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Age-related changes in small intestinal mucosa epithelium architecture and epithelial tight junction in rat models

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Background and aims

Functions of the intestinal mucosal barrier are often impaired in the elderly and are closely associated with many age-related diseases. However, mechanisms by which aging influences intestinal barrier function still remain unclear. The aim of this study was to investigate age-related changes in small intestinal morphology, bacteria contents and expression of epithelial tight junction (TJ) proteins.


Thirty Sprague–Dawley rats were divided into groups: young (3 months), adult (12 months), and old (24 months). The small intestinal mucosal architecture and TJ of intestinal epithelial cells were examined by light microscopy and transmission electron microscopy. Jejunum and cecum contents were cultured to identify and measure bacterial species. mRNA expression of Zonula occludens-1 (ZO-1) and occludin were measured by semi-quantitative RT-PCR. Protein expression of ZO-1 and occludin were detected by immunohistochemistry and Western blot.


Normal ileum villi, which were thick and regularly arranged, though increasingly scattered and atrophic in character with shorter and narrower dimensions (P < 0.01), were observed in old rats, along with an elevated number of Gram-positive and Gram-negative bacteria in the jejunum. The TJs of intestinal epithelial cells, as detected by transmission electron microscopy, were wider and discontinuous in old rats. Age-induced down-regulation of mRNA expression and decreased protein expression of ZO-1 and occludin were observed in the ileum (P < 0.01).


Our study indicated that age-related intestinal barrier dysfunction may be associated with mucosal atrophy, damages to TJ structure, increased small intestine bacteria counts, and decreased epithelial TJ protein.

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  1. Katz D, Hollander D, Said HM, Dadufalza V (1987) Aging-associated increase in intestinal permeability to polyethylene glycol 900. Dig Dis Sci 32(3):285–288

    Article  CAS  PubMed  Google Scholar 

  2. Ma TY, Hollander D, Dadufalza V, Krugliak P (1992) Effect of aging and caloric restriction on intestinal permeability. Exp Gerontol 27(3):321–333. doi:10.1016/0531-5565(92)90059-9

    Article  CAS  PubMed  Google Scholar 

  3. Schiffrin EJ, Morley JE, Donnet-Hughes A, Guigoz Y (2010) The inflammatory status of the elderly: the intestinal contribution. Mutat Res 690(1–2):50–56. doi:10.1016/j.mrfmmm.2009.07.011

    Article  CAS  PubMed  Google Scholar 

  4. Caruso C, Magrone T, Jirillo E (2010) Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Part I. Curr Pharm Des 16(6):583

    Article  CAS  PubMed  Google Scholar 

  5. Cevenini E, Caruso C, Candore G, Capri M, Nuzzo D, Duro G, Rizzo C, Colonna-Romano G, Lio D, Di Carlo D, Palmas MG, Scurti M, Pini E, Franceschi C, Vasto S (2010) Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches. Curr Pharm Des. 16(6):609–618

    Google Scholar 

  6. Musch MW, Walsh-Reitz MM, Chang EB (2006) Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption. Am J Physiol Gastrointest Liver Physiol 290(2):G222–G231. doi:10.1152/ajpgi.00301.2005

    Article  CAS  PubMed  Google Scholar 

  7. Dokladny K, Ye D, Kennedy JC, Moseley PL, Ma TY (2008) Cellular and molecular mechanisms of heat stress-induced up-regulation of occludin protein expression: regulatory role of heat shock factor-1. Am J Pathol 172(3):659–670. doi:10.2353/ajpath.2008.070522

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Fink MP (2003) Intestinal epithelial hyperpermeability: update on the pathogenesis of gut mucosal barrier dysfunction in critical illness. Curr Opin Crit Care 9(2):143–151

    Article  PubMed  Google Scholar 

  9. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkila J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 5(5):e10667. doi:10.1371/journal.pone.0010667

    Article  PubMed Central  PubMed  Google Scholar 

  10. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HM, Coakley M, Lakshminarayanan B, O’Sullivan O, Fitzgerald GF, Deane J, O’Connor M, Harnedy N, O’Connor K, O’Mahony D, van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O’Toole PW (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488(7410):178–184. doi:10.1038/nature11319

    Article  CAS  PubMed  Google Scholar 

  11. Lauritano EC, Valenza V, Sparano L, Scarpellini E, Gabrielli M, Cazzato A, Ferraro PM, Gasbarrini A (2010) Small intestinal bacterial overgrowth and intestinal permeability. Scand J Gastroenterol 45(9):1131–1132. doi:10.3109/00365521.2010.485325

