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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Biomarkers | Research

Interrelationships and determinants of aging biomarkers in cord blood

Authors: Brigitte Reimann, Dries S. Martens, Congrong Wang, Akram Ghantous, Zdenko Herceg, Michelle Plusquin, Tim S. Nawrot

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

Increasing evidence supports the concept of prenatal programming as an early factor in the aging process. DNA methylation age (DNAm age), global genome-wide DNA methylation (global methylation), telomere length (TL), and mitochondrial DNA content (mtDNA content) have independently been shown to be markers of aging, but their interrelationship and determinants at birth remain uncertain.

Methods

We assessed the inter-correlation between the aging biomarkers DNAm age, global methylation, TL and mtDNA content using Pearson's correlation in 190 cord blood samples of the ENVIRONAGE birth cohort. TL and mtDNA content was measured via qPCR, while the DNA methylome was determined using the human 450K methylation Illumina microarray. Subsequently, DNAm age was calculated according to Horvath's epigenetic clock, and mean global, promoter, gene-body, and intergenic DNA methylation were determined. Path analysis, a form of structural equation modeling, was performed to disentangle the complex causal relationships among the aging biomarkers and their potential determinants.

Results

DNAm age was inversely correlated with global methylation (r = -0.64, p < 0.001) and mtDNA content (r = − 0.16, p = 0.027). Cord blood TL was correlated with mtDNA content (r = 0.26, p < 0.001) but not with global methylation or DNAm age. Path analysis showed the strongest effect for global methylation on DNAm age with a decrease of 0.64 standard deviations (SD) in DNAm age for each SD (0.01%) increase in global methylation (p < 0.001). Among the applied covariates, newborn sex and season of delivery were the strongest determinants of aging biomarkers.

Conclusions

We provide insight into molecular aging signatures at the start of life, including their interrelations and determinants, showing that cord blood DNAm age is inversely associated with global methylation and mtDNA content but not with newborn telomere length. Our findings demonstrate that cord blood TL and DNAm age relate to different pathways/mechanisms of biological aging and can be influenced by environmental factors already at the start of life. These findings are relevant for understanding fetal programming and for the early prevention of noncommunicable diseases.

Graphical Abstract

Appendix
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Metadata
Title
Interrelationships and determinants of aging biomarkers in cord blood
Authors
Brigitte Reimann
Dries S. Martens
Congrong Wang
Akram Ghantous
Zdenko Herceg
Michelle Plusquin
Tim S. Nawrot
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03541-1

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