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.