Childhood adversity, accelerated GrimAge, and associated health consequences

Abstract

Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and cardiometabolic disease. Epigenetic alterations are one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why cardiometabolic health can vary greatly between individuals with similar Body Mass Index (BMIs). We evaluated two independent cross-sectional cohorts of adults without known medical illness, one of which explicitly recruited individuals with early life stress (ELS) and control participants (n = 195), and the other a general community sample (n = 477). In these cohorts, we examine associations between childhood adversity, epigenetic aging, and metabolic health. Childhood adversity was associated with increased GrimAge Acceleration (GAA) in both cohorts, both utilizing a dichotomous yes/no classification (both p < 0.01) as well as a continuous measure using the Childhood Trauma Questionnaire (CTQ) (both p < 0.05). Further investigation demonstrated that CTQ subscales for physical and sexual abuse (both p < 0.05) were associated with increased GAA in both cohorts, whereas physical and emotional neglect were not. In both cohorts, higher CTQ was also associated with higher BMI and increased insulin resistance (both p < 0.05). Finally, we demonstrate a moderating effect of BMI on the relationship between GAA and insulin resistance where GAA correlated with insulin resistance specifically at higher BMIs. These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical and metabolic health effects.

Keywords: Childhood adversity; Childhood trauma; Epigenetic aging; GrimAge; Health outcomes.

Figure 1:

(A) In the LIFE study, GrimAge is strongly correlated with Chronologic Age in both Cases (red, those with ELS) and Controls (blue, those without ELS). Individuals with ELS Have higher GrimAge than those without. (B) In the LIFE study, GrimAge Acceleration is elevated in Cases compared to Controls. (C) In the LIFE study, The Childhood Trauma Questionnaire (CTQ) score is positively associated with GrimAge Acceleration. As would be expected, Cases (red) have higher CTQ scores than Controls (blue). (D) In the Yale Stress Center study, GrimAge is strongly correlated with Chronologic Age in both individuals with high (red) and low (blue) childhood adversity. High childhood adversity does correlate with higher GrimAge. (E) In the Yale Stress Center study, High childhood adversity correlates with higher GrimAge Acceleration. (F) In the Yale Stress Center study, the CTQ score is positively associated with GrimAge Acceleration.

Figure 2:

(A) In the LIFE study, GrimAge Acceleration is positively associated with HOMA-IR in individuals with elevated BMI (interaction term: beta = 0.018, p = 0.0034). (B) In the Yale Stress Center study, GrimAge Acceleration is associated with elevated HOMA-IR in individuals with elevated BMI (interaction term: beta = 0.012, p = 0.0044). Plots represent the relationship between GrimAge Acceleration and HOMA-IR at representative values of BMI modeled as a continuous variable (HOMA-IR ~ GAA*BMI) in individuals with obesity (red), overweight (yellow), and those without overweight or obesity (blue).