The circadian clock and pathology of the ageing brain

Dysfunction of the circadian clock contributes to the age-associated decline of brain functions. Here, the authors examine the evidence for this link and the potential underlying molecular mechanisms such as the circadian control of brain metabolism and hormone secretion. Ageing leads to a functional deterioration of many brain systems, including the circadian clock — an internal time-keeping system that generates ∼24-hour rhythms in physiology and behaviour. Numerous clinical studies have established a direct correlation between abnormal circadian clock functions and the severity of neurodegenerative and sleep disorders. Latest data from experiments in model organisms, gene expression studies and clinical trials imply that dysfunctions of the circadian clock contribute to ageing and age-associated pathologies, thereby suggesting a functional link between the circadian clock and age-associated decline of brain functions. Potential molecular mechanisms underlying this link include the circadian control of physiological processes such as brain metabolism, reactive oxygen species homeostasis, hormone secretion, autophagy and stem cell proliferation.