Comparative proteomic analysis identifies biomarkers for renal aging.
Comparative proteomic analysis identifies biomarkers for renal aging.
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比较蛋白质组学分析确定肾脏衰老的生物标志物
DOI：
10.18632/aging.104007
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发表时间：
2020-11-06
期刊：
影响因子：
--
通讯作者：
Deng H
中科院分区：
文献类型：
--
作者：
Yi M;Ma Y;Zhu S;Luo C;Chen Y;Wang Q;Deng H
蛋白质组学长期以来一直被应用于衰老分子特征的表征。由于用于蛋白质组学分析的方法和仪器不同，需要进行数据集间验证以识别潜在的衰老生物标志物。在这项研究中，我们使用比较蛋白质组学分析，在小鼠肾脏蛋白质组和谷胱甘肽组的轮廓与年龄相关的变化。我们在三个不同的数据集中确定了108种在年轻和老年小鼠肾脏中差异表达的蛋白质;从这些蛋白质中，27种蛋白质被确定为潜在的肾脏衰老生物标志物，包括磷酸烯醇丙酮酸羧激酶（Pck 1），CD 5抗原样蛋白（Cd 5l），醛脱氢酶1（Aldh 1a 1）和尿调蛋白。我们的研究结果还表明，过氧化物酶体蛋白在老年小鼠中显著下调，而IgG上调，这表明过氧化物酶体退化可能是肾脏衰老的标志。谷胱甘肽组分析表明，过氧化氢酶和谷氧还蛋白-1（Glrx 1）的下调显着增加蛋白谷胱甘肽在老年小鼠。此外，烟酰胺单甘肽（NMN）给药显著增加了老年小鼠肾脏中过氧化物酶体的数量，表明NMN增强了过氧化物酶体的生物合成，并表明它可能有利于减少肾损伤。总之，我们的数据确定了肾脏衰老的新的潜在生物标志物，并为了解肾脏中与年龄相关的变化提供了宝贵的资源。
Proteomics have long been applied into characterization of molecular signatures in aging. Due to different methods and instrumentations employed for proteomic analysis, inter-dataset validation needs to be performed to identify potential biomarkers for aging. In this study, we used comparative proteomics analysis to profile age-associated changes in proteome and glutathionylome in mouse kidneys. We identified 108 proteins that were differentially expressed in young and aged mouse kidneys in three different datasets; from these, 27 proteins were identified as potential renal aging biomarkers, including phosphoenolpyruvate carboxykinase (Pck1), CD5 antigen-like protein (Cd5l), aldehyde dehydrogenase 1 (Aldh1a1), and uromodulin. Our results also showed that peroxisomal proteins were significantly downregulated in aged mice, whereas IgGs were upregulated, suggesting that peroxisome deterioration might be a hallmark for renal aging. Glutathionylome analysis demonstrated that downregulation of catalase and glutaredoxin-1 (Glrx1) significantly increased protein glutathionylation in aged mice. In addition, nicotinamide mononucleotide (NMN) administration significantly increased the number of peroxisomes in aged mouse kidneys, indicating that NMN enhanced peroxisome biogenesis, and suggesting that it might be beneficial to reduce kidney injuries. Together, our data identify novel potential biomarkers for renal aging, and provide a valuable resource for understanding the age-associated changes in kidneys.
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