衰老过程的特征是结构退化和功能衰退,以及适应性和抵抗力减弱。衰老的肾脏表现出各种结构和功能损害。在衰老的小鼠中,观察到毛皮变薄和变白,与年轻组相比,肾脏指数显着增加。生化指标显示肌酐水平升高,尿素氮和血清尿酸,提示肾功能受损.组织学分析揭示了肾小球增大和硬化,严重的透明变性,毛细血管闭塞,淋巴细胞浸润,肾小管和肾小球纤维化,胶原蛋白沉积增加。电子显微镜下的观察显示基底膜增厚,改变了脚部的突起,并增加系膜和系膜基质。分子标记分析提示衰老相关β-半乳糖苷酶上调,p16-INK4A,和老年小鼠肾脏中的DNA损伤标记γH2AX。在代谢组学中,总共鉴定出62种明显不同的代谢物,并丰富了10条途径。我们建议瓜氨酸,多巴胺,和硫酸吲哚酚有可能成为未来与衰老相关的肾脏损害的标志物。磷酸化蛋白质组学分析确定了1,555种蛋白质中的6,656个磷酸化位点,注释了62条路径,并表明在微小染色体维持复合物成分2(Mcm2)的Ser27位点磷酸化增加,在异质核核糖核蛋白K(hnRNPK)的Ser284位点降低,这些修饰通过蛋白质印迹得到证实。这些分子中的磷酸化变化可能通过影响基因组不稳定性而导致衰老。在两个组学中都检测到了11条常见的途径,包括精氨酸生物合成,嘌呤代谢和不饱和脂肪酸的生物合成,等。,与衰老和肾功能不全密切相关。
The process of aging is characterized by structural degeneration and functional decline, as well as diminished adaptability and resistance. The aging kidney exhibits a variety of structural and functional impairments. In aging mice, thinning and graying of fur were observed, along with a significant increase in kidney indices compared to young mice. Biochemical indicators revealed elevated levels of creatinine, urea nitrogen and serum uric acid, suggesting impaired kidney function. Histological analysis unveiled glomerular enlargement and sclerosis, severe hyaline degeneration, capillary occlusion, lymphocyte infiltration, tubular and glomerular fibrosis, and increased collagen deposition. Observations under electron microscopy showed thickened basement membranes, altered foot processes, and increased mesangium and mesangial matrix. Molecular marker analysis indicated upregulation of aging-related β-galactosidase, p16-INK4A, and the DNA damage marker γH2AX in the kidneys of aged mice. In metabolomics, a total of 62 significantly different metabolites were identified, and 10 pathways were enriched. We propose that citrulline, dopamine, and indoxyl sulfate have the potential to serve as markers of kidney damage related to aging in the future. Phosphoproteomics analysis identified 6656 phosphosites across 1555 proteins, annotated to 62 pathways, and indicated increased phosphorylation at the Ser27 site of Minichromosome maintenance complex component 2 (Mcm2) and decreased at the Ser284 site of heterogeneous nuclear ribonucleoprotein K (hnRNP K), with these modifications being confirmed by western blotting. The phosphorylation changes in these molecules may contribute to aging by affecting genome stability. Eleven common pathways were detected in both omics, including arginine biosynthesis, purine metabolism and biosynthesis of unsaturated fatty acids, etc., which are closely associated with aging and renal insufficiency.