Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, China.
Key Laboratory of Epidemiology of Major Diseases, (Peking University), Ministry of Education, Beijing, 100191, China.
BMC Med. 2024 Jul 10;22(1):289. doi: 10.1186/s12916-024-03511-y.
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.
背景:表观遗传时钟被认为是衰老的有前途的生物标志物,包括由单个 CpG 位点训练的原始时钟和由 CpG 位点的主成分 (PC) 训练的主成分时钟。遗传和环境因素对表观遗传时钟的影响尚不清楚,特别是对于主成分时钟。
方法:我们在中国国家双胞胎登记处(CNTR)的 477 对同性别双胞胎中构建了单变量双胞胎模型,以估计五个表观遗传时钟(GrimAge、PhenoAge、DunedinPACE、PCGrimAge 和 PCPhenoAge)的遗传率。此外,我们还研究了 134 对同性别双胞胎在 5 年内遗传和环境因素对表观遗传时钟的纵向变化。
结果:表观遗传时钟的遗传率在 0.45 到 0.70 之间,主成分时钟的遗传率高于原始时钟。对于五个表观遗传时钟,纵向稳定性为中等到高度,主要归因于遗传效应。基线和随访表观遗传时钟之间的遗传相关性为中等到高度。在基线和随访时都出现了特殊的独特环境因素。主成分时钟的纵向稳定性和独特环境相关性均高于原始时钟。
结论:对于五个表观遗传时钟,它们有可能识别衰老干预措施。高纵向稳定性主要归因于遗传因素,而表观遗传时钟随时间的变化主要归因于独特环境因素的变化。鉴于主成分和原始时钟之间遗传和环境因素以及纵向稳定性的差异,需要使用主成分时钟进一步验证原始时钟研究的结果。
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