Prenatal and early life influences on epigenetic age in children: A study of mother–offspring pairs from two cohort studies
Open accessAbstract
DNA methylation-based biomarkers of aging are highly correlated with actual age. Departures of methylation-estimated age from actual age can be used to define epigenetic measures of child development or age acceleration (AA) in adults. Very little is known about genetic or environmental determinants of these epigenetic measures of aging. We obtained DNA methylation profiles using Infinium HumanMethylation450 BeadChips across five time-points in 1018 mother-child pairs from the Avon Longitudinal Study of Parents and Children. Using the Horvath age estimation method, we calculated epigenetic age for these samples. AA was defined as the residuals from regressing epigenetic age on actual age. AA was tested for associations with cross-sectional clinical variables in children. We identified associations between AA and sex, birth weight, birth by caesarean section and several maternal characteristics in pregnancy, namely smoking, weight, BMI, selenium and cholesterol level. Offspring of non-drinkers had higher AA on average but this difference appeared to resolve during childhood. The associations between sex, birth weight and AA found in ARIES were replicated in an independent cohort (GOYA). In children, epigenetic AA measures are associated with several clinically relevant variables, and early life exposures appear to be associated with changes in AA during adolescence. Further research into epigenetic aging, including the use of causal inference methods, is required to better our understanding of aging.
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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 [116]
The Discussion’s Conclusions report associations between prenatal and early-life factors and epigenetic age in children; Materials and Methods (Study population) describes offspring DNA-methylation measurements at birth and during childhood. The grouped citations do not assign this source to a specific part of the sentence, so the whole claim must be assessed. This paper does not establish the placental, telomere-biology, or mitochondrial-function parts. (LLM, conf=0.86)
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- Authors
- Simpkin, A. J., Hemani, G., Suderman, M., Gaunt, T. R., Lyttleton, O., Mcardle, W. L., Ring, S. M., Sharp, G. C., Tilling, K., Horvath, S., Kunze, S., Peters, A., Waldenberger, M., Ward-Caviness, C., Nohr, E. A., Sørensen, T. I. A., Relton, C. L., & Smith, G. D.
- Affiliations
- MRC Integrative Epidemiology Unit (GB)
- University of Bristol (GB)
- University of California, Los Angeles (US)
- Helmholtz Munich (DE)
- University of Southern Denmark (DK)
- University of Copenhagen (DK)
- Corresponding author
- Simpkin, Andrew J.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-11-05
- Volume
- 25
- Issue
- 1
- Pages
- 191-201
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC4690495
- OpenAlex
- W2158554646
- Cited by
- 246
- References
- 31
- Citations by year
- 2026: 14 · 2025: 7 · 2024: 24 · 2023: 22 · 2022: 18 · 2021: 30 · 2020: 57 · 2019: 19 · 2018: 22 · 2017: 21 · 2016: 11 · 2015: 1
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Human Molecular Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Explore Bristol Research (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- UK Economic & Social Research Council (RES-060-23-0011)
- UK Medical Research Council (G0601625, G0600705 and MR/L011824/1)
- European Research Council (269874)
- the BBSRC (BBI025751/1 and BB/I025263/1)
- the Medical Research Council (MRC) and the Wellcome Trust (102215/2/13/1)
- NIH
- the auspices of the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/2, MC_UU_12013/8, MRC_UU_12013/9)
- German Federal Ministry of Education and Research (01ZX1313A-2014)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- epigenetic age, accelerated aging, DNA methylation, prenatal exposure, early life exposure, mother-child pairs, birth weight, cesarean section, maternal smoking, maternal cholesterol, sex differences, adolescence, child development, Avon Longitudinal Study of Parents and Children
- MeSH terms
- Aging, Birth Weight, Child, Humans, Longitudinal Studies, Mothers, Cohort Studies, DNA Methylation, Epigenesis, Genetic
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