Prenatal and childhood lead exposure is prospectively associated with biological markers of aging in adolescence

Abstract

Few studies have related early life lead exposure to adolescent biological aging, a period characterized by marked increases in maturational tempo. We examined associations between prenatal and childhood lead exposure and adolescent biological age (mean 14.5 years) utilizing multiple epigenetic clocks including: intrinsic (IEAA), extrinsic (EEAA), Horvath, Hannum, PhenoAge, GrimAge, Skin-Blood, Wu, PedBE, as well as DNA methylation derived telomere length (DNAmTL). Epigenetic clocks and DNAmTL were calculated via adolescent blood DNA methylation measured by Infinium MethylationEPIC BeadChips. We constructed general linear models (GLMs) with individual lead measures predicting biological age. We additionally examined sex-stratified models and lead by sex interactions, adjusting for adolescent age and lead levels, maternal smoking and education, and proportion of cell types. We also estimated effects of lead exposure on biological age using generalized estimating equations (GEE). First trimester blood lead was positively associated with a 0.14 increase in EEAA age in the GLMs though not the GEE models (95%CI 0.03, 0.25). First and 2nd trimester blood lead levels were associated with a 0.02 year increase in PedBE age in GLM and GEE models (1st trimester, 95%CI 0.004, 0.03; 2nd trimester, 95%CI 0.01, 0.03). Third trimester and 24 month blood lead levels were associated with a -0.06 and -0.05 decrease in Skin-Blood age, respectively, in GLM models. Additionally, 3rd trimester blood lead levels were associated with a 0.08 year decrease in Hannum age in GLM and GEE models (95%CI -0.15, -0.01). There were multiple significant results in sex-stratified models and significant lead by sex interactions, where males experienced accelerated biological age, compared to females who saw a decelerated biological age, with respect to IEAA, EEAA, Horvath, Hannum, and PedBE clocks. Further research is needed to understand sex-specific relationships between lead exposure and measures of biological aging in adolescence and the trajectory of biological aging into young adulthood.

Keywords: Biological age; Child development; Epigenetic clock; Lead exposure.