steroid hormones, estrogen and progesterone, which have known influences on cognitive function, regulate the expression of RbAp48.