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Unveiling the Role of Air Pollution in Accelerating Brain Aging
Secondary Supervisor(s): Professor Zongbo Shi
University of Registration: University of Birmingham
BBSRC Research Themes: Integrated Understanding of Health (Ageing)
Project Outline
This project seeks to investigate the mechanisms by which particulate matter (PM) crosses the blood-brain barrier (BBB) and impacts brain health, with a particular focus on brain aging. As air pollution becomes an increasing global concern, understanding its effects on the neurological system is vital. The research utilizes a sophisticated BBB-on-a-chip model to mimic real-world exposure scenarios and simulate how PM interacts with brain cells. The project will focus on various types of PM, including fine and ultrafine particles, to evaluate how these pollutants penetrate the BBB and contribute to neuroinflammation, oxidative stress, and neurodegeneration.
The endpoints for assessing the impact of PM on brain aging will include key markers such as DNA damage, telomere shortening, mitochondrial dysfunction, and the expression of pro-inflammatory cytokines. These markers are critical in understanding how environmental pollutants accelerate the aging process in the brain. In particular, the study will examine how PM induces oxidative stress, a major driver of cellular aging, leading to mitochondrial damage and ultimately affecting cognitive function. The project also explores autophagy and protein aggregation, processes involved in clearing damaged proteins, which are disrupted during aging and linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s.
The research will be divided into several stages. The first involves the synthesis and characterization of different types of PM, focusing on their physical and chemical properties. Next, the project will develop and validate the BBB-on-a-chip model, which closely replicates the unique structure of the human BBB, to observe how PM crosses this barrier and interacts with neurons, astrocytes, and endothelial cells. The project will incorporate advanced labeling techniques and synchrotron-based imaging to trace the movement of PM through the BBB and into the brain, molecular methods to dissect the mechanisms underlying the PM-induced brain aging.
The long-term effects of PM exposure will also be a major focus, particularly in how it relates to accelerated brain aging. The research will examine how chronic exposure to PM alters the brain’s epigenetic landscape, including changes in DNA methylation patterns and histone modifications, which are closely associated with aging. These epigenetic changes can affect gene expression, leading to an increased risk of cognitive decline and the onset of age-related diseases.
The expected outcomes of this project will have far-reaching implications, not only for advancing the scientific understanding of how environmental pollutants affect brain aging but also for shaping public health policies. The data generated from this research will help to inform guidelines on air quality standards, particularly in urban areas with high levels of pollution. This research aims to provide a scientific foundation for the development of preventive measures and interventions to mitigate the neurotoxic effects of air pollution, potentially contributing to strategies aimed at reducing the incidence of neurodegenerative diseases in aging populations.