Age and Sex Effects on Blood Retrotransposable Element Expression Levels: Findings From the Population-Based Rhineland Study.

Retrotransposable elements (RTEs) have been implicated in the pathogenesis of several age-associated diseases. Although model systems indicate that age- and sex-dependent loss of heterochromatin increases RTE expression, data from large human studies are lacking. Here we assessed the expression levels of 795 blood RTE subfamilies in 2467 participants of the population-based Rhineland Study. We found that the expression of more than 98% of RTE subfamilies increased with both chronological and biological age. Moreover, the expression of heterochromatin regulators involved in RTE silencing was negatively related to the expression of 690 RTE subfamilies. Finally, we observed sex differences in 42 RTE subfamilies, with higher expression in men. The genes mapped to sex-related RTEs were enriched in immune response-related pathways. Importantly, we validated our key findings in an independent population-based cohort. Our findings indicate that RTEs and their repressors are markers of aging and that their dysregulation is linked to inflammation, especially in men.