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Access to the article is free, however registration and sign-in are required. Daily time keeping in many organisms depends on internal circadian clocks that temporally organize biological functions relative to each other as well as the environment. These clocks generate rhythms in physiology and behavior by using circuits of gene expression that are organized in negative-feedback loops. The studies of Nakahata et al. and Ramsey et al. propose the addition of a new negative-feedback loop to this circuitry that involves the metabolite nicotinamide adenine dinucleotide (NAD+) and the protein SIRTUIN1 (SIRT1). The new loop suggests connections between the circadian clock and SIRT1-dependent functions associated with cell survival, development, inflammation, and metabolism.
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