Abstract
BackgroundBy 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.MethodsYoung (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.ResultsDigestible 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.ConclusionIn 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.
Highlights
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
A high-fat diet, but not aging, affects intestinal function and morphology To analyze changes in the ability of the intestine of aging mice to respond to a high-fat challenge, young and old male C57BL/6J mice were exposed to a control low-fat (10E%) or to a high-fat diet (45E%) and sacrificed at the age of 4 and 21 months
The specific diets were provided for two weeks since the results of our previous study showed a clear response in young mice fed a high-fat diet for this time period [3]
Summary
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. We have shown that physiological adaptations in the small intestine to dietary challenges may play a causal role in the development of diseases such as obesity and/or insulin resistance [3] To enable these exclusive functions, the intestine has a unique and highly specialized tissue structure. A high efficiency of digestion and absorption is made possible by an enormous surface area created by intestinal folds, villi, microvilli, crypts and the glycocalyx in the small intestinal lumen. This large surface area facilitates optimal contact between food and digestive enzymes and creates a huge capacity for active and passive up-take of nutrients. Besides a mucous layer present on top of a continues layer of epithelial cells covering the surface of the intestine, a wide variety of immunological cells and tissue structures are present in the mucosa and submucosa of the intestinal wall [1,4,5]
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