The rate of epigenetic drift scales with maximum lifespan across mammals.
The rate of epigenetic drift scales with maximum lifespan across mammals.
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DOI：
10.1038/s41467-023-43417-6
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发表时间：
2023-11-25
影响因子：
16.6
通讯作者：
Parrott, Benjamin B.
中科院分区：
文献类型：
--
作者：
Bertucci-Richter, Emily M.;Parrott, Benjamin B.
表观遗传漂移或“紊乱”增加了小鼠的寿命，并被认为是表观遗传时钟信号的基础。虽然表观遗传漂移在决定跨物种最长寿命方面的作用一直存在争议，但缺乏对这一假说的强有力的测试。在这里，我们测试不同水平的基因组分辨率的表观遗传障碍是否解释了四种哺乳动物的最长寿命。我们发现，在所有物种和所测试的所有基因组分辨率的所有水平上，表观遗传紊乱随着年龄的增长而增加。无序积累的速度在寿命较短的物种中发生得更快，并与物种调整后的最大寿命相对应。虽然胞嘧啶-磷酸-鸟嘌呤二核苷酸(“CPGS”)的密度与年龄相关疾病的累积速度呈负相关，但它不能完全解释不同物种之间的差异。我们的发现支持这样的假设，即表观遗传漂移的速度解释了最大寿命，并部分支持了CpG密度缓冲表观遗传漂移的假设。表观遗传漂移被假设为有助于表观遗传时钟信号和跨物种寿命的差异。在这里，作者展示了表观遗传漂移的经验衡量标准，在四个哺乳动物物种中具有最大寿命，并在非随机的基因组位置积累。
Epigenetic drift or “disorder” increases across the mouse lifespan and is suggested to underlie epigenetic clock signals. While the role of epigenetic drift in determining maximum lifespan across species has been debated, robust tests of this hypothesis are lacking. Here, we test if epigenetic disorder at various levels of genomic resolution explains maximum lifespan across four mammal species. We show that epigenetic disorder increases with age in all species and at all levels of genomic resolution tested. The rate of disorder accumulation occurs faster in shorter lived species and corresponds to species adjusted maximum lifespan. While the density of cytosine-phosphate-guanine dinucleotides (“CpGs”) is negatively associated with the rate of age-associated disorder accumulation, it does not fully explain differences across species. Our findings support the hypothesis that the rate of epigenetic drift explains maximum lifespan and provide partial support for the hypothesis that CpG density buffers against epigenetic drift. Epigenetic drift has been hypothesized to contribute to epigenetic clock signals and variation in lifespan across species. Here, the authors show that an empirical measure of epigenetic drift scales with maximum lifespan across four mammal species and accumulates in non-random genomic locations.
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