Mislocalized nucleic acids: the inflammatory engine of vascular aging

The accumulation of nucleic acids outside their normal compartments—nucleus and mitochondria—emerges as a central mechanism of vascular aging, according to an open-access review that for the first time connects chronic age-related inflammation to a prothrombotic state termed "coagul-aging." When DNA and RNA fragments relocalize to the cytosol, pattern-recognition sensors like cGAS-STING and TLR9 detect them as infectious threats, triggering innate immune cascades that produce type I interferons and proinflammatory cytokines while simultaneously activating coagulation's contact pathway via factor XII. This process, known as "thrombo-inflammation," evolved to contain infection and repair tissue damage but becomes maladaptive when chronically activated, perpetuating vascular injury and thrombotic risk. The mechanism suggests that removing mislocalized nucleic acids could simultaneously interrupt both chronic inflammation and hypercoagulability characteristic of aging, positioning nucleic acid dysregulation as a more fundamental therapeutic target than current approaches of selective immune suppression.