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Halting ageing: cGAS-STING pathway insights

Aug 18, 2023

The cGAS–STING signaling pathway contributes significantly to chronic inflammation and functional deterioration associated with ageing, indicating its potential as a therapeutic target to combat neurodegeneration in later life.

August 2023 – Nature

 

Key takeaways

 

  • Inhibition of age-related inflammation: Targeting the cGAS-STING signaling pathway can suppress the inflammatory response of senescent cells, which are significant contributors to age-related inflammation. This suggests that pharmacological inhibition of this pathway could be a strategy to mitigate chronic inflammation associated with ageing
  • Improvement in physical and cognitive functions: Inhibition of the STING pathway in aged mice led to improvements in muscle strength, physical endurance, and cognitive functions. This indicates that the cGAS-STING pathway plays a role in the decline of physical and cognitive abilities during ageing
  • Reduction of brain ageing markers: Inhibiting STING resulted in reduced microglial activation and protected against the loss of neurons in the brain, which are common markers of brain ageing. This points to the potential of STING inhibitors in protecting against age-related neurodegenerative changes
  • Mitochondrial DNA as an inflammatory trigger: Mitochondrial DNA (mtDNA) released into the cytosol of aged microglia can activate the cGAS-STING pathway, leading to inflammatory responses. This suggests that maintaining mitochondrial integrity and preventing the release of mtDNA could be another target for reducing age-related inflammation and its associated functional decline

 

Read the article at: Gulen, M.F., Samson, N., Keller, A. et al. cGAS–STING drives ageing-related inflammation and neurodegeneration. Nature 620, 374–380 (2023). https://doi.org/10.1038/s41586-023-06373-1