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.