Increased susceptibility of aging gastric mucosa to injury: The mechanisms and clinical implications

World Journal of Gastroenterology

Volumn 20, Issue 16, 2014, Pages 4467-4482

  Tarnawski, Andrzej S ^a   Ahluwalia, Amrita ^a   Jones, Michael K ^a  

^a VA LONG BEACH HEALTHCARE SYSTEM   (United States)

Author keywords

Aging gastric mucosa; Apoptosis; Hypoxia; Injury; Phosphatase and tensin homologue deleted on chromosome ten pten; Survivin

Indexed keywords

ACETYLSALICYLIC ACID; ALCOHOL; BILE ACID; HYDROTALCITE; KARYOPHERIN ALPHA; KLOTHO PROTEIN; MELATONIN; NONSTEROID ANTIINFLAMMATORY AGENT; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; SODIUM CHLORIDE; TELOMERASE; UNCLASSIFIED DRUG; VASCULOTROPIN; GASTROINTESTINAL AGENT;

AGING; APOPTOSIS; ARTICLE; COLD STRESS; DEFENSE MECHANISM; DISEASE PREDISPOSITION; DNA DAMAGE; HELICOBACTER INFECTION; HELICOBACTER PYLORI; HUMAN; HYPOXIA; LIPID PEROXIDATION; MOLECULAR PATHOLOGY; NONHUMAN; STOMACH MUCOSA BLOOD FLOW; STOMACH MUCOSA INJURY; AGE; ANIMAL; DRUG EFFECTS; METABOLISM; PATHOLOGY; RISK FACTOR; SIGNAL TRANSDUCTION; STOMACH DISEASES; STOMACH MUCOSA; TREATMENT OUTCOME;

AGE FACTORS; AGING; ANIMALS; GASTRIC MUCOSA; GASTROINTESTINAL AGENTS; HUMANS; RISK FACTORS; SIGNAL TRANSDUCTION; STOMACH DISEASES; TREATMENT OUTCOME;

EID: 84899659455     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i16.4467     Document Type: Article

References (69)

