Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging.
Level 5 - mechanism / opinion, no new human data
Animal research without human clinical data.
PubMed 28802039 · doi:10.1016/j.cell.2017.07.042
What was done
Circadian transcriptomics and biochemical analyses were performed in young and old mice fed either ad libitum or a calorically restricted diet. Investigators evaluated circadian gene expression across the liver, epidermal stem cells, and skeletal muscle stem cells, and measured hepatic NAD+-related metabolites and global protein acetylation oscillations across the daily cycle.
What was found
The abstract reports no numerical values. Caloric restriction reprogrammed the circadian transcriptome in mouse liver in a tissue-specific manner compared to epidermal and muscle stem cells. Genes that gained de novo circadian oscillation under caloric restriction were enriched for SIRT1 targets. Daily rhythmic global protein acetylation, which was lost in old ad libitum-fed mice, was robustly rescued by caloric restriction.
Why it matters
This work demonstrates that dietary restriction can preserve circadian metabolic control during aging by sustaining rhythmic NAD+ metabolism and cyclical protein acetylation in the liver.
Limits
Findings are limited to mice and require confirmation in human metabolic physiology. Exact sample sizes, animal strains, ages, dietary protocols, and quantitative statistical values were not reported in the abstract.
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.