Talevi Valentina, Lee Hang-Mao, Liu Dan, Beyer Marc D, Salomoni Paolo, Breteler Monique M B, Aziz N Ahmad
Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Fundamental Research, Nuclear Function Group, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Aging Cell. 2025 Aug;24(8):e70092. doi: 10.1111/acel.70092. Epub 2025 May 4.
Retrotransposable elements (RTEs) have been implicated in the pathogenesis of several age-associated diseases. Although model systems indicate that age- and sex-dependent loss of heterochromatin increases RTE expression, data from large human studies are lacking. Here we assessed the expression levels of 795 blood RTE subfamilies in 2467 participants of the population-based Rhineland Study. We found that the expression of more than 98% of RTE subfamilies increased with both chronological and biological age. Moreover, the expression of heterochromatin regulators involved in RTE silencing was negatively related to the expression of 690 RTE subfamilies. Finally, we observed sex differences in 42 RTE subfamilies, with higher expression in men. The genes mapped to sex-related RTEs were enriched in immune response-related pathways. Importantly, we validated our key findings in an independent population-based cohort. Our findings indicate that RTEs and their repressors are markers of aging and that their dysregulation is linked to inflammation, especially in men.
逆转座元件（RTEs）与几种年龄相关疾病的发病机制有关。尽管模型系统表明异染色质的年龄和性别依赖性丧失会增加RTE的表达，但缺乏来自大型人类研究的数据。在这里，我们评估了基于人群的莱茵兰研究中2467名参与者的795个血液RTE亚家族的表达水平。我们发现，超过98%的RTE亚家族的表达随着实际年龄和生物学年龄的增长而增加。此外，参与RTE沉默的异染色质调节因子的表达与690个RTE亚家族的表达呈负相关。最后，我们观察到42个RTE亚家族存在性别差异，男性表达更高。映射到与性别相关的RTEs的基因在免疫反应相关途径中富集。重要的是，我们在一个独立的基于人群的队列中验证了我们的关键发现。我们的研究结果表明，RTEs及其抑制剂是衰老的标志物，它们的失调与炎症有关，尤其是在男性中。
