Ageing disrupts vesicle transport in brain endothelial cells, impairing cellular recycling and barrier integrity. This dysfunction, linked to decreased Arf6 protein and increased Apoe cargo, accelerates vascular ageing and may contribute to neurodegenerative decline, highlighting a crucial mechanism in brain health and longevity.
March 2024 – Nature Aging
Key takeaways
- Vesicular transport declines with age: Ageing brain endothelial cells show a marked reduction in vesicle-mediated transport, especially in key pathways such as endocytosis and receptor recycling. This impairs the blood–brain barrier’s function and highlights how cellular trafficking deteriorates with age, potentially accelerating cognitive and vascular decline
- Arf6 is a key ageing regulator: The small GTPase Arf6, which governs membrane recycling and endocytosis, was significantly downregulated in aged endothelial cells. Experimental manipulation confirmed Arf6’s critical role in maintaining transport integrity, suggesting it as a molecular lever to modulate ageing processes in the brain vasculature
- Apoe links to accelerated ageing: Apoe-deficient mice displayed proteomic signatures mirroring those of older animals, indicating that loss of Apoe function accelerates endothelial ageing. This reinforces Apoe’s role in brain health and suggests that Apoe modulation may influence the trajectory of neurovascular ageing and associated disease risks
- Proteomics reveals what genes miss: Unlike transcriptomic data, proteomics captured functional shifts such as vesicle cargo accumulation and receptor dysregulation. This highlights the importance of studying proteins directly to uncover age-related cellular dysfunctions that influence longevity, resilience, and brain vitality
Read the article at: Todorov-Völgyi, Katalin, et al. “Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging.” Nature Aging, vol. 4, 2024, pp. 595–612. https://doi.org/10.1038/s43587-024-00598-z.
