Blood-based omics biomarkers for monitoring functional decline, incident disease risk, and intervention responses (360G-Wellcome-338263_Z_25_Z)

Aging is the leading risk factor for chronic diseases. As the global elderly population is projected to nearly double by 2050 and the prevalence of age- related diseases rises, there is an urgent need for tools to quantify biological aging, assess disease risk, and guide public health interventions. Biological aging is the progressive decline of physiological functions due to accumulating molecular and cellular damage, varying across individuals and organs. Traditional aging biomarkers lack sensitivity and organ specificity, but advances in proteomics and machine learning enabled estimation of biological ages for eleven organs, robustly predicting disease and mortality risk from a simple blood test. However, clinical translation is hindered by limited proteomic data availability and short-term protein fluctuations. To address this, I will utilise blood DNA methylation data to develop epigenetic proxies (EpiScores) for >4,000 proteins and organ-specific biological aging. EpiScores provide more stable estimates of long-term exposures, showing higher test-retest reliability and predictive power than direct protein measurements. My PhD will evaluate the clinical utility of these EpiScores by examining their associations with physical and cognitive decline, disease outcomes, mortality, and responsiveness to interventions. This work could advance disease risk prediction, patient stratification, and personalised strategies for anti-aging and disease interventions.