Klotho, Aging, and the Failing Kidney.

Front Endocrinol (Lausanne)

Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.

Published: May 2021

AI Article Synopsis

  • Klotho is a gene linked to aging in mammals, regulating phosphate levels and the action of fibroblast growth factors, particularly FGF23.
  • The decline in Klotho levels with age is associated with phosphate toxicity, making Klotho a key target for therapies aimed at age-related diseases, especially chronic kidney disease (CKD).
  • Various strategies, including Klotho administration and modulation of diet and gut microbiota, have been explored to boost Klotho expression, showing promise for enhancing health and resilience in aging populations.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481361PMC
http://dx.doi.org/10.3389/fendo.2020.00560DOI Listing

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