衰老对 C57BL/6J 小鼠小肠和结肠的结构、功能和分子影响的分析。
Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6J mice.
机构信息
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
出版信息
BMC Med Genomics. 2012 Aug 28;5:38. doi: 10.1186/1755-8794-5-38.
BACKGROUND
By regulating digestion and absorption of nutrients and providing a barrier against the external environment the intestine provides a crucial contribution to the maintenance of health. To what extent aging-related changes in the intestinal system contribute to the functional decline associated with aging is still under debate.
METHODS
Young (4 M) and old (21 M) male C57BL/6J mice were fed a control low-fat (10E%) or a high-fat diet (45E%) for 2 weeks. During the intervention gross energy intake and energy excretion in the feces were measured. After sacrifice the small and large intestine were isolated and the small intestine was divided in three equal parts. Swiss rolls were prepared of each of the isolated segments for histological analysis and the luminal content was isolated to examine alterations in the microflora with 16S rRNA Q-PCR. Furthermore, mucosal scrapings were isolated from each segment to determine differential gene expression by microarray analysis and global DNA methylation by pyrosequencing.
RESULTS
Digestible energy intake was similar between the two age groups on both the control and the high-fat diet. Microarray analysis on RNA from intestinal scrapings showed no marked changes in expression of genes involved in metabolic processes. Decreased expression of Cubilin was observed in the intestine of 21-month-old mice, which might contribute to aging-induced vitamin B12 deficiency. Furthermore, microarray data analysis revealed enhanced expression of a large number of genes involved in immune response and inflammation in the colon, but not in the small intestine of the 21-month-old mice. Aging-induced global hypomethylation was observed in the colon and the distal part of the small intestine, but not in the first two sections of the small intestine.
CONCLUSION
In 21-month old mice the most pronounced effects of aging were observed in the colon, whereas very few changes were observed in the small intestine.
背景
肠道通过调节营养物质的消化和吸收，并为机体提供抵御外界环境的屏障，为维持健康提供了至关重要的作用。肠道系统与年龄相关的变化在多大程度上导致与衰老相关的功能下降仍存在争议。
方法
将年轻（4 月龄）和年老（21 月龄）雄性 C57BL/6J 小鼠分别用低脂（10E%）或高脂（45E%）饮食喂养 2 周。干预期间，测量总能量摄入和粪便中的能量排泄。处死动物后，分离小肠和大肠，将小肠分为 3 等份。为了进行组织学分析，从小肠各段制备瑞士卷，分离管腔内容物，用 16S rRNA Q-PCR 检查微生物群的变化。此外，从小肠各段分离黏膜刮取物，通过微阵列分析确定差异基因表达，通过焦磷酸测序测定全基因组 DNA 甲基化。
结果
在控制饮食和高脂饮食下，两组年龄组的可消化能量摄入量相似。来自肠道刮取物的 RNA 的微阵列分析显示，代谢过程相关基因的表达没有明显变化。在 21 月龄的小鼠中观察到 Cubilin 的表达下调，这可能导致衰老诱导的维生素 B12 缺乏。此外，微阵列数据分析显示，在 21 月龄小鼠的结肠中，大量参与免疫反应和炎症的基因表达增强，但在小肠中没有。在结肠和小肠远端观察到衰老诱导的全基因组低甲基化，但在小肠的前两段没有。
结论
在 21 月龄的小鼠中，衰老的最显著影响发生在结肠，而在小肠中观察到的变化很少。
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