An integrated approach to dissect determinants, risk
factors and pathways of ageing of the immune system
Objective 1. To assess the role of quantitative variation of circulating immune cell subtypes and soluble factors (cytokines and antibodies) in immunosenescence, and identify genetic and modifiable environmental exposures (including smoking, diet, alcohol intake and physical activity) contributing to this variation in a large population cohort of volunteers over a broad spectrum of ages.
Objective 2. To assess the extent and genetic bases of ‘subclinical’ autoreactivity during ageing and its correlation with chronic viral infections, contractions in the B & T cell repertoire and the other cellular and humoral immune traits assessed in AIM 1.
Objective 3. To elucidate the functional and transcriptional properties of those cell types that show the strongest age-related changes, and whose circulating levels are affected by known genetic variants, and combine all available data to reveal pathways, biomarkers for early diagnosis and therapeutic targets to prevent or minimize the negative features of immunosenescence.