Research Paper Volume 12, Issue 24 pp 24604—24622
Control of lifespan and survival by Drosophila NF-κB signaling through neuroendocrine cells and neuroblasts
- 1 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- 2 Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
- 3 Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Received: June 29, 2020 Accepted: September 29, 2020 Published: November 24, 2020https://doi.org/10.18632/aging.104196
How to Cite
Copyright: © 2020 Khor and Cai. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
We report a comparative analysis of the effects of immune activation in the fly nervous system using genetic activation models to target Drosophila NF-κB within Toll versus Imd pathways. Genetic gain-of-function models for either pathway pan-neuronally as well as in discrete subsets of neural cells including neuroendocrine insulin-producing cells (IPCs) or neuroblasts reduce fly lifespan, however, these phenotypes in IPCs and neuroblasts are stronger with Toll activation than Imd activation. Of note, while aging is influenced more by Toll/NF-κB activation in IPCs during adulthood, neuroblasts influence aging more substantially during development. The study then focused on Toll/NF-κB inhibition, revealing that IPCs or neuroblasts are important for the effects of lifespan and healthspan extension but in a life stage-dependent manner while some of these effects display sexual dimorphism. Importantly, co-inhibition of Toll/NF-κB pathway in IPCs and neuroblasts increased fly lifespan greater than either cell population, suggesting that independent mechanisms might exist. Toll/NF-κB inhibition in IPCs was also sufficient to enhance survival under various fatal stresses, supporting the additional benefits to fly healthspan. In conclusion, IPCs and neuroblasts are important for Drosophila NF-κB for controlling lifespan.