Proteomic profiling reveals age-related changes in transporter proteins in the human blood-brain barrier.

Xujia Zhou, Mina Azimi, Niklas Handin, Andrew Riselli, Bianca Vora, Eden Chun, Zilong Dang, Eric Huang, Sook Wah Yee, Per Artursson, Kathleen M Giacomini

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA. · pubmed

Paper

Abstract

The Blood-Brain Barrier (BBB) is a selective barrier that regulates the entry of molecules including nutrients, environmental toxins, and therapeutic medications into the brain. Its function continues to evolve postnatally, through aging, and disease states. Here we present a global proteomics analysis focused on the ontogeny and aging of proteins in human brain microvessels (BMVs), predominantly composed of brain endothelial cells. Our proteomic study quantified 6,223 proteins and revealed possible age-related alterations in BBB permeability due to basement membrane component changes through the early developmental stage and age-dependent changes in transporter expression. Age dependent expression changes were observed within nutrient transporters and transporters that play critical roles in drug disposition. This research 1) provides important information on the mechanisms that drive changes in the metabolic content of the brain with age and 2) enables the creation of physiologically based pharmacokinetic models for CNS drug distribution across different life stages.

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Research summary

The paper claims that age-related changes in transporter proteins in the blood-brain barrier may affect brain metabolism and drug distribution. This research is relevant as it explores the biological mechanisms underlying aging processes, specifically how the blood-brain barrier's function changes with age, which could inform strategies for longevity and age-related health improvements.

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