Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
- Technische Universität Dresden, Germany
- King's College London, United Kingdom
- Imperial College London, United Kingdom
- University of Birmingham, United Kingdom
Abstract
The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα-expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity. We link this heterogeneity to differences in gene expression and proliferation. Beta-cells with high NF-kB signaling proliferate significantly less compared to their neighbors with low activity. The NF-kB signalinghi cells also exhibit premature upregulation of socs2, an age-related gene that inhibits beta-cell proliferation. Together, our results show that NF-kB activity marks the asynchronous decline in beta-cell proliferation with advancing age.
Data availability
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Age-related Islet Inflammation Marks the Proliferative Decline of Pancreatic Beta-cells in ZebrafishPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106938).
Article and author information
Author details
Funding
DFG-Center for Regenerative Therapies Dresden
- Nikolay N Ninov
German Center for Diabetes Research
- Nikolay N Ninov
Deutsche Forschungsgemeinschaft
- Nikolay N Ninov
European Foundation for the Study of Diabetes
- Nikolay N Ninov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marianne Bronner, California Institute of Technology, United States
Ethics
Animal experimentation: Experiments were conducted in accordance with the Animal Welfare Act and with permissionof the Landesdirektion Sachsen, Germany (AZ 24-9168, TV38/2015, A12/2016, A5/2017).
Version history
- Received: October 23, 2017
- Accepted: April 5, 2018
- Accepted Manuscript published: April 6, 2018 (version 1)
- Accepted Manuscript updated: April 10, 2018 (version 2)
- Version of Record published: May 9, 2018 (version 3)
Copyright
© 2018, Janjuha et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
eLife 7:e32965.
https://doi.org/10.7554/eLife.32965
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