title: Klotho suppresses RIG-I-mediated senescence-associated inflammation.
abstract: It is well known that aged or senescent cells develop a complex senescence-associated secretory phenotype (SASP), which is observed both in culture and in vivo. However, the mechanisms underlying the induction of the SASP are largely unknown. We demonstrate that retinoic-acid-inducible gene-I (RIG-I) is induced through the ataxia telangiectasia mutated-interferon regulatory factor 1 (ATM-IRF1) axis in senescent cells and that RIG-I signalling mediates the expression of two important mediators of inflammation, interleukin-6 (IL-6) and IL-8. Klotho has been associated with ageing. We show here that the intracellular, but not the secreted, form of klotho interacts with RIG-I and that this interaction inhibits RIG-I-induced expression of IL-6 and IL-8 both in vitro and in vivo. Our study uncovers a mechanism in which klotho functions as an anti-ageing factor through the suppression of RIG-I-mediated inflammation.
authors.affiliation: National Key Laboratory of Protein Engineering and Plant Gene Engineering, LSC, Peking University, Beijing 100871, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Su
authors.initials: S
authors.lastname: Wu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Ren
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D010641:Phenotype; D011971:Receptors, Immunologic; D015398:Signal Transduction
chemical_list: D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6; D016209:Interleukin-8; D011971:Receptors, Immunologic; D005966:Glucuronidase; D000090265:Klotho Proteins; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases