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With increasing age, however, nicotinamide adenine dinucleotide levels and sirtuin activity steadily decrease, and the decline is further exacerbated by obesity and sedentary lifestyles. Activation of sirtuins or nicotinamide adenine dinucleotide repletion induces angiogenesis, insulin sensitivity, and other health benefits in a wide range of age-related cardiovascular and metabolic disease models. Human clinical trials testing agents that activate SIRT1 or boost nicotinamide adenine dinucleotide levels are in progress and show promise in their ability to improve the health of cardiovascular and metabolic disease patients.<\/jats:p>","DOI":"10.1161\/circresaha.118.312498","type":"journal-article","created":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T14:24:07Z","timestamp":1536848647000},"page":"868-885","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":475,"title":["Sirtuins and NAD\n                    <sup>+<\/sup>\n                    in the Development and Treatment of Metabolic and Cardiovascular Diseases"],"prefix":"10.1161","volume":"123","author":[{"given":"Alice E.","family":"Kane","sequence":"first","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, MA (A.E.K., D.A.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Sinclair","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Harvard Medical School, Boston, MA (A.E.K., D.A.S.)"},{"name":"Department of Pharmacology, The University of New South Wales, Sydney, Australia (D.A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80493-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.19.2570"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80219-6"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35001622"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110148297"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.93"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.04.002"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092250"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2013.12.004"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.033"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2009.00544.x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802917105"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.08.014"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.07.013"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10815"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.01.031"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12220"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.12.001"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00527-X"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600244"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.016"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03354"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00121-09"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08778"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.057"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.11.013"},{"key":"e_1_3_4_28_2","first-page":"1","article-title":"SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability.","volume":"7","author":"Li L","year":"2016","unstructured":"Li, L, Shi, L, Yang, S, Yan, R, Zhang, D, Yang, J, He, L, Li, W, Yi, X, Sun, L, Liang, J, Cheng, Z, Shi, L, Shang, Y, Yu, W. 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