Klotho Protein: A Multifaceted Guardian of Healthy Aging and Its Therapeutic Potential

Abstract

The Klotho protein, encoded by the KL gene, has garnered significant attention as a pivotal biomolecule in the field of aging research. Its expression levels are closely correlated with both lifespan and overall health status, exerting influence over critical physiological processes such as metabolic homeostasis, oxidative stress response, and inflammation modulation. This review aims to systematically examine the multifaceted roles of Klotho within the context of aging and its implications for various age-associated disorders. We highlight the emerging evidence suggesting that Klotho may serve as a key regulator in age-related pathologies, including cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Furthermore, we explore the potential of Klotho as a therapeutic target, positing that interventions aimed at enhancing Klotho activity could offer novel strategies for alleviating the health burdens experienced by the aging population.

Keywords: Klotho; aging; inflammation; oxidative stress; population aging.

Figure 1

Klotho protein-mediated network of signaling pathways. This figure shows the multiple biological pathways Klotho protein is involved in and its intermolecular interactions. Klotho induces PF4 production, which affects cognitive function after crossing the blood-brain barrier. In calcium and phosphorus metabolism, FGF23 binds to the α-Klotho-FGFR complex, activating the FGF signaling pathway to maintain balance. FGF19 and FGF21 bind to β-Klotho-FGFR complexes for metabolic regulation. In the Nrf2-GR pathway, increased Klotho leads to Nrf2 binding to antioxidant response element (ARE), enhancing glutathione reductase (GR) expression and activity. Klotho is also involved in Wnt/β-catenin and TGF-β pathways. In the Wnt/β-catenin pathway, it may affect β-catenin – related processes, and in the TGF-β pathway, it inhibits receptor binding and reduces oxidative stress. Overall, these pathways highlight Klotho’s significance in health maintenance and anti – aging.

Figure 2

Klotho Protein Detection Protocol and Clinical Application. This diagram presents the clinical application scenario of Klotho protein. Firstly, blood and urine samples of patients are collected, these are then subjected to laboratory testing using quantitative methods such as ELISA to measure Klotho protein concentrations. Secondly, the test results will be compared. Lower levels of Klotho may indicate a higher risk of chronic kidney disease (CKD) and cardiovascular disease (CVD), while higher levels might be associated with longevity or other conditions. Finally, combined with all diagnostic information such as clinical examination and laboratory tests, personalized treatment strategies are regularly monitored to evaluate therapeutic efficacy. (Some of the icons above are from BioGDP.com).