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. Author manuscript; available in PMC: 2015 Aug 1.
Published in final edited form as: Trends Cell Biol. 2014 Apr 29;24(8):464–471. doi: 10.1016/j.tcb.2014.04.002

Figure 3.

Figure 3

Synthesis of NAD+ is regulated by the circadian clock and declines with age. The oscillating clock consists of the heterodimeric complex of core circadian transcription factors BMAL1 and CLOCK. The BMAL1/CLOCK complex controls the Nampt gene encoding the key NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT), rendering NAD+ production and SIRT1 activity circadian in peripheral tissues. SIRT1 negatively regulates the transcriptional activity of the BMAL1/CLOCK complex, completing a novel circadian-regulatory feedback loop. In the suprachiasmatic nucleus (SCN), SIRT1 also regulates Bmal1 and Clock expression levels via the complex with PGC-1α and RORα. Chronic inflammation, particularly induced by inflammatory cytokines such as TNF-α, might affect NAMPT-mediated NAD+ biosynthesis and BMAL1/CLOCK-mediated circadian transcription in peripheral tissues and the SCN, causing a decline in the amplitude of the circadian clock with age.