Wang Yuhong, Sun Zhongjie
Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK 73104-0901, USA.
Ageing Res Rev. 2009 Jan;8(1):43-51. doi: 10.1016/j.arr.2008.10.002. Epub 2008 Oct 31.
Klotho is a new anti-aging gene. Genetic mutation of klotho causes multiple premature aging-like phenotypes and strikingly shortens lifespan. Overexpression of the klotho gene in mice suppresses aging and extends lifespan which may involve the mechanism of suppression of insulin signaling and oxidant stress. Klotho functions as a cofactor/coreceptor regulating fibroblast growth factor (FGF) 23 signaling. Klotho acts as a glucuronidase and activates ion channel TRPV5. Klotho protects against endothelial dysfunction and regulates the production of nitric oxide. Klotho also influences intracellular signaling pathways including p53/p21, cAMP, protein kinase C (PKC) and Wnt signaling pathways. The discovery of klotho has a great impact on aging research. The purpose of this review is to provide the recent progress and future directions of klotho research. Specifically, this review will cover: klotho and aging, structure and expression of the klotho gene, localization of klotho expression, source of circulating klotho, current understanding of klotho functions, and signaling pathways of klotho.
klotho是一种新的抗衰老基因。klotho的基因突变会导致多种早衰样表型，并显著缩短寿命。在小鼠中过表达klotho基因可抑制衰老并延长寿命，这可能涉及抑制胰岛素信号传导和氧化应激的机制。klotho作为一种辅助因子/共受体，调节成纤维细胞生长因子（FGF）23信号传导。klotho作为一种葡萄糖醛酸酶，激活离子通道TRPV5。klotho可防止内皮功能障碍并调节一氧化氮的产生。klotho还影响细胞内信号通路，包括p53/p21、cAMP、蛋白激酶C（PKC）和Wnt信号通路。klotho的发现对衰老研究产生了重大影响。本综述的目的是提供klotho研究的最新进展和未来方向。具体而言，本综述将涵盖：klotho与衰老、klotho基因的结构和表达、klotho表达的定位、循环klotho的来源、对klotho功能的当前理解以及klotho的信号通路。
