Externe en interne factoren van ongezond ouder worden

Risk factors, irrespective of whether they originate from the environment or are innate, differentiate unhealthy ageing from the average or optimal lifecourse. These risk factors, in the context of this dissertation termed external and internal drivers of ill health, operate "silently" in the perinatal phase of life, during childhood and young adulthood, but if unattended ultimately cause target organ damage and debilitating health problems. The objective of my doctoral research was to study these external and internal drivers of unhealthy ageing. In line with the title of this dissertation, I structured my research around three themes: (i) exposure to lead as the prototype of a ubiquitously distributed environmental pollutant and therefore an external driver of ill health; (ii) studies focusing on the urinary proteome, which reflects body-wide pathogenic processes that are fuelled by internal drivers, and (iii) clinical risk factors, which arise through the interplay between external and internal drivers of ill health. These studies were conducted in children, young lead workers, and population and patient cohorts, thereby covering the whole human life span. With its focus on external and internal drivers of ill health and their interaction, this dissertation fulfilled its stated objectives. As an ultimate goal, I hope that these findings will be translated in to practice and future research with the aim of the timely prevention of unhealthy ageing early in life, long before usually irreversible target organ damage and the associated morbidity lead to a decrease in quality-adjusted life years and premature mortality.