Very Slow Turnover of β-Cells in Aged Adult Mice

Abstract

Although many signaling pathways have been shown to promote β-cell growth, surprisingly little is known about the normal life cycle of preexisting β-cells or the signaling pathways required for β-cell survival. Adult β-cells have been speculated to have a finite life span, with ongoing adult β-cell replication throughout life to replace lost cells. However, little solid evidence supports this idea. To more accurately measure adult β-cell turnover, we performed continuous long-term labeling of proliferating cells with the DNA precursor analog 5-bromo-2-deoxyuridine (BrdU) in 1-year-old mice. We show that β-cells of aged adult mice have extremely low rates of replication, with minimal evidence of turnover. Although some pancreatic components acquired BrdU label in a linear fashion, only 1 in ∼1,400 adult β-cells were found to undergo replication per day. We conclude that adult β-cells are very long lived.