Mechanisms underlying the functions of sleep in aging during starvation in Caenorhabditis elegans

von Yin Wu
Kumulative Dissertation
Datum der mündl. Prüfung:2019-06-28
Erschienen:2019-09-12
Betreuer:Prof. Dr. Henrik Bringmann
Gutachter:Prof. Dr. Ralf Heinrich
Gutachter:Prof. Dr. Nils Brose
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-7601

 

 

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Description:PhD Thesis of Yin Wu

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Abstract: Sleep is vital for living organisms. Disruption of sleep is a hallmark of natural aging. A growing body of evidence suggests that sleep serves roles in nervous system-specific functions as well as general cell physiological functions related to aging. However, the molecular mechanisms underlying the connection between sleep and aging are still poorly understood. In this study, I have focused on starvation-induced sleep in larval C. elegans, and aimed to figure out the sleep functions and the mechanism that connect sleep, starvation, survival, and aging. First, I found that the sleep-promoting neuron RIS is activated by starvation through sirtuin signaling and PTEN by further activating the longevity regulators AMP kinase and FoxO, respectively. Next, I discovered that the potential functions of sleep are involved in several fundamental physiological mechanisms such as proteostasis, apoptotic cell death, and autophagy as well as the aging process in starved larval C. elegans. Lastly, I identified a novel protective anti-aging mechanism of sleep in arrested L1 larval worms, which interacts with the mitochondrial respiratory chain, TOR signaling and the unfolded protein response in regulating survival and aging during food deprivation. The discoveries in this study suggest that sleep is required to ensure the survival by counteracting aging processes of larval C. elegans during prolonged starvation, and sleep acts as a predictor for the longevity of the starvation-induced developmental arrest. As a fundamental process, sleep presents a beneficial strategy to protect living organisms against aging and starvation in the larval period. These findings indicate that the functions of sleep have been selected for early in evolution and might be conserved in humans.
Keywords: aging; sleep; sleep-active RIS neuron; developmental arrest of c. elegans; starvation; C. elegans; lifespan; functions of sleep
 
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