Age-related cognitive deficits are often associated with loss of cholinergic activity within the neurotrophin-dependent cholinergic neurons that project from the basal forebrain to the hippocampus. The cause of reduced cholinergic function is unknown, but alterations in transcription factor-signaling pathways causing altered gene expression may cause decreased specific tissue function, resulting in loss of cholinergic activity. We measured transcription factor Nuclear Factor kappa B by electrophoretic mobility shift assay and Western analysis in young and aged rat brain tissues and report that basal levels of Nuclear Factor kappa B DNA-binding activity increase in the hippocampus and basal forebrain with age to significantly higher levels at 30 months of age. This age-associated increase in binding activity is associated with increased translocation of p65 to the nucleus. These data show an age-associated alteration in Nuclear Factor kappa B signal transduction pathways that may contribute to age-associated decreases in specific tissue function.