Schematic model of the circadian clock (pacemaker) input and output signals. Light signaling directly influences neurons in the central clock in the hypothalamic suprachiasmatic nuclei, thereby modulating the self-sustained clock circadian regulation. The outputs of the circadian system include a large array of physiological, metabolic, and neuronal functions. Disruption of clock function can cause dramatic pathophysiological effects. Some metabolites appear to feed back to the central pacemaker and function as “adjusting signals.” This is the case for NAD+ (nicotinamide adenine dinucleotide), which is used by SIRT1 as coenzyme (Nakahata et al. 2009). CCG, Clock-controlled genes.