Impact of Dietary Interventions on Noncoding RNA Networks and mRNAs Encoding Chromatin-Related Factors

Dietary interventions dramatically affect metabolic disease and lifespan in various aging models. Here, we profiled liver microRNA (miRNA), coding, and long non-coding RNA (lncRNA) expression by high-throughput deep sequencing in mice across multiple energy intake and expenditure interventions. Strikingly, three dietary intervention network design patterns were uncovered: (1) lifespan-extending interventions largely repressed the expression of miRNAs, lncRNAs, and transposable elements; (2) protein-coding mRNAs with expression positively correlated with long lifespan are highly targeted by miRNAs; and (3) miRNA-targeting interactions mainly target chromatin-related functions. We experimentally validated miR-34a, miR-107, and miR-212-3p targeting of the chromatin remodeler Chd1 and further demonstrate that Chd1 knockdown mimics high-fat diet and aging-induced gene expression changes and activation of transposons. Our findings demonstrate lifespan-extending diets repress miRNA-chromatin remodeler interactions and safeguard against deregulated transcription induced by aging and lifespan shortening diets, events linked by microRNA, chromatin, and ncRNA crosstalk.