Circadian Rhythms

Circadian Oscillations

Science Signaling  05 May 2009:
Vol. 2, Issue 69, pp. ec157
DOI: 10.1126/scisignal.269ec157

The 24-hour day-night cycle plays an important role in mammalianphysiology and behavior, and, as most travelers are well aware,there is an intimate link between our built-in circadian clocksand metabolic rhythms. This link is in part forged by the proteindeacetylase SIRT1, which regulates the clock’s molecular circuitry.SIRT1 uses as a cofactor the cellular metabolite NAD+, whichis synthesized through a salvage pathway that includes the enzymenicotinamide phosphoribosyltransferase (NAMPT) (see the Perspectiveby Wijnen). Ramsey et al.and Nakahata et al. nowshow that NAMPT and NAD+ levels oscillate during the daily 24-hourcycle and that this oscillation is regulated by the circadianclock. Furthermore, the oscillations in NAD+ modulate the activityof SIRT1 feeding back into the circadian clock.

K. M. Ramsey, J. Yoshino, C. S. Brace, D. Abrassart, Y. Kobayashi, B. Marcheva, H.-K. Hong, J. L. Chong, E. D. Buhr, C. Lee, J. S. Takahashi, S. Imai, J. Bass, Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324, 651–654 (2009). [Abstract] [Full Text]

Y. Nakahata, S. Sahar, G. Astarita, M. Kaluzova, P. Sassone-Corsi, Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324, 654–657 (2009). [Abstract] [Full Text]

H. Wijnen, A circadian loop asSIRTs itself. Science 324, 598–599 (2009). [Summary] [Full Text]