Objective: Aging is a major risk factor for the development of atherosclerosis. Apart from remodelling of the vascular wall including an increased vascular stiffness, endothelial function declines with age. The loss of elasticity of other human tissues has recently been attributed not only to a stiffening of the extracellular matrix, but also to an increase in stiffness of the individual cell. Aldosterone is known to be a key factor in these processes and an aldosterone-induced increase in the expression of the epithelial natrium channel (ENaC) by endothelial cells (ECs) seems to be involved. Here, we hypothesise that ECs exposed to a physiological concentration of aldosterone stiffen during aging. Therefore, we investigated changes in mechanical EC properties during the aging process and assessed the expression of ENaC. Methods: Human endothelial cells (HUVECs and EA.hy 926) were cultured in a physiological concentration of aldosterone (0.1 nM) for up to four weeks with or without its receptor antagonist spirolactone (100 nM). Cell stiffness and ENaC expression were measured weekly by atomic force microscopy and RT-PCR, respectively. Results: HUVECs stiffen significantly (2.5 fold) over four weeks. Spironolactone attenuates this effect by 38%. Concomitantly, the ENaC expression measured in EA.hy 926 gradually increases up to 1.4 fold and can be blocked by spironolactone. Conclusion: ECs stiffen and increasingly express ENaC during aging. This could contribute to the age-related decline of EC function and vessel stiffening leading to atherosclerosis. Apparently, spironolactone exerts anti-aging properties in vascular endothelium.