Ariadel-Cobo Diana G, Estébanez Brisamar, González-Arnáiz Elena, García-Pérez María Pilar, Rivera-Viloria Marta, Pintor de la Maza Begoña, Barajas-Galindo David Emilio, García-Sastre Diana, Ballesteros-Pomar María D, Cuevas María J
Institute of Biomedicine (IBIOMED), University of León, 24071 León, Spain.
Department of Endocrinology and Nutrition, Complejo Asistencial Universitario de León (CAULE), 24071 León, Spain.
Int J Mol Sci. 2025 Feb 23;26(5):1915. doi: 10.3390/ijms26051915.
The gene is recognized for its anti-aging properties. Its downregulation leads to aging-like phenotypes, whereas overexpression can extend lifespan. Klotho protein exists in three forms: α-klotho, β-klotho and γ-klotho. The α-klotho has two isoforms: a membrane-bound form, primarily in the kidney and brain, and a secreted klotho protein present in blood, urine, and cerebrospinal fluid. Klotho functions as a co-receptor for fibroblast growth factor-23 (FGF23), regulating phosphate metabolism. The membrane-bound form controls various ion channels and receptors, while the secreted form regulates endocrine FGFs, including FGF19 and FGF21. The interaction between β-klotho and FGF21 in muscle is critical in the development of sarcopenic obesity. This systematic review, registered in PROSPERO and conducted following PRISMA guidelines, evaluates klotho levels in individuals with obesity or sarcopenic obesity. The study includes overweight, obese, and sarcopenic obese adults compared to those with a normal body mass index. After reviewing 713 articles, 20 studies were selected, including observational, cross-sectional, cohort studies, and clinical trials. Significant associations between klotho levels and obesity, metabolic syndrome (MS), and cardiovascular risk were observed. Exercise and dietary interventions positively influenced klotho levels, which were linked to improved muscle strength and slower decline. Klotho is a potential biomarker for obesity, MS, and sarcopenic obesity. Further research is needed to explore its mechanisms and therapeutic potential.
该基因因其抗衰老特性而被认可。其下调会导致衰老样表型，而过表达则可延长寿命。klotho蛋白以三种形式存在：α-klotho、β-klotho和γ-klotho。α-klotho有两种异构体：一种膜结合形式，主要存在于肾脏和大脑中，另一种分泌型klotho蛋白存在于血液、尿液和脑脊液中。Klotho作为成纤维细胞生长因子23（FGF23）的共受体，调节磷酸盐代谢。膜结合形式控制各种离子通道和受体，而分泌形式调节内分泌FGFs，包括FGF19和FGF21。β-klotho与肌肉中的FGF21之间的相互作用在肌肉减少性肥胖的发展中至关重要。这项在PROSPERO注册并按照PRISMA指南进行的系统评价，评估了肥胖或肌肉减少性肥胖个体的klotho水平。该研究纳入了超重、肥胖和肌肉减少性肥胖的成年人，并与体重指数正常的人进行比较。在审查了713篇文章后，选择了20项研究，包括观察性研究、横断面研究、队列研究和临床试验。观察到klotho水平与肥胖、代谢综合征（MS）和心血管风险之间存在显著关联。运动和饮食干预对klotho水平有积极影响，这与肌肉力量改善和下降减缓有关。Klotho是肥胖、MS和肌肉减少性肥胖的潜在生物标志物。需要进一步研究以探索其机制和治疗潜力。
