Hypermethylation of CpG islands located in the promoter regions of genes is a major event in the development of the majority of cancer types, due to the subsequent aberrant silencing of important tumor suppressor genes. KLOTHO; a novel gene associated primarily with suppressing senescence has been shown to contribute to tumorigenesis as a result of its impaired function. Recently the relevance ...

The Klotho gene codes for a type-i membrane protein that exists in two forms—as a transmembrane protein and as a secreted protein. Particularly the secreted form of Klotho suppresses oxidative stress and growth factor signaling and regulates ion channels and transporters. it was reported that Klotho overexpression suppresses insulin/iGF-1 signaling. This signaling pathway was indicated as a cen...

Fibrotic aortic valve disease (FAVD) is an important cause of aortic stenosis, yet currently there is no effective treatment for FAVD due to its unknown etiology. The purpose of this study was to investigate whether deficiency in the anti-aging Klotho gene (KL) promotes high-fat-diet-induced FAVD and to explore the underlying molecular mechanism. Heterozygous Klotho-deficient (KL(+/-) ) mice an...

We propose that ageing is linked to colonic carcinogenesis through crosstalk between Wnt activity and signalling pathways related to ageing and senescence: progerin, klotho and mTOR. Mutations in the Wnt signalling pathway are responsible for the majority of colorectal cancers (CRCs); however, hyperactivation of Wnt signalling by butyrate, a breakdown product of dietary fibre, induces CRC cell ...

The functional interaction between fibroblast growth factor 23 (FGF-23) and Klotho in the control of vitamin D and phosphate homeostasis is manifested by the largely overlapping phenotypes of Fgf23- and Klotho-deficient mouse models. However, to date, targeted inactivation of FGF receptors (FGFRs) has not provided clear evidence for an analogous function of FGFRs in this process. Here, by means...

The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis-stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2...

Klotho is a recently identified antiaging gene. Brain endothelin-1 (ET1) is important in the regulation of blood pressure (BP). We hypothesized that silence of brain klotho potentiates cold-induced elevation of BP via the endothelin pathway. To silence brain klotho, we constructed adeno-associated virus (AAV) carrying rat klotho small interference hairpin RNA (KL-shRNA). AAV carrying ET1-shRNA ...

Chronic kidney disease (CKD) is a global health burden of growing incidence and prevalence. As renal function declines disturbances in mineral metabolism, such as hyperphosphatemia and secondary hyperparathyroidism, inevitably develop. These metabolic changes are closely associated with poor prognosis and survival. The bonederived hormone fibroblast growth factor-23 (FGF23) and its co-receptor ...