Senescent cells undergo permanent cell-cycle arrest and secrete inflammatory factors, a phenotype referred to as the 'senescence-associated secretory phenotype' (SASP). In Nature Cell Biology, Ablasser and colleagues show that the DNA-sensing pathway cGAS–STING regulates the production of SASP factors and promotes senescence in a paracrine way. Mouse embryonic fibroblasts deficient in cGAS or STING do not undergo proliferative arrest and produce less of the cytokines IL-6 and TNF and chemokine CXCL10 in culture, a phenotype 'rescued' by conditioned medium from wild-type senescent cells or by recombinant interferon-β. cGAS localizes together with the chromatin fragments that appear at the nuclear–cytoplasmic interface of senescent nuclei. In vivo, cGAS- and STING-deficient mice show less upregulation of SASP factors such as IL-6, CXCL10, Cdkn2a and p21 after irradiation or stimulation with oncogenic transposable elements. Because SASP is a late event in the development of senescence, cGAS–STING might amplify inflammation in cells already on the senescence track.
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Visan, I. Amplifying senescence. Nat Immunol 18, 961 (2017). https://doi.org/10.1038/ni.3827
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DOI: https://doi.org/10.1038/ni.3827