Adverse childhood experiences (ACEs) (e.g., physical abuse, sexual abuse, emotional neglect, loss of a close family member) are a large societal problem, often with long-lasting health consequences. Previous research has shown that ACEs are highly prevalent. In the general population, more than half of people retrospectively report at least one, and more than a quarter two or more, types of ACEs (Felitti et al., 1998; Dube et al., 2001). In addition, ACEs are found to be related to poor health outcomes, including various mental health problems (e.g., depression, anxiety, post-traumatic stress disorder [PTSD], suicidal ideation), substance abuse problems, self-reported illness, obesity, and overall morbidity (Felitti et al., 1998; Widom, 1999; Dube et al., 2001, 2003; Anda et al., 2006, 2010; Widom et al., 2007; Brown et al., 2009; Green et al., 2010; Heim et al., 2010; Kessler et al., 2010; Heim and Binder, 2012; Moffitt and the Klaus-Grawe Think Tank, 2013). ACEs have also been found to be associated with increased risk for many somatic diseases, especially with diseases of aging including cancer, autoimmune, cardiovascular diseases and early mortality (Felitti et al., 1998; Brown et al., 2009; Rich-Edwards et al., 2012; Kelly-Irving et al., 2013; Tomasdottir et al., 2015). Although it is largely accepted that ACEs increase risk for poor health outcomes, mechanisms of the association are still not fully understood (Moffitt and the Klaus-Grawe Think Tank, 2013).

Following a pioneering study by Epel et al. (2004), research on the association of stress and telomere-related processes has rapidly emerged. Accelerated cell aging—indexed by altered telomere maintenance—might be one mechanism that partially explains the association between ACEs and long-term health complaints. Telomeres are repeated non-coding deoxyribonucleic acid (DNA) sequences—TTAGGG nucleotide tandem repeats – at the end of chromosomes, protecting the coded sequences (Blackburn, 1991). Telomeres shorten during cell division, caused by an incomplete replication of the chromosome ends (Blackburn, 2000, 2001). When telomeres are critically short, cells become genomically unstable and can malfunction in cell-specific ways (Blackburn, 2000). Telomeres tend to shorten with age, which makes telomere length (TL) an interesting marker of biological aging (Cawthon et al., 2003; Blackburn, 2005; Aubert and Lansdorp, 2008; Takubo et al., 2010). Interestingly, shorter telomeres are correlated with several psychiatric disorders (Lindqvist et al., 2015; Schutte and Malouff, 2015; Darrow et al., 2016; Ridout et al., 2016; Li et al., 2017a; Epel and Prather, 2018), somatic diseases (Honig et al., 2006; Willeit et al., 2010), and early mortality (Cawthon et al., 2003).

A fast-growing body of research describes the association between ACEs and TL over the life course. Various reviews in the broader context of the association between stress and TL have recently been published focusing in detail on early life stress and telomeres (Shalev, 2012; Price et al., 2013; Ridout et al., 2015), perceived stress and TL (Schutte and Malouff, 2014; Mathur et al., 2016), childhood exposure to violence and TL (Moffitt and the Klaus-Grawe Think Tank, 2013), violence and telomeres (Oliveira et al., 2016), caregiving experiences and telomeres (Blaze et al., 2015), and psychosocial factors and TL (Starkweather et al., 2014). Additionally, recent meta-analyses describe the association between early life adversity and TL (Ridout et al., 2017), childhood trauma and accelerated telomere erosion (Li et al., 2017b) and childhood psychosocial stressors and TL (Hanssen et al., 2017). Overall, these analyses reported negative associations between ACEs and TL with aggregated small effect sizes [Ridout et al. (2017) Cohen's d = −0.35; Hanssen et al. (2017) r = −0.082; and Li et al. (2017b) r = −0.05]. Epel and Prather (2018) summarized the current empirical evidence, concluding that “these meta-analyses demonstrate the robustness of the association [childhood stressors and telomere length] across published studies” (p. 5). However, all three meta-analyses reported a high between-study heterogeneity of effects, which they tried to explain in further moderator analyses. In their moderator analyses Ridout et al. (2017) showed “that differences in developmental timing of adversity exposure and comorbidities likely contributed to the heterogeneity” (p. 12), Li et al. (2017b) concluded that “the heterogeneous feature of childhood trauma may be one of the major potential sources of heterogeneity in outcomes” (p. 68), and Hanssen et al. (2017) found greater effect sizes for categorical compared to continuous measures of stressors, and for shorter durations between stressor and TL measures. Hence, a possible explanation for the observed heterogeneity in findings are attributes related to the characteristics and measurement of stressors. A deeper understanding about the different aspects of ACEs might help to explain the diversity in reported associations.

