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Updated: Sep 30, 2025

Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Phosphate and Cellular Senescence
Ming Chang Hu1,2, Orson W Moe3,4,5
1Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA. ming-chang.hu@utsouthwestern.edu.
Abstract:
Cellular senescence is one type of permeant arrest of cell growth and one of increasingly recognized contributor to aging and age-associated disease. High phosphate and low Klotho individually and synergistically lead to age-related degeneration in multiple organs. Substantial evidence supports the causality of high phosphate in cellular senescence, and potential contribution to human aging, cancer, cardiovascular, kidney, neurodegenerative, and musculoskeletal diseases. Phosphate can induce cellular senescence both by direct phosphotoxicity, and indirectly through downregulation of Klotho and upregulation of plasminogen activator inhibitor-1. Restriction of dietary phosphate intake and blockage of intestinal absorption of phosphate help suppress cellular senescence. Supplementation of Klotho protein, cellular senescence inhibitor, and removal of senescent cells with senolytic agents are potential novel strategies to attenuate phosphate-induced cellular senescence, retard aging, and ameliorate age-associated, and phosphate-induced disorders.
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