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Reduced intestinal motility, mucosal barrier function, and inflammation in aged monkeys

  • Published:
The journal of nutrition, health & aging

Abstract

Objective

We aimed to examine the general health and intestinal physiology of young and old non-human primates with comparable life histories and dietary environments.

Design

Vervet monkeys (Chlorcebus aethiops sabaeus) in stable and comparable social and nutritional environments were selected for evaluation. Health phenotype, circulating cytokines and biomarkers of microbial translocation (MT) were measured (n=26-44). Subsets of monkeys additionally had their intestinal motility, intestinal permeability, and fecal microbiomes characterized. These outcomes document age-related intestinal changes present in the absence of nutritional stressors, which are all known to affect gastrointestinal motility, microbiome, and MT.

Results

We found that old monkeys have greater systemic inflammation and poor intestinal barrier function as compared to young monkeys. Old monkeys have dramatically reduced intestinal motility, and all changes in motility and MT are present without large differences in fecal microbiomes.

Conclusion

We conclude that deteriorating intestinal function is a feature of normal aging and could represent the source of inflammatory burden yet to be explained by disease or diet in normal aging human primate populations. Intestinal changes were seen independent of dietary influences and aging within a consistent environment appears to avoid major microbiome shifts. Our data suggests interventions to promote intestinal motility and mucosal barrier function have the potential to support better health with aging.

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References

  1. Collerton, J., Martin-Ruiz, C., Davies, K., Hilkens, C. M., Isaacs, J., Kolenda, C., Parker, C., Dunn, M., Catt, M., Jagger, C., von Zglinicki, T., and Kirkwood, T. B. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev 2012;133, 456–466

    Article  CAS  PubMed  Google Scholar 

  2. Adriaensen, W., Mathei, C., Vaes, B., van Pottelbergh, G., Wallemacq, P., and Degryse, J. M. Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study. Age 2014;36, 9723

    Article  PubMed  PubMed Central  Google Scholar 

  3. Atzmon, G., Schechter, C., Greiner, W., Davidson, D., Rennert, G., and Barzilai, N. Clinical phenotype of families with longevity. J Am Geriatr Soc 2004;52, 274–277

    Article  PubMed  Google Scholar 

  4. Shimizu, I., Yoshida, Y., Suda, M., and Minamino, T. (2014) DNA damage response and metabolic disease. Cell metabolism 2014;20, 967–977

    Article  CAS  PubMed  Google Scholar 

  5. Levine, M. E., and Crimmins, E. M. The impact of insulin resistance and inflammation on the association between sarcopenic obesity and physical functioning. Obesity (Silver Spring) 2012;20, 2101–2106

    Article  CAS  Google Scholar 

  6. Payette, H., Roubenoff, R., Jacques, P. F., Dinarello, C. A., Wilson, P. W., Abad, L. W., and Harris, T. Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study. J Am Geriatr Soc 2003;51, 1237–1243

    Article  PubMed  Google Scholar 

  7. Souza, R. B., and Powers, C. M. Differences in hip kinematics, muscle strength, and muscle activation between subjects with and without patellofemoral pain. J Orthop Sports Phys Ther 2009;39, 12–19

    Article  PubMed  Google Scholar 

  8. Schaap, L. A., Pluijm, S. M., Deeg, D. J., Harris, T. B., Kritchevsky, S. B., Newman, A. B., Colbert, L. H., Pahor, M., Rubin, S. M., Tylavsky, F. A., and Visser, M. Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci 2009;64, 1183–1189

    Article  PubMed  Google Scholar 

  9. Ogawa, K., Kim, H. K., Shimizu, T., Abe, S., Shiga, Y., and Calderwood, S. K. Plasma heat shock protein 72 as a biomarker of sarcopenia in elderly people. Cell Stress Chaperones 2012;17, 349–359

