Aging disrupts blood-brain and blood-spinal cord barrier homeostasis, but does not increase paracellular permeability.

Mitchell J Cummins, Ethan T Cresswell, Renee J Bevege, Doug W Smith

Neurobiology of Aging and Dementia Laboratory, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.Neurobiology of Aging and Dementia Laboratory, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia. · pubmed

Paper

Abstract

Blood-CNS barriers protect the CNS from circulating immune cells and damaging molecules. It is thought barrier integrity becomes disrupted with aging, contributing to impaired CNS function. Using genome-wide and targeted molecular approaches, we found aging affected expression of predominantly immune invasion and pericyte-related genes in CNS regions investigated, especially after middle age, with spinal cord being most impacted. We did not find significant perturbation of endothelial cell junction genes or proteins, nor were vascular density or pericyte coverage affected by aging. We evaluated barrier paracellular permeability using small molecular weight tracers, serum protein extravasation, CNS water content, and iron labelling measures. We found no evidence for age-related increased barrier permeability in any of these tests. We conclude that blood-brain (BBB) and blood-spinal cord barrier (BSCB) paracellular permeability does not increase with normal aging in mouse. Whilst expression changes were not associated with increased permeability, they may represent an age-related primed state whereby additional insults cause increased leakiness.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates the effects of aging on the blood-brain and blood-spinal cord barriers, which are critical for CNS health and function. While it does not find increased permeability with aging, it explores gene expression changes that could relate to age-related vulnerabilities. This focus on barrier integrity and its implications for CNS function aligns with longevity research, although the findings are more descriptive than transformative. The impact is limited as it primarily confirms existing notions rather than providing novel insights or solutions to aging-related issues.

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