Identification of proteins potentially associated with renal aging in rats

Abstract

We established a young (Y)-old (O) rat kidney transplantation model. With this model, we detected no age-related differences in renal structure between Y→Y and Y→O kidneys or O→O and O→Y kidneys. However, we did detect differences in levels of the senescence markers β-gal and p16 as well as the inflammatory cytokines TNF-α and IL-1β. Using proteomics analysis we detected 66 proteins associated with suppression of aging and 73 proteins associated with enhancement of aging. After construction of a protein-protein interaction network, a total of 73 nodes and 99 edges were analyzed using MCODE, and three significant modules were selected. GO and KEGG analyses showed that these proteins were mainly located in mitochondria and were largely related to oxidative stress. Among them, SOD1 expression was lower in Y→O than Y→Y kidneys and higher in O→Y than O→O kidneys. Acetylated (Ac)-NF-κB showed the opposite expression profile. In addition, SOD1 expression was higher in primary tubular epithelial cells from young rats than old rats, and SOD1 knockdown led to increased Ac-NF-κB expression. These findings suggest the local renal environment, particularly oxidative stress/mitochondrial function, affects renal aging.

Identifying the Antiproliferative Effect of Astragalus Polysaccharides on Breast Cancer: Coupling Network Pharmacology With Targetable Screening From the Cancer Genome Atlas

“…The CytoNCA plug-in performs topology analysis based on “betweenness (BC),” “closeness (CC),” “degree (DC),” “eigenvector (EC),” “local average connectivity-based method (LC),” “network (NC),” “subgraph (SC),” and “information (IC)” (17). The plug-in MCODE was used with the default parameters (degree cut-off ≥ 2, node score cut-off ≥ 0.2, K-core ≥ 2, and max depth = 100) (18). Subsequently, based on these two analyses, the main nodes in the PPI network were identified comprising the main DEGS that can be used as biomarkers of BC.…”

Effect of Youthful Blood Environment and Its Key Stem Cell Factor on Renal Interstitial Fibrosis in Elderly Mice

“…In our previous study, we have identi ed that youthful blood environment can reduce the extent of agerelated increase in kidney brosis area using parabiotic mice model [9]. However, when the elderly rat kidney was transplanted into a young rat, no obvious change in kidney brosis of the elderly rat was observed [10]. In this study, we further sought to clarify the effect of blood environmental change on senile renal interstitial brosis.…”

“…In our previous study, we observed lower expressions of renal senescence markers and decreased kidney fibrosis area in elderly HP mice after 5 weeks of shared blood circulation but with no obvious change in renal function [9]. Furthermore, the expressions of renal senescence markers were decreased 16 weeks after transplantation of an elderly rat kidney to a young rat; however, no obvious changes were observed with respect to kidney fibrosis and renal function [10]. Kidney tissue damage and function loss were significantly alleviated in elderly HP mice after ischemia-reperfusion injury, compared to the control old ischemia-reperfusion injury mice [11].…”

Effects of Donor-Recipient Age Difference in Renal Transplantation, an Investigation on Renal Function and Fluid Proteome

“…In contrast, an old internal environment increases the inflammatory and apoptotic levels in kidneys from young donors and promotes kidney aging. 6 , 7 Appropriate interventions delay and reverse kidney aging. 13 Changes in the aging status of kidneys affect renal function.…”

“…[3][4][5] By virtue of an animal model of heterochronic parabiosis and a model of heterochronic renal transplantation, our previous study found that a young internal environment improved the aging of the kidney. 6,7 In addition, employment of an animal model of heterochronic parabiosis with bilateral renal ischemia-reperfusion injury (IRI) revealed that a young internal environment alleviated IRI in elderly kidneys. 8 These studies provide the basic research evidence for increasing the age limit of kidney transplant donors.…”