cGAS–STING drives ageing-related inflammation and neurodegeneration

🤖 Plain-English Summary

Abstract Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease 1 . Single-nucleus RNA-sequencing analysis of microglia and hippocampi of a cGAS gain-of-function mouse model demonstrates that engagement of cGAS in microglia is sufficient to direct ageing-associated transcriptional microglial states leading to bystander cell inflammation, neurotoxicity and impaired memory capacity.

🔑 Key Findings

• Multiple factors can contribute to ageing-associated inflammation 2 ; however, the molecular pathways that transduce aberrant inflammatory signalling and their impact in natural ageing remain unclear.
• Here we show that the cGAS–STING signalling pathway, which mediates immune sensing of DNA 3 , is a critical driver of chronic inflammation and functional decline during ageing.
• Blockade of STING suppresses the inflammatory phenotypes of senescent human cells and tissues, attenuates ageing-related inflammation in multiple peripheral organs and the brain in mice, and leads to an improvement in tissue function.

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