Author:
Muela-Zarzuela Inés,Suarez-Rivero Juan Miguel,Gallardo-Orihuela Andrea,Wan Chun,Izawa Kumi,Gregorio-Procopio Marta de,Coillin Isabelle,Ryffel Bernhard,Kitaura Jiro,Sanz Alberto,Zglinicki Thomas von,Mbalaviele Gabriel,Cordero Mario D.
Abstract
AbstractSenescence is a cellular aging-related process triggered by different stresses and characterized by the secretion of various inflammatory factors referred to as the senescence-associated secretory phenotype (SASP). Here, we present evidence that the inflammasome sensor, NLRP1, is a key mediator of senescence induced by irradiation both in vitro and in vivo. The NLRP1 inflammasome promotes senescence by regulating the expression of p16, p21, p53, and SASP in Gasdermin D (GSDMD)-dependent manner as these responses are reduced in conditions of NLRP1 insufficiency or GSDMD inhibition. Mechanistically, the NLRP1 inflammasome is activated downstream of the cytosolic DNA sensor cGMP-AMP (cGAMP) synthase (cGAS) in response to genomic damage. These findings provide a rationale for inhibiting the NLRP1 inflammasome-GSDMD axis to treat senescence-driven disorders.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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