Among other mechanisms, oxidative stress has been postulated to play an important role in the rate of ageing. Oxidative damage contributes to the hallmarks of ageing and essential components in... Show moreAmong other mechanisms, oxidative stress has been postulated to play an important role in the rate of ageing. Oxidative damage contributes to the hallmarks of ageing and essential components in pathological pathways which are thought to drive multiple age-related diseases. Nonetheless, results from studies testing the hypothesis of oxidative stress in ageing and diseases showed controversial results. While observational studies mainly found detrimental effects of high oxidative stress levels on disease status, randomized clinical trials examining the effect of antioxidant supplementation on disease status generally showed null effects. However, re-evaluations of these counterinitiative observations are required considering the lack of reliability and specificity of traditionally used biomarkers for measuring oxidative stress. To facilitate these re-evaluations, this review summarizes the basic knowledge of oxidative stress and the present findings regarding the role of oxidative damage in ageing and age-related diseases. Meanwhile, two approaches are highlighted, namely proper participants selection, together with the development of reliable biomarkers. We propose that oxidized vitamin E metabolites may be used to accurately monitor individual functional antioxidant level, which might serve as promising key solutions for future elucidating the impact of oxidative stress on ageing and age-related diseases. Show less
The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more... Show moreThe general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular disease, cognitive decline and cancer. For all analyses we used data of the participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We have shown that subjects carrying genetic variants coding for a high pro-inflammatory profile or a low anti-inflammatory profile have an increased risk to develop cardiovascular disease and cognitive decline. Moreover, they tend to have an increased risk of dying as a consequence of cancer. Furthermore we have provided first evidence that the process of epigenetics can play an important role in the patho-physiology of age-related diseases. Future research is necessary to investigate how we can corporate these results into clinical practice. For example, Anti-inflammatory and immunosuppressive mechanisms may be attractive targets for disease prevention and/or treatment. Show less
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
