L1 drives IFN in senescent cells and promotes age-associated inflammation.
Nature
; 566(7742): 73-78, 2019 02.
Article
in En
| MEDLINE
| ID: mdl-30728521
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interferon Type I
/
Cellular Senescence
/
Long Interspersed Nucleotide Elements
/
Inflammation
Type of study:
Risk_factors_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nature
Year:
2019
Document type:
Article
Affiliation country:
United States