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Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence
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Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence
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Journal Article
Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence
2017
Overview
Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells. The activation of cGAS, in turn, triggers the production of SASP factors via stimulator of interferon genes (STING), thereby promoting paracrine senescence. We demonstrate that diverse stimuli of cellular senescence engage the cGAS–STING pathway
in vitro
and we show cGAS-dependent regulation of senescence following irradiation and oncogene activation
in vivo
. Our findings provide insights into the mechanisms underlying cellular senescence by establishing the cGAS–STING pathway as a crucial regulator of senescence and the SASP.
Glück
et al.
find that the DNA-sensing component cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments produced in senescent cells leading to STING-mediated production of SASPs, which promotes paracrine senescence.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/31
/ 13/51
/ 13/89
/ 13/95
/ 14/63
/ 38/77
/ 64/60
/ Aging
/ AMP
/ Analysis
/ Animals
/ Cells
/ Cellular Senescence - radiation effects
/ Chromatin - radiation effects
/ DNA
/ Female
/ Genotype
/ Immunity, Innate - radiation effects
/ Male
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Nucleotidyltransferases - genetics
/ Nucleotidyltransferases - immunology
