Environomics Future Science Platform, Indian Oceans Marine Research Centre, Commonwealth Scientific and Industrial Research Organisation, Crawley, Western Australia, Australia.
Oceans and Atmosphere, Commonwealth Scientific and Industrial Research Organisation, Hobart, Tasmania, Australia.
Sci Rep. 2019 Dec 12;9(1):17866. doi: 10.1038/s41598-019-54447-w.
Biological ageing and its mechanistic underpinnings are of immense biomedical and ecological significance. Ageing involves the decline of diverse biological functions and places a limit on a species' maximum lifespan. Ageing is associated with epigenetic changes involving DNA methylation. Furthermore, an analysis of mammals showed that the density of CpG sites in gene promoters, which are targets for DNA methylation, is correlated with lifespan. Using 252 whole genomes and databases of animal age and promotor sequences, we show a pattern across vertebrates. We also derive a predictive lifespan clock based on CpG density in a selected set of promoters. The lifespan clock accurately predicts maximum lifespan in vertebrates (R = 0.76) from the density of CpG sites within only 42 selected promoters. Our lifespan clock provides a wholly new method for accurately estimating lifespan using genome sequences alone and enables estimation of this challenging parameter for both poorly understood and extinct species.
生物衰老及其机制基础具有巨大的医学和生态意义。衰老涉及多种生物功能的衰退，并限制了一个物种的最大寿命。衰老与涉及 DNA 甲基化的表观遗传变化有关。此外，对哺乳动物的分析表明，基因启动子中 CpG 位点的密度（DNA 甲基化的靶点）与寿命相关。利用 252 个全基因组和动物年龄及启动子序列数据库，我们在脊椎动物中展示了一种模式。我们还从一组选定的启动子中 CpG 密度推导了一个预测寿命的时钟。这个寿命时钟仅通过 42 个选定的启动子中的 CpG 位点密度，就能准确预测脊椎动物的最大寿命（R=0.76）。我们的寿命时钟为仅使用基因组序列准确估计寿命提供了一种全新的方法，并能够为了解甚少和已灭绝的物种估计这一具有挑战性的参数。
