{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:53:39Z","timestamp":1781790819593,"version":"3.54.5"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiac arrhythmia and dysfunction increase with age and are closely associated with declining nicotinamide adenine dinucleotide levels. Nicotinamide, a critical nicotinamide adenine dinucleotide precursor, has shown protective effects in experimental models of aging\u2010related cardiac diseases. However, its dose\u2010dependent cardiac\u2010specific adverse effects and underlying mechanisms warrant investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The effects of nicotinamide (10\u2013100\u2009mmol\/L) on the contractility and calcium transient of HL\u20101 cardiomyocytes, lifespan, and cardiac function of\n                      <jats:italic toggle=\"no\">Drosophila<\/jats:italic>\n                      , as well as arrhythmia susceptibility of ex\u00a0vivo Langendorff mouse hearts were assessed. SERCA2a (sarcoplasmic\/endoplasmic reticulum Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010ATPase 2a) acetylation was analyzed by immunoprecipitation followed by Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Acute perfusion with 10\u2009mmol\/L nicotinamide had limited influence on aging\u2010related atrial fibrillation susceptibility in ex\u00a0vivo mouse and\n                      <jats:italic toggle=\"no\">Drosophila<\/jats:italic>\n                      hearts. Short\u2010term dietary nicotinamide (10\u2009mmol\/L) in late life protected against aging\u2010induced arrhythmia and contractile dysfunction exclusively in male\n                      <jats:italic toggle=\"no\">Drosophila<\/jats:italic>\n                      . In contrast, lifelong exposure or doses &gt;20\u2009mmol\/L caused dose\u2010dependent adverse cardiac effects, including impaired contractility and calcium transient amplitude and kinetics in HL\u20101 cardiomyocyte and shortened lifespan in\n                      <jats:italic toggle=\"no\">Drosophila<\/jats:italic>\n                      , with impaired excitability and increased arrhythmia in both models. In ex\u00a0vivo mouse hearts, 100\u2009mmol\/L nicotinamide induced ventricular arrhythmia and cardiac arrest.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Nicotinamide exhibits dual effects on aging\u2010related arrhythmia and cardiac dysfunction, with its efficacy highly dependent on dose, duration, and biological context. Although a moderate dose in late life may be protective, chronic or excessive intake induces arrhythmia and impairs cardiac function across species, likely through disrupted cardiac excitability and dysregulated calcium handling. These findings underscore the importance of cautious and context\u2010specific application of nicotinamide in clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046761","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T10:47:04Z","timestamp":1779706024000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Effects of Nicotinamide on Aging\u2010Related Arrhythmia: Protective at Low Dose, Proarrhythmic at Higher Doses"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3476-9075","authenticated-orcid":false,"given":"Liangyu","family":"Hu","sequence":"first","affiliation":[{"name":"Wageningen University","place":["Wageningen, the 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