The Circadian NAD⁺ Metabolism: Impact on Chromatin Remodeling and Aging

Figure 1

Importance of circadian clock in maintaining health and healthy aging. (a) CLOCK and BMAL1 activate an array of genes by binding to E-box elements on their promoter. Per and Cry transcripts are two of the target genes and PER/CRY repress CLOCK/BMAL1 activity to drive 24-hour rhythmicity (circadian rhythm). CCGs including nampt transcripts show circadian oscillations to maintain cellular, interorgan, and systemic functions, thereby contributing to healthy aging (b). CCGs: clock-controlled genes; NAD⁺: nicotinamide adenine dinucleotide; NAM: nicotinamide; NMN: nicotinamide mononucleotide; NR: nicotinamide riboside; NAMPT: nicotinamide phosphoribosyltransferase; NMNAT1~3: NMN adenylyltransferase 1, NMN adenylyltransferase 2, and NMN adenylyltransferase 3; NRK1 and NRK2: nicotinamide ribose kinase 1 and nicotinamide ribose kinase 2.