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Abstract: TH-PO418

Biomarkers of the Aging Kidney: A Proteomic Analysis of Renal Microstructures at Different Cortical Depths

Session Information

Category: Glomerular Diseases

  • 1301 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Alexander, Mariam P., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Pandey, Akhilesh, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Mullan, Aidan F., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Larson, Nicholas B., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Denic, Aleksandar, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sachdeva, Gunveen, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Asghar, Muhammad Sohaib, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Rule, Andrew D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

While we have improved understanding of age-related microstructural changes of the glomeruli & tubulointerstitium, the molecular processes are unclear. We performed proteomic profiling of glomeruli & tubulointerstitium at different cortical depths in young & aged human kidneys to identify a signature of aging.

Methods

Laser capture microdissection of non-scarred glomeruli & tubulointerstitium from superficial & deep cortex from 16 young (mean age, 30y) &16 old (mean age, 78y) radical nephrectomy wedge-sections with <10% fibrosis (non-tumor) followed by mass spectrometry–based proteomics.

Results

A total of 3228 & 3652 proteins were identified in the glomeruli & tubulointerstitium compartment, respectively. Protein signatures between old & young, differentially expressed at p<0.05 (ANOVA with a Holm-Bonferroni correction) with an absolute log2 fold change >1 were identified as potential markers for aging (Figure 1). More proteins were differentially expressed in the deep (19) vs superficial cortex (7). The glomeruli of older people, from the superficial cortex , showed decreased APOL1 & AHSG (Fetuin-A), [role in CKD], & PHGDH, [serine biosynthesis] & glomeruli of older people from deep cortex showed decreased complement factor D & GAS2 [regulator of apoptosis & senescence]. The glomeruli of older people from deep cortex, showed increased CSTA [anti-apoptotic role] & ApoD [an anti-stress protein induced by oxidative stress]. Superficial tubulointerstitium of older people showed increased HKDC1 [glucose homeostasis], & α-crystallin B chain [p53-target gene for apoptosis]. The deep tubulointerstitium of older people, showed overexpression of proteins involved in mitochondrial function, as well asTIMP3 & elastin [increased in diabetic nephropathy].

Conclusion

Proteins, particularly of deep cortex, that regulate matrix remodeling, mitochondrial function, inflammation, & metabolic homeostasis may play a role in aging.

Figure 1

Funding

  • NIDDK Support