A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin.
A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin.
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DOI：
10.7554/elife.59201
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发表时间：
2020-11-12
期刊：
影响因子：
7.7
通讯作者：
Ferrucci L
中科院分区：
文献类型：
--
作者：
Levine M;McDevitt RA;Meer M;Perdue K;Di Francesco A;Meade T;Farrell C;Thrush K;Wang M;Dunn C;Pellegrini M;de Cabo R;Ferrucci L
衰老的强大生物标志物已经从人类的DNA甲基化和最近的小鼠中开发出来。这项研究的目的是在大鼠中产生一种新的表观遗传时钟-一种具有独特的物理，生理和生化特性的模型-通过结合行为数据，无监督机器学习和网络分析来识别表观遗传信号，不仅跟踪年龄，而且与表型衰老有关。使用简化代表性亚硫酸氢盐测序（RRBS）数据训练Fischer 344 CDF（F344）大鼠中的表观遗传年龄（DNAmAge）测量。在独立样本中，该测量与年龄相关（r = 0.93），并在调整年龄和细胞计数后与身体功能相关（p=5.9e-3）。在雄性C57 BL/6小鼠中，DNAmAge也被发现与年龄相关（r = 0.79），并且响应于热量限制而降低。我们的签名由基因间区域中的CpG驱动，这些区域与H3 K9 me 3、H3 K27 me 3和E2 F1转录因子结合显示出实质性重叠。
Robust biomarkers of aging have been developed from DNA methylation in humans and more recently, in mice. This study aimed to generate a novel epigenetic clock in rats—a model with unique physical, physiological, and biochemical advantages—by incorporating behavioral data, unsupervised machine learning, and network analysis to identify epigenetic signals that not only track with age, but also relates to phenotypic aging. Reduced representation bisulfite sequencing (RRBS) data was used to train an epigenetic age (DNAmAge) measure in Fischer 344 CDF (F344) rats. This measure correlated with age at (r = 0.93) in an independent sample, and related to physical functioning (p=5.9e-3), after adjusting for age and cell counts. DNAmAge was also found to correlate with age in male C57BL/6 mice (r = 0.79), and was decreased in response to caloric restriction. Our signatures driven by CpGs in intergenic regions that showed substantial overlap with H3K9me3, H3K27me3, and E2F1 transcriptional factor binding.