Comparative proteomic analysis identifies biomarkers for renal aging

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.