{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:31:28Z","timestamp":1790645488122,"version":"4.1.0"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"\n Background<\/jats:title>\n \n Impaired generation and signaling of nitric oxide (\n NO)<\/jats:styled-content>\n contribute substantially to cardiovascular (\n CV<\/jats:styled-content>\n ) risk (\n CVR<\/jats:styled-content>\n ) associated with hypertension, hyperlipidemia, and diabetes mellitus. In our rapidly aging society, advanced age is, in itself, a consistent and independent\n CVR<\/jats:styled-content>\n factor. Many processes involved in aging are modulated by\n NO<\/jats:styled-content>\n . We therefore postulated that aging might be independently associated with impaired\n NO<\/jats:styled-content>\n signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n In a prospective cohort study of 204 subjects (mean age 63\u00b16 at study entry), we evaluated the effects of 4\u00a0years of aging on parameters of\n NO<\/jats:styled-content>\n generation and effect, including platelet aggregability and responsiveness to\n NO<\/jats:styled-content>\n , and plasma concentrations of the\n NO<\/jats:styled-content>\n synthase inhibitor, asymmetric dimethylarginine (\n ADMA<\/jats:styled-content>\n ). Clinical history, lipid profile, high\u2010sensitivity C\u2010reactive protein, routine biochemistry, and 25\u2010hydroxyvitamin D levels were obtained at study entry and after 4\u00a0years of follow\u2010up. Aging was associated with marked deterioration of responsiveness of platelets to\n NO<\/jats:styled-content>\n (\n P<\/jats:italic>\n <0.0001) and increases in plasma\n ADMA<\/jats:styled-content>\n concentrations (\n P<\/jats:italic>\n <0.0001). There was a significant correlation between changes in these parameters over time (\n r<\/jats:italic>\n =0.2;\n P<\/jats:italic>\n =0.013). On multivariable analyses, the independent correlates of deterioration of responsiveness of platelets to\n NO<\/jats:styled-content>\n were female gender (\u03b2=0.17;\n P<\/jats:italic>\n =0.034) and low vitamin D concentrations (\u03b2=0.16;\n P<\/jats:italic>\n =0.04), whereas increases in\n ADMA<\/jats:styled-content>\n were associated with presence of diabetes (\u03b2=0.16;\n P<\/jats:italic>\n =0.03) and impaired renal function (\u03b2=0.2;\n P<\/jats:italic>\n =0.004).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Aging is associated with marked impairment of determinants of\n NO<\/jats:styled-content>\n generation and effect, to an extent which is commensurate with adverse impact on\n CV<\/jats:styled-content>\n outcomes. This deterioration represents a potential target for therapeutic interventions.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.000973","type":"journal-article","created":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T04:08:48Z","timestamp":1408421328000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":84,"title":["Aging of the Nitric Oxide System: Are We as Old as Our NO?"],"prefix":"10.1161","volume":"3","author":[{"given":"Aaron L.","family":"Sverdlov","sequence":"first","affiliation":[{"name":"University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doan T.M.","family":"Ngo","sequence":"additional","affiliation":[{"name":"University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai P.A.","family":"Chan","sequence":"additional","affiliation":[{"name":"University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliy Y.","family":"Chirkov","sequence":"additional","affiliation":[{"name":"University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Horowitz","sequence":"additional","affiliation":[{"name":"University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","volume-title":"World Population Ageing: 1950\u20132050","author":"Department of Economic and Social Affairs. 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