Pancreatic β-cells and neurons (the brain) are two major frailty points in the NAD World because these two cell types have very low levels of iNAMPT. These particular cell types likely depend on extracellular NMN, which is speculated to be synthesized by eNAMPT secreted by adipose tissue, and maintain optimal NAD levels for their functions. Chronic inflammation, which is caused by inflammatory cytokines and oxidative stress, decreases NAMPT and NAD levels in multiple tissues, contributing to the pathogenesis of age-associated metabolic complications, such as type 2 diabetes. It still remains unclear whether chronic inflammation in adipose tissue also decreases plasma eNAMPT levels and remotely affects the functions of “frailty” cell types. More details for the concept of the NAD World are given in the text.