期刊论文详细信息
BMC Medical Genomics
Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6J mice
Michael Muller2  Lisette C de Groot1  Ellen Kampman1  Mechteld M Grootte Bromhaar2  Shohreh Keshtkar1  Carolien Lute1  Noortje IJssennagger2  Mark V Boekschoten2  Nicole JW de Wit2  Wilma T Steegenga1 
[1] Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands;The Netherlands Nutrigenomics Centre, TI Food and Nutrition, Wageningen, The Netherlands
关键词: Microbiota;    Morphology;    C57BL/6J mice;    DNA methylation;    Diet;    Fat;    Transcriptomics;    Colon;    Small intestine;    Aging;   
Others  :  1134714
DOI  :  10.1186/1755-8794-5-38
 received in 2012-04-27, accepted in 2012-08-17,  发布年份 2012
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【 摘 要 】

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.

【 授权许可】

   
2012 Steegenga et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Garrett WS, Gordon JI, Glimcher LH: Homeostasis and inflammation in the intestine. Cell 2010, 140(6):859-870.
  • [2]Santaolalla R, Fukata M, Abreu MT: Innate immunity in the small intestine. Curr Opin Gastroenterol 2011, 27(2):125-131.
  • [3]de Wit NJ, Bosch-Vermeulen H, de Groot PJ, Hooiveld GJ, Bromhaar MM, Jansen J, Muller M, van der Meer R: The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice. BMC Med Genomics 2008, 1:14. BioMed Central Full Text
  • [4]Meier J, Sturm A: The intestinal epithelial barrier: does it become impaired with age? Dig Dis 2009, 27(3):240-245.
  • [5]Barbosa T, Rescigno M: Host-bacteria interactions in the intestine: homeostasis to chronic inflammation. Wiley Interdiscip Rev Syst Biol Med 2010, 2(1):80-97.
  • [6]Benelam B: Satiety and the anorexia of ageing. Br J Community Nurs 2009, 14(8):332-335.
  • [7]Bhutto A, Morley JE: The clinical significance of gastrointestinal changes with aging. Curr Opin Clin Nutr Metab Care 2008, 11(5):651-660.
  • [8]Drozdowski L, Thomson AB: Aging and the intestine. World J Gastroenterol 2006, 12(47):7578-7584.
  • [9]McDonald RB, Ruhe RC: Changes in food intake and its relationship to weight loss during advanced age. Interdiscip Top Gerontol 2010, 37:51-63.
  • [10]Salles N: Basic mechanisms of the aging gastrointestinal tract. Dig Dis 2007, 25(2):112-117.
  • [11]Lee EK, Jung KJ, Choi J, Kim HJ, Han YK, Jeong KS, Ji AR, Park JK, Yu BP, Chung HY: Molecular basis for age-related changes in ileum: involvement of Bax/caspase-dependent mitochondrial apoptotic signaling. Exp Gerontol 2010, 45(12):970-976.
  • [12]Martin K, Kirkwood TB, Potten CS: Age changes in stem cells of murine small intestinal crypts. Exp Cell Res 1998, 241(2):316-323.
  • [13]Trbojevic-Stankovic JB, Milicevic NM, Milosevic DP, Despotovic N, Davidovic M, Erceg P, Bojic B, Bojic D, Svorcan P, Protic M, et al.: Morphometric study of healthy jejunal and ileal mucosa in adult and aged subjects. Histol Histopathol 2010, 25(2):153-158.
  • [14]Woudstra T, Thomson AB: Nutrient absorption and intestinal adaptation with ageing. Best Pract Res Clin Gastroenterol 2002, 16(1):1-15.
  • [15]Kirkwood TB: Intrinsic ageing of gut epithelial stem cells. Mech Ageing Dev 2004, 125(12):911-915.
  • [16]Lappinga PJ, Abraham SC, Murray JA, Vetter EA, Patel R, Wu TT: Small intestinal bacterial overgrowth: histopathologic features and clinical correlates in an underrecognized entity. Arch Pathol Lab Med 2010, 134(2):264-270.
  • [17]Rana SV, Bhardwaj SB: Small intestinal bacterial overgrowth. Scand J Gastroenterol 2008, 43(9):1030-1037.
  • [18]Tiihonen K, Ouwehand AC, Rautonen N: Human intestinal microbiota and healthy ageing. Ageing Res Rev 2010, 9(2):107-116.
  • [19]Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkila J, Monti D, Satokari R, Franceschi C, et al.: Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One 2010, 5(5):e10667.
  • [20]Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, et al.: Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA 2011, 108(Suppl 1):4586-4591.
  • [21]Maegawa S, Hinkal G, Kim HS, Shen L, Zhang L, Zhang J, Zhang N, Liang S, Donehower LA, Issa JP: Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res 2010, 20(3):332-340.
  • [22]Englander EW: Gene expression changes reveal patterns of aging in the rat digestive tract. Ageing Res Rev 2005, 4(4):564-578.
  • [23]Bolstad BM, Irizarry RA, Astrand M, Speed TP: A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 2003, 19(2):185-193.
  • [24]Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP: Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 2003, 31(4):e15.
  • [25]Dai MH, Wang PL, Boyd AD, Kostov G, Athey B, Jones EG, Bunney WE, Myers RM, Speed TP, Akil H, et al.: Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Research 2005., 33(20)
  • [26]Wang X, Seed B: A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res 2003, 31(24):e154.
  • [27]Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000, 132:365-386.
