Between a ROCK and a Hard Place

Many, if not all, aspects of biology are temporally controlled to align our temperaments and behavior with a 24-hour world. Such rhythms are driven by the dynamic interplay of a master molecular clock, housed in the suprachiasmatic nucleus, and peripheral tissue clocks, all conditioned by environmental inputs, most of which we poorly understand.1 Expression of ≈20% of genes in most tissues oscillates in a circadian fashion,2 and the tightly regulated transcriptional regulation of the clock is complemented by additional controls—by microRNAs3 and posttranslational4 and epigenetic modifications.5 Further underscoring the importance of this system, the molecular clock is highly conserved, exhibits marked elemental redundancy, and is central among the networks that link biological networks that are prominent in distinct tissues.1Article see p 104 Longstanding clinical interest in circadian rhythms has been fostered by temporal variability in the incidence of symptoms of many diseases1—asthma, endogenous depression, myocardial infarction, and stroke among them—as well as in the efficacy and metabolism of commonly used drugs.6 Coincident with the diurnal pattern of cardiovascular events, diurnal variations have been reported in the pressor response to infused vasoconstrictors, sympathetic nerve activity, the renin–angiotensin system, QT …