Melatonin and sirtuins: A “not-so unexpected” relationship
Open accessAbstract
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.
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Melatonin increases SIRT1 expression in the CNS and protects brain in different experimental conditions via activating SIRT1/Nrf2 signaling pathways.
“It has been reported that melatonin increases SIRT1 expression in the CNS and protects brain in different experimental conditions via activating SIRT1/Nrf2 signaling pathways (37).”
From Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway (2019) · cites this paper as [37]
SIRT1 is a key molecule that can mediate many functions of melatonin.
“It is well known that SIRT1 is a key molecule that can mediate many functions of melatonin (9, 37).”
From Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway (2019) · cites this paper as [37]
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Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas
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- Authors
- Mayo, J. C., Sainz, R. M., González Menéndez, P., Cepas, V., Tan, D., & Reiter, R. J.
- Affiliations
- Universidad de Oviedo (ES)
- Departamento de Morfología y Biología Celular Facultad de Medicina Universidad de Oviedo Oviedo Spain
- Department of Cell Systems and Anatomy University of Texas Health Science Center at San Antonio (UTHSCSA) San Antonio TX USA
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Mayo, Juan C.
- Venue
- Journal of Pineal Research
- Publisher
- Wiley
- Published
- 2017-02-14
- Volume
- 62
- Issue
- 2
- ISSN
- 0742-3098 (ISSN-L)
- 1600-079X
- OpenAlex
- W2575397619
- Semantic Scholar
- 8171e70f748c6825a14b4df4a35754957f4fdc56
- Cited by
- 175
- References
- 213
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 20 · 2023: 18 · 2022: 24 · 2021: 15 · 2020: 16 · 2019: 18 · 2018: 30 · 2017: 16
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Pineal Research (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministerio de Economía y Competitividad (MINECO‐13‐BFU2012‐38779)
- Federación Española de Enfermedades Raras
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melatonin, sirtuins, SIRT1, SIRT3, histone deacetylase, epigenetic regulation, cancer cells, cytoprotection, neurodegenerative diseases, aging, caloric restriction, glutaminolysis, glycolysis, mitochondrial metabolism
- MeSH terms
- Animals, Humans, Melatonin, Sirtuins
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