    Article  CAS  PubMed  Google Scholar 

  10. Ghosh, S., Lertwattanarak, R., Garduno Jde, J., Galeana, J. J., Li, J., Zamarripa, F., Lancaster, J. L., Mohan, S., Hussey, S., and Musi, N. Elevated muscle TLR4 expression and metabolic endotoxemia in human aging. J Gerontol A Biol Sci Med Sci 2015;70, 232–246

    Article  PubMed  Google Scholar 

  11. Stehle, J. R., Leng, X., Kitzman, D. W., Nicklas, B. J., Kritchevsky, S. B., and High, K. P. Lipopolysaccharide-binding protein, a surrogate marker of microbial translocation, is associated with physical function in healthy older adults. J Gerontol A Biol Sci Med Sci 2012;67, 1212–1218

    Article  PubMed  PubMed Central  Google Scholar 

  12. Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Collado, P. S., Almar, M., Martinez-Florez, S., de Paz, J. A., Gonzalez-Gallego, J., and Cuevas, M. J. Wholebody vibration improves the anti-inflammatory status in elderly subjects through tolllike receptor 2 and 4 signaling pathways. Mech Ageing Dev 2015;150, 12–19

    Article  CAS  PubMed  Google Scholar 

  13. Rera, M., Clark, R. I., and Walker, D. W. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A 2012;109, 21528–21533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J. P., Druart, C., Bindels, L. B., Guiot, Y., Derrien, M., Muccioli, G. G., Delzenne, N. M., de Vos, W. M., and Cani, P. D. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A 2013;110, 9066–9071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tiihonen, K., Ouwehand, A. C., and Rautonen, N. Human intestinal microbiota and healthy ageing. Ageing research reviews 2010;9, 107–116

    Article  PubMed  Google Scholar 

  16. Claesson, M. J., Jeffery, I. B., Conde, S., Power, S. E., O’Connor, E. M., Cusack, S., Harris, H. M., Coakley, M., Lakshminarayanan, B., O’Sullivan, O., Fitzgerald, G. F., Deane, J., O’Connor, M., Harnedy, N., O’Connor, K., O’Mahony, D., van Sinderen, D., Wallace, M., Brennan, L., Stanton, C., Marchesi, J. R., Fitzgerald, A. P., Shanahan, F., Hill, C., Ross, R. P., and O’Toole, P. W. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012;488, 178–184

    CAS  PubMed  Google Scholar 

  17. Haberthur, K., Engelman, F., Barron, A., and Messaoudi, I. Immune senescence in aged nonhuman primates. Exp Gerontol 2010;45, 655–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Morley, J. E. Constipation and irritable bowel syndrome in the elderly. Clinics in geriatric medicine 2007;23, 823–832, vi-vii

    Article  PubMed  Google Scholar 

  19. Amar, J., Burcelin, R., Ruidavets, J. B., Cani, P. D., Fauvel, J., Alessi, M. C., Chamontin, B., and Ferrieres, J. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr 2008;87, 1219–1223

    CAS  PubMed  Google Scholar 

  20. Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., and Burcelin, R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008;57, 1470–1481

    Article  CAS  PubMed  Google Scholar 

  21. Kavanagh, K., Wylie, A. T., Tucker, K. L., Hamp, T. J., Gharaibeh, R. Z., Fodor, A. A., and Cullen, J. M. Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates. American Journal of Clinical Nutrition 2013;98, 349–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Atkins, H. M., Willson, C. J., Silverstein, M., Jorgensen, M., Floyd, E., Kaplan, J. R., and Appt, S. E. Characterization of ovarian aging and reproductive senescence in vervet monkeys (Chlorocebus aethiops sabaeus). Comparative medicine 2014;64, 55–62

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Kavanagh, K., Fairbanks, L. A., Bailey, J. N., Jorgensen, M. J., Wilson, M., Zhang, L., Rudel, L. L., and Wagner, J. D. Characterization and heritability of obesity and associated risk factors in vervet monkeys. Obesity (Silver Spring) 2007;15, 1666–1674

