Biological Aging in Childhood and Adolescence Following Experiences of Threat and Deprivation: A Systematic Review and Meta-Analysis

Abstract

Life history theory argues that exposure to early-life adversity (ELA) accelerates development, although existing evidence for this varies. We present a meta-analysis and systematic review testing the hypothesis that ELA involving threat (e.g., violence exposure) will be associated with accelerated biological aging across multiple metrics, whereas exposure to deprivation (e.g., neglect, institutional rearing) and low-socioeconomic status (SES) will not. We meta-analyze 46 studies (n=64,925) examining associations of ELA with pubertal timing and cellular aging (telomere length and DNA methylation age), systematically review 19 studies (n=2276) examining ELA and neural markers of accelerated development (cortical thickness and amygdala-prefrontal cortex functional connectivity) and evaluate whether associations of ELA with biological aging vary according to the nature of adversity experienced. ELA overall was associated with accelerated pubertal timing (d=-0.12) and cellular aging (d=-0.32). Moderator analysis revealed that ELA characterized by threat (d=-0.26), but not deprivation or SES, was associated with accelerated pubertal development. Similarly, exposure to threat-related ELA was associated with accelerated cellular aging (d=-0.43), but not deprivation or SES.Systematic review revealed associations between ELA and accelerated cortical thinning, with threat-related ELA consistently associated with thinning in ventromedial prefrontal cortex, and deprivation and SES associated with thinning in frontoparietal, default, and visual networks.There was no consistent association of ELA with amygdala-PFC connectivity. These findings suggest specificity in the types of early environmental experiences associated with accelerated biological aging and highlight the importance of evaluating how accelerated aging contributes to health disparities and whether this process can be mitigated through early intervention.

Analysis of socioeconomic disadvantage and pace of aging measured in saliva DNA methylation of children and adolescents

“…These clocks showed the expected associations with children's chronological age (r = 0.66-0.81 in an age range of 8-18 years). However, the difference between participants' epigenetic ages and their chronological ages, i.e., epigenetic age acceleration, did not differ between children experiencing different levels of socioeconomic risk, consistent with results from a recent meta-analysis (23). Measures of epigenetic age acceleration also appear to be less sensitive to racial/ethnic group differences in childhood and adolescence (22).…”

“…Not all types of adversity show evidence of association with clock measurements. In particular, low childhood socioeconomic status, which is consistently associated with shorter healthy lifespan, is not consistently associated with epigenetic clock measures of aging (23).…”

Mechanisms linking childhood trauma exposure and psychopathology: a transdiagnostic model of risk and resilience

“…In a recent meta-analysis-including 43 studies of pubertal timing with 114,450 participants and 11 studies of cellular aging with 1560 participants-we found that the association between ELA and accelerated biological development was specific to adversities involving exposure to trauma. Specifically, children exposed to trauma exhibited accelerated biological aging in measures of pubertal development and cellular aging, but children exposed to deprivation (e.g., neglect) and low socioeconomic status did not exhibit this pattern of accelerated aging [110]. These results support dimensional models of adversity arguing that different forms of earlylife adversity have unique influences on cognitive, emotional, and neurobiological development [32][33][34].…”

Associations of waking cortisol with DHEA and testosterone across the pubertal transition: Effects of threat-related early life stress

“…The single previous longitudinal investigation operationalized ELS as a composite of parent-reported depression, perceived stress, and family expressed anger (Ruttle et al, 2015). There is evidence that different forms of ELS have differential effects on psychobiological development (King et al, 2019;Lambert et al, 2017;Sheridan et al, 2017) and, in particular, that exposure to environmental threat (as opposed to deprivation) accelerates biological development (Colich et al, 2019;Del Giudice et al, 2011). Therefore, measures that combine exposure to different forms of ELS make it difficult to identify directional hypotheses or to determine what form of stress confers risk.…”

“…Given evidence that exposure to environmental threat (as opposed to deprivation) accelerates biological development (Colich et al, 2019;Del Giudice et al, 2011), we hypothesized that greater severity of threat-related ELS is associated with stronger positive coupling between change in cortisol and change in DHEA, and with weaker positive coupling between change in cortisol and change in testosterone across development.…”