将甲基化动态与哺乳动物的最大寿命联系起来的基本方程。

Fundamental equations linking methylation dynamics to maximum lifespan in mammals.

机构信息

Department of Human Genetics, University of California, Los Angeles, CA, USA.

Department of Biostatistics, University of California, Los Angeles, CA, USA.

出版信息

Nat Commun. 2024 Sep 16;15(1):8093. doi: 10.1038/s41467-024-51855-z.

DOI:10.1038/s41467-024-51855-z

PMID:39285199

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11405513/

Abstract

We describe a framework that addresses concern that the rate of change in any aging biomarker displays a trivial inverse relation with maximum lifespan. We apply this framework to methylation data from the Mammalian Methylation Consortium. We study the relationship of lifespan with the average rate of change in methylation (AROCM) from two datasets: one with 90 dog breeds and the other with 125 mammalian species. After examining 54 chromatin states, we conclude three key findings: First, a reciprocal relationship exists between the AROCM in bivalent promoter regions and maximum mammalian lifespan: AROCM 1/MaxLifespan. Second, the correlation between average methylation and age bears no relation to maximum lifespan, Cor(Methyl,Age) ⊥ MaxLifespan. Third, the rate of methylation change in young animals is related to that in old animals: Young animals' AROCM Old AROCM. These findings critically hinge on the chromatin context, as different results emerge in other chromatin contexts.

摘要

我们描述了一个框架，旨在解决这样一种担忧，即任何衰老生物标志物的变化率与最大寿命呈微不足道的反比关系。我们将该框架应用于哺乳动物甲基化联盟的甲基化数据。我们研究了寿命与甲基化平均变化率（AROCM）之间的关系，该研究来自两个数据集：一个包含 90 个犬种，另一个包含 125 种哺乳动物。在检查了 54 种染色质状态后，我们得出了三个关键发现：首先，二价启动子区域中 AROCM 与最大哺乳动物寿命之间存在一种相互关系：AROCM 1/MaxLifespan。其次，平均甲基化与年龄之间的相关性与最大寿命无关，Cor（Methyl，Age） ⊥ MaxLifespan。第三，年轻动物的甲基化变化率与老年动物的甲基化变化率有关：年轻动物的 AROCM Old AROCM。这些发现关键取决于染色质背景，因为在其他染色质背景下会出现不同的结果。