Aging of the nitric oxide system: are we as old as our NO?

BACKGROUND: Impaired generation and signaling of nitric oxide (NO) contribute substantially to cardiovascular (CV) risk (CVR) associated with hypertension, hyperlipidemia, and diabetes mellitus. In our rapidly aging society, advanced age is, in itself, a consistent and independent CVR factor. Many processes involved in aging are modulated by NO. We therefore postulated that aging might be independently associated with impaired NO signaling. METHODS AND RESULTS: In a prospective cohort study of 204 subjects (mean age 63±6 at study entry), we evaluated the effects of 4 years of aging on parameters of NO generation and effect, including platelet aggregability and responsiveness to NO, and plasma concentrations of the NO synthase inhibitor, asymmetric dimethylarginine (ADMA). Clinical history, lipid profile, high-sensitivity C-reactive protein, routine biochemistry, and 25-hydroxyvitamin D levels were obtained at study entry and after 4 years of follow-up. Aging was associated with marked deterioration of responsiveness of platelets to NO (P<0.0001) and increases in plasma ADMA concentrations (P