Klotho suppresses RIG-I-mediated senescence-associated inflammation

Abstract

The senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells, but the mechanisms underlying cytokine secretion were unknown. Klotho, a protein with purported anti-ageing effects, is now shown to inhibit RIG-I-mediated secretion of IL-6 and IL-8 during replicative senescence. 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.

Cite this article

Liu, F., Wu, S., Ren, H. et al. Klotho suppresses RIG-I-mediated senescence-associated inflammation. Nat Cell Biol 13, 254–262 (2011). https://doi.org/10.1038/ncb2167

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