Nicotinamide riboside functions during development while beta-hydroxybutyrate functions during adulthood to extend C....

Nicotinamide riboside (NR), a form of vitamin B3 and a nicotinamide adenine dinucleotide (NAD ⁺ ) precursor, has been shown to activate the mitochondrial unfolded protein response (UPR ^mt ) and extend the lifespan when supplemented to C. elegans. The ketone body and histone deacetylase (HDAC) inhibitor beta-hydroxybutyrate (BHB) has also been shown to extend C. elegans lifespan. Experiments were performed that showed that NR extended lifespan by acting almost exclusively during larval development, while BHB extended lifespan by acting during adulthood, and the combination of NR during development and BHB during adulthood unexpectedly decreased lifespan. This suggests that hormesis is involved in the lifespan-altering effects of BHB and NR and that they are inducing parallel longevity pathways that converge on a common downstream target.