Histone mark age of human tissues and cell types

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-01-01 DOI:10.1126/sciadv.adk9373

Lucas Paulo de Lima Camillo, Muhammad Haider Asif, Steve Horvath, Erica Larschan, Ritambhara Singh

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Abstract

Aging is a complex and multifaceted process involving many epigenetic alterations. One key area of interest in aging research is the role of histone modifications, which can dynamically regulate gene expression. Here, we conducted a pan-tissue analysis of the dynamics of seven key histone modifications during human aging. Our histone-specific age prediction models showed surprisingly accurate performance, proving resilient to experimental and artificial noise. Simulation experiments for comparison with DNA methylation age predictors revealed competitive performance. Moreover, gene set enrichment analysis uncovered several critical developmental pathways for age prediction. Different from DNA methylation age predictors, genes known to be involved in aging biology are among the most important ones for the models. Last, we developed a pan-tissue pan-histone age predictor, suggesting that age-related epigenetic information is degenerated across the epigenome. This research highlights the power of histone marks as input for creating robust age predictors and opens avenues for understanding the role of epigenetic changes during aging.

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组蛋白标志着人体组织和细胞类型的年龄

衰老是一个复杂的、多方面的过程，涉及许多表观遗传改变。衰老研究的一个关键领域是组蛋白修饰的作用，它可以动态调节基因表达。在这里，我们对人类衰老过程中七个关键组蛋白修饰的动态进行了泛组织分析。我们的组蛋白特异性年龄预测模型显示出惊人的准确性能，证明对实验和人工噪声具有弹性。与DNA甲基化年龄预测因子比较的模拟实验揭示了竞争表现。此外，基因集富集分析揭示了预测年龄的几个关键发育途径。与DNA甲基化年龄预测因子不同，已知参与衰老生物学的基因是模型中最重要的基因之一。最后，我们开发了一个泛组织泛组蛋白年龄预测器，表明与年龄相关的表观遗传信息在整个表观基因组中退化。这项研究强调了组蛋白标记作为创建稳健年龄预测因子的输入的力量，并为理解衰老过程中表观遗传变化的作用开辟了途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.