The Role of TGF-β Ligands on Mobility and Exercise Performance in Drosophila

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Authors
Savone, Marco
Issue Date
2022
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Thesis
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en_US
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Abstract
Endurance exercise has become a successful method for improving mobility decline associated with age, slowing the occurrence of many age-related diseases, and boosting metabolic health. Although chronic endurance exercise promotes the health benefits mentioned, the molecular pathways governing these adaptations are not fully understood. Drosophila has emerged as a useful model for understanding the physiological processes of endurance exercise because of their short lifespans and the ability to conduct large genetic screens using genetic manipulation. Here, we take advantage of the fly’s instinctual negative geotaxis behavior to assess the effects of chronic endurance exercise on fly metabolism combined with RNAi expression of TGF-β ligands myostatin and follistatin in the muscle. The activity of myostatin and follistatin RNAi alters fly fatigue tolerance and climbing speed compared to wild-type flies. We find that endurance exercise training improves climbing speed in follistatin flies and endurance in both myostatin and follistatin flies. Among the proteins that play critical roles in the pathways stemming from exercise, AKT is critical for comparing with myostatin to better understand its effects with exercise metabolism. The connection between AKT phosphorylation and myostatin shows how myostatin is required for normal phosphorylation of AKT following exercise training. Lifespan of myostatin flies is drastically influenced by exercise as we find that exercised myostatin RNAi flies live longer than unexercised myostatin RNAi flies. These results indicate that myostatin and follistatin are critical secreted factors that influence the metabolic adaptations derived from endurance exercise training in Drosophila.
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31 p.
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Kalamazoo College
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U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.
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