Exploring predictors of health and ageing in the UK Biobank

Human health and life expectancy have improved considerably over the past two centuries. Although some individuals maintain good health across the lifespan, many individuals spend a significant part of their life with age-related diseases, functional impairments and reduced quality of life. Individuals with mental disorders are at an increased risk of morbidity, have a lower life expectancy and may biologically age faster than people without mental disorders. To further improve population health, it is essential to better understand the biological, behavioural, sociodemographic and environmental factors that may contribute to differences in health and ageing. Using data from the UK Biobank, a multicentre, community-based observational study of more than 500,000 middleaged and older adults, I conducted multiple epidemiological analyses to examine (1) predictors of health in the general population and (2) health and ageing in individuals with a history of mental disorders. In Chapter 2, I explored associations between three measures of health status and sociodemographic, psychosocial, lifestyle and environmental factors. In Chapter 3, I investigated how different combinations of subjective and objective health predicted all-cause mortality and leading causes of death in the United Kingdom. In Chapters 4 to 6, I examined associations between age and physiological biomarkers in individuals with a history of depression, bipolar disorder and anxiety disorders. In Chapter 7, I examined the all-cause mortality risk associated with frailty in individuals with a history of mental disorders. Finally, in Chapter 8, I examined differences in leukocyte telomere length between individuals with and without a history of mental disorders and explored associations between telomere length, age and polygenic risk scores. Maintaining good health throughout the lifespan involves a complex interplay between a multitude of risk factors, health behaviours, genetic predispositions and environmental exposures. The findings of this thesis highlight that there are many potential pathways to further improve population health and life expectancy and to reduce the excess mortality in individuals with mental disorders.