title: Melatonin and sirtuins: A "not-so unexpected" relationship.
abstract: Epigenetic modifications, including methylation or acetylation as well as post-transcriptional modifications, are mechanisms used by eukaryotic cells to increase the genome diversity in terms of differential gene expression and protein diversity. 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-induced anti-aging, cancer, or neurodegenerative disease. Interestingly, melatonin, a nighttime-produced 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.
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.|Instituto Universitario Oncológico del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain.
authors.forename: Juan C
authors.identifier: http://orcid.org/0000-0002-0882-2047
authors.initials: JC
authors.lastname: Mayo
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.|Instituto Universitario Oncológico del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Sainz
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.|Instituto Universitario Oncológico del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: González Menéndez
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.|Instituto Universitario Oncológico del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Cepas
authors.affiliation: Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, USA.
authors.forename: Dun-Xian
authors.initials: DX
authors.lastname: Tan
authors.affiliation: Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, USA.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
mesh_terms: D000818:Animals; D006801:Humans; D008550:Melatonin / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D037761:Sirtuins; D008550:Melatonin
keywords: SIRT1; SIRT3; aging; apoptosis post-translational modification; cancer; deacetylases; mitochondria