title: Aging of the nitric oxide system: are we as old as our NO?
abstract: 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.
  
  
  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<0.0001). There was a significant correlation between changes in these parameters over time (r=0.2; P=0.013). On multivariable analyses, the independent correlates of deterioration of responsiveness of platelets to NO were female gender (β=0.17; P=0.034) and low vitamin D concentrations (β=0.16; P=0.04), whereas increases in ADMA were associated with presence of diabetes (β=0.16; P=0.03) and impaired renal function (β=0.2; P=0.004).
  
  
  CONCLUSIONS
  Aging is associated with marked impairment of determinants of NO generation and effect, to an extent which is commensurate with adverse impact on CV outcomes. This deterioration represents a potential target for therapeutic interventions.
authors.affiliation: University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia (A.L.S., D.T.N., W.P.C., Y.Y.C., J.D.H.).
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Sverdlov
authors.affiliation: University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia (A.L.S., D.T.N., W.P.C., Y.Y.C., J.D.H.).
authors.forename: Doan T M
authors.initials: DT
authors.lastname: Ngo
authors.affiliation: University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia (A.L.S., D.T.N., W.P.C., Y.Y.C., J.D.H.).
authors.forename: Wai P A
authors.initials: WP
authors.lastname: Chan
authors.affiliation: University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia (A.L.S., D.T.N., W.P.C., Y.Y.C., J.D.H.).
authors.forename: Yuliy Y
authors.initials: YY
authors.lastname: Chirkov
authors.affiliation: University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia (A.L.S., D.T.N., W.P.C., Y.Y.C., J.D.H.).
authors.forename: John D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D010974:Platelet Aggregation; D011446:Prospective Studies
chemical_list: D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: aging; endothelium; nitric oxide; platelets