Telomere length and early severe social deprivation: linking early adversity and cellular aging

Abstract

Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity.

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

“…In terms of biological mechanisms, prenatal psychosocial stress exposure could affect cellular aging through several mechanisms: changes in immune function, changes in metabolic and oxidative stress-related pathways, and/or changes in telomerase activity. These changes, in turn, may be mediated by epigenetic modifications, thereby setting up long-term trajectories (27,51). Stress is transduced from the pregnant mother to her fetus through various pathways, including transplacental transport of the stress hormone cortisol, maternal stress-induced release of placental hormones that enter the fetal circulation (e.g., placental corticotrophin-releasing hormone), and maternal stress-induced effects on placental physiology, including alterations in blood flow and changes in metabolism impacting oxygen and glucose availability and use (52,53).…”

“…Many, but not all, studies in humans have found an association between exposure to adverse conditions in early postnatal life (infancy and childhood) and subsequent telomere length (24)(25)(26)(27)(28). One important question that has yet to be addressed to our awareness is whether exposure to stress during intrauterine development can produce variations in telomere length, thereby potentially setting up a long-term trajectory at birth that defines or contributes to individual susceptibility for complex, common age-related diseases.…”

Social disadvantage, genetic sensitivity, and children’s telomere length

“…The TL literature has focused almost exclusively on adults, although several studies have used retrospective reports to measure childhood conditions (10), and one prospective study has examined the association between childhood conditions between ages 5 and 10 and TL (27) and a second study determined that the duration of exposure to institutional care between 22 and 54 mo was negatively associated with telomere length (12). A second limitation of current TL literature is that most studies are based on samples of middle-class whites; research on minority children and children from low-income families is sparse.…”

“…First, we focus on children, whereas prior research has focused primarily on adults, with few exceptions (12). Second, we examine a sample of African American boys whereas prior research has used mostly samples of whites.…”

Life Course Research Agenda (LCRA), Version 1.0

“…For example, it is well known that children who are abused, neglected, and placed into the foster care system can experience dramatically altered life course trajectories (Zlotnick et al 2012;Tyler and Schmitz 2013;Patterson et al 2015). Initial studies examining the impact of adversity, institutional placement, and out-of-home care have suggested how such experiences can alter neurobiological functioning and cellular processes associated with the regulation of cellular aging and longevity (Drury et al 2012;Karatsoreos and McEwen 2013). Life course health development research could improve these interventions in regard to their capacity to improve long-term trajectories for children in foster care and other vulnerable populations, including young people involved in the juvenile justice system and children with chronic and debilitating medical conditions and impairments (Zlotnick et al 2012).…”