Epel and Lithgow (2014) stated that research must form a “common knowledge base and taxonomy for describing stressors and stress responses” (p. 11) to bridge the gap between basic and clinical research on aging and stress. Epel et al. (2018) further pointed out that “a large but disjointed literature shows that stress affects slow-acting biological processes in the brain and body, accelerating diseases of aging” (p. 146), but that despite this agreement one major barrier that prevents research progress is the “lack of consistency and thoroughness in stress measurement”(p. 146). This lack of a common knowledge base, consistency and thoroughness in stress measures can also be seen in the field of early life stressors and childhood adversities. Specifically, these conceptual issues lead to a large heterogeneity of reported prevalence and incidence rates of early traumatic stressors and ACEs (Heim and Binder, 2012; Moffitt and the Klaus-Grawe Think Tank, 2013). It can also be seen in the reviews and meta-analyses discussed here that use varying stress -frameworks but overall overlap to a great degree in their included studies.

In search of a common knowledge base and taxonomy, Epel et al. (2018) proposed a working model focusing on stress as “an emergent process that involves interactions between individual and environmental factors, historical and current events, allostatic states, and psychological and physiological reactivity” (p. 146). This model comprises different research perspectives on stress and introduces a more precise language for describing stress measures. Within this framework, stress consists of an exposure within in a specific context that elicits a stress-related response. Stressor exposure characteristics (SECs) are defined along different dimensions: timescale for stress measurements (acute, event-based, daily, chronic), developmental life stages of stress exposures, stress assessment windows (measurement timeframe; proximity of assessment to the stressor in years), and stressor attributes (duration, severity, controllability, life domain, target of stressor, potential of the stressor to elicit harmful response). However, it is unknown to what extend the proposed SECs can be applied to a diverse body of literature focused on ACEs and TL.

Therefore, the main aim of the current paper is to review the fast-growing body of literature on the associations between ACEs and TL order to find explanations for the heterogeneity in findings. The included sample of studies will be reviewed based on important study design characteristics and the SECs proposed by Epel et al. (2018). This will help us to better understand the complex relationship between ACEs and TL.

To be included in the current review, studies had to report on ACEs, assessed by means of a questionnaire or interview, on TL, and on a statistical measure of association between these two. Hereinafter, ACEs are defined as the broad array of harmful, perceived traumatic stressors during a child's development before the age of 18. This includes childhood traumatic experiences, all forms of childhood maltreatment including abuse and neglect, and childhood exposure to violence, and the combination of these factors with further potentially harmful circumstances. Multiple search methods were used to avoid biased retrieval of studies (Rosenthal, 1995). First, a computerized search of relevant databases was conducted: PubMed, PsycInfo, Web of Science, and Google Scholar up to the 26th of April 2018. The following key words were used in varying combinations: “childhood adversit^*,” “early life stress” or “childhood trauma” and “telomere length.” Second, the combination of several instruments reported in the papers to assess ACEs with “telomere length” was examined: Childhood Trauma Questionnaire [CTQ] (Bernstein et al., 1994, 2003); Childhood Trauma Interview [CTI] (Foote and Lovejoy, 1995); Adverse Childhood Experiences [ACE] Questionnaire (Felitti et al., 1998); and the Early Trauma Inventory [ETI] (Bremner et al., 2000). Third, reference lists from relevant reviews on the association between ACEs and TL (Shalev, 2012; Price et al., 2013; Ridout et al., 2015, 2017; Oliveira et al., 2016; Epel and Prather, 2018) were examined for possible additional studies. Finally, reference lists of all included papers were checked for potentially relevant additional articles. One eligible paper by Schaakxs et al. (2015) was excluded, because another paper from the same research group (Schaakxs et al., 2016) used the same sample.

