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

Research output: Contribution to journalArticle

Authors

  • Sharan Janjuha
  • Sumeet Pal Singh
  • Anastasia Tsakmaki
  • Neda Mousavy Gharavy
  • Priyanka Murawala
  • Judith Konantz
  • Sarah Birke
  • Guy Rutter
  • Gavin Bewick
  • Nikolay Ninov

Colleges, School and Institutes

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 NFkB signaling 44 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
JournalElife
Early online date6 Apr 2018
Publication statusPublished - 9 May 2018