A conserved NAD+ binding pocket that regulates protein-protein interactions during aging
NAD+ binding modulates protein interactions
An unexpected function of the oxidized form of nicotinamide adenine dinucleotide (NAD+) could underlie some effects of aging and propensity to age-related diseases. Li et al. found that the protein DBC1 (deleted in breast cancer 1) contains a domain that specifically binds NAD+. Binding of NAD+ inhibited the interaction of DBC1 with PARP1 [poly(adenosine diphosphate–ribose) polymerase 1], an enzyme important in DNA repair. The activity of PARP1 is inhibited by interaction with DBC1. Thus, the reduced abundance of NAD+ associated with aging may decrease PARP1 activity by promoting the interaction of PARP1 with DBC1. This mechanism could help explain the reported rejuvenating actions of NAD+ supplementation in older animals.