Question: What are the lifecourse determinants, heritability and pathways of healthy ageing (HA) phenotypes?
Conditions: Ageing, all morbidities and all-cause and cause-specific mortality.
Exposure: All potentially age-related variables.
Synopsis: The lifecourse approach to HA seeks to understand and inform steps to moderate the onset or rate of ageing by focusing on the early identification and determinants of accelerated ageing. We aim to define, develop and test measures of HA, as currently no common definition or standard measure exists, and use them to investigate the lifecourse determinants and heritability of HA, and the relationship with the ?epigenetic clock?. Ageing is a major risk factor for a wide ranges of morbidities and premature mortality. This research will use data from UK Biobank to improve our understanding of the determinants and causal pathways of healthy ageing status. This knowledge will help to inform potential intervention targets for the prevention of premature ageing or unhealthy ageing trajectories. Using data from all individuals with information on all available variables and health outcomes, we will develop: a HA score based on variables with evidence for a functional biological link with ageing; a second HA score using a hypothesis-free approach to explore all age-related variables, and a third measure using a time-to-event for incident morbidities approach. We will examine the heritability of the scores using ?Genome Complex Trait Analysis?. ?Mendelian Randomization? will be used to determine causal influences on HA trajectories, and the associations of the scores with mortality will be explored. We will include the full cohort in our analysis.