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

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.

SUBMITTER: Lin A

PROVIDER: S-EPMC8494482 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Lin Audrie A Mertens Andrew N AN Arnold Benjamin F BF Tan Sophia S Lin Jue J Stewart Christine P CP Hubbard Alan E AE Ali Shahjahan S Benjamin-Chung Jade J Shoab Abul K AK Rahman Md Ziaur MZ Famida Syeda L SL Hossen Md Saheen MS Mutsuddi Palash P Akther Salma S Rahman Mahbubur M Unicomb Leanne L Naved Ruchira Tabassum RT Mamun Md Mahfuz Al MMA Parvin Kausar K Dhabhar Firdaus S FS Kariger Patricia P Fernald Lia Ch LC Luby Stephen P SP Colford John M JM

eLife 20210908

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 34494545

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Project description:BackgroundTelomere length has been associated with the occurrence and progression of common chronic and age-related diseases, and in younger populations, may represent a biomarker of disease susceptibility. Early childhood is a critical period for telomere biology as this period is characterized by a rapid decline in telomere length due to a large turnover of highly proliferative cells and may represent a period of unique sensitivity to environmental insults. Arsenic (As) exposure has been associated with both telomere lengthening and shortening in adults and children and some evidence suggests the effects may differ by level and timing of exposure.ObjectivesGiven the lack of clarity across studies, we investigated the association between urinary As and leukocyte telomere length among 476 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort.MethodsIn a series of multivariable models, adjusted for key covariates, we examined associations between urinary As and relative telomere length (RTL) of whole blood DNA.ResultsWe observed small but consistent, negative associations between urinary As and RTL, such that a doubling of urinary As was associated with a -0.017 (95% CI: -0.030, -0.005; p = 0.0056) decrease in RTL, in fully adjusted models. We also observed a somewhat stronger inverse relationship between urinary As concentration and RTL among children born to fathers ≥ 30 years of age at the time of birth, than those < 30 years; however, we did not observe a statistically significant interaction.DiscussionOur study suggests that As influences RTL, with detectable associations in early to mid-childhood. Further studies are needed to confirm our findings and investigate the potential long-term impacts of telomere shortening in childhood on later life health outcomes. Additional studies exploring how dose and timing of exposure may relate to RTL are critical to understanding As's relationship to telomere length.

Project description:ObjectiveAutism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. The balance between antioxidant capacity and oxidative stress (OS) induced free radicals may be crucial during the pathophysiological development of ASD.MethodsIn this study, 96 children with ASD who met the diagnostic and statistical manual of mental disorders were collected, and the number of children in the typical development (TD) group was matched by 1:1. Digital PCR (dPCR) for telomere length (TL) expression in ASD in peripheral blood leukocytes. Urine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) content were measured by tandem triple quadrupole mass spectrometry and corrected by urinary creatinine levels. The levels of superoxide dismutase (SOD), catalase (CAT), and capacity (AOC) were detected by kits.ResultsThe TL of the ASD group was shorter than the TD group (p < 0.01) and had some accurate predictive significance for the identification of ASD (AUC = 0.632, 95% CI: 0.533-0.710, p = 0.002). Both 8-OHdG content and SOD activity in the ASD group were significantly higher than those in the TD group (p < 0.05). Shortened TL (Monofactor: 2.20 (1.22, 3.96), p = 0.009; Multifactor: 2.22 (1.22, 4.00), p = 0.008) and reduced CAT activity (Monofactor: 2.31 (1.28, 4.17), p = 0.006; Multifactor: 2.31 (1.28, 4.18), p = 0.006) are risk factors for the development of ASD, while reduced 8-OHdG content (Monofactor: 0.29 (0.14, 0.60), p = 0.001; Multifactor: 0.27 (0.13, 0.57), p = 0.001) and reduced SOD activity (Monofactor: 0.55 (0.31, 0.98), p = 0.042; Multifactor: 0.54 (0.30, 0.98), p = 0.042) are protective factors for the development of ASD.ConclusionIn this study, TL and OS were significantly different between the ASD group and the TD group. As guanine-rich telomere sequences were likely damaged by oxygen free radicals, creating OS, which is a factor in the incidence and progression of ASDs. In conclusion, oxidative damage occurs in the bodies of children with ASD, which may lead to sustained disease progression and severe clinical manifestations. We assume that timely supplementation of antioxidants is very likely to be a potential treatment for early intervention in children with ASD. Identification and detection of OS-related biomarkers may contribute to early diagnosis and timely interventions in young patients with ASD.

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

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

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