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大多数逆转录转座子在人类血液中的表达与生物衰老相关。

Expression of most retrotransposons in human blood correlates with biological aging.

机构信息

Comprehensive Cancer Centre, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.

MRC LMS, Imperial College London, London, United Kingdom.

出版信息

Elife. 2024 Oct 17;13:RP96575. doi: 10.7554/eLife.96575.

DOI:10.7554/eLife.96575
PMID:39417397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11486490/
Abstract

Retrotransposons (RTEs) have been postulated to reactivate with age and contribute to aging through activated innate immune response and inflammation. Here, we analyzed the relationship between RTE expression and aging using published transcriptomic and methylomic datasets of human blood. Despite no observed correlation between RTE activity and chronological age, the expression of most RTE classes and families except short interspersed nuclear elements (SINEs) correlated with biological age-associated gene signature scores. Strikingly, we found that the expression of SINEs was linked to upregulated DNA repair pathways in multiple cohorts. We also observed DNA hypomethylation with aging and the significant increase in RTE expression level in hypomethylated RTEs except for SINEs. Additionally, our single-cell transcriptomic analysis suggested a role for plasma cells in aging mediated by RTEs. Altogether, our multi-omics analysis of large human cohorts highlights the role of RTEs in biological aging and suggests possible mechanisms and cell populations for future investigations.

摘要

反转录转座子（RTEs）随着年龄的增长而被推测重新激活，并通过激活固有免疫反应和炎症导致衰老。在这里，我们使用已发表的人类血液转录组和甲基化组数据集来分析 RTE 表达与衰老之间的关系。尽管没有观察到 RTE 活性与实际年龄之间存在相关性，但大多数 RTE 类和家族的表达（除了短散在核元件（SINEs）外）与与生物学年龄相关的基因特征评分相关。引人注目的是，我们发现 SINEs 的表达与多个队列中上调的 DNA 修复途径有关。我们还观察到随着年龄的增长 DNA 去甲基化，以及除 SINEs 外，甲基化减少的 RTE 中的 RTE 表达水平显著增加。此外，我们的单细胞转录组学分析表明浆细胞在 RTE 介导的衰老中起作用。总的来说，我们对大型人类队列的多组学分析强调了 RTEs 在生物学衰老中的作用，并提出了可能的机制和细胞群体供未来研究。

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