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人类组织和细胞类型的组蛋白标记年龄。

Histone mark age of human tissues and cell types.

作者信息

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

机构信息

School of Biological Sciences, University of Cambridge, Cambridge, UK.

School of Clinical Medicine, University of Cambridge, Cambridge, UK.

出版信息

Sci Adv. 2025 Jan 3;11(1):eadk9373. doi: 10.1126/sciadv.adk9373. Epub 2025 Jan 1.

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.

摘要

衰老过程复杂且多面,涉及众多表观遗传改变。衰老研究中一个关键的关注领域是组蛋白修饰的作用,其可动态调控基因表达。在此,我们对人类衰老过程中七种关键组蛋白修饰的动态变化进行了全组织分析。我们的组蛋白特异性年龄预测模型展现出惊人的准确性能,对实验噪声和人为噪声具有抗性。与DNA甲基化年龄预测指标进行比较的模拟实验显示出具有竞争力的性能。此外,基因集富集分析揭示了几个用于年龄预测的关键发育途径。与DNA甲基化年龄预测指标不同,已知参与衰老生物学过程的基因是这些模型中最重要的基因之一。最后,我们开发了一种全组织全组蛋白年龄预测指标,表明与年龄相关的表观遗传信息在整个表观基因组中逐渐退化。这项研究凸显了组蛋白标记作为创建稳健年龄预测指标的输入信息的作用,并为理解衰老过程中表观遗传变化的作用开辟了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be04/11691649/cb54118d0a08/sciadv.adk9373-f1.jpg

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