Immune signalling pathway links ageing and neurodegeneration

The PTEG contributed to a study led by the Ablasser lab (SV, EPFL), which describes how low-grade inflammation driven by cGAS/STING contributes to age-related decline and impairment. cGAS/STING is a molecular signaling pathway that detects the presence of aberrant DNA in cells, and involves two proteins, cyclic GMP–AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). When activated, cGAS/STING is known to trigger an immune response, for instance as a part of a defense mechanism against viral and bacterial infections. Strikingly, by inhibiting STING protein, the researchers were able to suppress inflammatory responses in senescent cells and tissues, leading to improvements in aging tissue function. The GECF helped to decipher, notably by single-nuclei RNA-seq techniques, the specific patterns of gene activity in microglia, the brain’s first-line-of-defense immune cells, that are triggered by STING activation. These gene-activation patterns matched those arising in microglia in distinct neurodegenerative conditions, such as Alzheimer`s disease and ageing. These results demonstrate that the cGAS/STING molecular signaling pathway plays a critical role in driving chronic inflammation and functional decline during aging. Furthermore they advance our understanding of age-related inflammation and also offer potential strategies for slowing cognitive deterioration in age-associated neurodegenerative conditions.