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Open Access Highly Accessed Research article

Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6J mice

Wilma T Steegenga1*, Nicole JW de Wit12, Mark V Boekschoten12, Noortje IJssennagger12, Carolien Lute1, Shohreh Keshtkar1, Mechteld M Grootte Bromhaar12, Ellen Kampman1, Lisette C de Groot1 and Michael Muller12

Author Affiliations

1 Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands

2 The Netherlands Nutrigenomics Centre, TI Food and Nutrition, Wageningen, The Netherlands

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BMC Medical Genomics 2012, 5:38  doi:10.1186/1755-8794-5-38

Published: 28 August 2012

Abstract

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.

Keywords:
Aging; Small intestine; Colon; Transcriptomics; Fat; Diet; DNA methylation; C57BL/6J mice; Morphology; Microbiota