NAD + Controls Circadian Reprogramming through PER2 Nuclear Translocation to Counter Aging.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model and bench mechanistic research without human clinical data.
PubMed 32369735 · doi:10.1016/j.molcel.2020.04.010
What was done
Investigated the mechanisms by which the NAD+ precursor nicotinamide riboside (NR) affects circadian function and metabolism in aged mice. Evaluated genome-wide BMAL1 chromatin binding, PER2 post-translational modifications (acetylation and phosphorylation), circadian transcriptional oscillations, mitochondrial respiration rhythms, and evening behavioral activity.
What was found
NR supplementation promoted PER2 K680 deacetylation, which primed PER2 phosphorylation within a domain controlling nuclear transport and stability, thereby inhibiting PER2 clock repression. In aged mice, NAD+ repletion restored dampened genome-wide BMAL1 chromatin binding, transcriptional oscillations, rhythmic mitochondrial respiration, and late-evening physical activity back to youthful levels. The abstract does not provide exact numerical values, effect sizes, or variance measures.
Why it matters
Demonstrates a direct biochemical pathway linking cellular NAD+ availability to core molecular clock reprogramming, suggesting a potential mechanism to address circadian and metabolic deterioration in aging.
Limits
Findings are restricted to animal and in vitro models; direct translation to human circadian physiology and aging remains unproven. The abstract lacks specific sample sizes, dosage protocols, quantitative effect sizes, and evaluation of potential long-term adverse effects.
Cited by
- supports NAD synthesis and NAD-dependent metabolic processes are regulated by circadian time-of-day cues, and age-related loss of chronosynchrony in mice disrupts the NAD system.