Figure 2.

Responses of NAD⁺ biosynthetic enzymes and sirtuins to nutritional and environmental cues in aging/longevity control. (a) Responses of PNC1 and sirtuins in budding yeast Saccharomyces cerevisiae and invertebrates (worms and flies) to caloric restriction (CR) and stress. When PNC1 levels increase in response to CR or stress in these organisms, the NAD⁺ biosynthetic flux increases and nicotinamide levels decrease, both contributing to the enhancement of sirtuin activity. (b) Responses of NAMPT and sirtuins in mammals to CR, exercise, and stress. Upregulation of NAMPT activates sirtuins primarily through the increase in NAD⁺ biosynthesis because nicotinamide levels are normally much lower in mammals, compared to yeast. CR, caloric restriction; NAD⁺, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase.