NAD World 3.0: the importance of the NMN transporter and eNAMPT in mammalian aging and longevity control.

Over the past five years, systemic NAD⁺ (nicotinamide adenine dinucleotide) decline has been accepted to be a key driving force of aging in the field of aging research. The original version of the NAD World concept was proposed in 2009, providing an integrated view of the NAD⁺-centric, systemic regulatory network for mammalian aging and longevity control. The reformulated version of the concept, the NAD World 2.0, was then proposed in 2016, emphasizing the importance of the inter-tissue communications between the hypothalamus and peripheral tissues including adipose tissue and skeletal muscle. There has been significant progress in our understanding of the importance of nicotinamide mononucleotide (NMN), a key NAD⁺ intermediate, and nicotinamide phosphoribosyltransferase (NAMPT), particularly extracellular NAMPT (eNAMPT). With these exciting developments, the further reformulated version of the concept, the NAD World 3.0, is now proposed, featuring multi-layered feedback loops mediated by NMN and eNAMPT for mammalian aging and longevity control.