As people age, their immune system gradually declines, increasing vulnerability to both chronic and acute diseases. This decline varies across individuals due to genetic, environmental, and lifestyle factors, underscoring the need for an accessible measure of “immune health.” In our nine-year longitudinal study of 140 healthy adults, we constructed an immune-ageing trajectory and developed IMM-AGE, a single metric that describes the state of the immune system. Early findings suggest that IMM-AGE may outperform existing measures in predicting all-cause mortality and cardiovascular risk, pointing to an underappreciated immune-cardiovascular axis. These results, however, remain preliminary. To fully understand this relationship, we now aim to leverage our newly developed proteomics-based IMM-AGE signature within the UK Biobank’s large-scale cohort.
Our specific aims are:
1. Identify baseline features of participants who go on to experience incident CV events. We will characterise the clinical and molecular profile of participants with no prior CV disease at enrolment who subsequently experience an incident CV event during follow-up, compared with matched individuals who remain event-free.
2. Characterize the association between immune aging and CV morbidity. We will apply a proteomic signature of IMM-AGE and test its association with CV morbidity. Because CV disease is multifactorial, we will use modern statistical methods for high-dimensional matching and adjustment to isolate the specific contribution of immune ageing from traditional risk factors.
3. Identify factors that mitigate the impact of immune ageing on CV outcomes. We will identify “risk-reducing” factors that appear to buffer or modify the impact of immune ageing on CV outcomes.
Overall, this project will clarify how immune ageing, as reflected in the blood proteome, predicts CV disease and which modifiable factors may mitigate that risk, helping to inform more personalised prevention strategies.
