Changes in transposable elements expression in male and female mice liver throughout aging.

Abstract

Aging has traditionally been studied through the lens of protein-coding genes, with a strong bias toward data derived from male organisms. As a result, the role of non-coding elements and potential sex-specific differences remains largely unexplored. Transposable elements (TEs), mobile sequences capable of altering genome structure and regulating gene expression, have recently gained attention for their roles in development and aging. However, despite this growing interest, key aspects of TE expression dynamics are still poorly characterized, particularly in female tissues. To address this gap, we analyzed TE expression in RNA-Seq liver tissue from male (8, 26, 60, 78, and 104 weeks) and female (3, 24, 48, and 72 weeks) mice. Our results reveal distinct TE expression trends between sexes. While previous studies report increased TE expression with aging, we identified a subset of TEs with decreasing expression over time, differing between males and females. We also observed inverse expression trends between a few TEs and their nearby genes, supporting a potential regulatory relationship. We identified TEs with changing expression (CE TEs) through age associated with nearby genes showing strong expression correlations (|ρ|≥ 0.6). In males, correlated genes such as Txnrd2, Mthfd1, and Dkk3 are involved in redox regulation, one-carbon metabolism, and Wnt signaling, respectively, while in females, Thrb and Cd55 are linked to metabolic regulation and immune protection. These associations suggest that TE activity may be functionally coupled to transcriptional programs relevant to liver physiology and aging. These findings highlight the importance of examining TE expression in both sexes and suggest their potential regulatory roles in age-related liver physiology.