The circadian clock and pathology of the ageing brain

Recent data suggest that the circadian clock regulates cognitive functions such as memory and mood in a sleep-dependent and sleep-independent manner.Some circadian clock proteins are important regulators of longevity; for example, BMAL1, NPAS2, CRY and PER.Circadian rhythms in sleep and behaviour are significantly affected by ageing; this impairment can contribute to the cognitive decline of the ageing brain.Circadian rhythms in sleep and behaviour are markedly disturbed in patients with Alzheimer's disease, Parkinson's disease and Huntington's disease.Circadian clock disruption can serve as a biomarker of progression in a neurodegenerative disease.Circadian-clock-dependent control of metabolism, oxidative stress response, DNA repair and autophagy can contribute to brain ageing and neurodegeneration.Restoration of circadian clock function in animal models of neurodegeneration improves cognitive performance and increases the lifespan of these animals.Restoration of circadian rhythms with combined light and melatonin therapy improves sleep quality in humans.