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Contemporary Oncology
eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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abstract:
Review paper

LINE-1 retrotransposon activation drives age-associated inflammation via cytoplasmic cDNA-STING/type I interferon signalling: therapeutic potential of reverse transcriptase inhibition

Arshad Mehmood
1
,
Yue Zhu Xue
2
,
Habab Merghani Yassin
3
,
Mohammad Zubair
4
,
Syed Adnan Rahmat
5
,
Aftab Ahmad
6

  1. Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
  2. Clinical Laboratory, Hebei General Hospital, Shijiazhuang 050051, Hebei, China
  3. Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia
  4. Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
  5. Cancer Institute, The Fourth Hospital of Hebei Medical University/ The Tumour Hospital of Hebei Province, Shijiazhuang, China
  6. Research Centre, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumour Hospital, Shijiazhuang, Hebei Province 050011, China
Contemp Oncol (Pozn) 2025; 29 (3)
DOI: https://doi.org/10.5114/wo.2025.152369
Online publish date: 2025/06/26
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Retrotransposable elements are harmful at several levels, and host surveillance systems fail to consider all these elements in severe effects. The key role of retrotransposon in aging and age-associated diseases remains unclear. We summarise whether LINE-1 retrotransposable elements transcriptionally derepress and activate type-I interferon response during cellular senescence. Type-I interferon response is the late senescence phenotype that maintains the senescence-associated secretory phenotype. Cytoplasmic LINE-1 cDNA activates type-I interferon response, while LINE-1 reverse transcriptase inhibitors suppress it. The nucleoside reverse transcriptase inhibitor lamivudine downregulates activation of type-I interferon and age-associated inflammation in tissues in the treatment of aging. Activation of retrotransposons is a key factor in sterile inflammation, which is a hallmark of aging, and LINE-1 reverse transcriptase is an important target for the treatment of age-associated diseases. Nucleoside reverse transcriptase inhibitor lamivudine downregulates activation of type-I interferon and age-associated inflammation.
keywords:

aging, inflammation, LINE-1, type-I interferon
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