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Updated: May 26, 2026
08:18
Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Indoxyl sulfate induces nephrovascular senescence
Toshimitsu Niwa1, Hidehisa Shimizu
1Department of Advanced Medicine for Uremia, Nagoya University School of Medicine, Showa-ku, Nagoya, Japan. tniwa@med.nagoya-u.ac.jp
Summary
Indoxyl sulfate accelerates chronic kidney disease (CKD) and cardiovascular disease progression by inducing cell senescence in the kidneys and blood vessels. AST-120, an oral sorbent, may reduce indoxyl sulfate levels in CKD patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Toxicology
Background:
- Indoxyl sulfate accumulates in chronic kidney disease (CKD) patients.
- Indoxyl sulfate is a precursor to kidney and vascular disease progression.
Purpose of the Study:
- To investigate the mechanisms by which indoxyl sulfate accelerates CKD and cardiovascular disease.
- To explore the role of indoxyl sulfate in inducing cell senescence and its downstream effects.
Main Methods:
- Administration of indoxyl sulfate to hypertensive rats.
- Analysis of renal and aortic tissues for markers of senescence, fibrosis, and calcification.
- Investigation of reactive oxygen species (ROS) and signaling pathways (NF-κB, p53).
Main Results:
- Indoxyl sulfate induced proximal tubular cell senescence, kidney fibrosis, and reduced Klotho expression in rats.
- Indoxyl sulfate promoted aortic calcification, thickening, and vascular smooth muscle cell senescence in rats.
- Indoxyl sulfate increased ROS production and activated NF-κB and p53 pathways in renal and vascular cells.
Conclusions:
- Indoxyl sulfate accelerates CKD and cardiovascular disease progression by inducing nephrovascular cell senescence.
- Targeting indoxyl sulfate, potentially with oral sorbents like AST-120, may offer a therapeutic strategy for CKD and cardiovascular complications.
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