Telomere length is associated with growth in children in rural Bangladesh.

Audrie Lin,Leanne Unicomb,Christine P Stewart,Ruchira Tabassum Naved,Syeda L Famida,Mahbubur Rahman,Salma Akther,Jue Lin,Kausar Parvin,Palash Mutsuddi,Shahjahan Ali,Patricia Kariger,Mahfuz Al Mamun ,Saheen Hossen ,Lia C H Fernald ,Stephen P Luby ,Jade Benjamin‐Chung ,Ziaur Rahman ,Firdaus S Dhabhar ,Abul K Shoab ,Alan Hubbard ,Andrew Mertens ,Benjamin F Arnold ,Simon Tan ,John M Colford

doi:10.7554/elife.60389

Abstract

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. 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. 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. 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 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories. Funded by the Bill and Melinda Gates Foundation. NCT01590095.

Highlights

Children living in low-income countries are often exposed to a broad array of environmental insults leading to malnutrition, impaired development, and early mortality
telomere length (TL) and anthropometry measurements were available from 662 children at
Our findings suggest that TL is associated with linear growth in the first year of life

Summary

Introduction

Children living in low-income countries are often exposed to a broad array of environmental insults leading to malnutrition, impaired development, and early mortality We hypothesized that early life interventions designed to improve nutrition and decrease environmental faecal contamination would reduce infections and inflammation – exposures associated with TL attrition – and, thereby, slow TL attrition The interventions improved linear growth (length-for-age Z scores) but were unexpectedly associated with shortened TL during the first year of life 2017; Luby et al, 2018), findings that challenged the prevailing paradigm that early-life stressors shorten TL (Ridout et al, 2015) and motivated the hypothesis of the present study: that accelerated TL attrition in early life could be associated with improved growth. 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).

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Discussion

Conclusion