Discovery of a Potent Nicotinamide Phosphoribosyltransferase Activator for Improving Aging-associated Dysfunctions

Nicotinamide
adenine dinucleotide (NAD+) plays a crucial
role in the cellular energy metabolism pathway. Nicotinamide phosphoribosyltransferase
(NAMPT) is a rate-limiting enzyme involved in the biosynthesis of
NAD+. Herein, a series of new NAMPT activators were designed
to increase the NAD+ levels and improve aging-associated
dysfunctions. In particular, compound C8 effectively
activated NAMPT and promoted the biosynthesis of NAD+.
Furthermore, we demonstrated that NAMPT activator C8 possessed
excellent antiaging effects both in vitro and in vivo. Activator C8 showed potent activity
in delaying aging in senescent HL-7702 cells and extended the lifespan
of Caenorhabditis elegans. In a naturally
aging mouse model, compound C8 effectively alleviated
age-related dysfunctions and markers. Therefore, NAMPT activator C8 represented a promising lead compound for the treatment
of age-related diseases.