The binding of advanced glycation endproducts (AGEs) to their receptors is known to cause changes in cell function during normal ageing and is implicated in the pathogenesis of cardiovascular disease. In this study, expression of the AGE-receptor 3 (AGE-R3) and the receptor for AGEs (RAGE) was compared on the mRNA and protein level in the ageing human heart. Western blot and RT-PCR analysis of the AGE receptors from the cardiac auricles in senescent and adult patients was performed and compared with young controls. Whereas the expressions of AGE-R3 as well as RAGE protein were significantly upregulated in the senescent population, only the upregulation of RAGE is associated with reduced heart function. Therefore, our results support a pathophysiological function for RAGE in the ageing human heart.