NEW YORK – Researchers have found that adverse childhood experiences such as emotional negligence, physical violence, physical negligence, and household substance abuse are associated with accelerated biological aging in midlife.
In a study published in JAMA Network Open on Monday, a team led by researchers from Northwestern University calculated five DNA methylation-based epigenetic aging measurements that are associated with biological long-term health among people who self-reported adverse childhood experiences (ACEs).
Their findings showed that people with four or more ACEs were likely to have older biological ages compared with their chronological ages, irrespective of their socioeconomic status in early or later life.
"This suggests that ACEs may lead to a faster molecular aging process, which could affect people's future disease risk," corresponding author, Lifang Hou, professor of preventive medicine at Northwestern University's Feinberg School of Medicine, told GenomeWeb.
For this study, Hou, co-corresponding author Brian Joyce, a research assistant at Feinberg, and colleagues used data from participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a multicenter prospective cohort study across four field centers in the US.
Around 5,115 male and female participants aged 18 to 30 years with self-reported Black or White race were enrolled in the study. ACEs were self-reported by the participants in a questionnaire, which asked how often a participant had experienced each of the events before they turned 18. After excluding participants with missing data, blood samples were drawn at two time points — 15 years (895 subjects) and 20 years (867 subjects).
"Previous studies have demonstrated that stress, violence, and some environmental chemicals accelerate epigenetic aging; however, no one had done a longitudinal study on how adverse childhood experiences may affect epigenetic aging later in life," said Hou.
The researchers analyzed DNA methylation levels in the blood samples and calculated the participants' epigenetic age accelerations (EAA) using five estimators: intrinsic EAA, extrinsic EAA (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Dunedin Pace of Aging (DunedinPACE).
"The intrinsic EAA and extrinsic EAA estimators talk more about biological aging in the blood and immune system, whereas PhenoAA and GrimAge talk more about lifespan of the participants. Finally, DunedinPACE tells us more about the rate of aging," said lead author Kyeezu Kim, a postdoctoral student in Hou's laboratory.
Together, the findings suggested that ACEs may be associated with increased EAA through pathways with disrupted cellular properties and immunity, inflammation, and endocrine system disruption owing to the exposure to toxic stress in childhood, the authors wrote, further noting that this information "may inform future interventions to reduce or mitigate deleterious epigenetic outcomes associated with ACEs."
Meanwhile, the researchers also noted that they observed consistent associations across subgroups, suggesting that the association of ACEs to EAA outcomes was true regardless of demographics.
Highlighting the limitations, the authors noted that since ACEs were self-reported, there is a possibility of recall bias and that this study did not include ACEs related to sexual abuse, parental separation or divorce, parental mental illness, or parental incarceration. "These unaccounted elements may have induced residual confounding in associations found in our study," they wrote.
The authors would next like to conduct the same study in different and larger cohorts to confirm their findings.
In an accompanying commentary in JAMA Network Open, authors led by Erin Dunn, a psychiatry and neurodevelopment researcher at Massachusetts General Hospital, noted that this study brings much needed attention to health outcomes associated with childhood adversity and how epigenetic clocks may be used to understand biological associations between adversity and later health outcomes.