Association of early-life factors with biological age acceleration and the mediating effect of social environment risks in middle-aged and older adults

Abstract Background Adverse early-life events influence the health with ageing throughout the life course. However, the effects of combined early-life risks on ageing acceleration in adults and the roles of social environment risks remain unknown. Objective To investigate associations of maternal smoking, breastfeeding and birth weight with accelerated biological age (BA), and to explore genetic-predicted effect and mediating effect of social environment risks. Design Population-based prospective cohort. Setting UK Biobank. Subjects 151 773 participants. Methods We used Klemera–Doubal BA (KDM-BA), PhenoAge and leukocyte telomere length (LTL) as BA biomarkers. Associations of early-life risk factors and score with BA acceleration were estimated using linear regression models. Genetic risk score (GRS) was calculated based on genetic variations for maternal smoking and birth weight. Polysocial risk scores (PsRS) for each BA were calculated by summing the number of dichotomised social environment factors significantly associated with each of the three BA biomarkers. Results Maternal smoking, non-breastfeeding and low birth weight were individually associated with BA acceleration. The early-life risk score was significantly associated with accelerated KDM-BA and PhenoAge and shorter LTL. The effects of GRS on accelerated BA were in the same direction. The BA-specific PsRS mediated the accelerated KDM-BA and PhenoAge and shorter LTL by 8.37%, 22.34% and 7.90%, respectively. Conclusions Our findings demonstrated a dose-dependent association of combined early-life risks with accelerated BA in middle-aged and older adults, partially mediated by social environment risks. The findings highlight the importance of early identification and surveillance of high-risk individuals for ageing acceleration during adulthood.