The association between adverse childhood experiences and epigenetic age acceleration in the Canadian longitudinal study on aging (<scp>CLSA</scp>)

Joshi, Divya; González, Andrea; Lin, David; Raina, Parminder

doi:10.1111/acel.13779

Cited by 28 publications

(17 citation statements)

References 45 publications

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“…In terms of the different epigenetic clocks, we observed significant relationships between the number and type of ACEs with epigenetic age acceleration in women during pregnancy, measured using PCs of both the PhenoAge and GrimAge DNAm clocks, but not with Horvath or Hannum DNAm clocks. Consistent with these findings, previous evidence found cumulative and individual ACEs were associated with accelerated epigenetic aging, measured by GrimAge 51 and PhenoAge. 27 The lack of association between maternal ACEs and epigenetic aging using the first-generation clocks (e.g., Hannum and Horvath clocks) may arise from the limitations of these clocks in predicting disease phenotypes and all-cause mortality, as these clocks were intended, and trained, as predictors of chronological age.…”

Section: Discussionsupporting

confidence: 85%

Mother’s childhood adversity is associated with accelerated epigenetic aging in pregnancy and in male newborns

Dye

Monk

et al. 2023

Preprint

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BackgroundAdverse childhood experiences (ACEs) are correlated with accelerated epigenetic aging, but it is not clear whether altered epigenetic aging from childhood adversities persists into adulthood and can be transmitted to the next generation. Thus, we tested whether mothers’ childhood adversity is associated with accelerated epigenetic aging during pregnancy and in their newborn offspring.MethodsData were from the Avon Longitudinal Study of Parents and Children (ALSPAC) sub-study, Accessible Resource for Integrated Epigenomic Studies (ARIES). Women provided retrospective self-reports during pregnancy of ACE exposure. DNA methylation was measured in mothers during pregnancy and cord blood at birth. Estimates of epigenetic age acceleration were calculated using Principal Components of Horvath, Hannum skin & blood, GrimAge, PhenoAge, and DunedinPACE epigenetic clocks for mothers; and the Knight and Bohlin cord blood clocks for newborns. Associations between a cumulative maternal ACE score and epigenetic age acceleration were estimated using linear regression models, adjusting for maternal age at pregnancy, smoking during pregnancy, education, and pre-pregnancy BMI. Models for offspring were stratified by sex and additionally adjusted for gestation age.ResultsMothers’ total ACE score was positively associated with accelerated maternal PhenoAge and GrimAge. In newborn offspring, mothers’ total ACE score was positively associated with accelerated epigenetic aging in males using the Bohlin clock, but not in females using either epigenetic clock. We found male offsprings’ epigenetic age was accelerated in those born to mothers exposed to neglect using the Knight clock; and parental substance abuse using the Bohlin clock.ConclusionOur results show that mothers’ ACE exposure is associated with DNAm age acceleration in male offspring, supporting the notion that DNAm age could be a marker of intergenerational biological embedding of mothers’ childhood adversity. This is consistent with findings on vulnerability of male fetuses to environmental insults.

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Section: Discussionsupporting

confidence: 85%

Mother’s childhood adversity is associated with accelerated epigenetic aging in pregnancy and in male newborns

Dye

Monk

et al. 2023

Preprint

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“…Our findings were consistent with results from previous studies that observed associations of ACEs exposure with increased EAA, [27][28][29][30][31][32][33]…”

Section: Discussionsupporting

confidence: 63%

“…Despite findings of prior research, few studies have examined the association between ACEs and EAA by race or sex, especially among adults . Furthermore, given that prior studies assessed the association of ACEs with EAA measured once, understanding the association over time remains challenging.…”

Section: Introductionmentioning

confidence: 99%

“…Another study 32 found positive associations among older females between having 4 or more ACEs and increased EAA. In Joshi et al, 33 a higher burden of ACEs was associated with increased EAA among people at middle age or older.…”

Section: Introductionmentioning

confidence: 99%

“…Prior studies observed associations between ACEs and shorter telomere length . More recently, researchers identified associations between ACEs and DNA methylation–based epigenetic age acceleration (EAA) . DNA methylation reflects exposures throughout an individual’s life; thus, EAA may serve as a useful tool to investigate associations between early life adversity and health in later life.…”

Section: Introductionmentioning

confidence: 99%

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Association of Adverse Childhood Experiences With Accelerated Epigenetic Aging in Midlife

