Abstract
Beta-cell replication dramatically declines with age. Here, we report that the level of CENP-A, a protein required for cell division, declines precipitously with age in an islet-specific manner. CENP-A is essentially undetectable after age 29 in humans. However, exocrine cells retain CENP-A expression. The decline in islet-cell CENP-A expression is more striking in humans than in mice, where CENP-A expression continues to be detectable at low levels even in elderly mice. The mechanism by which CENP-A declines appears to be post-transcriptional, as there was no correlation between CENP-A mRNA levels and age or islet purity. This finding has implications for efforts to induce beta-cell replication as a treatment for diabetes.
Highlights
Inducing beta-cell replication as a means of increasing beta-cell mass is a major goal of diabetes research
Centromere Protein A (CENP-A) protein decreases with age in human islets, but not exocrine cells
In the human fetal pancreas, where 7 different pancreases were examined, 100% of beta-cells exhibited nuclear staining for CENP-A (Figure 1a, d). This staining occurred in a punctuate pattern and no difference was observed in the pattern of CENP-A between beta-cells and other cells in the pancreas
Summary
Inducing beta-cell replication as a means of increasing beta-cell mass is a major goal of diabetes research. There has been tremendous controversy about the extent to which beta-cells replicate, but it is becoming increasingly clear that in adult animals and humans, the rate of beta-cell turnover, whether by replication or neogenesis, is low under most circumstances [1,2,3]. Beta-cells have been found to replicate in a small number of physiologically relevant settings, including during embryogenesis and early in postnatal life, during pregnancy, and in response to obesity [4]. In humans, it appears that postnatal beta-cell replication is more variable than in mice, but there are indications that most takes place during infancy [5]. A similar finding, in humans came from examination by radiocarbon dating and BrdU incorporation [3]
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