医学分子生物学杂志 ›› 2025, Vol. 22 ›› Issue (5): 508-515.doi: 10.3870/j.issn.1672-8009.2025.05.014

• 衰老与慢性疾病专题 • 上一篇    下一篇

LINE-1 逆转座子在细胞衰老和衰老相关疾病中的机制研究与应用前景 #br#

  

  1. 天津医科大学肿瘤医院肿瘤分子诊断中心, 国家恶性肿瘤临床医学研究中心, 天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心, 天津市肿瘤免疫与生物治疗重点实验室 天津市, 300060
  • 出版日期:2025-09-30 发布日期:2025-10-09
  • 基金资助:
    天津市教委科研计划项目 (No. 2023KJ089)

Mechanism and Application Prospects of LINE-1 Transposons in Cellular Senescence and Age-Related Diseases #br#

  1. Molecular Diagnosis Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjins Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjing, 300060, China
  • Online:2025-09-30 Published:2025-10-09

摘要: 长散布核元件 1 (long interspersed nuclear element-1, LINE-1) 是人类基因组中唯一具备自主转座活性的逆转座子, 对人体多项生理功能发挥关键的调控作用, 其活性状态与细胞衰老及机体老化进程密切关联在生理状态下, LINE-1 通过 DNA 甲基化等表观遗传机制被严格沉默; 而在衰老或细胞应激条件下,这些调控机制发生失衡, 导致 LINE-1 异常活化异常活化的 LINE-1 可通过诱发 DNA 双链断裂插入性突变及 cGAS-STING 通路激活等一系列生物学效应, 诱导基因组不稳定及炎症性衰老相关分泌表型 ( senescence-associated secretory phenotype, SASP) 释放, 上述效应协同加剧端粒功能障碍, 共同推动肿瘤神经退行性疾病及心血管疾病等衰老相关疾病的发生发展文章综述了 LINE-1 活性异常作为年龄相关疾病的重要驱动因素, 通过基因组不稳定性表观遗传改变等途径加速疾病进展的核心机制, 且强调 LINE-1 有望成为衰老相关疾病的生物标志物及潜在治疗靶点

关键词: 逆转座子, 长散布核元件 1, 细胞衰老, 生物标志物, 治疗靶点

Abstract: The long interspersed nuclear element-1 ( LINE-1) is the only retrotransposon inthe human genome capable of autonomous activity, and it plays an essential role in regulating many physiological processes. Its activity is closely connected to cellular aging and the overall aging of theorganism. Normally, LINE-1 remains tightly suppressed through epigenetic mechanisms such asDNA methylation. However, during aging or cellular stress, this control can become disrupted,leading to abnormal activation of LINE-1. When activated inappropriately, LINE-1 can cause harmthrough several pathways, including creating DNA double-strand breaks, inserting itself into new locations in the genome ( insertional mutagenesis), and triggering the cGAS-STING immune response pathway. These effects contribute to genomic instability and promote the formation of the senescence-associated secretory phenotype ( SASP). Collectively, these processes worsen telomere dysfunction and increase the risk of age-related diseases like cancer, neurodegenerative conditions,and heart disease. This review emphasizes how dysregulated LINE-1 activity considerably contributesto aging and related diseases. It focuses on its main mechanisms, particularly how it accelerates disease progression by destabilizing the genome and altering epigenetic regulation. What ’ s more,LINE-1 shows promise as a biomarker for age-associated conditions and as a potential target for therapeutic intervention.

Key words:

retrotransposons, long interspersed nuclear element-1, cellular senescence, biomarkers, therapeutic targets

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