Although many signaling pathways have been shown to promote ␤-cell growth, surprisingly little is known about the normal life cycle of preexisting ␤-cells or the signaling pathways required for ␤-cell survival. Adult ␤-cells have been speculated to have a finite life span, with ongoing adult ␤-cell replication throughout life to replace lost cells. However, little solid evidence supports this idea. To more accurately measure adult ␤-cell turnover, we performed continuous long-term labeling of

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... oliferating cells with the DNA precursor analog 5-bromo-2-deoxyuridine (BrdU) in 1-year-old mice. We show that ␤-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 ϳ1,400 adult ␤-cells were found to undergo replication per day. We conclude that adult ␤-cells are very long lived. . BrdU, 5-bromo-2-deoxyuridine; DAPI, 4Ј,6 diamino-2-phenylindole; TUNEL, transferase-mediated dUTP nick-end labeling.