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NLRP1 inflammasome modulates senescence and senescence-associated secretory phenotype
- Source :
- bioRxiv
- Publication Year :
- 2023
- Publisher :
- Cold Spring Harbor Laboratory, 2023.
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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.
- Subjects :
- Article
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- bioRxiv
- Accession number :
- edsair.doi.dedup.....0ea7ce9d74df7122c1d11e6335819f66