GENETIC AND ENVIRONMENTAL INFLUENCES ON AGEING WELL IN THE UK BIOBANK

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Human ageing is characterised by wide variation in lifespan and the period people remain healthy and active, with some older people becoming frail in their sixties while others remain fit into their nineties and beyond. Although these differences have a significant genetic component, the underlying mechanisms in humans are still unclear. Conventional risk factors such as smoking are important, but there is uncertainty about many other conventional risk factors in later life. If we understood why some people age well we should be able to help those who age less well to remain disability free and active for longer. At the laboratory level there is increasing evidence that the onsets of many age-related conditions can be simultaneously delayed or even partially reversed in mice. Centenarian groups show delayed onsets of the common conditions of ageing and this health advantage is partially inherited in offspring. In previous work we showed that the offspring of long lived parents have strikingly lower incidence rates of cancers, heart disease, diabetes and cognitive impairment in later life. The aim of this project is to identify novel risk factors and genetic variants associated with ageing well. Our underlying aim is to find new ways of helping those who age less successfully by applying insights gained from those who age well. We propose two main work packages (WP), both focussing on the 215,000 respondents aged 60 to 69 years old in UK Biobank study baseline: WP1: Identifying factors associated with the best health status in the seventh decade of life: We will define those at best health status (i.e. ageing well) as those free of major diseases (cardiovascular disease, stroke, diabetes, depression or cancer) and who are consistently in the healthiest range of measures of muscle strength, cognition, lung function, bone mineral density and blood pressure. WP2: Identifying factors associated with parental longevity: We have identified data on Biobank respondents who are the offspring of two long lived (non-adoptive) parents or one long lived and one intermediate lived parent. We will include only those who are free of cancer, myocardial infarction, stroke or diabetes (yielding 15,000 disease free offspring of longer lived parents and over 50,000 respondents with intermediate lived parents at baseline). We will examine all the major measured factors available in the Biobank data, including measures of early life circumstances and health behaviours. Genome wide association studies (GWAS) will identify associated variants. Independent replication will be carried out through already agreed collaborations with EPIC-Norfolk and the Framingham Heart Study. Fine characterisation of top findings will be carried out in ageing cohorts with genomic data and samples and very detailed health measures. The investigator team brings together experienced scientists from the Universities of Exeter and Cambridge. This group will be supported by international leaders in the relevant fields, who have both agreed to serve as consultants for the project and will collaborate in the replication of findings in independent population studies. By building on UK Biobank and other existing ageing studies we have greatly reduced the costs of this project. Outputs will include robust estimates of a wide range of conventional markers associated with ageing well, providing for a firmer basis for prevention. We expect to detect novel genetic variants, which should provide new clues to the biological influences on the timing of onset of common age related diseases. According to the UK Health and Social Care Information Centre, people aged 65 and over account for 54% of inpatient bed days, 60% of all prescribed items and 67% of social care clients. Even small improvements in ageing trajectories could have very major impacts on older people (our 'future selves'), carers, plus health and social care systems.