  • [28]Salonen A, Nikkilä J, Jalanka-Tuovinen J, Immonen O, Rajilic-Stojanovic M, Kekkonen RA, Palva A, de Vos WM: Comparative analysis of fecal DNA extraction methods with phylogenetic microarray: effective recovery of bacterial and archaeal DNA using mechanical cell lysis. J Microbiol Methods 2010. In Press, Corrected Proof
  • [29]Cevenini E, Caruso C, Candore G, Capri M, Nuzzo D, Duro G, Rizzo C, Colonna-Romano G, Lio D, Di Carlo D, et al.: Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches. Curr Pharm Des 2010, 16(6):609-618.
  • [30]Flurkey K, Currer JM, Harrison DE: The Mouse in Aging Research. In The Mouse in Biomedical Research. 2nd edition. Edited by Fox JG, Davisson MT, Quimby FW, Barthold SW, Newcomer CE, Smith AL. Elsevier Inc; 2007:637-672.
  • [31]http://research.jax.org/faculty/harrison/ger1vLifespan1.html
  • [32]Lee HM, Greeley GH Jr, Englander EW: Age-associated changes in gene expression patterns in the duodenum and colon of rats. Mech Ageing Dev 2001, 122(4):355-371.
  • [33]Kozyraki R: Cubilin, a multifunctional epithelial receptor: an overview. J Mol Med 2001, 79(4):161-167.
  • [34]Baik HW, Russell RM: Vitamin B12 deficiency in the elderly. Annu Rev Nutr 1999, 19:357-377.
  • [35]Wolters M, Strohle A, Hahn A: Cobalamin: a critical vitamin in the elderly. Prev Med 2004, 39(6):1256-1266.
  • [36]Selhub J, Troen A, Rosenberg IH: B vitamins and the aging brain. Nutr Rev 2010, 68(Suppl 2):S112-S118.
  • [37]Miller AL: The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 2003, 8(1):7-19.
  • [38]McCully KS: Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr 2007, 86(5):1563S-1568S.
  • [39]Tucker KL, Hannan MT, Qiao N, Jacques PF, Selhub J, Cupples LA, Kiel DP: Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study. J Bone Miner Res 2005, 20(1):152-158.
  • [40]Vaes BL, Lute C, van der Woning SP, Piek E, Vermeer J, Blom HJ, Mathers JC, Muller M, de Groot LC, Steegenga WT: Inhibition of methylation decreases osteoblast differentiation via a non-DNA-dependent methylation mechanism. Bone 2010, 46(2):514-523.
  • [41]Corazza GR, Frazzoni M, Gatto MR, Gasbarrini G: Ageing and small-bowel mucosa: a morphometric study. Gerontology 1986, 32(1):60-65.
  • [42]Holt PR, Pascal RR, Kotler DP: Effect of aging upon small intestinal structure in the Fischer rat. J Gerontol 1984, 39(6):642-647.
  • [43]Lipski PS, Bennett MK, Kelly PJ, James OF: Ageing and duodenal morphometry. J Clin Pathol 1992, 45(5):450-452.
  • [44]Warren PM, Pepperman MA, Montgomery RD: Age changes in small-intestinal mucosa. Lancet 1978, 2(8094):849-850.
  • [45]Lang PO, Govind S, Michel JP, Aspinall R, Mitchell WA: Immunosenescence: Implications for vaccination programmes in adults. Maturitas 2011, 68(4):322-330.
  • [46]Ostan R, Bucci L, Capri M, Salvioli S, Scurti M, Pini E, Monti D, Franceschi C: Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation 2008, 15(4–6):224-240.
  • [47]Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, Leeuwenburgh C: Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 2009, 8(1):18-30.
  • [48]Jylhava J, Hurme M: Gene variants as determinants of longevity: focus on the inflammatory factors. Pflugers Arch 2010, 459(2):239-246.
  • [49]Iannitti T, Palmieri B: Inflammation and genetics: an insight in the centenarian model. Hum Biol 2011, 83(4):531-559.
  • [50]Rakoff-Nahoum S, Bousvaros A: Innate and adaptive immune connections in inflammatory bowel diseases. Curr Opin Gastroenterol 2010, 26(6):572-577.
  • [51]Woodmansey EJ: Intestinal bacteria and ageing. J Appl Microbiol 2007, 102(5):1178-1186.
  • [52]Biagi E, Candela M, Franceschi C, Brigidi P: The aging gut microbiota: new perspectives. Ageing Res Rev 2011, 10(4):428-429.
  • [53]Yasui Y, Tanaka T: Protein expression analysis of inflammation-related colon carcinogenesis. J Carcinog 2009, 8:10.
  • [54]Hussain SP, Hofseth LJ, Harris CC: Radical causes of cancer. Nat Rev Cancer 2003, 3(4):276-285.
  • [55]Lashner BA, Provencher KS, Bozdech JM, Brzezinski A: Worsening risk for the development of dysplasia or cancer in patients with chronic ulcerative colitis. Am J Gastroenterol 1995, 90(3):377-380.
  • [56]Fearon ER: Molecular genetics of colorectal cancer. Annu Rev Pathol 2011, 6:479-507.
  • [57]McCart AE, Vickaryous NK, Silver A: Apc mice: models, modifiers and mutants. Pathol Res Pract 2008, 204(7):479-490.
  • [58]Clapper ML, Cooper HS, Chang WC: Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions. Acta Pharmacol Sin 2007, 28(9):1450-1459.
  • [59]Bissahoyo A, Pearsall RS, Hanlon K, Amann V, Hicks D, Godfrey VL, Threadgill DW: Azoxymethane is a genetic background-dependent colorectal tumor initiator and promoter in mice: effects of dose, route, and diet. Toxicological sciences: an official journal of the Society of Toxicology 2005, 88(2):340-345.
  • [60]Carmona FJ, Esteller M: Epigenomics of human colon cancer. Mutat Res 2010, 693(1–2):53-60.
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