Age changes in stem cells of murine small intestinal crypts

Age changes in stem cells of murine small intestinal crypts
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DOI:
10.1006/excr.1998.4001
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发表时间:
1998-06-15
影响因子:
3.7
通讯作者:
Potten, CS
Potten, CS
中科院分区:
医学3区
文献类型:
--
作者:
Martin, K;Kirkwood, TBL;Potten, CS

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在许多类型的分化细胞中可以看到细胞衰老,但干细胞的年龄变化以前没有被清楚地证明。干细胞的变化可能对衰老过程非常重要,因为干细胞数量和功能完整性随年龄的任何下降都可能导致组织中功能和增殖稳态的进行性恶化。小鼠小肠的干细胞提供了一个极好的模型系统,因为这些细胞占据了靠近Lieberkuhn隐窝底部的明确位置。我们检查了5至32个月大的小鼠,发现小肠组织学和干细胞对低剂量辐射的凋亡反应与年龄相关。细胞凋亡的隐窝是集中在周围的干细胞的位置,并可以显着升高暴露于辐射或细胞毒性剂,这表明“自杀”受损的干细胞可能是一个重要的系统,长期的组织维护。将5、15、18和29个月龄的动物暴露于1或8戈伊伽马辐照。与年轻和中年组相比,在29个月大的动物中观察到1戈伊γ射线照射后细胞凋亡水平增加两倍。在8戈伊照射后,所有年龄组的细胞凋亡水平均较高,年龄效应不太明显。这些数据表明,干细胞确实会随着年龄的增长而发生一些功能性变化。(C)北京:科学出版社.
Cell senescence is seen in many types of differentiated cells but age changes in stem cells have not previously been clearly demonstrated. Changes in stem cells may be of great importance for the ageing process, because any decline with age in the numbers and functional integrity of stem cells can lead to progressive deterioration of function and of proliferative homeostasis in tissues. Stem cells of the murine small intestine provide an excellent model system because these cells occupy a well-defined position near the base of the crypts of Lieberkuhn. We examined mice aged between 5 and 32 months and found age-related alterations in the histology of the small intestine and in the apoptotic response of stem cells to low-dose irradiation. Apoptosis in the crypts is concentrated around the stem cell position and can be markedly elevated by exposure to radiation or cytotoxic agents, suggesting that "suicide" of damaged stem cells may be an important system for long-term tissue maintenance. Animals aged 5, 15, 18, and 29 months were exposed to either 1 or 8 Gy gamma irradiation. A twofold increase in the level of apoptosis was seen following 1 Gy gamma irradiation in the 29-month-old animals, compared to the young and middle-age groups. After 8 Gy irradiation the level of apoptosis in all age groups was high and the age effect less pronounced. The data suggest that stem cells do undergo some functional alteration with age. (C) 1998 Academic Press.