Systemic regulation of the age-related decline of pancreatic beta-cell replication

  1. Yuval Dor1
  1. 1Department of Developmental Biology and Cancer Research and Molecular Biology, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
  2. 2Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
  1. Corresponding author: Dr. Yuval Dor, E-mail: yuvald{at}ekmd.huji.ac.il

Abstract

The frequency of pancreatic beta-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, in particular the decline of Polycomb genes and accumulation of p16/INK4. Here we demonstrate that a systemic factor found in the young circulation is able to increase the proliferation rate of old pancreatic beta-cells. Old mice parabiosed to young mice have increased beta-cell replication compared with unjoined old mice or old mice parabiosed to old mice. In addition, we demonstrate that old beta-cells transplanted into young recipients have increased replication rate compared with cells transplanted into old recipients ; conversely, young beta-cells transplanted into old mice decrease their replication rate compared with young cells transplanted into young recipients. The expression of p16/Ink4A mRNA did not change in heterochronic parabiosis, suggesting the involvement of other pathways. We conclude that systemic factors contribute to the replicative decline of old pancreatic beta-cells.

  • Received February 1, 2013.
  • Accepted April 22, 2013.

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  1. Diabetes
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