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Citation
Kounatidis, I., Chtarbanova, S., Cao, Y., Hayne, M., Jayanth, D., Ganetzky, B., Ligoxygakis, P. (2017). NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration.  Cell Rep. 19(4): 836--848.
FlyBase ID
FBrf0235391
Publication Type
Research paper
Abstract

During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant.

Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC5413584 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Rep.
    Title
    Cell reports
    ISBN/ISSN
    2211-1247
    Data From Reference
    Genes (17)