CHIP in the aging brain

The proposed project seeks to uncover the effects of clonal hematopoiesis (CH) and inflammation on brain aging in health and disease. CH is a common, age-related phenomenon wherein somatic mutations in hematopoietic stem cells undergo clonal expansion and drive systemic inflammation, potentially influencing the onset and progression of neurological disease. The goal of this study is to evaluate the effects of clonal hematopoiesis (CH) on brain aging across healthy and diseased states, with an emphasis on understanding how CH and aging propagate inflammation in the brain to modulate disease progression. Using genomic sequencing data from peripheral blood and brain tissue samples from The Religious Orders Study and Memory and Aging Project (ROSMAP) Study, we will apply validated pipelines developed by our group to identify CH (PMID: 36652671) in the cohort. We will then correlate CH status with inflammatory marker expression based on differential expression and pathway analysis using RNA-seq and proteomics data. Additionally, we will leverage neuroimaging data and clinical phenotypes including disease onset and severity to determine the effect of CH on inflammation-mediated pathologies of the brain. This project will be conducted in collaboration with Dr. Michael Rauh at Queen’s University / Dr. Robert Vanner at University Health Network. Drs. Rauh and Vanner jointly supervise PhD student Marco Buttigieg who will be carrying out the research. Our combined expertise in clonal hematopoiesis, aging, and inflammation leaves us well positioned to further our understanding of brain health with aging.

As we age, a common condition called clonal hematopoiesis (CH) can develop when there are mutations in the stem cells that produce our immune (white blood) cells. These mutations are passed on to new immune cells, causing them to produce too much inflammation. This inflammation raises the risk of chronic diseases like heart disease and cancer. Some studies have shown that CH and its related inflammation can have both harmful and protective effects on brain aging and neurodegenerative diseases. Our research is studying the role of CH and inflammation in brain health and aging. We will use genetic data from blood and brain samples to determine whether or not each study participant has CH. We will then measure how inflammation and markers of brain aging differ between people with and without CH.