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Cited by 20Epigenetics and DNA MethylationBirth, Development, and HealthTelomeres, Telomerase, and Senescence

Associations of four biological age markers with child development: A multi-omic analysis in the European HELIX cohort

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Robinson, Oliver, Lau, ChungHo E, Joo, Sungyeon, Andrusaityte, Sandra, Borras, Eva, de Prado-Bert, Paula, Chatzi, Lida, Keun, Hector C +12 more·2023·eLife
DOI 10.7554/elife.85104PMC PMC10338035

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Abstract

Background: While biological age in adults is often understood as representing general health and resilience, the conceptual interpretation of accelerated biological age in children and its relationship to development remains unclear. We aimed to clarify the relationship of accelerated biological age, assessed through two established biological age indicators, telomere length and DNA methylation age, and two novel candidate biological age indicators, to child developmental outcomes, including growth and adiposity, cognition, behavior, lung function and the onset of puberty, among European school-age children participating in the HELIX exposome cohort. Methods: The study population included up to 1173 children, aged between 5 and 12 years, from study centres in the UK, France, Spain, Norway, Lithuania, and Greece. Telomere length was measured through qPCR, blood DNA methylation, and gene expression was measured using microarray, and proteins and metabolites were measured by a range of targeted assays. DNA methylation age was assessed using Horvath’s skin and blood clock, while novel blood transcriptome and ‘immunometabolic’ (based on plasma proteins and urinary and serum metabolites) clocks were derived and tested in a subset of children assessed six months after the main follow-up visit. Associations between biological age indicators with child developmental measures as well as health risk factors were estimated using linear regression, adjusted for chronological age, sex, ethnicity, and study centre. The clock derived markers were expressed as Δ age (i.e. predicted minus chronological age). Results: Transcriptome and immunometabolic clocks predicted chronological age well in the test set ( r =0.93 and r =0.84 respectively). Generally, weak correlations were observed, after adjustment for chronological age, between the biological age indicators. Among associations with health risk factors, higher birthweight was associated with greater immunometabolic Δ age, smoke exposure with greater DNA methylation Δ age, and high family affluence with longer telomere length. Among associations with child developmental measures, all biological age markers were associated with greater BMI and fat mass, and all markers except telomere length were associated with greater height, at least at nominal significance (p<0.05). Immunometabolic Δ age was associated with better working memory (p=4 e–3) and reduced inattentiveness (p=4 e–4), while DNA methylation Δ age was associated with greater inattentiveness (p=0.03) and poorer externalizing behaviors (p=0.01). Shorter telomere length was also associated with poorer externalizing behaviors (p=0.03). Conclusions: In children, as in adults, biological aging appears to be a multi-faceted process and adiposity is an important correlate of accelerated biological aging. Patterns of associations suggested that accelerated immunometabolic age may be beneficial for some aspects of child development while accelerated DNA methylation age and telomere attrition may reflect early detrimental aspects of biological aging, apparent even in children. Funding: UK Research and Innovation (MR/S03532X/1); European Commission (grant agreement numbers: 308333; 874583).

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  • Placental and offspring epigenetic signatures, telomere biology and mitochondrial function provide measurable molecular readouts of prenatal exposure at birth or during childhood.

    “Placental and offspring epigenetic signatures, telomere biology and mitochondrial function provide measurable molecular readouts of prenatal exposure at birth or during childhood [116,117,118].”

    From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [117]

    The Results (Biological clock associations with health risk factors; page unavailable) report a nominal association between maternal smoking during pregnancy and children’s DNA methylation age, supporting a childhood molecular readout of one prenatal exposure. The paper also measures telomere length in children, but our copy does not establish it as a readout of prenatal exposure; it does not report placental signatures, mitochondrial function, or measurements at birth. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Robinson, O., Lau, C. E., Joo, S., Andrusaityte, S., Borras, E., de Prado-Bert, P., Chatzi, L., Keun, H. C., Grazuleviciene, R., Gutzkow, K. B., Maitre, L., Martens, D. S., Sabido, E., Siroux, V., Urquiza, J., Vafeiadi, M., Wright, J., Nawrot, T. S., Bustamante, M., & Vrijheid, M.
Affiliations
  • MRC Centre for Environment and Health (GB)
  • Μedical Research Council Centre for Environment and Health, Imperial College London
  • Department of Environmental Science, Vytautas Magnus University
  • Center for Genomics Regulation, Barcelona Institute of Science and Technology
  • Universitat Pompeu Fabra (UPF)
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California
  • Imperial College London (GB)
  • Division of Climate and Environmental Health, Norwegian Institute of Public Health
  • Hasselt University (BE)
  • Centre National de la Recherche Scientifique (FR)
  • University of Crete (GR)
  • Bradford Royal Infirmary (GB)
  • Universitat Pompeu Fabra (ES)
Corresponding author
Robinson, Oliver
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2023-06-06
Volume
12
Pages
108036
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.85104
PMC
PMC10338035
OpenAlex
W4379508447
Cited by
20
References
97
Citations by year
2026: 6 · 2025: 9 · 2024: 5
FWCI
1.78
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • Document Server@UHasselt (UHasselt) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Vytautas Magnus University (submittedVersion, cc-by)
Funders
  • UK Research and Innovation (MR/S03532X/1)
  • European Commission (308333 874583)
  • Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2017SGR595)
  • Departament de Salut de la Generalitat de Catalunya (SLT017/20/000119)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
biological age, telomere length, DNA methylation age, child development, childhood adiposity, growth, puberty onset, lung function, working memory, inattention, externalizing problems, birth weight, smoke exposure, family affluence, exposome, multi-omics integration, biomarkers
MeSH terms
Multiomics, Adult, Aging, Child, Child, Preschool, Humans, Infant, Obesity, Risk Factors, Biomarkers, DNA Methylation, Epigenesis, Genetic

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