Background Biomarkers of ageing based on DNA methylation (DNAm) have recently been developed. The first (Hannum and Horvath) and second generation (Levine and GrimAge) DNAm biomarkers predict survival, age-related disease and functional capabilities better than chronological age alone; with second generation biomarkers showing more consistent and stronger associations. In the first study of its kind, we examine the association between growth in early life, pubertal timing and DNAm age biomarkers in mid-life.
Methods Participants from the Medical Research Council (MRC) National Survey of Health and Development who had information on DNAm were analysed (NSHD, n=1,376). Four DNAm age acceleration (AgeAccel) biomarkers were calculated when participants were aged 53 years: AgeAccelHannum, AgeAccelHorvath, AgeAccelLevine and AgeAccelGrim. Birthweight and weight and height across infancy, childhood and adolescence were measured. Pubertal timing was established using age at menarche (girls) and pubertal stage at 14–15 years (boys). The relationship between weight and height change in infancy (2–4), childhood (4–7) and adolescence (7–15) and AgeAccel was investigated using regression with conditional growth measures; sex-specific residuals from a regression of current size on previous size. Linear regression models examined associations between pubertal timing and AgeAccel. We replicated analyses using height and weight from late childhood (7 y) to adolescence (16 y) and pubertal timing among 240 participants at 45 years from The National Child and Development Study (NCDS).
Results A one standard deviation (SD) increase in weight gain between 7 and 15 years was associated with 0.50 years (95% CI: 0.21, 0.80) higher AgeAccelGrim and, with 0.22 years (95% CI: -0.11, 0.55) higher AgeAccelLevine. This was replicated in NCDS. For linear growth, there was some evidence that more rapid growth between 2 and 4 years was associated with lower AgeAccelLevine (-0.39 years [95% CI: -0.74, -0.050) and AgeAccelGrim (-0.24 years [95% CI: -0.54, 0.06]). There was no evidence that relative weight gain and linear growth during childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and any of the AgeAccel biomarkers at 53 years. Women who reached menarche ≥12 years had 1.20 years (95% CI: 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche <12 years; however this was not replicated in NCDS.
Conclusion Our findings support the use of the second generation DNAm age biomarkers as markers of ageing and reinforces the idea that faster gains in weight during adolescence has lasting implications for healthy ageing.
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