Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.
Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.
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DOI：
10.1186/s13059-017-1186-2
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发表时间：
2017-03-28
期刊：
影响因子：
12.3
通讯作者：
Ideker T
中科院分区：
文献类型：
--
作者：
Wang T;Tsui B;Kreisberg JF;Robertson NA;Gross AM;Yu MK;Carter H;Brown-Borg HM;Adams PD;Ideker T
随着我们年龄的增长，全球但可预测的变化会影响DNA甲基化，充当一种分子时钟。这个时钟可以通过减少寿命的条件来加速，这就提出了一个问题，即它是否也可以被减慢，例如，通过增加寿命的条件。小鼠是研究哺乳动物衰老的特别有吸引力的生物体;然而，表观遗传时钟迄今为止仅在人类中制定。我们首先研究了小鼠和人类是否经历了甲基化组随年龄变化的相似模式。我们发现CpG位点的甲基化随着年龄的增长而改变，这两个物种在衰老过程中表现出甲基化紊乱的增加。基于此分析，我们使用107只0.2至26.0月龄小鼠的肝脏甲基化组制定了小鼠表观遗传衰老模型。为了检查表观遗传衰老特征是否通过促进长寿的干预措施减缓，我们分析了来自延长寿命条件的小鼠的28个额外的甲基化组，包括Prop 1df/df侏儒症，卡路里限制或饮食雷帕霉素。我们发现，用这些延长寿命的干预措施治疗的小鼠在表观遗传年龄上比未经治疗的野生型年龄匹配对照组显着年轻。这项研究表明，延长寿命的条件可以减缓与小鼠肝脏表观遗传时钟相关的分子变化。本文的在线版本（doi：10.1186/s13059-017-1186-2）包含补充材料，可供授权用户使用。
Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers. The online version of this article (doi:10.1186/s13059-017-1186-2) contains supplementary material, which is available to authorized users.