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Among these modifying enzymes, sirtuins, a class III histone deacetylase (HDAC) enzymes, are of particular importance. Sirtuins regulate the cell cycle, DNA repair, cell survival, and apoptosis, thus having important roles in normal and cancer cells. Sirtuins can also regulate metabolic pathways by changing preference for glycolysis under aerobic conditions as well as glutaminolysis. These actions make sirtuins a major target in numerous physiological processes as well as in other contexts such as calorie restriction\u2010induced anti\u2010aging, cancer, or neurodegenerative disease. Interestingly, melatonin, a nighttime\u2010produced indole synthesized by pineal gland and many other organs, has important cytoprotective effects in many tissues including aging, neurodegenerative diseases, immunomodulation, and cancer. The pleiotropic actions of melatonin in different physiological and pathological conditions indicate that may be basic cellular targeted for the indole. Thus, much research has focused attention on the potential mechanisms of the indole in modulating expression and\/or activity of sirtuins. Numerous findings report a rise in activity, especially on SIRT1, in a diversity of cells and animal models after melatonin treatment. This contrasts, however, with data reporting an inhibitory effect of melatonin on this sirtuin in some tumor cells. This review tabulates and discusses the recent findings relating melatonin with sirtuins, particularly SIRT1 and mitochondrial SIRT3, showing the apparent dichotomy with the differential actions documented in normal and in cancer cells.<\/jats:p>","DOI":"10.1111\/jpi.12391","type":"journal-article","created":{"date-parts":[[2017,1,21]],"date-time":"2017-01-21T14:16:44Z","timestamp":1485008204000},"source":"Crossref","is-referenced-by-count":157,"title":["Melatonin and sirtuins: A \u201cnot\u2010so unexpected\u201d relationship"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0882-2047","authenticated-orcid":false,"given":"Juan C.","family":"Mayo","sequence":"first","affiliation":[{"name":"Departamento de Morfolog\u00eda y Biolog\u00eda Celular Facultad de Medicina Universidad de Oviedo Oviedo Spain"},{"name":"Instituto Universitario Oncol\u00f3gico del Principado de Asturias (IUOPA) University of Oviedo Oviedo 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