Misplaced nucleic acids as a trigger of coagul-aging

Area of Science:

• Biomedical Science
• Immunology
• Vascular Biology

Background:

• Aging is characterized by inflammaging (chronic sterile inflammation) and coagul-aging (procoagulant shift).
• Inflammation and coagulation are interconnected, involving innate immunity and thrombin.
• Endogenous nucleic acids (DNA, RNA, RNA:DNA hybrids) are emerging as key mediators at the inflammation-coagulation nexus.

Purpose of the Study:

• To review the sources, forms, and functions of misplaced nucleic acids in aging.
• To explore the role of nucleic acids in linking inflammaging and coagul-aging.
• To identify novel therapeutic targets and biomarkers for age-related vascular risk.

Main Methods:

• Literature review focusing on endogenous nucleic acids, pattern recognition receptors, and thrombo-inflammation.
• Analysis of mechanisms by which nucleic acids trigger inflammatory and coagulation pathways.
• Synthesis of evidence linking nucleic acid accumulation to age-related vascular pathology.

Main Results:

• Accumulated nucleic acids, from senescent cells and retroelements, activate pattern recognition receptors (e.g., cGAS-STING, TLR9).
• Nucleic acids promote inflammation (cytokine release, tissue factor) and directly activate coagulation (Factor XII).
• A cumulative nucleic acid burden acts as a molecular trigger for thrombo-inflammatory responses.

Conclusions:

• Misplaced endogenous nucleic acids are central to the convergence of inflammaging and coagul-aging.
• Targeting nucleic acid accumulation or their downstream effects offers novel therapeutic strategies.
• Nucleic acid-based biomarkers may aid in risk stratification for age-related vascular diseases.