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.
Maywood
Elizabeth S
ES
MRC Laboratory of Molecular Biology, Hills Rd, Cambridge CB2 2QH, UK. mha@mrc-lmb.cam.ac.uk
O'Neill
John
J
Wong
Gabriel K Y
GK
Reddy
Akhilesh B
AB
Hastings
Michael H
MH
D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D015534:Trans-Activators; D056926:CLOCK Proteins; C538943:CLOCK protein, human