Factors of biological ageing: does it all go together when it goes? (360G-Wellcome-221890_Z_20_Z)

Ageing-related cognitive decline carries a huge personal, societal, and financial cost. Understanding its underlying mechanisms with a view to ameliorating age-related cognitive decline is a huge challenge. It is essential to identify biomarkers of cognitive ageing and their potential determinants. Brain structural imaging markers in older age, their correspondence with proteomic and other biomarkers, and their potential determinants, are poorly characterised. Our understanding is informed by cross-sectional studies (which cannot fully reflect the dynamic within-person processes of ageing) and mainly univariate longitudinal data (i.e. describing how brain regions individually decline over time): most aspects of brain structure decline, on average. However, these approaches do not tell us whether there are important patterns of coordinated change, nor are they well- aligned with other levels of biological explanation. Such information could potentially aid stratification of risk and identification of important clusters of determinants of brain and cognitive ageing. I will apply cutting- edge factor-analytic methods to large longitudinal datasets to detect and validate patterns of correlated biological changes (brain structure, serum proteomic and DNA transcriptomic). I will test how these dimensions of ageing are associated with each other and with cognitive ageing, and use several techniques to ascertain their lifestyle, genetic and epigenetic predictors.