Aging is an independent risk factor for the development of cardiovascular disease. Vascular aging is mainly characterized by endothelial dysfunction, which, in turn, is primarily attributable to increased superoxide (O(2)(*)(-)) formation with age. To date, the source of this age-associated increased O(2)(*)(-) production remains obscure. We investigated whether like in hyperglycemia or hypertension protein kinase C (PKC)-mediated activation of the NAD(P)H oxidase system is involved. Here we show that both PKC translocation, necessary for its activation, and expression of the cytosolic subunits of the NAD(P)H oxidase, p47(phox) and p67(phox), remain unchanged with age. Therefore, we suggest that oxidative stress-associated vascular aging mechanistically differs from endothelial dysfunction seen in the context of other cardiovascular risk factors, for which the PKC/NAD(P)H oxidase pathway has been shown responsible.