Klotho: A Potential Therapeutic Target in Aging and Neurodegeneration Beyond Chronic Kidney Disease

NDT Plus Pub Date : 2023-11-03 DOI:10.1093/ckj/sfad276

Mehmet Kanbay, Sidar Copur, Lasin Ozbek, Ali Mutlu, Daniel Cejka, Paola Ciceri, Mario Cozzolino, Mathias Loberg Haarhaus

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Abstract

Abstract Klotho, a multifunctional protein, acts as a co-receptor in FGF23, and exerts its impact through various molecular pathways, including Wnt, HIF, IGF-1 pathways. The physiological significance of Klotho is the regulation of vitamin D and phosphate metabolism, as well as serving as a vital component in aging and neurodegeneration. The role of Klotho in aging and neurodegeneration in particular has gained considerable attention. Hereby, in this narrative review, we highlighted several key insights into the molecular basis and physiological function of Klotho and synthesized current research on the role of Klotho in neurodegeneration and aging. Klotho deficiency was associated with cognitive impairment, reduced growth, diminished longevity, and the development of age-related diseases in vivo. Serum Klotho levels showed a decline in individuals with advanced age and those affected by chronic kidney disease, establishing its potential diagnostic significance. Additionally, multiple medications have been demonstrated to influence Klotho levels. Therefore, this comprehensive review suggests that Klotho could open the door to novel interventions aimed at addressing the challenges of aging and neurodegenerative disorders.

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Klotho:除慢性肾脏疾病外，衰老和神经退行性变的潜在治疗靶点

Klotho是一种多功能蛋白，在FGF23中作为共受体，通过多种分子途径发挥作用，包括Wnt、HIF、IGF-1途径。Klotho的生理意义是调节维生素D和磷酸盐代谢，并在衰老和神经变性中发挥重要作用。特别是Klotho在衰老和神经退行性变中的作用已经引起了相当大的关注。因此，在这篇综述中，我们重点介绍了Klotho的分子基础和生理功能，并综合了Klotho在神经变性和衰老中的作用的研究现状。Klotho缺乏症与体内认知障碍、生长减缓、寿命缩短和年龄相关疾病的发展有关。血清Klotho水平在老年人和慢性肾脏疾病患者中显示下降，确立了其潜在的诊断意义。此外，多种药物已被证明可以影响Klotho水平。因此，这项综合综述表明，Klotho可能为解决衰老和神经退行性疾病挑战的新干预措施打开大门。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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