Highlights d Mission duration was associated with significant decreases in epigenetic aging d Decreases in PhenoAge, a morbidity biomarker, remained significant post-mission d There were significant changes in estimated proportions of some white blood cells d Only decreases in NK cells remained significant post-mission

Emerging research suggests associations of physical and psychosocial stressors with epigenetic aging. Although this work has included early-life exposures, data on maternal exposures and epigenetic aging of their children remain sparse. Using longitudinally collected data from the California, Salinas Valley CHAMACOS study, we examined relationships between maternal Adverse Childhood Experiences (ACEs) reported up to 18 years of life, prior to pregnancy, with eight measures (Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length) of blood leukocyte epigenetic age acceleration (EAA) in their children at ages 7, 9, and 14 years (N = 238 participants with 483 observations). After adjusting for maternal chronological age at delivery, pregnancy smoking/alcohol use, parity, child gestational age, and estimated leukocyte proportions, higher maternal ACEs were significantly associated with at least a 0.76-year increase in child Horvath and Intrinsic EAA. Higher maternal ACEs were also associated with a 0.04 kb greater DNAm estimate of telomere length of children. Overall, our data suggests that maternal preconception ACEs are associated with biological aging in their offspring in childhood and that preconception ACEs have differential relationships with EAA measures, suggesting different physiologic utilities of EEA measures. Studies are necessary to confirm these findings and to elucidate potential pathways to explain these relationships, which may include intergenerational epigenetic inheritance and persistent physical and social exposomes.

Gestational age (GA) is an important determinant of child health and disease risk. Two epigenetic GA clocks have been developed using DNA methylation (DNAm) patterns in cord blood. We investigate the accuracy of GA clocks and determinants of epigenetic GA acceleration (GAA), a biomarker of biological ageing. We hypothesize that prenatal and birth characteristics are associated with altered GAA, thereby disrupting foetal biological ageing. We examined 372 mother-child pairs from the Center for the Health Assessment of Mothers and Children of Salinas study of primarily Latino farmworkers in California. Chronological GA was robustly correlated with epigenetic GA (DNAm GA) estimated by the Knight ( r = 0.48, p < 2.2x10 −16 ) and Bohlin clocks ( r = 0.67, p < 2.2x10 −16 ) using the Illumina 450K array in cord blood samples collected at birth. GA clock performance was robust, though slightly lower, using DNAm profiles from the Illumina EPIC array in a smaller subsample (Knight: r = 0.39, p < 3.5x10 −5 ; Bohlin: r = 0.60, p < 7.7x10 −12 ). After adjusting for confounders, high maternal serum triglyceride levels (Bohlin: β = −0.01 days per mg/dL, p = 0.03), high maternal serum lipid levels (Bohlin: β = −4.31x10 −3 days per mg/dL, p = 0.04), preterm delivery (Bohlin: β = −4.03 days, p = 9.64x10 −4 ), greater maternal parity (Knight: β = −4.07 days, p = 0.01; Bohlin: β = −2.43 days, p = 0.01), and male infant sex (Knight: β = −3.15 days, p = 3.10x10 −3 ) were associated with decreased GAA.Prenatal and birth characteristics affect GAA in newborns. Understanding factors that accelerate or delay biological ageing at birth may identify early-life targets for disease prevention and improve ageing across the life-course. Future research should test the impact of altered GAA on the long-term burden of age-related diseases.

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Background Zika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust pediatric mortality risk metrics are needed to help guide life plans and clinical decision making for these patients. Although common etiologies of pediatric and adult mortality differ, early life health can impact adult outcomes—potentially through DNA methylation. Hence, in this pilot study, we take an early step in identifying pediatric mortality risk metrics by examining associations of ZIKV infection and associated congenital microcephaly with existing adult DNA methylation-based mortality biomarkers: GrimAge and Zhang’s mortality score (ZMS). Methods Mortality measures were calculated from previously published HumanMethylationEPIC BeadChip data from 44 Brazilian children aged 5–40 months (18 with ZIKV-associated microcephaly; 7 normocephalic, exposed to ZIKV in utero; and 19 unexposed controls). We used linear models adjusted for chronological age, sex, methylation batch and white blood cell proportions to evaluate ZIKV and mortality marker relationships. Results We observed significant decreases in GrimAge-component plasminogen activator inhibitor-1 [PAI-1; β = −2453.06 pg/ml, 95% confidence interval (CI) −3652.96, −1253.16, p = 0.0002], and ZMS-site cg14975410 methylation (β = −0.06, 95% CI −0.09, −0.03, p = 0.0003) among children with microcephaly compared to controls. PAI-1 (β = −2448.70 pg/ml, 95% CI −4384.45, −512.95, p = 0.01) and cg14975410 (β = 0.01, 95% CI −0.04, 0.06, p = 0.64) results in comparisons of normocephalic, ZIKV-exposed children to controls were not statistically significant. Conclusion Our results suggest that elements of previously-identified adult epigenetic markers of mortality risk are associated with ZIKV-associated microcephaly, a known contributor to pediatric mortality risk. These findings may provide insights for efforts aimed at developing pediatric mortality markers.