About half of the mammalian genome is comprised of repetitive and mobile DNA elements. While their role in evolution and phenotype variation is well understood, their physiological function in the some remains largely unexplored. Recent work from our lab established an important epistatic role of L1 retrotransposable elements in driving the progression of pathological aging via chromatin remodeling (Della Valle et al Sci. Trans. Med. 2022). Complementary unpublished results from our lab indicate an unanticipated positive role of cytoplasmic L1 RNA also in tissue homeostasis and regeneration. The project will focus on the investigation on the mechanistic role of retrotransposon RNA mediated response in both epigenome and tissue repair plasticity, and the exploration of RNA based potential therapeutic strategies.