WHAT'S KNOWN ON THIS SUBJECT: Poor health in children is associated with exposure to family violence and disruption. Telomere length has been hypothesized to be a lasting biological indicator of exposure to early adversity and potentially predictive of negative health outcomes throughout the life course. WHAT THIS STUDY ADDS:Telomere length reflects exposure to family violence and disruption and may be an early indicator of the biological impact of early adversity. Children exposed to interpersonal violence and family disruptions had significantly shorter telomeres. Gender moderated these associations. abstract BACKGROUND: To enhance the understanding of biological mechanisms connecting early adversity and negative health, we examine the association between family interpersonal violence and disruption and telomere length in youth. These specific exposures were selected because of their established links with negative health consequences across the life-course.

Research in the last decade has explored the length of telomeres, the protective ends of eukaryotic chromosomes, as a biomarker for the cumulative effects of environmental exposures and life experiences as well as a risk factor for major diseases. With a growing interest in telomere biology across biomedical, epidemiological and public health research, it is critical to ensure that the measurement of telomere length is performed with high precision and accuracy. Of the several major methods utilized to determine telomere length, quantitative PCR (qPCR) remains the most cost-effective and suitable method for large-scale epidemiological and population studies. However, inconsistencies in recent reports utilizing the qPCR method highlight the need for a careful methodological analysis of each step of this process. In this review, we summarize each critical step in qPCR telomere length assay, including sample type selection, sample collection, storage, processing issues and assay procedures. We provide guidance and recommendations for each step based on current knowledge. It is clear that a collaborative and rigorous effort is needed to characterize and resolve existing issues related to sample storage, both before and after DNA extraction, as well as the impact of different extraction protocols, reagents and post extraction processing across all tissue types (e.g. blood, saliva, buccal swabs, etc.) to provide the needed data upon which best practices for TL analyses can be agreed upon. Additionally, we suggest that the whole telomere research community be invited to collaborate on the development and implementation of standardized protocols for the assay itself as well as for reporting in scientific journals. The existing evidence provides substantial support for the continuation of telomere research across a range of different exposures and health outcomes. However, as with any technological or methodologic advance in science, reproducibility, reliability and rigor need to be established to ensure the highest quality research.

Objective To explore racial differences in newborn telomere length (TL) and the effect moderation of the sex of the infant while establishing the methodology for the use of newborn blood spots for telomere length analyses. Study design Pregnant mothers were recruited from the Greater New Orleans area. TL was determined using MMQ-PCR on DNA extracted from infant blood spots. Demographic data and other covariates were obtained via maternal report prior to infant birth. Birth outcome data were obtained from medical records and maternal report. Results Black infants weighed significantly less than white infants at birth, and had significantly longer TL than White infants (p=0.0134), with the strongest effect observed in Black female infants. No significant differences in gestational age were present. Conclusions Significant racial differences in TL were present at birth in this sample, even after controlling for a range of birth outcomes and demographic factors. As longer initial TL is predictive of more rapid TL attrition across the life course, these findings provide evidence that, even at birth, biological vulnerability to early life stress may differ by race and sex.

Objectives Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the percent time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. Materials and Methods We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. Results An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. Discussion These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children.

The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.