Age-related islet inflammation marks the proliferative decline of pancreatic beta-cells in zebrafish

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sharan Janjuha - , German Research Foundation, Helmholtz-Zentrum Dresden-Rossendorf, Dresden University of Technology (Author)
  • Sumeet Pal Singh - , Pancreatic beta-cell Biology and Regeneration (Junior Research Group), German Research Foundation, DFG Ctr Regenerat Therapies Dresden Cluster Exc (Author)
  • Anastasia Tsakmaki - , Queen Mary University of London (Author)
  • S. Neda Mousavy Gharavy - , Imperial College London (Author)
  • Priyanka Murawala - , German Research Foundation, DFG Ctr Regenerat Therapies Dresden Cluster Exc (Author)
  • Judith Konantz - , Core Facility Fish, German Research Foundation, DFG Ctr Regenerat Therapies Dresden Cluster Exc (Author)
  • Sarah Birke - , German Research Foundation (Author)
  • David J. Hodson - , University of Birmingham (Author)
  • Guy A. Rutter - , Imperial College London (Author)
  • Gavin A. Bewick - , Queen Mary University of London (Author)
  • Nikolay Ninov - , German Center for Neurodegenerative Diseases, Dresden site (Partner: DZNE of the Helmholtz Association), Chair of Cell Biology and Regeneration of β-Cells, German Research Foundation, DFG Ctr Regenerat Therapies Dresden Cluster Exc, University Hospital Vienna, Dresden University of Technology, German Center for Diabetes Research (Author)

Abstract

The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is 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 tnf alpha-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 signaling(hi) 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.

Details

Original languageEnglish
Number of pages24
JournaleLife
Volume7
Publication statusPublished - 6 Apr 2018
Peer-reviewedYes

External IDs

PubMed 29624168
Scopus 85046843174

Keywords

Keywords

  • Endoplasmic-reticulum stress, Large gene lists, In-vivo, Life, Replication, Activation, Apoptosis, Survival, Pathway, Glucose