    Article  PubMed  Google Scholar 

  12. Corazza GR, Menozzi MG, Strocchi A, Rasciti L, Vaira D, Lecchini R, Avanzini P, Chezzi C, Gasbarrini G (1990) The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology 98(2):302–309. doi:S0016508590000440

    CAS  PubMed  Google Scholar 

  13. Singh VV, Toskes PP (2004) Small bowel bacterial overgrowth: presentation, diagnosis, and treatment. Curr Treat Options Gastroenterol 7(1):19–28

    Article  PubMed  Google Scholar 

  14. Meier J, Sturm A (2009) The intestinal epithelial barrier: does it become impaired with age? Dig Dis 27(3):240–245. doi:00022855610.1159/000228556

    Article  PubMed  Google Scholar 

  15. Chen YM, Zhang JS, Duan XL (2003) Changes of microvascular architecture, ultrastructure and permeability of rat jejunal villi at different ages. World J Gastroenterol 9(4):795–799

    PubMed  Google Scholar 

  16. Lee EK, Jung KJ, Choi J, Kim HJ, Han YK, Jeong KS, Ji AR, Park JK, Yu BP, Chung HY (2010) Molecular basis for age-related changes in ileum: involvement of Bax/caspase-dependent mitochondrial apoptotic signaling. Exp Gerontol 45(12):970–976. doi:10.1016/j.exger.2010.08.019

    Article  CAS  PubMed  Google Scholar 

  17. Wang L, Li J, Li Q, Zhang J, Duan XL (2003) Morphological changes of cell proliferation and apoptosis in rat jejunal mucosa at different ages. World J Gastroenterol 9(9):2060–2064

    PubMed  Google Scholar 

  18. Guigoz Y, Dore J, Schiffrin EJ (2008) The inflammatory status of old age can be nurtured from the intestinal environment. Curr Opin Clin Nutr Metab Care 11(1):13–20. doi:10.1097/MCO.0b013e3282f2bfdf

    Article  PubMed  Google Scholar 

  19. Tiihonen K, Ouwehand AC, Rautonen N (2010) Human intestinal microbiota and healthy ageing. Ageing Res Rev 9(2):107–116. doi:10.1016/j.arr.2009.10.004

    Article  PubMed  Google Scholar 

  20. Elphick DA, Chew TS, Higham SE, Bird N, Ahmad A, Sanders DS (2005) Small bowel bacterial overgrowth in symptomatic older people: can it be diagnosed earlier? Gerontology 51(6):396–401. doi:10.1159/000088704

    Article  CAS  PubMed  Google Scholar 

  21. Hopkins MJ, Sharp R, Macfarlane GT (2001) Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut 48(2):198–205

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Suzuki H (2011) Age-dependent changes in intraepithelial lymphocytes (IELs) of the small intestine, cecum, and colon from young adult to aged mice. Arch Gerontol Geriatr 55(2):261–270. doi:10.1016/j.archger.2011.07.009

    Article  PubMed  Google Scholar 

  23. Clayburgh DR, Shen L, Turner JR (2004) A porous defense: the leaky epithelial barrier in intestinal disease. Lab Invest 84(3):282–291. doi:10.1038/labinvest.37000503700050

    Article  CAS  PubMed  Google Scholar 

  24. Mooradian AD, Haas MJ, Chehade JM (2003) Age-related changes in rat cerebral occludin and zonula occludens-1 (ZO-1). Mech Ageing Dev 124(2):143–146 (pii: S0047637402000416)

    Article  CAS  PubMed  Google Scholar 

  25. Gonzalez-Mariscal L, Tapia R, Chamorro D (2008) Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta 1778(3):729–756. doi:10.1016/j.bbamem.2007.08.018

    Article  CAS  PubMed  Google Scholar 

  26. Subramanian VS, Marchant JS, Ye D, Ma TY, Said HM (2007) Tight junction targeting and intracellular trafficking of occludin in polarized epithelial cells. Am J Physiol Cell Physiol 293(5):C1717–C1726. doi:10.1152/ajpcell.00309.2007

    Article  CAS  PubMed  Google Scholar 

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This work was supported by the Lijieshou Intestinal Barrier Foundation (LJS-2008018) and the National Natural Science Foundation of China (81100263).

Conflict of interest

The authors declared that they had no conflict of interest.

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Correspondence to Yu Hu.

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W. Ren and K. Wu contributed equally to this work.

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Ren, Wy., Wu, Kf., Li, X. et al. Age-related changes in small intestinal mucosa epithelium architecture and epithelial tight junction in rat models. Aging Clin Exp Res 26, 183–191 (2014).

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