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NLRP1 inflammasome modulates senescence and senescence-associated secretory phenotype.
- Source :
-
BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 28. Date of Electronic Publication: 2023 Mar 28. - Publication Year :
- 2023
-
Abstract
- Senescence 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.
Details
- Language :
- English
- ISSN :
- 2692-8205
- Database :
- MEDLINE
- Journal :
- BioRxiv : the preprint server for biology
- Accession number :
- 36798300
- Full Text :
- https://doi.org/10.1101/2023.02.06.527254