NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR

Research on the biology of NAD+ has been gaining momentum, offering many critical insights into the pathogenesis of age-associated functional decline and diseases. Notably, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has demonstrated preventive and therapeutic effects, improving age-related pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD+ intermediates can exhibit distinct behaviors, with their fates appearing to depend on the tissue distribution and expression levels of NAD+ biosynthetic enzymes, nucleotidases, and presumptive transporters. A comprehensive concept connecting NAD+ metabolism to the control of aging and longevity in mammals has been proposed, setting the stage to test whether these exciting preclinical results can be translated to improve human health.