Melatonin and brain inflammaging

• Autores: Hardeland, Rüdiger; Cardinali, Daniel Pedro; Brown, Gregory M.; Pandi Perumal, Seithikurippu R.
• Año de publicación: 2015
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Postprint del documento publicado en Progress in Neurobiology Vol. 127-128, 2015; ISSN 0301-0082
• Materia: MEDICINA; MELATONINA; CEREBRO; INFLAMACION; MITOCONDRIA; ENFERMEDAD DE ALZHEIMER; ENVEJECIMIENTO
• Institución: Pontificia Universidad Católica Argentina

Fil: Hardeland, Rüdiger. University of Goettingen. Johann Friedrich Blumenbach Institute of Zoology and Anthropology; Alemania
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Brown, Gregory M. University of Toronto. Faculty of Medicine. Department of Psychiatry; Canada
Fil: Pandi Perumal, Seithikurippu R. Clinical & Translational Research Institute. New York University Medical Center. Department of Population Health. Division of Health and Behavior. Center for Healthful Behavior Change; Estados Unidos
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.