Lee Seung-Hee, Itkin-Ansari Pamela, Levine Fred
Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Aging (Albany NY). 2010 Nov;2(11):785-90. doi: 10.18632/aging.100220.
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.
β细胞复制随年龄增长而显著下降。在此,我们报告称,细胞分裂所需的蛋白质CENP-A的水平在胰岛中随年龄急剧下降。在人类中,29岁以后基本上检测不到CENP-A。然而,外分泌细胞仍保留CENP-A表达。胰岛细胞中CENP-A表达的下降在人类中比在小鼠中更为显著,在小鼠中,即使是老年小鼠,CENP-A表达仍可在低水平检测到。CENP-A下降的机制似乎是转录后水平的,因为CENP-A mRNA水平与年龄或胰岛纯度之间没有相关性。这一发现对诱导β细胞复制作为糖尿病治疗方法的研究具有启示意义。