780B Poster - 12. Physiology, metabolism and aging
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Blair Schneider ¹; Shixiang Sun ¹; Moonsook Lee ¹; Wenge Li ¹; Jay Cadiz ¹; Nicholas Skvir ²; Nicola Neretti ²; Jan Vijg ^1,3; Julie Secombe ^1,4

Affiliations:
1) Department of Genetics, Albert Einstein College of Medicine, Bronx, NY; 2) Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI; 3) Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY; 4) Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY

Keywords:
t. other (Transposons); z. other (Transposons)

Across all metazoans, aging correlates with functional decline. One potential contributor this is the expression and mobilization of retrotransposons (RTs), which are mobile genetic elements capable of self-replication and insertion into new genomic locations. RT expression and copy number have been shown to increase with age within multiple model organisms. Our goal is to determine de novo RT insertion number and genomic location within somatic cells of Drosophila. By carrying out whole genome sequencing from individual indirect flight muscle (IFM) nuclei from young and old female flies, RT insertions increase with age, with one of the most age-associated new insertions being from the element 412. However, unlike many RTs, the expression of 412 mRNA does not increase with age but remains constant throughout life. Additionally, this increase in RT insertion with age may not occur in all tissues, as when we purified nuclei from whole female thoraces that reflect a range of distinct cell types, we do not observe an age-associated increase in RT insertions. To determine the biological impact of 412 expression and/or insertion, we ubiquitously knocked down the expression of 412 using an inducible shRNA transgene and CRISPRi. This significantly extended female median and maximum lifespan. However, performance in several assays of health was not improved when 412 was knocked down, indicating that longevity is being targeted irrespective of changes to health. Since, we observe increase in 412 insertions in IFM, we also knocked down 412 specifically in this tissue and saw an increase in female lifespan, consistent with the importance of TE insertions in this cell type. In contrast, lifespan was unaltered by knocking down 412 in fat body. To understand the basis for the increased lifespan caused by reducing 412 expression we carried out RNA-sequencing using thoraces of control and 412 knockdown animals. These data suggest that knockdown flies may have improved mitochondrial function as several components of the electron transport chain are significantly upregulated. We are currently testing if the NADH/NAD and ATP levels differ as one of the classic hallmarks of aging is mitochondrial dysfunction. Importantly, our data highlight that the expression and/or mobilization of RTs is associated with the aging process potentially through a more efficient metabolic process.