A decade of epigenetic change in aging twins: Genetic and environmental contributions to longitudinal DNA methylation

Abstract

Background

Epigenetic changes may result from the interplay of environmental exposures and genetic influences and contribute to differences in age‐related disease, disability, and mortality risk. However, the etiologies contributing to stability and change in DNA methylation have rarely been examined longitudinally.

Methods

We considered DNA methylation in whole blood leukocyte DNA across a 10‐year span in two samples of same‐sex aging twins: (a) Swedish Adoption Twin Study of Aging (SATSA; N = 53 pairs, 53% female; 62.9 and 72.5 years, SD = 7.2 years); (b) Longitudinal Study of Aging Danish Twins (LSADT; N = 43 pairs, 72% female, 76.2 and 86.1 years, SD=1.8 years). Joint biometrical analyses were conducted on 358,836 methylation probes in common. Bivariate twin models were fitted, adjusting for age, sex, and country.

Results

Overall, results suggest genetic contributions to DNA methylation across 358,836 sites tended to be small and lessen across 10 years (broad heritability M = 23.8% and 18.0%) but contributed to stability across time while person‐specific factors explained emergent influences across the decade. Aging‐specific sites identified from prior EWAS and methylation age clocks were more heritable than background sites. The 5037 sites that showed the greatest heritable/familial–environmental influences ( p < 1E−07) were enriched for immune and inflammation pathways while 2020 low stability sites showed enrichment in stress‐related pathways.

Conclusions

Across time, stability in methylation is primarily due to genetic contributions, while novel experiences and exposures contribute to methylation differences. Elevated genetic contributions at age‐related methylation sites suggest that adaptions to aging and senescence may be differentially impacted by genetic background.

Abstract

Individual differences in late‐life methylation for 358,836 cytosine–guanine dinucleotide (CpG) probes are due partly to genetic influences that contribute to stability across 10 years while non‐shared factors, including environmental experiences unique to individuals, contribute to new influences on methylation patterns, as indicated by the r _A, r _D, and r _E. Aging‐related CpG sites show greater heritable influences on methylation consistent with genetic regulation of biological aging rates.