articleAging CellJan 1, 2026GOLD OA

Systemic LINE ‐1 RNA in Plasma Extracellular Vesicles Drives Neuroinflammation and Cognitive Dysfunction via cGAS ‐ STING Pathway in Aging

SYShuyi YuQCQian ChengQYQian YuZCZhuang CuiHZH Z Chen

Shandong Provincial Hospital · Shandong First Medical University · +1 more institution

PubMed
Indexed incrossrefdoajpubmed

Abstract

Aging is characterized by systemic inflammation and progressive cognitive decline, yet the molecular pathways linking peripheral aging signals to central nervous system dysfunction remain elusive. Here, we identify plasma extracellular vesicle (EV)-derived long interspersed nuclear element-1 (LINE-1) RNA as a potent systemic aging factor mediating neuroinflammation and cognitive impairment in humans and mice. Plasma EV LINE-1 RNA levels markedly increase with age and strongly correlate with established brain aging biomarkers, including neurofilament light chain (NFL). Utilizing mouse models, we demonstrate that EVs from aged individuals penetrate the blood-brain barrier, deliver LINE-1 RNA to microglia, and…

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Topics & keywords

Topics
Keywords
  • Neuroinflammation
  • Extracellular vesicle
  • Inflammation
  • Cognitive decline
  • Extracellular vesicles
  • Central nervous system
  • Transcription factor
  • Extracellular
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