title: Klotho, phosphate and inflammation/ageing in chronic kidney disease.
abstract: Evidence is emerging for the inflammatory nature of many ageing-associated diseases, including atherosclerosis, vascular calcification, diabetes and chronic kidney disease (CKD), among others. Ageing itself results in chronic low-grade inflammation that promotes end-organ damage. Inflammatory organ damage, in turn, may contribute to inflammation. Recent research has identified the kidney-secreted hormone Klotho as a central player at the ageing-inflammation interface. Thus, systemic or local renal inflammation decreases kidney Klotho expression. Klotho down-regulation may be induced by specific cytokines such as tumour necrosis factor-α or TWEAK through the canonical activation of the inflammatory transcription factor nuclear factor kappa B (NFκB) and, specifically RelA. In addition, inflammatory cytokines lead to the epigenetic inactivation of Klotho transcription. Klotho itself has antioxidant and anti-inflammatory properties and the canonical NFκB component RelA is one of its targets. Klotho is a key regulator of phosphate balance and a role of phosphate in ageing has been shown. However, the potential relationship between phosphate and inflammation requires further clarification. A correct understanding of these interactions may lead to the design of novel therapeutic approaches to CKD and CKD-related inflammatory and ageing features as well as to inflammation/ageing in general.
authors.affiliation: IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Izquierdo
authors.forename: María V
authors.initials: MV
authors.lastname: Perez-Gomez
authors.forename: María D
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.forename: Ana B
authors.initials: AB
authors.lastname: Sanz
authors.forename: Olga
authors.initials: O
authors.lastname: Ruiz-Andres
authors.forename: Jonay
authors.initials: J
authors.lastname: Poveda
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D005966:Glucuronidase / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D000090265:Klotho Proteins; D051379:Mice; D010710:Phosphates / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000209:etiology*
chemical_list: D010710:Phosphates; D005966:Glucuronidase; D000090265:Klotho Proteins