A multi-omic characterization of human fibroblasts overexpressing LINE-1

Transposable elements (TEs) are mobile genetic elements that constitute large fractions of eukaryotic genomes (~38-45% of the mouse and human genomes, respectively). In humans, the most abundant family of TEs is Long Interspersed Element-1 (LINE-1 or L1). These are implicated in a number of aging-related phenotypes, including genome instability, mitochondrial dysfunction, and cellular senescence. Here, we electroporate IMR-90 and WI-38 fibroblasts with LINE-1 overexpressing plasmids (and their corresponding controls). The objective of this study is to 1) determine if known senescence and senescence associated secretory phenotype (SASP) markers are altered by cells overexpressing LINE-1 and 2) globally characterize transcriptomic and proteomic changes associated with elevated LINE-1 expression. Though some senescence markers (CCL2, IL6, and MMP3) are altered in fibroblasts following treatment with drugs targeting LINE-1, a comprehensive analysis of TE-associated SASP factors remains to be conducted. This information will clarify the molecular mechanisms by which transposons may modulate cellular senescence, specifically, and cellular dysfunction, more generally, and open new avenues for therapeutic intervention.