Klotho, ageing and the failing kidney

Buchanan, S., Combet, E. , Stenvinkel, P. and Shiels, P.G. (2020) Klotho, ageing and the failing kidney. Frontiers in Endocrinology, 11, 560. (doi: 10.3389/fendo.2020.00560) (PMID:32982966) (PMCID:PMC7481361)

Abstract

Klotho has been recognised as a gene involved in the ageing process in mammals for over thirty 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 ageing 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 ageing; 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 ageing.

• Item Type: Articles
• Additional Information: Funding: PS was supported by the Swedish Heart and Lung Foundation (No. 20160384), as well as the Strategic Research Programme in Diabetes at Karolinska Institutet (Swedish Research Council Grant No. 2009-1068). PS was supported by independent Ph.D. Partnership awards between the University of Glasgow and Constant Pharma Ltd. and 4D Pharma limited.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Buchanan, Dr Sarah and Shiels, Professor Paul and Combet Aspray, Professor Emilie
• Authors: Buchanan, S., Combet, E., Stenvinkel, P., and Shiels, P.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Frontiers in Endocrinology
• Publisher: Frontiers Media
• ISSN: 1664-2392
• ISSN (Online): 1664-2392
• Copyright Holders: Copyright © 2020 Buchanan, Combet, Stenvinkel and Shiels
• First Published: First published in Frontiers in Endocrinology 11:560
• Publisher Policy: Reproduced under a Creative Commons license