Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment.

This study used microarray analysis to examine age-related changes in gene expression 6 and 12 h following a single estradiol injection in ovariectomized mice. Estradiol-responsive gene expression at the 6 h time point was reduced in aged (18 months) animals compared with young (4 months) and middle-aged (MA, 12 months) mice. Examination of gene clustering within biological and functional pathways indicated that young and MA mice exhibited increased expression of genes for cellular components of the synapse and decreased expression of genes related to oxidative phosphorylation and mitochondrial dysfunction. At the 12 h time point, estradiol-responsive gene expression increased in aged animals and decreased in young and MA mice compared with the 6 h time point. Gene clustering analysis indicated that aged mice exhibited increased expression of genes for signaling pathways that are rapidly influenced by estradiol. The age differences in gene expression for rapid signaling pathways may relate to disparity in basal pathway activity and estradiol mediated activation of rapid signaling cascades.