ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Clin Epigenetics. 2020; 12: 55. PMID: 32264940.

A large body of evidence has documented the long-term consequences of adverse childhood experiences (ACEs) on social and health outcomes in later life (1). However, the underlying mechanisms remain unclear. Epigenetic mechanisms may explain the lasting effects of early life adversity (2). ‘Epigenetic clocks’ are sets of DNA methylation (DNAm) markers (CpG sites) that accurately predict chronological aging (3) and higher DNAm-predicted age relative to chronological age [DNAm age acceleration (AA)] is associated with higher risks for cardiovascular disease, cancer, and all-cause mortality (4). DNAm AA has also been associated with childhood exposure to adversity, including parental depression, violence, sexual abuse, low socioeconomic status, and cumulative exposure to sexual abuse, physical abuse, or neglect (5). Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a potential mediator between childhood adversity, epigenetics, and poor health in later life. DNAm AA has also been associated with elevated diurnal and baseline salivary cortisol in adolescents.

Here, the authors investigated the associations of individual types of ACEs, as well as cumulative ACE exposure, with DNAm AA and plasma cortisol concentrations in the prospective population-based UK Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort (n =974). Cumulative ACE exposure, emotional abuse, and physical abuse between age 0 and 14 years were each associated with older DNAm AA at age 17 years in girls but not in boys. These findings indicate a sex dimorphic epigenetic response to early life adversities, where girls appear to be more vulnerable than boys.

The present study adds to a growing body of evidence that suggest that effects from early life adversities may affect the individual later in life and that epigenetic mechanisms may partly explain how these effects may persist throughout the life-span. Understanding the mechanisms by which epigenetic mechanisms mediate these effects is important in order to determine how to ameliorate or prevent long-term negative effects.

References:

1. Taylor-Robinson DC, Straatmann VS, Whitehead M. Adverse childhood experiences or adverse childhood socioeconomic conditions? Lancet Public Health. 2018; 3:e262–3.

2. Relton CL, Davey SG. Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment. PLoS Med. 2010; 7:e1000356.

3. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, et al. Genome- wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013; 49:359–67.

4. Marioni RE, Harris SE, Shah S, McRae AF, von Zglinicki T, Martin-Ruiz C, et al. The epigenetic clock and telomere length are independently associated with chronological age and mortality. Int J Epidemiol. 2016; 47:356.

5. Wolf EJ, Maniates H, Nugent N, Maihofer AX, Armstrong D, Ratanatharathorn A. Traumatic stress and accelerated DNA methylation age: a meta-analysis. Psychoneuroendocrinology. 2018; 92:123–34.