Title |
Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
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Published in |
eLife, April 2018
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DOI | 10.7554/elife.32965 |
Pubmed ID | |
Authors |
Sharan Janjuha, Sumeet Pal Singh, Anastasia Tsakmaki, S Neda Mousavy Gharavy, Priyanka Murawala, Judith Konantz, Sarah Birke, David J Hodson, Guy A Rutter, Gavin A Bewick, Nikolay Ninov |
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. |
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