Adverse events in both childhood and adulthood are associated with molecular, clinical and functional markers of ageing

Abstract Background Adverse events across the lifespan have been linked to poorer health outcomes, but the biological mechanisms remain unclear. The aim of this study was to quantify the independent and joint associations of adversity experienced in childhood and/or adulthood with molecular, clinical and functional markers of biological ageing. Methods We analysed data from up to 153,557 middle-aged and older adults in the UK Biobank. Adversity was assessed through questionnaires capturing five types of childhood and adulthood adverse events. Biological ageing markers included metabolomic age (MileAge) delta, a metabolomic mortality profile, the frailty index, telomere length and grip strength. Regression models were adjusted for age, sex, education, income, ethnicity and neighbourhood deprivation. Results Across childhood and adulthood exposures, adversity and its severity were most consistently associated with higher frailty index values. The strongest associations were observed in individuals exposed to multiple types of adverse events. Individuals who experienced adversity in both childhood and adulthood also had a metabolite-predicted age exceeding their chronological age and lower grip strength. Abuse was more consistently associated with biological ageing markers than neglect. Conclusions Cumulative exposure to adversity across childhood and adulthood is associated with older biological ageing profiles across multiple domains. These findings highlight biological ageing as a potential pathway linking adversity to poor health outcomes and premature mortality.