Circadian timing in health and disease.

Metabolic status varies predictably on a daily and seasonal basis in order to adapt to the cyclical environment. The hypothalamic circadian pacemaker of the suprachiasmatic nuclei (SCN) co-ordinates these metabolic cycles. Circadian timing is based upon a transcriptional/post-translational negative feedback loop involving a series of core clock genes and their products. Local molecular clocks in peripheral tissues are synchronised by a variety of autonomic, paracrine and endocrine cues reflective of SCN time, thereby ensuring internal temporal co-ordination and optimal metabolic function. Disturbances of this co-ordination, as occur in long-term shift work, have a major impact on health.