Figure 1

From: The NAD World 2.0: the importance of the inter-tissue communication mediated by NAMPT/NAD+/SIRT1 in mammalian aging and longevity control

Figure 1

The original concept of the NAD World.20 The NAD World is a systemic regulatory network that fundamentally connects NAD+ metabolism, biological rhythm, and aging and longevity control in mammals. Two critical components comprise the NAD World: the mammalian NAD+-dependent protein deacetylase SIRT1, and systemic NAD+ biosynthesis mediated by nicotinamide phosphoribosyltransferase (NAMPT). While SIRT1 functions as a key mediator that orchestrates metabolic responses to changes in nutritional availability in multiple tissues, NAMPT-mediated NAD+ biosynthesis functions as a pace maker that produces circadian-oscillatory NAD+ production and fine-tunes SIRT1 activity at a systemic level. NAMPT has intra- and extracellular forms in mammals, iNAMPT and eNAMPT, respectively. iNAMPT is ubiquitously expressed, but its levels are varied (The font size reflects a relative level of iNAMPT). eNAMPT, which is actively secreted from adipose tissue and has a higher enzymatic activity than iNAMPT, likely synthesizes nicotinamide mononucleotide (NMN) from nicotinamide (Nic) extracellularly. The availability of NMN is particularly important for tissues and organs that possess very low levels of iNAMPT, such as pancreatic β cells and central neurons. The concept of the NAD World provides several important predictions for the biological robustness and trade-offs in mammalian aging and longevity control. See text for details.