LINE-1 derepression in senescent cells triggers interferon and inflammaging
By M. Cecco, Takahiro Ito, Anna P. Petrashen, Amy E Elias, Nicholas Skvir, Steven W. Criscione, Alberto Caligiana, Greta Brocculi, E. Adney, J. Boeke and 11 more. Nature, 2019
910 citations recorded by the source corpus.
Retrotransposable elements are deleterious at many levels, and the failure of host surveillance systems for these elements can thus have negative consequences. However, the contribution of retrotransposon activity to ageing and age-associated diseases is not known. Here we show that during cellular senescence, L1 (also known as LINE-1) retrotransposable elements become transcriptionally derepressed and activate a type-I interferon (IFN-I) response. The IFN-I response is a phenotype of late senescence and contributes to the maintenance of the senescence-associated secretory phenotype. The IFN-I response is triggered by cytoplasmic L1 cDNA, and is antagonized by inhibitors of the L1 reverse transcriptase. Treatment of aged mice with the nucleoside reverse transcriptase inhibitor lamivudine downregulated IFN-I activation and age-associated inflammation (inflammaging) in several tissues. We propose that the activation of retrotransposons is an important component of sterile inflammation that is a hallmark of ageing, and that L1 reverse transcriptase is a relevant target for the treatment of age-associated disorders. During cellular senescence in human and mouse cells, L1 transposons become transcriptionally derepressed and trigger a type-1 interferon response, which contributes to age-associated inflammation and age-related phenotypes.
Subfields: Epidemiology, Immunology, Plant Science
View Paper: https://www.semanticscholar.org/paper/0ae0acc2753a44a6e86da612169e9d02f6f16fae
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Citations in the corpus
- Senescence and the SASP: many therapeutic avenues (2020, background): “Moreover, in very late replicative, stress, and OIS cells, the SASP becomes characterized by the expression of type-I interferons (IFN-I) (De Cecco et al. 2019).”