Circadian Control of the NAD+ Salvage Pathway by CLOCK-SIRT1

The 24-hour day-night cycle plays an important role in mammalian physiology and behavior and, as most travelers are well aware, there is an intimate link between our in-built circadian clocks and metabolic rhythms. This link is in part forged by the protein deacetylase SIRT1, which regulates the clock's molecular circuitry. SIRT1 uses as a cofactor the cellular metabolite NAD+, which is synthesized through a salvage pathway that includes the enzyme nicotinamide phosphoribosyltransferase (NAMPT) (see the Perspective by [Wijnen][1] ). Ramsey et al. (p. [651][2]; published online 19 March) and Nakahata et al. (p. [654][3], published online 12 March) now show that NAMPT and NAD+ levels oscillate during the daily 24-hour cycle and that this oscillation is regulated by the circadian clock. Furthermore, the oscillations in NAD+ modulate the activity of SIRT1 feeding back into the circadian clock. [1]: /lookup/doi/10.1126/science.1174132 [2]: /lookup/doi/10.1126/science.1171641 [3]: /lookup/doi/10.1126/science.1170803