A total of 38 studies were eligible for inclusion in this review. First, we collected information on the following sample characteristics: sample size, sex, age (of the sample), sample origin, study design (cross-sectional [case-control], longitudinal), sample composition, telomere assay approach, and covariates. Additionally, we collected the following ACEs characteristics: questionnaire (specific instrument [e.g., CTQ], modified specific instrument, item, score, total score), and age at adversity exposure. Further, ACEs characteristics were assessed using the proposed SECs defined by Epel et al. (2018). This included: timescale of the used stress measurement (i.e., acute, event-based, daily, chronic); developmental life stages (i.e., childhood only, adolescence only, childhood and adolescence); stress assessment window (i.e., measurement timeframe [e.g., retrospective or prospective]; proximity of assessment to the stressor in years [i.e., duration in years between exposure and assessment]); and stressor attributes (duration, severity, controllability, life domain, target of stressor, potential of the stressor to elicit harmful response). For a detailed definition of the SECs, please refer to Appendix A. “Stress typology for stress measurement” within the model proposed by Epel et al. (2018) (p.163). Moreover, main findings of the ACEs-TL association were summarized and coded (shorter, none, longer, mixed). In a second step, studies were grouped into categories: sample size (<400, >400), age (<25, 25–45, >45), sex (male, female) and population (clinical vs. non-clinical) and reviewed regarding their overall findings.

Information regarding sample characteristics, ACEs characteristics and main findings are presented in Table 1. Further information regarding main and sub-findings are presented in Table 2. Additional supplementary characteristics including the type of adversity and nature of the ACEs-TL association are provided in the supplementary materials (Supplementary Table 1). Information was extracted and coded by the first author (DB) and double checked by one of the co-authors (Dd'H). Differences in extracted information and coding were solved by further discussing these issues.

The aim of the current review was to review the literature on the associations between ACEs and TL in an attempt to highlight how heterogeneity in sample and stressor characteristics contributes to findings. Overall, the sample of studies we reviewed indicates a negative association between ACEs and TL, although many papers presented mixed findings and a quarter of eligible studies found no relationship between ACEs and TL. These findings are consistent with recently published meta-analyses investigating the association between early adversity, childhood trauma and childhood psychosocial stressors and TL. All three studies showed significant small negative associations with TL (Hanssen et al., 2017; Li et al., 2017b; Ridout et al., 2017). These meta-analyses further reported high between-study heterogeneity of effects. Considering possible moderators within our sample of studies indicates that results of larger samples seem to be less conclusive than results of smaller samples. In addition, studies investigating participants younger than 25 more often find ACEs to be negatively associated with TL compared to older samples. Furthermore, results from studies of non-clinical samples more often report negative associations between ACEs and TL than do studies of clinical samples. Using the SECs proposed by Epel et al. (2018) to examine characteristics of the included ACEs shows a lack of detailed information on SECs in many studies. At least four findings (sample size, age, psychopathology, and ACEs characteristics) need to be discussed in more detail to find explanations for the heterogeneity and inconclusiveness of reported findings.

First, with regard to sample size, we observed that findings of larger samples are less conclusive compared to findings of smaller samples. This might be explained by the fact that larger samples can control for more additional variables and potential confounds. These additional factors might moderate, mediate, conceal or suppress the direct, independent impact of ACEs, as many of these variables in larger models are inter-correlated (e.g., adversities, mental health problems, negative life-styles, and smoking status).

Second, we observed that studies with younger participants more often find negative associations than studies with older participants. This is in line with Ridout et al. (2017) who reported in their moderator analyses that the smaller the duration between ACEs exposure and age at TL assessment, the larger the magnitude of effect sizes. They explained this finding by pointing to the fact that studies of children assume no smoking amongst participants, and that adversities early in childhood tend to be associated with larger effects (Ridout et al., 2017). Similar results were found by Hanssen et al. (2017). Another potential explanation, according to the healthy survivor effect, might be that participants within older samples drop out due to morbidity or early mortality, which is in turn associated with shorter telomeres (Mather et al., 2011; Kuffer et al., 2016; Schaakxs et al., 2016; Oliveira et al., 2017). Moreover, Schaakxs et al. (2016) argued that “a possible explanation for these null findings in older adults may be that older adults have been exposed to numerous competing causes for shortened TL, such as somatic diseases or an unhealthy lifestyle over the life span. These other TL-damaging factors may suppress the independent impact of psychosocial stressors.” (p. 441).