    Article  CAS  Google Scholar 

  24. Beaufrere, A. M., Neveux, N., Patureau Mirand, P., Buffiere, C., Marceau, G., Sapin, V., Cynober, L., and Meydinal-Denis, D. Long-term intermittent glutamine supplementation repairs intestinal damage (structure and functional mass) with advanced age: assessment with plasma citrulline in a rodent model. The journal of nutrition, health & aging 2014;18, 814–819

    Article  CAS  Google Scholar 

  25. Park, Y. W., Zhu, S., Palaniappan, L., Heshka, S., Carnethon, M. R., and Heymsfield, S. B. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 2003;163, 427–436

    Article  PubMed  PubMed Central  Google Scholar 

  26. Einstein, F. H., Huffman, D. M., Fishman, S., Jerschow, E., Heo, H. J., Atzmon, G., Schechter, C., Barzilai, N., and Muzumdar, R. H. Aging per se increases the susceptibility to free fatty acid-induced insulin resistance. J Gerontol A Biol Sci Med Sci 2010;65, 800–808

    Article  PubMed  Google Scholar 

  27. Timmerman, K. L., Lee, J. L., Fujita, S., Dhanani, S., Dreyer, H. C., Fry, C. S., Drummond, M. J., Sheffield-Moore, M., Rasmussen, B. B., and Volpi, E. Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults. Diabetes 2010;59, 2764–2771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tran, L., and Greenwood-Van Meerveld, B. Age-associated remodeling of the intestinal epithelial barrier. J Gerontol A Biol Sci Med Sci 2013;68, 1045–1056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. McDougal, J. N., Miller, M. S., Burks, T. F., and Kreulen, D. L. Age-related changes in colonic function in rats. The American journal of physiology 1984;247, G542–546

    CAS  PubMed  Google Scholar 

  30. Southwell, B. R., Koh, T. L., Wong, S. Q., King, S. K., Ong, S. Y., Lee, M., Farmer, P. J., Peck, C. J., Sutcliffe, J. R., Stanton, M. P., Keck, J., Cook, D. J., Chow, C. W., and Hutson, J. M. Decrease in nerve fibre density in human sigmoid colon circular muscle occurs with growth but not aging. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society 2010;22, 439–445, e106

    Article  CAS  Google Scholar 

  31. Bitar, K., Greenwood-Van Meerveld, B., Saad, R., and Wiley, J. W. Aging and gastrointestinal neuromuscular function: insights from within and outside the gut. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society 2011;23, 490–501

    Article  CAS  Google Scholar 

  32. Martinez, C., Gonzalez-Castro, A., Vicario, M., and Santos, J. Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome. Gut and liver 2012;6, 305–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Costilla, V. C., and Foxx-Orenstein, A. E. Constipation: understanding mechanisms and management. Clinics in geriatric medicine 2014;30, 107–115

    Article  PubMed  Google Scholar 

  34. Saffrey, M. J. Aging of the mammalian gastrointestinal tract: a complex organ system. Age 2014;36, 9603

    Article  PubMed  Google Scholar 

  35. Bitar, K. N., and Patil, S. B. Aging and gastrointestinal smooth muscle. Mech Ageing Dev 125, 907-910

  36. Choi, S. J., Shively, C. A., Register, T. C., Feng, X., Stehle, J., High, K., Ip, E., Kritchevsky, S. B., Nicklas, B., and Delbono, O. Force-generation capacity of single vastus lateralis muscle fibers and physical function decline with age in African green vervet monkeys. J Gerontol A Biol Sci Med Sci 2012;68, 258–267

    Article  PubMed  PubMed Central  Google Scholar 

  37. Blijlevens, N. M., Donnelly, J. P., and DePauw, B. E. Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients. Bone marrow transplantation 2005;36, 703–707

    Article  CAS  PubMed  Google Scholar 

  38. Crenn, P., Coudray-Lucas, C., Thuillier, F., Cynober, L., and Messing, B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology 2000;119, 1496–1505

