Recent evidence shows that plasma proteome is a key connection between organ physiology, biological aging, and mortality. Circulating protein markers provide insight into organ-specific functional status. In this study, we propose a “liquid biopsy of organ-specific aging phenotypes” by using resources of the UK Biobank Pharma Proteomics Project, which measures thousands of plasma proteins. Our overarching goal is to decompose the circulating proteome of ~54,000 participants into organ-specific aging biomarkers and understand the disease progression trajectories. We aim to construct organ-age trajectory models that will capture the heterogeneity of biological aging across multiple organ systems sensitive to lifestyle factors, therapeutic interventions, and capable of capturing changes in trajectories in diseases.
To generate organ-specific proteome trajectories, we will use human blood proteomics data and map circulating proteins to their tissues of origin based on enrichment profiles from the GTEx v8 atlas. Proteins exhibiting !4-fold tissue-specific enrichment will be defined as organ-specific. Hence, we will develop a framework to track protein distinct aging patterns across different organs and population groups. One strength of this approach is the ability to relate the extracted proteomic patterns to patient-reported outcomes from the UK Biobank’s long-term cohort data. In this work, we will assess how lifestyle behaviours contribute to faster organ-specific aging reflected in organ-level protein patterns.
In summary, this project will create a verified map of organ-specific proteomic patterns, capable of outlining cell trajectories and significant markers for organ-aging and disease progression. By measuring the link between lifestyle factors and organ aging, we will allow for disease progression assessment. Ultimately, this framework provides a non-invasive way to track how lifestyle influences organ aging trajectories and disease progression.