Third, the sample composition of included studies varied strongly. Some of the studies focused on specific clinical populations and the impact of psychiatric disorders on TL. These studies included ACEs in their models as control variables. In contrast, other studies focused on the impact of ACEs on TL controlling for psychiatric conditions. We observed that studies with non-clinical populations more often report negative associations between ACEs and TL. This is in line with Ridout et al. (2017), who found effect sizes of smaller magnitude regarding the association of ACEs and TL in their moderator analyses, when looking at studies that included subjects with mental disorders. Epel and Prather (2018) recently proposed a triad model of stress exposures, psychopathology and telomere biology combining the meta-analytic evidence between the associations of stress and telomeres, stress and psychopathology, and psychopathology and telomeres. Having this triad in mind, when approaching TL from a psychopathological perspective, studies have to acknowledge that “expression of psychopathology may be strongly influenced by exposure to maltreatment” (Teicher and Samson, 2013, p. 1,114). This distinctive phenotypical expression of a psychiatric disorder (with vs. without maltreatment) might reveal distinct subtypes of disorders that are important to account for when determining the biological bases of these mental disorders (Teicher and Samson, 2013; Teicher et al., 2016). Moreover, possible direct associations of ACEs on TL might be mediated by the later development of mental disorders. Assuming that early adversities often precede psychopathology, psychiatric disorders might mediate the association of ACEs and TL. Hence, research on TL should acknowledge both perspectives: distinct subtypes of psychiatric disorders (with vs. without maltreatment) within clinical samples and the potential mediating effect of psychopathology in non-clinical samples.

Fourth, the current study further examined ACEs using the SECs recently proposed by Epel et al. (2018). Results showed an overall lack of details and lots of missing information. This makes it indeed very difficult to understand the adverse nature of these experiences with important characteristics and attributes not being measured or articulated. Differentiating between event-based and chronic exposures, the target of the exposure, and the duration, for instance, is very important in the context of trauma research as many childhood adversities are interpersonal and traumatic in nature (e.g., abuse and neglect, interpersonal loss, interpersonal conflict, interpersonal violence) and are targeted at either participants themselves or at close others (e.g., siblings or family members) (Widom et al., 2008; Moffitt and the Klaus-Grawe Think Tank, 2013). Chronic-occurring interpersonal events are often followed by a broad range of trauma-associated psychopathologies that are not captured within the classical framework of PTSD (Cook et al., 2005). These harmful responses can lead to diverse behavioral and emotional alterations, often referred to as complex trauma symptoms, as for example affective dysregulation, attentional and behavioral problems, self and relational deregulation (Briere et al., 2008; Greeson et al., 2011; Schmid et al., 2013). For this reason many experts emphasized the need for a more developmentally sensitive diagnostic system that takes account of the heterogeneity of psychopathology following early trauma (Cloitre et al., 2009; van der Kolk et al., 2009; D'Andrea et al., 2012; Schmid et al., 2013). This led to the inclusion of complex trauma symptoms within the PTSD section in the Diagnostic and Statistical Manual of Mental Disorders—Fifth Edition (DSM-5) and the inclusion of a complex PTSD disorder in the International Classification of Diseases 11th Revision (ICD-11). These complex trauma symptoms contain symptoms of affect dysregulation, negative self-concepts and interpersonal problems that are related to the traumatic exposure (Cloitre et al., 2013). Overall, the adversities included are all of a stressful, adverse, and traumatic nature. Most of these stressors have the potential to elicit harmful emotional responses (e.g., social threat, loss of control, shame) and behavioral alterations (e.g., role-change, impulsivity), but detailed and differentiating information is missing.

Overall, the included sample of studies indicates a negative association between ACEs and TL, but the diversity in sample and stressor characteristics makes it difficult to achieve a final and confident conclusion. From a developmental perspective, a more comprehensive evaluation of adversities using a common language and dimensional approaches to SECs might help to improve understanding of the complex associations between (early) stressors and health outcomes. Individuals are exposed to numerous competing and interacting exposures that might shorten TL over the life course. A focus on developmental trajectories combining early adversities, psychopathology and protective factors might help to develop enhanced approaches to reduce the stress-related health burden of our societies.

DB, CB, MS, and KS contributed to the conception of the paper. DB extracted all study and stressor characteristics and wrote the first draft of the manuscript. AOD, CB and DdH wrote sections of the manuscript and edited the paper. AOD, AE, JF, AdG, MS, KS, and CB critically revised the paper. All authors contributed to manuscript revision, read and approved the submitted version.