The Role of dTORC1 on Muscle Development, Function and Longevity in Drosophila

<p>The TORC1 signaling pathway is critical for cell growth and proliferation. It has been implicated in disorders ranging from diabetes and obesity to depression and cancer. Previous work has implicated the TORC1 pathway in the regulation of longevity and muscle function in a variety of model systems. In this study, we manipulated the activity of mTORC1 in muscle tissue by using the Drosophila GAL4/UAS system. We did this by knocking down both positive (Raptor) and negative (Tsc1) regulators of dTORC1 function in both cardiac and skeletal muscles. We observed that genetic inhibition of TORC1 in skeletal but not cardiac muscle leads to reduced viability using the skeletal muscle GAL4 drivers (C179-GAL4 and 24B-GAL4). Using climbing assays, we have also examined the effects of these manipulations on muscle function and have observed reduced y motility with both Raptor and Tsc1 inhibition in muscle. We found that activation of TORC1 in y skeletal muscle tissue also leads to signicant reductions in lifespan. Both the reduced muscle function and shortened lifespan are consistent with results obtained in a mouse model of muscle Tsc1 deletion. Expression of both positive and negative regulators of TORC1 specically in cardiac muscle using the Hand-GAL4 driver had no dramatic effects on either viability or longevity. These data provide insights into the role of muscle TORC1 activity in development, muscle function and longevity.</p