    Article  CAS  PubMed  Google Scholar 

  39. Gunther, C., Buchen, B., Neurath, M. F., and Becker, C. Regulation and pathophysiological role of epithelial turnover in the gut. Seminars in cell & developmental biology 2014;35, 40–50

    Article  Google Scholar 

  40. DelaRosa, O., Pawelec, G., Peralbo, E., Wikby, A., Mariani, E., Mocchegiani, E., Tarazona, R., and Solana, R. Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology 2006;7, 471–481

    Article  CAS  PubMed  Google Scholar 

  41. Ulgherait, M., Rana, A., Rera, M., Graniel, J., and Walker, D. W. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell reports 2014;8, 1767–1780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Goodrich, J. K., Waters, J. L., Poole, A. C., Sutter, J. L., Koren, O., Blekhman, R., Beaumont, M., Van Treuren, W., Knight, R., Bell, J. T., Spector, T. D., Clark, A. G., and Ley, R. E. Human genetics shape the gut microbiome. Cell 2014;159, 789–799

  43. Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y. Y., Keilbaugh, S. A., Bewtra, M., Knights, D., Walters, W. A., Knight, R., Sinha, R., Gilroy, E., Gupta, K., Baldassano, R., Nessel, L., Li, H., Bushman, F. D., and Lewis, J. D. Linking longterm dietary patterns with gut microbial enterotypes. Science 2011;334, 105–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lakshminarayanan, B., Stanton, C., O’Toole, P. W., and Ross, R. P. Compositional dynamics of the human intestinal microbiota with aging: implications for health. The journal of nutrition, health & aging 2014;18, 773–786

    Article  CAS  Google Scholar 

  45. Wei, X., Yang, Z., Rey, F. E., Ridaura, V. K., Davidson, N. O., Gordon, J. I., and Semenkovich, C. F. Fatty acid synthase modulates intestinal barrier function through palmitoylation of mucin 2. Cell host & microbe 2012;11, 140–152

    Article  CAS  Google Scholar 

  46. Sharma, R., Young, C., and Neu, J. Molecular modulation of intestinal epithelial barrier: contribution of microbiota. Journal of biomedicine & biotechnology 2010, 305879

    Google Scholar 

  47. Bruce-Keller, A. J., Salbaum, J. M., Luo, M., Blanchard, E. T., Taylor, C. M., Welsh, D. A., and Berthoud, H. R. Obese-type Gut Microbiota Induce Neurobehavioral Changes in the Absence of Obesity. Biological psychiatry 2015;77, 607–615

    Article  PubMed  Google Scholar 

  48. Sanchez, M., Panahi, S., and Tremblay, A. Childhood obesity: a role for gut microbiota? International journal of environmental research and public health 2015;12, 162–175

    Article  Google Scholar 

  49. Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., Waget, A., Delmee, E., Cousin, B., Sulpice, T., Chamontin, B., Ferrieres, J., Tanti, J. F., Gibson, G. R., Casteilla, L., Delzenne, N. M., Alessi, M. C., and Burcelin, R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56, 1761–1772

    Article  CAS  PubMed  Google Scholar 

  50. Moreno-Navarrete, J. M., Ortega, F., Serino, M., Luche, E., Waget, A., Pardo, G., Salvador, J., Ricart, W., Fruhbeck, G., Burcelin, R., and Fernandez-Real, J. M. Circulating lipopolysaccharide-binding protein (LBP) as a marker of obesity-related insulin resistance. Int J Obes (Lond) 2011;36, 1442–1449

    Article  Google Scholar 

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Correspondence to Kylie Kavanagh.

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Mitchell, E.L., Davis, A.T., Brass, K. et al. Reduced intestinal motility, mucosal barrier function, and inflammation in aged monkeys. J Nutr Health Aging 21, 354–361 (2017). https://doi.org/10.1007/s12603-016-0725-y

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  • DOI: https://doi.org/10.1007/s12603-016-0725-y

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