Dissecting epigenetic age acceleration in amyotrophic lateral sclerosis.

IF 2.6 4区医学 Q2 GENETICS & HEREDITY

Epigenomics Pub Date : 2025-09-30 DOI:10.1080/17501911.2025.2563502

Polina Merbaum, Ramona Zwamborn, Paul Hop, Project MinE Als Sequencing Consortium, Wouter van Rheenen, Jan Veldink

{"title":"Dissecting epigenetic age acceleration in amyotrophic lateral sclerosis.","authors":"Polina Merbaum, Ramona Zwamborn, Paul Hop, Project MinE Als Sequencing Consortium, Wouter van Rheenen, Jan Veldink","doi":"10.1080/17501911.2025.2563502","DOIUrl":null,"url":null,"abstract":"Aim: We compared signatures of epigenetic aging in amyotrophic lateral sclerosis (ALS) patients and healthy controls to investigate the role of potential confounders and genetic subgroups.Methods: We used whole-blood methylome profiles for 5,146 ALS patients and 2,156 controls available for Project MinE. We predicted biological age with three generations of epigenetic clocks and estimated age acceleration by regressing our model on control individuals to evaluate case/control differences. To investigate the contribution of C9orf72 expansions, we regressed the model on C9orf72-negative ALS patients. The predicted DunedinPACE pace of aging and telomere length additionally characterized aging dynamics.Results: We found that white blood cell type proportions confound the previously observed increase in the pace of biological aging in ALS. When correcting for cell counts, there is no evidence for accelerated epigenetic aging compared to controls, except for ALS patients with the C9orf72 repeat expansion. None of the epigenetic age acceleration scores contributed to survival.Conclusion: Our study revealed no significant difference in the pace of biological agingbetween ALS patients and controls, except for ALS patients carrying the C9orf72 mutation. We emphasize the importance of altered white blood cell proportions in general ALS pathophysiology as opposed to accelerated aging per se.","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-9"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17501911.2025.2563502","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Aim: We compared signatures of epigenetic aging in amyotrophic lateral sclerosis (ALS) patients and healthy controls to investigate the role of potential confounders and genetic subgroups.

Methods: We used whole-blood methylome profiles for 5,146 ALS patients and 2,156 controls available for Project MinE. We predicted biological age with three generations of epigenetic clocks and estimated age acceleration by regressing our model on control individuals to evaluate case/control differences. To investigate the contribution of C9orf72 expansions, we regressed the model on C9orf72-negative ALS patients. The predicted DunedinPACE pace of aging and telomere length additionally characterized aging dynamics.

Results: We found that white blood cell type proportions confound the previously observed increase in the pace of biological aging in ALS. When correcting for cell counts, there is no evidence for accelerated epigenetic aging compared to controls, except for ALS patients with the C9orf72 repeat expansion. None of the epigenetic age acceleration scores contributed to survival.

Conclusion: Our study revealed no significant difference in the pace of biological agingbetween ALS patients and controls, except for ALS patients carrying the C9orf72 mutation. We emphasize the importance of altered white blood cell proportions in general ALS pathophysiology as opposed to accelerated aging per se.

查看原文本刊更多论文

肌萎缩性侧索硬化症的解剖表观遗传年龄加速。

目的：我们比较了肌萎缩性侧索硬化症（ALS）患者和健康对照者的表观遗传衰老特征，以探讨潜在混杂因素和遗传亚群的作用。方法：我们使用了5146名ALS患者和2156名对照者的全血甲基组图谱。我们用三代表观遗传时钟预测生物年龄，并通过对对照个体的回归模型来估计年龄加速，以评估病例/对照组的差异。为了研究C9orf72扩增的贡献，我们对C9orf72阴性ALS患者的模型进行了回归。预测的DunedinPACE衰老速度和端粒长度也表征了衰老动态。结果：我们发现白细胞类型比例与先前观察到的ALS生物衰老速度的增加相混淆。当校正细胞计数时，除了C9orf72重复扩增的ALS患者外，没有证据表明与对照组相比会加速表观遗传衰老。所有的表观遗传年龄加速评分都与生存无关。结论：我们的研究显示，除了携带C9orf72突变的ALS患者外，ALS患者和对照组之间的生物衰老速度没有显著差异。我们强调白细胞比例改变在一般ALS病理生理中的重要性，而不是加速衰老本身。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Epigenomics GENETICS & HEREDITY-

CiteScore

5.80

自引率

2.60%

发文量

审稿时长

>12 weeks

期刊介绍： Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community. Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.