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Klotho, Aging, and the Failing Kidney

Authors
  • Buchanan, Sarah1
  • Combet, Emilie2
  • Stenvinkel, Peter3
  • Shiels, Paul G.1
  • 1 Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow , (United Kingdom)
  • 2 School of Medicine, Dentistry & Nursing, Human Nutrition, Glasgow Royal Infirmary, Glasgow , (United Kingdom)
  • 3 Division of Renal Medicine M99, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm , (Sweden)
Type
Published Article
Journal
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Publication Date
Aug 27, 2020
Volume
11
Identifiers
DOI: 10.3389/fendo.2020.00560
PMID: 32982966
PMCID: PMC7481361
Source
PubMed Central
Keywords
License
Unknown

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.

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