The epigenetic clock and physical development during childhood and adolescence: longitudinal analysis from a UK birth cohort.

Andrew J Simpkin,Susan M Ring,Steve Horvath,George Davey Smith,Caroline L Relton,Kate Tilling,Wendy L McArdle,Laura D Howe,Oliver Lyttleton,Tom R Gaunt

doi:10.1093/ije/dyw307

Andrew J Simpkin, Susan M Ring + Show 8 more

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https://doi.org/10.1093/ije/dyw307

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Abstract

Background: Statistical models that use an individual’s DNA methylation levels to estimate their age (known as epigenetic clocks) have recently been developed, with 96% correlation found between epigenetic and chronological age. We postulate that differences between estimated and actual age [age acceleration (AA)] can be used as a measure of developmental age in early life. Methods: We obtained DNA methylation measures at three time points (birth, age 7 years and age 17 years) in 1018 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Using an online calculator, we estimated epigenetic age, and thus AA, for each child at each time point. We then investigated whether AA was prospectively associated with repeated measures of height, weight, body mass index (BMI), bone mineral density, bone mass, fat mass, lean mass and Tanner stage. Results: Positive AA at birth was associated with higher average fat mass [1321 g per year of AA, 95% confidence interval (CI) 386, 2256 g] from birth to adolescence (i.e. from age 0–17 years) and AA at age 7 was associated with higher average height (0.23 cm per year of AA, 95% CI 0.04, 0.41 cm). Conflicting evidence for the role of AA (at birth and in childhood) on changes during development was also found, with higher AA being positively associated with changes in weight, BMI and Tanner stage, but negatively with changes in height and fat mass. Conclusions: We found evidence that being ahead of one’s epigenetic age acceleration is related to developmental characteristics during childhood and adolescence. This demonstrates the potential for using AA as a measure of development in future research.

Highlights

Statistical models that use an individual’s DNA methylation levels to estimate their age have been developed.[1,2,3,4,5] These methods have proved successful, with up to 96% correlation and a mean difference of 3 years found between estimated and actual age.[2]
We investigate the consequences of AA, by looking at standard measures of development, which have been repeatedly measured throughout childhood and adolescence: height, weight, body mass index (BMI), bone mineral density (BMD), bone mass, lean mass and fat mass
High correlations were observed in data sets comprising a wide range of chronological ages.[2]

Summary

Introduction

Statistical models that use an individual’s DNA methylation levels to estimate their age (known as epigenetic clocks) have been developed.[1,2,3,4,5] These methods have proved successful, with up to 96% correlation and a mean difference of 3 years found between estimated and actual age.[2]. Methods: We obtained DNA methylation measures at three time points (birth, age 7 years and age 17 years) in 1018 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Conflicting evidence for the role of AA (at birth and in childhood) on changes during development was found, with higher AA being positively associated with changes in weight, BMI and Tanner stage, but negatively with changes in height and fat mass. Conclusions: We found evidence that being ahead of one’s epigenetic age acceleration is related to developmental characteristics during childhood and adolescence. This demonstrates the potential for using AA as a measure of development in future research

Methods

Results

Conclusion