Telomere attrition alters extracellular vesicles conferring adverse impacts on neuronal viability and inflammatory response

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Telomere shortening is a hallmark of aging associated with various diseases, yet its impact on extracellular vesicles (EVs) remains poorly understood. We investigated EV abundance, size, cargo content, and functional implications in a human aging cohort and the telomerase reverse transcriptase null ( Tert -/- ) mice. Human plasma EVs showed reduced telomeric DNA cargo with age. In generation 3 (G3) Tert -/- mice with shortened telomeres, we observed a significant reduction in plasma EV concentration and tissue-specific changes in EV levels and telomeric DNA content. Proteomic analysis revealed altered protein levels related to inflammation and lipid metabolism in plasma- and tissue-derived EVs. Functionally, EVs from G3 Tert -/- mice stimulated a pro-inflammatory response in bone marrow-derived macrophages and exhibited neurotoxic effects on primary cultured neurons. These findings highlight the intricate interplay between telomere shortening and EV biology, underscoring the potential of EVs as intercellular mediators, biomarkers, and therapeutic targets for conditions associated with telomere loss.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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