Elucidating the underlying determinants of human ageing, with a focus on the brain and exceptional longevity
Approved Research ID: 98013
Approval date: January 31st 2023
Our population is ageing. Yet we still lack a comprehensive understanding of the underlying biological factors that contribute to human ageing. Individuals age at different rates, which may be specific for different organs, such as the ageing brain. In contrast, long-lived individuals often survive, delay or escape common age-related diseases and can be seen as models of healthy ageing. Longevity is moderately heritable suggesting genetic factors play a role in determining survival. Therefore, these individuals can be used to study the influence of genetics on successful ageing. This project aims to identify the different genetic and environmental factors and pathways associated with longevity and healthy ageing. In the UKB, longevity data is not available for the majority of participants so parental longevity will be used as a proxy. Other longevity-related traits will also be investigated, including healthy longevity, which will be defined as parental longevity plus the absence of common diseases. The project also aims to identify and study risk factors, especially vascular, that are associated with accelerated brain ageing measures in the UK Biobank cross-sectionally and longitudinally. We will also study the associations between brain health and the biological ages of other body systems, including cardiovascular, renal, endocrine, immune, metabolic, musculoskeletal, hepatic and pulmonary. Moreover, the brain vascular system, which is critical in maintaining the brain function, will be studied using the comprehensive imaging dataset. The duration of the project will be three years. The results of this project will increase our knowledge of the factors associated with longevity and healthy ageing, including the brain, and may facilitate innovative strategies to promote health in our ageing population.