Study summary · research use only
NAD(+) Controls Circadian Reprogramming through PER2 Nuclear Translocation to Counter Aging
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This mouse study examined whether nucleotide metabolism changes control circadian behavioral and genomic rhythms during aging, focusing on the NAD+ precursor nicotinamide riboside (NR) and the clock repressor PER2. The authors report that NR altered metabolic and stress-response pathways through inhibition of PER2, enhanced BMAL1 chromatin binding genome-wide via PER2 K680 deacetylation, and primed PER2 phosphorylation within a domain controlling nuclear transport and stability that is mutated in human advanced sleep phase syndrome. In old mice, NR was associated with restoration of BMAL1 chromatin binding, transcriptional oscillations, mitochondrial respiration rhythms, and late evening activity toward levels observed in younger animals.
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 PER2K680 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, transcriptional oscillations, mitochondrial respiration rhythms, and late evening activity are restored by NAD+ repletion to youthful levels with NR. These results reveal effects of NAD+ on metabolism and the circadian system with aging through the spatiotemporal control of the molecular clock.
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