# LINE-1 / Retrotransposon activation

LINE-1 (long interspersed nuclear element-1, or L1) is a type of 'jumping gene' (a retrotransposon) that makes up roughly 17% of your genome. It encodes two proteins (ORF1p and ORF2p) that run a copy-and-paste mechanism: a LINE-1 sequence is copied into RNA, then reverse-transcribed back into DNA and inserted somewhere new. In your normal body cells, LINE-1 is kept silent by DNA methylation, by H3K9me3 heterochromatin, and by the PIWI-piRNA system. But that silencing weakens with age, as heterochromatin erodes. Reactivated LINE-1 causes trouble. Its reverse-transcribed DNA can trip the cGAS-STING immune alarm. Its new insertions can destabilize the genome. And together these feed the inflammatory state of aged cells. Strikingly, reverse-transcriptase-inhibitor drugs like lamivudine have suppressed LINE-1-driven inflammation and extended healthspan in some mouse studies.

## Sources

- De Cecco M, Ito T, Petrashen AP, et al.. (2019). L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature. https://doi.org/10.1038/s41586-018-0784-9

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_Canonical: https://longevity-switzerland.com/en/glossary/line-1-retrotransposons · Part of Longevity Cities · Updated 2026-06-22_