Telomere length is associated with growth in children in rural Bangladesh
- University of California, Berkeley, United States
- University of California San Francisco, United States
- University of California, San Francisco, United States
- University of California, Davis, United States
- International Centre for Diarrhoeal Disease Research, Bangladesh, Bangladesh
- Stanford University, United States
- University of Miami, United States
Abstract
Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.
Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.
Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score (95% CI 0.05, 0.42; FDR-corrected p-value = 0.01)). TL was not associated with other outcomes.
Conclusions: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first two years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.
Funding: Funded by the Bill and Melinda Gates Foundation.
Data availability
The WASH Benefits data and code that support the findings of this study are available in Open Science Framework (https://osf.io/9snat/).
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WASH Benefits Bangladesh Analysis of Telomere and Growth OutcomesOpen Science Framework.
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WASH Benefits Bangladesh Analysis of Telomere OutcomesOpen Science Framework, https://doi.org/10.17605/OSF.IO/EVC98.
Article and author information
Author details
Funding
Bill and Melinda Gates Foundation (OPPGD759)
- John M Colford Jr.
National Institute of Allergy and Infectious Diseases (K01AI136885)
- Audrie Lin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Clinical trial registration: The trial was registered at ClinicalTrials.gov (NCT01590095).Human subjects: Primary caregivers of all children provided written informed consent. The study protocols were approved by human subjects committees at icddr,b (PR-11063 and PR-14108), the University of California, Berkeley (2011-09-3652 and 2014-07-6561) and Stanford University (25863 and 35583).
Copyright
© 2021, Lin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Telomere length is associated with growth in children in rural Bangladesh
eLife 10:e60389.
https://doi.org/10.7554/eLife.60389
Further reading
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Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD).
Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.
Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).
Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
