PDF(Pubmed)
Abstract：
BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks.
METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs.
RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks.
CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.
METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs.
RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks.
CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.
摘要：
背景：表观遗传时钟被认为是衰老的有希望的生物标志物，包括由各个CpG站点训练的原始时钟和由CpG站点的PC训练的主成分(PC)时钟。遗传和环境因素对表观遗传时钟的影响尚不清楚。特别是PC时钟。
方法：我们从中国国家双胞胎注册中心（CNTR）中构建了477对同性双胞胎的单变量双胞胎模型，以估计五个表观遗传钟（GrimAge，PhenoAge,DunedinPACE,PCGrimAge,和PCPhenoAge）。此外,我们调查了134对同性双胞胎5年中遗传和环境影响对表观遗传时钟的纵向变化。
结果：表观遗传时钟的遗传力范围为0.45至0.70，PC时钟的遗传力高于原始时钟。对于五个表观遗传时钟，纵向稳定性中等到高，主要是由于遗传效应。基线和后续表观遗传时钟之间的遗传相关性中等到高。在基线和后续行动中都出现了特殊的独特环境因素。PC时钟比原始时钟显示出更高的纵向稳定性和独特的环境相关性。
结论：对于五个表观遗传时钟，他们有可能识别衰老干预措施。高纵向稳定性主要是由于遗传因素，表观遗传时钟随时间的变化主要是由于独特环境因素的变化。考虑到遗传和环境因素的差异以及PC和原始时钟之间的纵向稳定性，原始时钟的研究结果需要用PC时钟进一步验证。
方法：我们从中国国家双胞胎注册中心（CNTR）中构建了477对同性双胞胎的单变量双胞胎模型，以估计五个表观遗传钟（GrimAge，PhenoAge,DunedinPACE,PCGrimAge,和PCPhenoAge）。此外,我们调查了134对同性双胞胎5年中遗传和环境影响对表观遗传时钟的纵向变化。
结果：表观遗传时钟的遗传力范围为0.45至0.70，PC时钟的遗传力高于原始时钟。对于五个表观遗传时钟，纵向稳定性中等到高，主要是由于遗传效应。基线和后续表观遗传时钟之间的遗传相关性中等到高。在基线和后续行动中都出现了特殊的独特环境因素。PC时钟比原始时钟显示出更高的纵向稳定性和独特的环境相关性。
结论：对于五个表观遗传时钟，他们有可能识别衰老干预措施。高纵向稳定性主要是由于遗传因素，表观遗传时钟随时间的变化主要是由于独特环境因素的变化。考虑到遗传和环境因素的差异以及PC和原始时钟之间的纵向稳定性，原始时钟的研究结果需要用PC时钟进一步验证。
