PerspectivePhysiology

Partitioning the circadian clock

Science  05 Sep 2014:
Vol. 345, Issue 6201, pp. 1122-1123
DOI: 10.1126/science.1259601

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Summary

Many physiological and behavioral events exhibit circadian rhythms, which are driven by internal circadian “clocks” that coordinate biological functions through the cyclic expression of at least 10 to 20% of the genes in any given tissue (1). The robustness of circadian rhythms deteriorates with age, and circadian perturbation results in the development of disorders such as diabetes, obesity, and brain dysfunction. Central to the mammalian clock is the complex of transcriptional regulatory proteins CLOCK and BMAL1 (2). A recent study by Masri et al. (3) proposes that SIRT1 and SIRT6, two sirtuin family members with nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity, regulate different facets of the CLOCK-BMAL1 network, and more surprisingly, control distinct classes of hepatic circadian genes. Partitioning circadian transcription by sirtuins suggests that in response to internal and external stimuli, circadian clocks selectively control sirtuin-dependent functions that are broadly associated with metabolism, stress resistance, inflammation, aging, and tissue regeneration, to provide organisms with plasticity to adapt to changing environments.