Integrated transcriptomics and metabolomics analysis reveal the molecular mechanism of unsaponifiable matter in delaying aging

Aging is one of the causes of cognitive dysfunction, which seriously affects people's quality of life. Unsaponifiable matter (USM) has antioxidant potential, but the molecular mechanisms that ameliorate aging and cognitive dysfunction are unknown. In this study, we used a galactose-induced brain aging mouse model and systematically analyzed the mechanism of USM in delaying aging in mice by detecting changes in serum and brain by metabolomics and transcriptomics. USM was compared with the model group, and non-targeted metabolomics identified 68 (15 up-regulated, 53 down-regulated) differentially metabolites, and transcriptomics identified 303 differentially expressed genes (228 up-regulated, 75 down-regulated). Combined multi-omics analyses showed that USM maintains normal brain function by regulating glycolytic processes, the tricarboxylic acid cycle (TCA), tryptophan metabolism, pyrimidine metabolism, the alanine, aspartate, and glutamate metabolism, and p38 mitogen-activated protein kinase (p38 MAPK) pathway. Meanwhile, USM increased neurotransmitter release from GABAergic synapses and cholinergic synapses by regulating synaptic vesicle cycling. In summary, USM increased energy metabolism and enhanced brain nerve signaling in the mouse brain, thereby delaying brain aging. This investigation offers novel perspectives into the molecular mechanism of USM to mitigate brain aging.