NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration

• DOI: 10.1016/j.celrep.2017.04.007
• Publication Date: 2017-04-25T17:01:03Z
• Authors: Ilias Kounatidis; Stanislava Chtarb...; Yang Cao; Margaret Hayne; Dhruv Jayanth; Barry Ganetzky; Petros Ligoxygakis
• Keywords: Immunosenescence

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