Cytosolic Self-DNA-A Potential Source of Chronic Inflammation in Aging

Aging is the consequence of a lifelong accumulation of stochastic damage to tissues and cellular components. Advancing age closely associates with elevated markers of innate immunity and low-grade chronic inflammation, probably reflecting steady increasing incidents of cellular and tissue damage over the life course. The DNA sensing cGAS-STING signaling pathway is activated by misplaced cytosolic self-DNA, which then initiates the innate immune responses. Here, we hypothesize that the stochastic release of various forms of DNA from the nucleus and mitochondria, e.g., because of DNA damage, altered nucleus integrity, and mitochondrial damage, can result in chronic activation of inflammatory responses that characterize the aging process. This cytosolic self-DNA-innate immunity axis may perturb tissue homeostasis and function that characterizes human aging and age-associated pathology. Proper techniques and experimental models are available to investigate this axis to develop therapeutic interventions.

Automated summary

Aging is caused by lifelong accumulation of random damage to cells and tissues, leading to increased innate immunity markers and low-grade chronic inflammation. Activation of the DNA sensing cGAS-STING signaling pathway by misplaced cytosolic self-DNA may result in chronic inflammation and characteristics of the aging process.