Activation of transposable elements during aging and neuronal decline in Drosophila

We report the surprising finding that several transposable elements are highly active in Drosophila brain during normal aging. We also show that mutations in Drosophila Argonaute 2 (dAgo2) exhibit exacerbated transposon expression in brain, progressive and age-dependent memory impairment and shortened lifespan. These findings suggest that transposon activation may contribute to age-dependent loss of neuronal function. Transposable elements (TEs) are highly abundant mobile genetic elements that constitute a large fraction of most eukaryotic genomes 1,2. Retrotransposons, which replicate through an RNA intermediate, represent approximately 40 % and 30 % of the human and Drosophila genomes respectively. Mounting evidence suggests that TEs can be active not only in the germline, but also in the brain. LINE-1 elements, for instance, are actively mobilized in normal mammalian brains during neurogenesis3–5, leading to genetic heterogeneity, which in principle could have a functional role in neurophysiology. However, because TEs are capable of replicating and inserting into new positions in the genome, they represent a massive reservoir of potential genomic instability as well as RNA-level toxicity. In fact, TE activation has been correlated with several neurodegenerative disorders6–13. We examined TE expression in Drosophila, where it is feasible to manipulate the TE control mechanisms and to measure physiological effects on the nervous system. We first used Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research