The lifespan of an organism is determined by a complex network of environmental-, genetic- and stochastic factors. Each of these components contributes to the wide variability in lifespan between... Show moreThe lifespan of an organism is determined by a complex network of environmental-, genetic- and stochastic factors. Each of these components contributes to the wide variability in lifespan between and within species. In recent years, it has been shown that 20-30 % of human lifespan is under genetic control. Furthermore, a number of longevity candidate genes have been identified. The majority of candidate genes have emerged from studies with model organisms, but also from the biology of human ageing. The objective of this thesis was to test the impact of the most prominent longevity candidate genes on the prevalence of age-related diseases and lifespan in humans. All studies presented in this thesis were performed within the Leiden 85-plus Study, which is a population-based prospective study of the oldest old. The results revealed that genetic variations in most of the candidate genes influence metabolism, prevalence of age-related diseases, cognitive functioning and lifespan. Therefore, the approach of analyzing the most prominent longevity candidate genes in humans, contributes to the identification of biological mechanisms that influence the prevalence of disease in old age and lifespan. Show less
