Hamann Lutz, Szwed Malgorzata, Mossakowska Malgorzata, Chudek Jerzy, Puzianowska-Kuznicka Monika
1Institute for Microbiology and Infection Immunology, Charité University Medical Center, CBF, Hindenburgdamm 27, 12203 Berlin, Germany.
2Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Immun Ageing. 2020 Mar 14;17:7. doi: 10.1186/s12979-020-00176-y. eCollection 2020.
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.
肥胖是多种与衰老相关疾病的风险因素，如2型糖尿病、心血管疾病和癌症。特别是，肥胖通过诱导血管衰老和慢性低度全身炎症引发心血管疾病，这种炎症也被称为 。受损细胞释放的分子及其被先天免疫系统识别是驱动 的机制之一。肥胖导致线粒体损伤，通过cGAS/STING途径导致由胞质mtDNA引发的内皮炎症。最近，我们发现STING SNP R293Q与当前吸烟者患衰老相关疾病的风险降低有关。由于当前吸烟会引发DNA损伤，这与肥胖类似，可能导致DNA释放到细胞质中，我们推测cGAS/STING途径也可能改变肥胖个体的衰老表型。因此，我们研究的目的是调查STING R293Q是否与肥胖个体的衰老相关疾病有关。我们确实表明，STING 293Q与预防这些受试者的多种衰老相关疾病（=0.014），特别是心血管疾病（=0.010）有关。因此，我们提供了首个证据，表明对肥胖进行分层可能会揭示决定衰老相关疾病风险的新基因位点。
