title: Melatonin and brain inflammaging.
abstract: Melatonin is known to possess several properties of value for healthy aging, as a direct and indirect antioxidant, protectant and modulator of mitochondrial function, antiexcitotoxic agent, enhancer of circadian amplitudes, immune modulator and neuroprotectant. It is levels tend to decrease in the course of senescence and are more strongly reduced in several neurodegenerative disorders, especially Alzheimer's disease, and in diseases related to insulin resistance such as diabetes type 2. Although the role of melatonin in aging and age-related diseases has been repeatedly discussed, the newly emerged concept of inflammaging, that is, the contribution of low-grade inflammation to senescence progression has not yet been the focus of melatonin research. This review addresses the multiple protective actions of melatonin and its kynuramine metabolites that are relevant to the attenuation of inflammatory responses and progression of inflammaging in the brain, i.e. avoidance of excitotoxicity, reduction of free radical formation by support of mitochondrial electron flux, prevention of NADPH oxidase activation and suppression of inducible nitric oxide synthase, as well as downregulation of proinflammatory cytokines. The experimental evidence is primarily discussed on the basis of aging and senescence-accelerated animals, actions in the immune system, and the relationship between melatonin and sirtuins, having properties of aging suppressors. Sirtuins act either as accessory components or downstream factors of circadian oscillators, which are also under control by melatonin. Inflammaging is assumed to strongly contribute to neurodegeneration of the circadian master clock observed in advanced senescence and, even more, in Alzheimer's disease, a change that affects countless physiological functions.
authors.affiliation: Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Goettingen, Berliner Str. 28, D-37073 Goettingen, Germany. Electronic address: rhardel@gwdg.de.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hardeland
authors.affiliation: BIOMED-UCA-CONICET, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, C1107AFD Buenos Aires, Argentina.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cardinali
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Toronto, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Brown
authors.affiliation: Center for Healthful Behavior Change (CHBC), Division of Health and Behavior, Department of Population Health, New York University Medical Center, Clinical & Translational Research Institute, 227 East 30th Street, New York, NY 10016, USA.
authors.forename: Seithikurippu R
authors.initials: SR
authors.lastname: Pandi-Perumal
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000276:immunology*; D006801:Humans; D000068884:Immunosenescence / Q000502:physiology; D008550:Melatonin / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000502:physiology
chemical_list: D008550:Melatonin
keywords: Aging; Alzheimer's disease; Circadian; Mitochondria; Neuroinflammation; Neuroprotection