Zürbig Petra, Decramer Stéphane, Dakna Mohammed, Jantos Justyna, Good David M, Coon Joshua J, Bandin Flavio, Mischak Harald, Bascands Jean-Loup, Schanstra Joost P
Mosaiques Diagnostics & Therapeutics AG, Hannover, Germany.
Proteomics. 2009 Apr;9(8):2108-17. doi: 10.1002/pmic.200800560.
Aging induces morphological changes of the kidney and reduces renal function. We analyzed the low molecular weight urinary proteome of 324 healthy individuals from 2-73 years of age to gain insight on human renal aging. We observed age-related modification of secretion of 325 out of over 5000 urinary peptides. The majority of these changes were associated with renal development before and during puberty, while 49 peptides were related to aging in adults. We therefore focussed the remainder of the study on these 49 peptides. The majority of these 49 peptides were also markers of chronic kidney disease, suggesting high similarity between aging and chronic kidney disease. Blinded evaluation of samples from healthy volunteers and diabetic nephropathy patients confirmed both the correlation of biomarkers with aging and with renal disease. Identification of a number of these aging-related peptides led us to hypothesize that reduced proteolytic activity is involved in human renal aging. Finally, among the 324 supposedly healthy individuals, some had urinary aging-related peptide excretion patterns typical of an individual significantly older than their actual age. In conclusion, these aging-related biomarkers may allow noninvasive detection of renal lesions in healthy persons and show high resemblance between human aging and chronic kidney disease. This similarity has to be taken into account when searching for biomarkers of renal disease.
衰老会引发肾脏的形态变化并降低肾功能。我们分析了324名年龄在2至73岁之间的健康个体的低分子量尿液蛋白质组，以深入了解人类肾脏衰老情况。我们观察到，在5000多种尿肽中，有325种的分泌存在与年龄相关的变化。这些变化大多与青春期之前及青春期期间的肾脏发育有关，而有49种肽与成年人的衰老相关。因此，我们将研究的剩余部分聚焦于这49种肽。这49种肽中的大多数也是慢性肾病的标志物，表明衰老与慢性肾病之间具有高度相似性。对健康志愿者和糖尿病肾病患者样本的盲法评估证实了生物标志物与衰老以及与肾病之间的相关性。对其中一些与衰老相关肽的鉴定使我们推测蛋白水解活性降低与人类肾脏衰老有关。最后，在这324名看似健康的个体中，有些人的尿液中与衰老相关的肽排泄模式显示出其实际年龄明显大于该个体实际年龄的特征。总之，这些与衰老相关的生物标志物可能有助于对健康人群的肾脏病变进行无创检测，并显示出人类衰老与慢性肾病之间的高度相似性。在寻找肾病生物标志物时必须考虑到这种相似性。
