Klotho, Aging, and the Failing Kidney

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2020 Sep 28

PMID 32982966

Citations 82

Authors

Sarah Buchanan

Emilie Combet

Peter Stenvinkel

Paul G Shiels

Affiliations

Soon will be listed here.

Abstract

Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.

Citing Articles

Aging and chronic kidney disease: epidemiology, therapy, management and the role of immunity.

Tang Y, Jiang J, Zhao Y, Du D Clin Kidney J. 2025; 17(9):sfae235.

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Interaction Effect of Estimated Pulse Wave Velocity and Serum Klotho Level on Chronic Kidney Disease.

Zou P, Li J, Chen L, Liu M, Nie H, Yan J Aging Med (Milton). 2025; 8(1):e70005.

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Suppression of Fibroblast Growth Factor 23 in UMR106 Osteoblast-Like Cells and MC3T3-E1 Cells by Adipokine Chemerin.

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Predictive value of circulating fibroblast growth factor-23 and Klotho on protein-energy wasting in patients undergoing hemodialysis.

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