Integrated Multiomics Reveals Intergenerational Brain Sensory System Remodeling Induced by Parental Intermittent Fasting

Integrated multiomics analysis shows that parental intermittent fasting (IF) before mating induces coordinated molecular remodeling in the cerebral cortex of fathers and F1 offspring never directly fasted, with both generations sharing signatures of olfactory, taste, synaptic, and neurometabolic pathways. Combining whole-genome bisulfite sequencing, transcriptomic, and proteomic data, IF triggered widespread cortical epigenetic remodeling in fathers; offspring showed sex-dependent differences in DNA methylation, gene expression, and protein abundance, involving conserved networks such as glutamatergic signaling, synaptic assembly, intracellular trafficking, cytoskeletal regulation, and stress response.