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.

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