Brain Inflammaging: Roles of Melatonin, Circadian Clocks and Sirtuins

Abstract

Inflammaging denotes the contribution of low-grade inflammation to aging and is of particular importance in the brain as it is relevant to development and progression of neurodegeneration and mental disorders resulting thereof. Several processes are involved, such as changes by immunosenescence, release of proinflammatory cytokines by DNA-damaged cells that have developed the senescence-associated secretory phenotype, microglia activation and astrogliosis because of neuronal overexcitation, brain insulin resistance, and increased levels of amyloid-β peptides and oligomers. Melatonin and sirtuin1, which are both part of the circadian oscillator system share neuroprotective and anti-inflammatory properties. In the course of aging, the functioning of the circadian system deteriorates and levels of melatonin and sirtuin1 progressively decline. Protective effects of melatonin and sirtuin1 are outlined and emphasis is given to possibilities of upregulating sirtuin1 by melatonin and circadian amplitude-enhancing actions of sirtuin1.