Liu Jiang-Feng, Wu Yue, Yang Ye-Hong, Wu Song-Feng, Liu Shu, Xu Ping, Yang Jun-Tao
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
School of Statistics and Data Science, Nankai University, Tianjin, 300071, China.
Proteome Sci. 2022 Aug 5;20(1):12. doi: 10.1186/s12953-022-00194-2.
Aging 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 are frequently obese with a fatty liver.
We applied mass spectrometry-based phosphoproteomics to obtain a global phosphorylation profile of the liver in mice aged 2 or 18 months. MaxQuant was used for quantitative analysis and PCA was used for unsupervised clustering.
Through phosphoproteome analysis, a total of 5,685 phosphosites in 2,335 proteins were filtered for quantitative analysis. PCA analysis of both the phosphoproteome and transcriptome data could distinguish young and old mice. However, from kinase prediction, kinase-substrate interaction analysis, and KEGG functional enrichment analysis done with phosphoproteome data, we observed high phosphorylation of fatty acid biosynthesis, β-oxidation, and potential secretory processes, together with low phosphorylation of the Egfr-Sos1-Araf/Braf-Map2k1-Mapk1 pathway and Ctnnb1 during aging. Proteins with differentially expressed phosphosites seemed more directly related to the aging-associated fatty liver phenotype than the differentially expressed transcripts. The phosphoproteome may reveal distinctive biological functions that are lost in the transcriptome.
In summary, we constructed a phosphorylation-associated network in the mouse liver during normal aging, which may help to discover novel antiaging strategies.
衰老 是一个复杂的生物学过程，伴随着随时间推移的功能衰退，影响着大多数生物。组学研究有助于全面了解衰老机制并发现潜在的干预方法。老年小鼠常伴有肥胖和脂肪肝。
我们应用基于质谱的磷酸化蛋白质组学技术，获得2月龄和18月龄小鼠肝脏的整体磷酸化图谱。使用MaxQuant进行定量分析，使用主成分分析（PCA）进行无监督聚类。
通过磷酸化蛋白质组分析，共筛选出2335个蛋白质中的5685个磷酸化位点进行定量分析。对磷酸化蛋白质组和转录组数据进行的PCA分析能够区分年轻小鼠和老年小鼠。然而，通过对磷酸化蛋白质组数据进行激酶预测、激酶-底物相互作用分析和KEGG功能富集分析，我们观察到衰老过程中脂肪酸生物合成、β-氧化和潜在分泌过程的磷酸化水平较高，而表皮生长因子受体（Egfr）-Sos1-Araf/Braf-丝裂原活化蛋白激酶激酶1（Map2k1）-丝裂原活化蛋白激酶1（Mapk1）信号通路和β-连环蛋白1（Ctnnb1）的磷酸化水平较低。磷酸化位点差异表达的蛋白质似乎比差异表达的转录本更直接地与衰老相关的脂肪肝表型相关。磷酸化蛋白质组可能揭示转录组中丧失的独特生物学功能。
总之，我们构建了正常衰老过程中小鼠肝脏的磷酸化相关网络，这可能有助于发现新的抗衰老策略。
