Dërmaku-Sopjani Miribane, Kolgeci Selim, Abazi Sokol, Sopjani Mentor
Department of Chemistry.
Mol Membr Biol. 2013 Dec;30(8):369-85. doi: 10.3109/09687688.2013.837518. Epub 2013 Oct 14.
The Klotho gene was identified as an 'aging suppressor' in mice. Overexpression of the Klotho gene extends lifespan and defective Klotho results in rapid aging and early death. Both the membrane and secreted forms of Klotho have biological activity that include regulatory effects on general metabolism and a more specific effect on mineral metabolism that correlates with its effect on aging. Klotho serves as a co-receptor for fibroblast growth factor (FGF), but it also functions as a humoral factor that regulates cell survival and proliferation, vitamin D metabolism, and calcium and phosphate homeostasis and may serve as a potential tumor suppressor. Moreover, Klotho protects against several pathogenic processes in a FGF23-independent manner. These processes include cancer metastasis, vascular calcification, and renal fibrosis. This review covers the recent advances in Klotho research and discusses novel Klotho-dependent mechanisms that are clinically relevant in aging and age-related diseases.
Klotho基因在小鼠中被鉴定为一种“衰老抑制因子”。Klotho基因的过表达可延长寿命，而Klotho基因缺陷则导致快速衰老和过早死亡。膜形式和分泌形式的Klotho均具有生物学活性，包括对一般代谢的调节作用以及对矿物质代谢的更特异性作用，这与其对衰老的影响相关。Klotho作为成纤维细胞生长因子（FGF）的共受体，但它也作为一种体液因子发挥作用，调节细胞存活和增殖、维生素D代谢以及钙和磷的稳态，并且可能作为一种潜在肿瘤抑制因子。此外，Klotho以FGF23非依赖的方式抵御多种致病过程。这些过程包括癌症转移、血管钙化和肾纤维化。本综述涵盖了Klotho研究的最新进展，并讨论了在衰老和年龄相关疾病中具有临床相关性的新型Klotho依赖机制。
