Nicotinamide Riboside Reverses Age-Related Circadian and Mitochondrial Decline: Preclinical Findings

Synopsis

Aging disrupts sleep patterns and circadian rhythms, which are linked to metabolic diseases and lower NAD+ levels. This study shows that supplementing with the NAD+ precursor nicotinamide riboside (NR) restores these rhythms by targeting the clock repressor protein PER2. NR enhances the binding of the core clock protein BMAL1 to DNA by promoting deacetylation and phosphorylation of PER2, which regulates its stability and movement in cells. In old mice, NR treatment rejuvenates weakened BMAL1 activity, gene expression cycles, mitochondrial function, and evening activity to levels seen in young mice. These findings reveal how NAD+ influences metabolism and the circadian clock during aging through precise regulation of clock proteins.

Journal

Molecular Cell