et al. 2023

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ImportanceAdverse childhood experiences (ACEs) are associated with the risk of poorer health, and identifying molecular mechanisms may lay the foundation for health promotion in people with ACEs.ObjectiveTo investigate the associations of ACEs with changes in epigenetic age acceleration (EAA), a biomarker associated with various health outcomes in middle-aged adults, in a population with balanced race and sex demographics.Design, Setting, and ParticipantsData for this cohort study were from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants in CARDIA underwent 8 follow-up exams from baseline (year 0 [Y0]; 1985-1986) to Y30 (2015-2016), and participant blood DNA methylation information was obtained at Y15 (2000-2001) and Y20 (2005-2006). Individuals from Y15 and Y20 with available DNA methylation data and complete variables for ACEs and covariates were included. Data were analyzed from September 2021 to August 2022.ExposuresParticipant ACEs (general negligence, emotional negligence, physical violence, physical negligence, household substance abuse, verbal and emotional abuse, and household dysfunction) were obtained at Y15.Main Outcomes and MeasuresThe primary outcome consisted of results from 5 DNA methylation–based EAA measurements known to be associated with biological aging and long-term health: intrinsic EAA (IEAA), extrinsic EAA (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), measured at Y15 and Y20. Linear regression and generalized estimating equations were used to assess associations of the burden of ACEs (≥4 vs &lt;4 ACEs) with EAA adjusting for demographics, health-related behaviors, and early life and adult socioeconomic status.ResultsA total of 895 participants for Y15 (mean [SD] age, 40.4 [3.5] years; 450 males [50.3%] and 445 females [49.7%]; 319 Black [35.6%] and 576 White [64.4%]) and 867 participants for Y20 (mean [SD] age, 45.4 [3.5] years; 432 males [49.8%] and 435 females [50.2%]; 306 Black [35.3%] and 561 White [64.7%]) were included after excluding participants with missing data. There were 185 participants with (20.7%) vs 710 participants without (79.3%) 4 or more ACEs at Y15 and 179 participants with (20.6%) vs 688 participants without (79.4%) 4 or more ACEs at Y20. Having 4 or more ACEs was positively associated with EAA in years at Y15 (EEAA: β = 0.60 years; 95% CI, 0.18-1.02 years; PhenoAA: β = 0.62 years; 95% CI = 0.13-1.11 years; GrimAA: β = 0.71 years; 95% CI, 0.42-1.00 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) and Y20 (IEAA: β = 0.41 years; 95% CI, 0.05-0.77 years; EEAA: β = 1.05 years; 95% CI, 0.66-1.44 years; PhenoAA: β = 0.57 years; 95% CI, 0.08-1.05 years; GrimAA: β = 0.57 years; 95% CI, 0.28-0.87 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) after adjusting for demographics, health-related behaviors, and socioeconomic status.Conclusions and RelevanceIn this cohort study, ACEs were associated with EAA among middle-aged adults after controlling for demographics, behavior, and socioeconomic status. These findings of the associations between early life experience and the biological aging process in midlife may contribute to health promotion in a life course perspective.

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Childhood Maltreatment and Longitudinal Epigenetic Aging

Chang,

Meier,

Maguire-Jack

et al. 2024

JAMA Netw Open

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ImportanceChild physical and emotional abuse and neglect may affect epigenetic signatures of accelerated aging several years after the exposure.ObjectiveTo examine the longitudinal outcomes of early-childhood and midchildhood exposures to maltreatment on later childhood and adolescent profiles of epigenetic accelerated aging.Design, Setting, and ParticipantsThis cohort study used data from the Future of Families and Child Wellbeing Study (enrolled 1998-2000), a US birth cohort study with available DNA methylation (DNAm) data at ages 9 and 15 years (assayed between 2017 and 2020) and phenotypic data at birth (wave 1), and ages 3 (wave 3), 5 (wave 4), 9 (wave 5), and 15 (wave 6) years. Data were analyzed between June 18 and December 10, 2023.ExposuresEmotional aggression, physical assault, emotional neglect, and physical neglect via the Parent-Child Conflict Tactics Scale at ages 3 and 5 years.Main Outcomes and MeasuresEpigenetic accelerated aging (DNAmAA) was measured using 3 machine learning–derived surrogates of aging (GrimAge, PhenoAge, and DunedinPACE) and 2 machine learning–derived surrogates of age (Horvath and PedBE), residualized for age in months.ResultsA total of 1971 children (992 [50.3%] male) representative of births in large US cities between 1998 and 2000 were included. Physical assault at age 3 years was positively associated with DNAmAA for PhenoAge (β = 0.073; 95% CI, 0.019-0.127), and emotional aggression at age 3 years was negatively associated with PhenoAge DNAmAA (β = −0.107; 95% CI, −0.162 to −0.052). Emotional neglect at age 5 years was positively associated with PhenoAge DNAmAA (β = 0.051; 95% CI, 0.006-0.097). Cumulative exposure to physical assault between ages 3 and 5 years was positively associated with PhenoAge DNAmAA (β = 0.063; 95% CI, 0.003-0.123); emotional aggression was negatively associated with PhenoAge DNAmAA (β = −0.104; 95% CI, −0.165 to −0.043). The association of these measures with age 15 years PhenoAge DNAmAA was almost fully mediated by age 9 years PhenoAge DNAm age acceleration. Similar patterns were found for GrimAge, DunedinPACE, and PhenoAge, but only those for PhenoAge remained after adjustments for multiple comparisons.Conclusions and RelevanceIn this cohort study, altered patterns of DNAmAA were sensitive to the type and timing of child maltreatment exposure and appeared to be associated with more proximate biological embedding of stress.

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The association between adverse childhood experiences and epigenetic age acceleration in the Canadian longitudinal study on aging (CLSA)

Cited by 28 publications

References 45 publications

Mother’s childhood adversity is associated with accelerated epigenetic aging in pregnancy and in male newborns

Mother’s childhood adversity is associated with accelerated epigenetic aging in pregnancy and in male newborns

Association of Adverse Childhood Experiences With Accelerated Epigenetic Aging in Midlife

Childhood Maltreatment and Longitudinal Epigenetic Aging

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