Investigating the Relationship of LINE-1 Expression and SIRT6 Rescue Across Rodent Species

SIRT6, a sirtuin protein, regulates various cellular processes including aging, DNA repair, metabolism, and inflammation (Tian et al., 2019). SIRT6 expression is intricately linked to the expression of transposable element LINE-1 (L1), which constitutes a substantial portion of the genomic DNA in mice and humans. L1 activity in somatic tissues has been implicated in various age-related diseases, including neurodegeneration and cancer (Simon et al., 2019). SIRT6 regulates L1 expression by engaging the KAP1 protein, which facilitates packaging of L1 in heterochromatin, thereby preventing its expression. Mice deficient in SIRT6 exhibit elevated levels of L1 expression, leading to shortened lifespan and chronic inflammation. Comparative analysis of SIRT6 and L1 expression across rodent species with varying lifespans revealed a correlation between SIRT6 rescue efficiency and maximum lifespan. Our investigation reveals that in longer-lived rodent species, SIRT6 may have evolved to efficiently repair double-strand breaks, underscoring its significance in longevity research. Longer-lived species exhibit lower L1 expression, indicating the effectiveness of SIRT6-mediated repression. Immunofluorescence staining further corroborated these findings, highlighting differences in SIRT6 rescue ability and L1 expression among rodent species. Our findings highlight the importance of understanding species-specific variations in SIRT6-mediated L1 repression. For non-rodent species, further investigation is needed to expand our findings. Additionally, further conducting additional immunofluorescence analyses will be needed to validate these conclusions.