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 inflamm-aging. Released molecules from damaged cells and their recognition by the innate immune system is one of the mechanisms driving inflamm-aging. 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 (P = 0.014) and, in particular, cardiovascular disease in these subjects (P = 0.010). Therefore, we provide the first evidence that stratification for obesity may reveal new genetic loci determining the risk for aging-related diseases.

中文翻译：

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队列研究的初步证据表明STING SNP R293Q对肥胖相关的心血管疾病具有保护作用

肥胖是一些与衰老相关的疾病的危险因素，例如2型糖尿病，心血管疾病和癌症。特别地，肥胖症通过诱发血管衰老和慢性低度全身性炎症（也称为炎症衰老）而引发心血管疾病。从受损细胞释放的分子及其被先天免疫系统识别的机制是导致炎症衰老的机制之一。肥胖导致线粒体损伤，导致通过cGAS / STING途径的胞质mtDNA触发内皮炎症。最近，我们显示出STING SNP R293Q与当前吸烟者患衰老相关疾病的风险降低有关。由于当前吸烟会触发DNA损伤，类似于肥胖，可能导致DNA释放到细胞质中，我们假设cGAS / STING途径也可以改变肥胖受试者的衰老表型。因此，我们的研究目的是调查STING R293Q是否与肥胖个体的衰老相关疾病有关。我们确实显示，STING 293Q与这些综合性衰老相关疾病的预防相关（P = 0.014），尤其是这些受试者的心血管疾病（P = 0.010）。因此，我们提供了第一个证据，即肥胖分层可能揭示新的遗传位点，从而决定了与衰老相关的疾病的风险。我们确实显示，STING 293Q与这些综合性衰老相关疾病的预防相关（P = 0.014），尤其是这些受试者的心血管疾病（P = 0.010）。因此，我们提供了第一个证据，即肥胖分层可能揭示新的遗传位点，从而决定了与衰老相关的疾病的风险。我们确实显示，STING 293Q与这些综合性衰老相关疾病的预防相关（P = 0.014），尤其是这些受试者的心血管疾病（P = 0.010）。因此，我们提供了第一个证据，即肥胖分层可能揭示新的遗传位点，从而决定了与衰老相关的疾病的风险。