Sopjani M, Rinnerthaler M, Kruja J, Dermaku-Sopjani M
(M. Sopjani) Faculty of Medicine of the University of Prishtina, Str. Bulevardi i Dëshmorëve, p.n., 10 000, Prishtina, Kosova.
Curr Mol Med. 2015;15(1):27-37. doi: 10.2174/1566524015666150114111258.
The Klotho protein deficiency is known to participate in premature aging. As an aging suppressor, Klotho is an important molecule in aging processes and its overexpression results in longevity. Due to many reasons, the insulin/insulin-like growth factor-1 (IGF-1) has been considered as a key pathway in aging research. The Klotho gene is closely related to this pathway. The Klotho gene encodes a transmembrane protein that after cleavage is also found as a secreted protein. Importantly, its overexpression suppresses insulin/IGF-1 signaling and thus extends the lifespan. In addition, Klotho participates in the regulation of several other intracellular signaling pathways, including regulation of FGF23 signaling, cAMP, PKC, transforming growth factor-β (TGF-β), p53/p21, and Wnt signaling. The aim of this review is to summarize current literature that shows the involvement of Klotho in the regulation of several intracellular pathways. The results of our review clearly indicate that Klotho participates in several intracellular signaling pathways, and by regulating them, Klotho is involved in aging and longevity.
已知klotho蛋白缺乏会导致早衰。作为一种衰老抑制因子，klotho是衰老过程中的重要分子，其过表达可延长寿命。由于多种原因，胰岛素/胰岛素样生长因子-1（IGF-1）被认为是衰老研究中的关键途径。klotho基因与该途径密切相关。klotho基因编码一种跨膜蛋白，该蛋白在裂解后也以分泌蛋白的形式存在。重要的是，其过表达会抑制胰岛素/IGF-1信号传导，从而延长寿命。此外，klotho参与调节其他几种细胞内信号通路，包括FGF23信号传导、cAMP、PKC、转化生长因子-β（TGF-β）、p53/p21和Wnt信号传导的调节。本综述的目的是总结当前文献，这些文献表明klotho参与调节多种细胞内途径。我们综述的结果清楚地表明，klotho参与多种细胞内信号通路，并通过调节这些通路参与衰老和长寿过程。
