ZFIN ID: ZDB-PUB-180407-3
Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish
Janjuha, S., Singh, S.P., Tsakmaki, A., Mousavy-Gharavy, N., Murawala, P., Konantz, J., Birke, S., Hodson, D.J., Rutter, G., Bewick, G., Ninov, N.N.
Date: 2018
Source: eLIFE   7: (Journal)
Registered Authors: Ninov, Nikolay, Singh, Sumeet Pal
Keywords: cell biology, zebrafish
Microarrays: GEO:GSE106938
MeSH Terms:
  • Aging*
  • Animals
  • Animals, Genetically Modified
  • Cell Proliferation*
  • Cells, Cultured
  • Gene Expression Profiling
  • Inflammation/immunology
  • Inflammation/metabolism
  • Inflammation/pathology*
  • Inflammation Mediators/metabolism*
  • Insulin-Secreting Cells/immunology
  • Insulin-Secreting Cells/metabolism
  • Insulin-Secreting Cells/pathology*
  • NF-kappa B/genetics
  • NF-kappa B/metabolism*
  • Signal Transduction
  • Single-Cell Analysis
  • Transcriptional Activation
  • Zebrafish/immunology
  • Zebrafish/physiology*
PubMed: 29624168 Full text @ Elife
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.