First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects - a cohort study.

Obesity is a risk factor for several aging-related diseases such as type 2 diabetes, cardiovascular disease, and cancer. Especially, cardiovascular disease is triggered by obesity by inducing vascular senescence and chronic low-grade systemic inflammation, also known as . Released molecules from damaged cells and their recognition by the innate immune system is one of the mechanisms driving Obesity results in mitochondrial damage, leading to endothelial inflammation triggered by cytosolic mtDNA via the cGAS/STING pathway. Recently, we have shown STING SNP R293Q to be associated with a decreased risk for aging-related diseases in current smokers. Since current smoking triggers DNA damage that, similar to obesity, may result in the release of DNA into the cytoplasm, we hypothesized that the cGAS/STING pathway can modify the phenotype of aging also in obese subjects. Therefore, the objective of our study was to investigate whether STING R293Q is associated with aging-related diseases in obese individuals. We indeed show that STING 293Q is associated with protection from combined aging-related diseases ( = 0.014) and, in particular, cardiovascular disease in these subjects ( = 0.010). Therefore, we provide the first evidence that stratification for obesity may reveal new genetic loci determining the risk for aging-related diseases.