Transposable elements as dynamic regulators of skeletal muscle development, regeneration and aging

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Transposable elements (TEs), once considered “junk” DNA, constitute nearly half of the mammalian genome and can replicate and reposition within the host genome. Advances in omics technologies have improved the capture and annotation of TEs, enabling functional studies. Here, we review TEs classification, structure, regulation, and annotation methods. TEs act as regulatory elements or non-coding RNAs, influencing gene networks and cell fate. While once thought inactive in somatic cells, recent evidence suggests that TEs remain transcriptionally active in various tissues, contributing to function. Focusing on skeletal muscle development, pathological regeneration, and aging, we discuss TEs expression patterns and their potential functional. TEs exhibit stage-specific expression during muscle development and are implicated in muscle-related diseases. Building on the transposon theory of aging, we summarize the increased TEs transcription and chromatin accessibility in aging muscle. Understanding TEs in skeletal muscle biology provides insights into muscle development and age-related functional decline. • Transposable elements comprise nearly half of mammalian genomes. • Omics advances enable systematic annotation and functional TE analysis. • TEs regulate gene networks via regulatory and noncoding RNA roles. • Skeletal muscle shows stage-specific and disease-associated TE expression. • TE reactivation increases during muscle aging and functional decline.