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LINE-1 retrotransposon activation drives age-associated inflammation via cytoplasmic cDNA-STING/type I interferon

Arshad Mehmood1, Yue Zhu Xue2, Habab Merghani Yassin3

  • 1Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.

Contemporary Oncology (Poznan, Poland)
|October 16, 2025
PubMed

Insights

LINE-1 retrotransposable elements activate type-I interferon response during cellular senescence, contributing to aging and inflammation. The drug lamivudine suppresses this activation, offering potential for treating age-associated diseases.

Area of Science:

  • Molecular Biology
  • Immunology
  • Gerontology

Background:

  • Retrotransposable elements, like LINE-1, pose risks to cellular health.
  • Their specific role in aging and associated diseases is not fully understood.
  • Cellular senescence involves complex molecular pathways, including immune responses.

Purpose of the Study:

  • To investigate the link between LINE-1 retrotransposable elements and type-I interferon response in cellular senescence.
  • To explore the therapeutic potential of targeting LINE-1 activity in aging.

Main Methods:

  • Analysis of LINE-1 transcriptional derepression during senescence.
  • Assessment of type-I interferon pathway activation.
  • Evaluation of LINE-1 reverse transcriptase inhibitors, including lamivudine.

Main Results:

  • LINE-1 elements derepress and activate type-I interferon response in senescent cells.
  • Cytoplasmic LINE-1 cDNA is implicated in this activation.
  • LINE-1 reverse transcriptase inhibitors, such as lamivudine, suppress the interferon response.
  • Lamivudine reduced age-associated inflammation in tissues.

Conclusions:

  • LINE-1 activation is a key driver of sterile inflammation in aging.
  • Targeting LINE-1 reverse transcriptase, for example with lamivudine, may be a viable strategy for treating age-associated inflammation and diseases.
Keywords:
LINE-1aginginflammationtype-I interferon

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