629. EXPLORING THE DYNAMICS OF L1 RETROTRANSPOSITION IN NATURAL AGING: INSIGHTS FROM THE MOUSE MODEL

Abstract Background Natural Aging is a process that results from the impact of the accumulation of a wide variety of molecular and cellular damage over time, which leads to a growing risk of disease both physically and mentally. Although the molecular mechanism of aging remains unclear, aging is associated with DNA damage in the cells by somatic SNVs, genomic rearrangements and chromosomal alterations. Long interspersed nuclear element-1 (L1) is a major type of retrotransposons constituting about 20% of mammalian genomes, some of which still could move into other genomic regions through retrotransposition (RT). Recent studies linked aging in the various tissues with the increased activity of retrotransposons including L1. Due to the difficulty of detection new RT events in vivo, we created a genetically modified mouse model L1-EGFP mice, in which the cells are labeled by EGFP expression only after the retrotransposition of the construct. Aims & Objectives Using the L1EGFP mouse, frequency and pattern of L1 RT in the brain and other tissues between young and old mice were examined. Method DNA and RNA were extracted from various tissues of both aged and young L1EGFP mice (n ≥ 60 total). The extracted DNA was used for qPCR targeting EGFP to quantify L1 RT levels in the genome, while the RNA was used for RNA-seq and qPCR to quantify L1 mRNA levels. Results Preliminary results indicated that L1 RT levels in three brain regions (prefrontal cortex, hippocampus, and cerebellum) do not differ significantly between aged and young groups. Discussion & Conclusions Current results suggested that aging may not have a substantial impact on L1 RT activity in the brain. We are currently extending our investigation to assess L1 RT activity in various tissues other than brain and to measure mRNA levels.