Expression of Most Retrotransposons in Human Blood Correlates with Biological Aging

Abstract Retrotransposons (RTEs) have been postulated to reactivate with age and contribute to aging through activated innate immune response and inflammation. Here, we systematically analyzed the relationship between RTEs expression and aging using published transcriptomic and methylomic datasets of human blood. Despite no observed correlation between RTEs activity and chronological age, most RTE classes and families except short interspersed nuclear elements (SINEs) correlate with age-associated gene signature scores. Strikingly, we found that the expression of SINEs is linked to upregulated DNA repair pathways in multiple cohorts. DNA hypomethylation with aging was observed across RTE classes and associated with increased RTEs expression in most RTE classes and families except SINEs. Additionally, our single-cell transcriptomic analysis suggests a role for plasma cells in aging mediated by RTEs. Altogether, our multi-omics analysis of large human cohorts highlights the role of RTEs in biological aging and suggests possible mechanisms and cell populations for future investigations.