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

LINE-1逆转录转座子激活通过胞质cDNA-STING/I型干扰素信号通路驱动与年龄相关的炎症:逆转录酶抑制剂的治疗潜力

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Abstract

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 transcriptio-nally 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 trans-criptase 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.

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