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Melatonin and sirtuins: A “not‐so unexpected” relationship
Author(s) -
Mayo Juan C.,
Sainz Rosa M.,
González Menéndez Pedro,
Cepas Vanesa,
Tan DunXian,
Reiter Russel J.
Publication year - 2017
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12391
Subject(s) - melatonin , biology , sirtuin , sirt6 , sirt3 , sirt2 , epigenetics , sirtuin 1 , histone deacetylase , acetylation , microbiology and biotechnology , senescence , dna methylation , histone , genetics , neuroscience , gene expression , downregulation and upregulation , gene
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.