NAD⁺ Controls Circadian Reprogramming through PER2 Nuclear Translocation to Counter Aging.

ABSTRACT: Disrupted sleep-wake and molecular circadian rhythms are a feature of aging associated with metabolic disease and reduced levels of NAD⁺, yet whether changes in nucleotide metabolism control circadian behavioral and genomic rhythms remains unknown. Here, we reveal that supplementation with the NAD⁺ precursor nicotinamide riboside (NR) markedly reprograms metabolic and stress-response pathways that decline with aging through inhibition of the clock repressor PER2. NR enhances BMAL1 chromatin binding genome-wide through PER2^K680 deacetylation, which in turn primes PER2 phosphorylation within a domain that controls nuclear transport and stability and that is mutated in human advanced sleep phase syndrome. In old mice, dampened BMAL1 chromatin binding, transcri

SUBMITTER: Levine DC 

PROVIDER: S-EPMC7275919 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature