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Citation
Badinloo, M., Nguyen, E., Suh, W., Alzahrani, F., Castellanos, J., Klichko, V.I., Orr, W.C., Radyuk, S.N. (2018). Overexpression of antimicrobial peptides contributes to aging through cytotoxic effects in Drosophila tissues.  Arch. Insect Biochem. Physiol. 98(4): e21464.
FlyBase ID
FBrf0239415
Publication Type
Research paper
Abstract

The innate immune response tends to become hyperactive and proinflammatory in older organisms. We investigated connections between activity of the immune-related genes and aging using the Drosophila model. A hallmark of Drosophila immunity is the production of antimicrobial peptides (AMP), whose expression is triggered via activation of the Toll and Imd immune pathways and regulated by NF-ĸB-like transcription factors, Dif/Dorsal and Relish. It was previously shown that overexpression of the upstream component of the immune pathways shortens lifespan via activation of the Relish-dependent immune response. Here we show that direct overexpression of the Relish target AMP genes broadly at high levels or in the fat body induced apoptosis, elicited depolarization of the mitochondria and significantly shortened lifespan. Underexpression of Relish in the fat body beginning in the second half of lifespan prevented overactivation of AMPs and extended longevity. Unlike infection-induced responses, the age-related increase in AMPs does not require the upstream recognition/transduction module of the Imd pathway. It does however require downstream elements, including Relish and Ird5, a component of the downstream IKK complex. Together, these results established causal links between high-level production of antimicrobial peptides and longevity.

PubMed ID
PubMed Central ID
PMC6039247 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Arch. Insect Biochem. Physiol.
    Title
    Archives of Insect Biochemistry and Physiology
    Publication Year
    1984-
    ISBN/ISSN
    0739-4462
    Data From Reference
    Genes (13)