title: The epigenetic clock and physical development during childhood and adolescence: longitudinal analysis from a UK birth cohort.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Simpkin
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Howe
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Tom R
authors.initials: TR
authors.lastname: Gaunt
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lyttleton
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: McArdle
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.affiliation: School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.|David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
mesh_terms: D000293:Adolescent; D001724:Birth Weight; D015992:Body Mass Index; D049628:Body Size; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D015233:Models, Statistical; D006113:United Kingdom
keywords: ALSPAC; ARIES; DNA methylation; epigenetic age; longitudinal data analysis; physical development