Phosphoproteome Profiling of Mouse Liver During Normal Aging
Abstract BackgroundAging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Omics studies help to comprehensively understand the mechanism of aging and discover potential intervention methods. Old mice were frequently obese with a fatty liver. MethodsWe applied mass spectrometry-based phosphoproteomics to obtain a global phosphorylation profile of liver in mice aged 2 or 18 months. A total of 5,685 phosphosites in 2,335 proteins were filtered for quantitative analysis. Phosphoproteome weakly separated young and old mice. ResultsCombining kinase prediction, kinase-substrate interaction analysis, and KEGG functional enrichment analysis, we observed high phosphorylation of fatty acid biosynthesis, b-oxidation, and potential secretory process, together with low phosphorylation of Egfr-Sos1-Araf/Braf-Map2k1-Mapk1 pathway and Ctnnb1 during aging. Proteins with differentially expressed phosphosites seemed more directly related to aging-associated fatty liver phenotype compared to the differentially expressed transcripts. Phosphoproteome may observe distinctive biological functions lost in transcriptome and proteome. ConclusionsIn summary, we constructed a phosphorylation-associated network in the liver of mice during normal aging, which may help to discover novel anti-aging strategies.