Insect hormone PTTH regulates lifespan through temporal and spatial activation of NF-κB signaling during metamorphosis

Abstract

The 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.

PTTH–Torso Signaling System Controls Developmental Timing, Body Size, and Reproduction through Regulating Ecdysone Homeostasis in the Brown Planthopper, Nilaparvata lugens

“…A recent study unveiled that PTTH governs longevity by modulating immune responses in adult Drosophila. PTTH mutants exhibited prolonged lifespan in both female and male adults, constitutive knockdown of Torso PG cells extended the lifespan in female flies, and conversely, constitutive knockdown of Torso in oenocytes resulted in a shortened lifespan [35]. In Bombyx, Zhang et al revealed reduced expressions of longevity pathway genes in Torso mutants [20].…”

Convergent evolution associated with the loss of developmental diapause may promote extended lifespan in bees

“…The near-universal loss of PTTH and torso only in species lacking prepupal diapause suggests strong selection against this pathway in the species that go through diapause during development. In Drosophila , reducing expression of PTTH or torso delays pupariation(Rewitz et al 2009; Shimell et al 2018; Kang et al 2023), while constitutively knocking down PTTH or torso in the PG results in prolonged adult lifespan, suggesting possible detrimental effects of PTTH and torso in adulthood (Kang et al 2023). This aligns with the antagonist pleiotropy theory of aging (Williams 1957), where genes like PTTH and torso confer benefits early in life (e.g.…”