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.