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Klotho, Aging, and the Failing Kidney
Sarah Buchanan1, Emilie Combet2, Peter Stenvinkel3
1Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.
Frontiers in Endocrinology
|September 28, 2020
Summary
Klotho, a protein regulating phosphate and vitamin D, declines with age. Therapies targeting Klotho show promise for aging-related diseases like chronic kidney disease.
Area of Science:
- Gerontology and aging research
- Molecular biology and genetics
- Metabolic and kidney disease research
Background:
- Klotho is a key regulator of phosphate homeostasis and fibroblast growth factor (FGF) signaling in mammals.
- The α-Klotho protein acts as the receptor for Fibroblast Growth Factor-23 (FGF23), influencing phosphate and vitamin D metabolism.
- Declining Klotho levels with age are linked to phosphate toxicity, a hallmark of mammalian aging.
Purpose of the Study:
- To explore Klotho's role in aging and its therapeutic potential for age-related diseases.
- To investigate senotherapeutic strategies targeting Klotho expression for mitigating age-associated functional decline.
- To highlight Klotho's direct involvement in the pathophysiology of chronic kidney disease (CKD).
Main Methods:
- Review of existing literature on Klotho function, aging, and therapeutic interventions.
- Analysis of senotherapeutic strategies including exogenous Klotho administration, Klotho agonists, and indirect modulation approaches.
- Examination of Klotho's role in phosphate homeostasis, vitamin D metabolism, and CKD.
Main Results:
- Modulation of Klotho activity presents a promising therapeutic target for the 'diseasome of aging'.
- Various senotherapeutic strategies, including direct and indirect approaches, aim to influence Klotho levels.
- These strategies hold potential for improving physiological function and resilience in aging populations.
Conclusions:
- Targeting Klotho offers a significant therapeutic avenue for age-related conditions, particularly CKD.
- Senotherapeutic interventions influencing Klotho may combat age-associated functional decline and improve health outcomes.
- Further research into Klotho modulation is crucial for developing effective anti-aging therapies.
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