cGAS-STING pathway

The cGAS-STING pathway is an innate immune sensing mechanism in which cyclic GMP-AMP synthase (cGAS) detects cytosolic double-stranded DNA — a signal of viral infection, nuclear damage or mitochondrial DNA leakage — and synthesises the second messenger cGAMP, which activates the endoplasmic-reticulum adaptor protein STING (stimulator of interferon genes). STING then drives transcription of type-I interferons and pro-inflammatory NF-κB target genes, generating a potent immune response. In the context of ageing, the pathway is aberrantly activated by micronuclei, cytoplasmic chromatin fragments from ruptured senescent-cell nuclear envelopes, and leaked mitochondrial DNA, making cGAS-STING a key amplifier of inflammaging and the SASP; pharmacological STING inhibitors are under early investigation as potential modulators of age-related inflammation.