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Accelerated DNA methylation aging and increased resilience in veterans: The biological cost for soldiering on.

ABSTRACT: Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n?=?96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication cohort, n?=?115 males). Primary measures included the Clinician Administered PTSD Scale for DSM-5 and the Connor-Davidson Resilience Scale (CD-RISC). DNAm age prediction was performed using the validated epigenetic clock calculator. Veterans with PTSD had increased PTSD symptom severity (P-value?=?3.75?×?10-34) and lower CD-RISC scores (P-value?=?7.5?×?10-8) than veterans without PTSD. DNAm age was significantly correlated with the chronological age (P-value?=?3.3?×?10-6), but DNAm age acceleration was not different between the PTSD and non-PTSD groups (P-value?=?0.24). Evaluating potential protective factors, we found that DNAm age acceleration was significantly associated with CD-RISC resilience scores in veterans with PTSD, these results remained significant after multiple testing correction (P-value?=?0.023; r?=?0.32). This finding was also replicated in an independent trauma-exposed civilian cohort (P-value?=?0.02; r?=?0.23). Post-hoc factor analyses revealed that this association was likely driven by "self-efficacy" items within the CD-RISC (P-value?=?0.015; r?=?0.35). These results suggest that among individuals already suffering from PTSD, some aspects of increased resilience might come at a biological cost.

SUBMITTER: Mehta D

PROVIDER: S-EPMC5991315 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Accelerated DNA methylation aging and increased resilience in veterans: The biological cost for soldiering on.

Mehta Divya D Bruenig Dagmar D Lawford Bruce B Harvey Wendy W Carrillo-Roa Tania T Morris Charles P CP Jovanovic Tanja T Young Ross McD RM Binder Elisabeth B EB Voisey Joanne J

Neurobiology of stress 20180201

Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n = 96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication co ...[more]

PMID: 29888306

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Project description:BackgroundAging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear.ObjectivesOur aim was to investigate the association of PAH exposure with methylation aging.MethodsWe trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians. We defined two aging indicators: δage, as methylation age minus chronological age; and aging rate, the ratio of methylation to chronological age. The association of PAH exposure with aging indicators was evaluated using linear regressions in three panels of healthy Chinese participants (N=539, among the aforementioned 989 Chinese participants) whose exposure levels were assessed by 10 urinary monohydroxy-PAH metabolites.ResultsWe developed a methylation age predictor providing accurate predictions in both Chinese individuals and Caucasian persons (R=0.94-0.96, RMSE=3.8-4.3). Among the 10 urinary metabolites that we measured, 1-hydroxypyrene and 9-hydroxyphenanthrene were associated with methylation aging independently of other OH-PAHs and risk factors; 1-unit increase in 1-hydroxypyrene was associated with a 0.53-y increase in Δage [95% confidence interval (CI): 0.18, 0.88; false discovery rate (FDR) FDR=0.004] and 1.17% increase in aging rate (95% CI: 0.36, 1.98; FDR=0.02), whereas for 9-hydroxyphenanthrene, the increase was 0.54-y for Δage (95% CI: 0.17, 0.91; FDR=0.004), and 1.15% for aging rate (95% CI: 0.31, 1.99; FDR=0.02). The association direction was consistent across the three Chinese panels with the association magnitude correlating with the panels' exposure levels; the association was validated by methylation data of purified leukocytes. Several cytosine-phosphoguanines, including those located on FHL2 and ELOVL2, were found associated with both aging indicators and monohydroxy-PAH levels.ConclusionsWe developed a methylation age predictor specific for Chinese populations but also accurate for Caucasian populations. Our findings suggest that exposure to PAHs may be associated with an adverse impact on human aging and epigenetic alterations in Chinese populations. https://doi.org/10.1289/EHP2773.

Dataset Information

Accelerated DNA methylation aging and increased resilience in veterans: The biological cost for soldiering on.

Publications

Accelerated DNA methylation aging and increased resilience in veterans: The biological cost for soldiering on.

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