Background DNA methylation-based biological age (DNAm age) is potentially an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its causes of variation. We investigated these causes across the lifespan. Methods We pooled genome-wide DNA methylation data for 4,217 people aged 0-92 years from 1,871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, dizygotic (DZ) twin, sibling, parent-offspring, and spouse pairs by cohabitation status. Genetic and environmental variance component models were fitted and compared. Results Twin pair correlations were -0.12 to 0.18 around birth, not different from zero (all P>0.29). For all pairs of relatives, their correlations increased with time spent living together (all P<0.02) at different rates (MZ>DZ and siblings>parent-offspring; P<0.001) and decreased with time spent living apart (P=0.02) at similar rates. These correlation patterns were best explained by cohabitation-dependent shared environmental factors, the effects of which were 1.41 (95% confidence interval [CI], 1.16 to 1.66) times greater for MZ pairs than for DZ and sibling pairs, and the latter were 2.03 (95% CI, 1.13 to 9.47) times greater than for parent-offspring pairs. Genetic factors explained 13% (95% CI, -10% to 35%) of variation (P=0.27). Conclusion Variation in DNAm age is mostly caused by environmental factors, including those shared to different extents by relatives while living together and whose effects persist into old age. The equal environment assumption of the classic twin study might not hold for epigenetic aging.

中文翻译：

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整个寿命中表观遗传老化变化的原因

背景DNA基于甲基化的生物学年龄（DNAm年龄）可能是成人健康的重要生物标志物。在特定年龄范围内的研究发现，导致其变异的原因差异很大。我们调查了整个生命周期中的这些原因。方法我们收集了来自1,871个家庭的4,217位0-92岁的人的全基因组DNA甲基化数据。使用Horvath表观遗传时钟计算DNAm年龄。我们通过同居状态估计了单卵双胎（MZ），双卵双胎（DZ），兄弟姐妹，父母后代和配偶对在DNAm年龄中的家族相关性。遗传和环境差异成分模型进行了拟合和比较。结果出生前后双胞胎对的相关性为-0.12至0.18，与零无差异（所有P> 0.29）。对于所有成对的亲戚，他们的相关性随着以不同比率（MZ> DZ和兄弟姐妹>父母-后代； P <0.001）一起生活在一起的时间（所有P <0.02）而增加，并且以相似比率随着分开生活的时间（P = 0.02）而降低。这些相关模式最好由同居相关的共享环境因素来解释，MZ对的影响是DZ和同胞对的1.41倍（95％置信区间[CI]，1.16至1.66）倍，而DZ和同胞对的影响为2.03 （95％CI，1.13至9.47）倍于亲子对。遗传因素解释了13％（95％CI，-10％至35％）的变异（P = 0.27）。结论DNAm年龄的变化主要是由环境因素引起的，包括亲戚在一起生活时在不同程度上共享的因素，其影响一直持续到老年。