Ptth regulates lifespan through innate immunity pathway inDrosophila

Abstract

AbstractThe prothoracicotropic hormone (Ptth) is well-known for its important role in controlling insect developmental timing and body size by promoting the biosynthesis and release of ecdysone. However, the role of Ptth in adult physiology is largely unexplored. Here we show thatPtthnull mutants (both males and females) show extended lifespan and healthspan, and exhibit increased resistance to oxidative stress. Transcriptomic analysis reveals that age-dependent upregulation of innate immunity pathway is attenuated byPtthmutants. Intriguingly, we find that Ptth regulates the innate immunity pathway, specifically in fly oenocytes, the homology of mammalian hepatocytes. We further show that oenocyte-specific overexpression of Relish shortens the lifespan, while oenocyte-specific downregulation of ecdysone signaling extends lifespan. Consistently, knocking downtorso, the receptor of Ptth in the prothoracic gland also promotes longevity of the flies. Thus, our data reveal a novel function of the insect hormone Ptth in longevity regulation and innate immunity in adultDrosophila.SignificanceThe function of Ptth is heavily studied in the insect development stage, especially molting and metamorphosis. However, we know very little about the role of Ptth in adult physiology. In this study, we find that Ptth regulates lifespan through the regulation of the innate immunity pathway in a tissue-specific manner inDrosophila. Similar to mammalian growth hormone, Ptth might be the key growth factor that controls longevity by targeting liver inflammation.