Genetic determinants of longevity: role of immunity?

DFG project PA 361/14-1

Why do apparently very similar people have markedly different life expectancies? Is it lifestyle, genetics, environmental pathogen exposure? The Leiden Longevity Study (LLS) is a unique longitudinal study of individuals genetically enriched for longer than average life-span and who have a 30% lower standardized mortality rate. Here, we propose to establish immune signatures (immune cell subsets and polyfunctional T cell assays by 11-colour flow cytometry) and virological status (CMV, EBV, and other herpesviruses) of LLS and control donors. We hypothesize that specific immune signatures will be identified which may mechanistically contribute to longevity of this rare population (offspring of 0.5% of the general population). We further hypothesize that CMV infection, which we have identified as a major driving force for “senescence” of the immune system in other longitudinal studies, will impact on immunity in a different manner in LLS offspring compared to controls. In addition, we will compare these parameters with those of another remarkable long-lived population, namely Danish monozygotic twins both surviving to the age of at least 85 yr. Finally, it will be established whether these immune signatures are predictive for mortality using a retrospective analysis in the longitudinal Leiden 85+ study. Knowledge of immune status and mode of interaction with CMV in genetically long-lived individuals may reveal physiological mechanisms contributing to longer, healthier lives.