Child mortality, hypothalamic-pituitary-adrenal axis activity and cellular aging in mothers

PLoS One. 2017 May 25;12(5):e0177869. doi: 10.1371/journal.pone.0177869. eCollection 2017.

Abstract

Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers' hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity. Child mortality data were collected in 2000 and 2013. HPAA activity was assessed by quantifying cortisol levels in first morning urinary specimens collected every other day for seven weeks in 2013. Telomere length (TL) was quantified using qPCR in 55 women from buccal specimens collected in 2013.

Results: Shorter TL with increasing age was only observed in women who experienced child mortality (p = 0.015). Women with higher average basal cortisol (p = 0.007) and greater within-individual variation (standard deviation) in basal cortisol (p = 0.053) presented shorter TL. Non-parametric bootstrapping to estimate mediation effects suggests that HPAA activity mediates the effect of child mortality on TL. Our results are, thus, consistent with the hypothesis that traumatic events can influence cellular aging and that HPAA activity may play a mediatory role. Future large-scale longitudinal studies are necessary to confirm our results and further explore the role of the HPAA in cellular aging, as well as to advance our understanding of the underlying mechanisms involved.

MeSH terms

  • Adult
  • Cellular Senescence / physiology*
  • Child
  • Child Mortality / trends*
  • Cohort Studies
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiology*
  • Longitudinal Studies
  • Middle Aged
  • Mothers
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiology*
  • Stress, Psychological / physiopathology
  • Telomere / metabolism

Substances

  • Hydrocortisone

Grants and funding

This project was funded by a Canadian Institutes of Health Research Post-Doctoral Fellowship to CKB (http://www.cihr-irsc.gc.ca/e/193.html); a Canadian Institutes of Health Research Training Grant to CWH (http://www.cihr-irsc.gc.ca/e/193.html); a Child and Family Research Institute Graduate Studentship to SLW (http://www.cfri.ca/); a Child and Family Research Institute salary award to WPR (http://www.cfri.ca/); a Natural Sciences and Engineering Research Council of Canada Discovery Grant to RMA (http://www.nserc-crsng.gc.ca/index_eng.asp); a Canadian Institutes of Health Research (Institute for Gender and Health) Operating Grant #106705 (http://www.cihr-irsc.gc.ca/e/193.html), a Simon Fraser University President’s Start-up Grant (https://www.sfu.ca/vpacademic/FinBdgt_Mgmnt/prsg.html), a Simon Fraser University Community Trust Endowment Fund Grant through Simon Fraser University’s Human Evolutionary Studies Program (https://www.sfu.ca/vpresearch/ctef.html), and a Michael Smith Foundation for Health Research Career Investigator Scholar Award (http://www.msfhr.org/) to PAN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.