1. Tarnawski A, Pai R, Deng X, Ahluwalia A, Khomenko T, Tanigawa T, Akahoshi T, Sandor Z, Szabo S. Aging gastropathy- novel mechanisms: hypoxia, up-regulation of multifunctional phosphatase PTEN, and proapoptotic factors. Gastroenterology 2007; 133: 1938-1947. [PMID: 18054565 DOI: 10.1053/j.gastro.2007.08.037]
2. Hollander D, Tarnawski A, Stachura J, Gergely H. Morphologic changes in gastric mucosa of aging rats. Dig Dis Sci 1989; 34: 1692-1700. [PMID: 2582982 DOI: 10.1007/BF01540046]
3. Kang JM, Kim N, Kim JH, Oh E, Lee BY, Lee BH, Shin CM, Park JH, Lee MK, Nam RH, Lee HE, Lee HS, Kim JS, Jung HC, Song IS. Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons. Am J Physiol Gastrointest Liver Physiol 2010; 299: G1147-G1153. [PMID: 20724528 DOI: 10.1152/ajpgi.00218.2010]
4. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 2008; 135: 41-60. [PMID: 18549814 DOI: 10.1053/j.gastro. 2008.05.030]
5. Tarnawski AS, Ahluwalia A, Jones MK. The mechanisms of gastric mucosal injury: focus on microvascular endothelium as a key target. Curr Med Chem 2012; 19: 4-15. [PMID: 22300071 DOI: 10.2174/092986712803414079]
6. Tarnawski AS, Ahluwalia A. Molecular mechanisms of epithelial regeneration and neovascularization during healing of gastric and esophageal ulcers. Curr Med Chem 2012; 19: 16-27. [PMID: 22300072 DOI: 10.2174/092986712803414088]
7. Tarnawski A, Krause WJ, Ivey KJ. Effect of glucagon on aspirin-induced gastric mucosal damage in man. Gastroenterology 1978; 74: 240-245. [PMID: 620896]
8. Ichikawa Y, Tarnawski A, Sarfeh IJ, Ishikawa T, Shimada H. Distorted microangioarchitecture and impaired angiogenesis in gastric mucosa of portal hypertensive rats. Gastroenterology 1994; 106: 702-708. [PMID: 7509763]
9. Tarnawski A, Stachura J, Hollander D, Sarfeh IJ, Bogdal J. Cellular aspects of alcohol-induced injury and prostaglandin protection of the human gastric mucosa. Focus on the mucosal microvessels. J Clin Gastroenterol 1988; 10 Suppl 1: S35-S45. [PMID: 3183341 DOI: 10.1097/00004836-198812001-00008]
10. Lee M, Feldman M. Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirininduced injury in rats. Gastroenterology 1994; 107: 1746-1750. [PMID: 7958687]
11. Grønbech JE, Lacy ER. Role of gastric blood flow in impaired defense and repair of aged rat stomachs. Am J Physiol 1995; 269: G737-G744. [PMID: 7491966]
12. Lee M. Age-related changes in gastric mucosal bicarbonate secretion in rats. Age 1996; 19: 55-58. [DOI: 10.1007/ BF02434071]
13. Lee M, Feldman M. Age-related changes in gastric mucosal glycoprotein synthesis in rats basally and in response to acute aspirin exposure. [abstract]. Gastroenterology 1993; 104: A131
14. Lee M. Age-related changes in gastric blood flow in rats. Gerontology 1996; 42: 289-293. [PMID: 8940652 DOI: 10.1159/000213805]
15. Tsukimi Y, Okabe S. Changes in gastric function and healing of chronic gastric ulcers in aged rats. Jpn J Pharmacol 1995; 68: 103-110. [PMID: 7494371 DOI: 10.1254/jjp.68.103]
16. Vogiagis D, Glare EM, Misajon A, Brown W, O'Brien PE. Cyclooxygenase-1 and an alternatively spliced mRNA in the rat stomach: effects of aging and ulcers. Am J Physiol Gastrointest Liver Physiol 2000; 278: G820-G827. [PMID: 10801275]
17. Cryer B, Redfern JS, Goldschmiedt M, Lee E, Feldman M. Effect of aging on gastric and duodenal mucosal prostaglandin concentrations in humans. Gastroenterology 1992; 102: 1118-1123. [PMID: 1551520]
18. Goto H, Sugiyama S, Ohara A, Hoshino H, Hamajima E, Kanamori S, Tsukamoto Y, Ozawa T. Age-associated decreases in prostaglandin contents in human gastric mucosa. Biochem Biophys Res Commun 1992; 186: 1443-1448. [PMID: 1510674 DOI: 10.1016/S0006-291X(05)81568-2]
19. Feldman M, Cryer B. Effects of age on gastric alkaline and nonparietal fluid secretion in humans. Gerontology 1998; 44: 222-227. [PMID: 9657083 DOI: 10.1159/000022014]
20. Majumdar AP, Moshier JA, Arlow FL, Luk GD. Biochemical changes in the gastric mucosa after injury in young and aged rats. Biochim Biophys Acta 1989; 992: 35-40. [PMID: 2665819 DOI: 10.1016/0304-4165(89)90047-0]
21. Lee M, Hardman WE, Cameron I. Age-related changes in gastric mucosal repair and proliferative activities in rats exposed acutely to aspirin. Gerontology 1998; 44: 198-203. [PMID: 9657079 DOI: 10.1159/000022010]
22. Goto H, Tachi K, Hisanaga Y, Kamiya K, Ohmiya N, Niwa Y, Hayakawa T. Exacerbatory mechanism responsible for water immersion stress-induced gastric lesions in aged rats compared with young rats. Clin Exp Pharmacol Physiol 2001; 28: 659-662. [PMID: 11473533 DOI: 10.1046/j.1440-1681.2001.03497. x]
23. Lee M, Feldman M. The aging stomach: implications for NSAID gastropathy. Gut 1997; 41: 425-426. [PMID: 9391235 DOI: 10.1136/gut.41.4.425]
24. Miyake H, Inaba N, Kato S, Takeuchi K. Increased susceptibility of rat gastric mucosa to ulcerogenic stimulation with aging. Role of capsaicin-sensitive sensory neurons. Dig Dis Sci 1996; 41: 339-345. [PMID: 8601380 DOI: 10.1007/ BF02093826]
25. Seo PJ, Kim N, Kim JH, Lee BH, Nam RH, Lee HS, Park JH, Lee MK, Chang H, Jung HC, Song IS. Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats. Gut Liver 2012; 6: 210-217. [PMID: 22570750 DOI: 10.5009/gnl.2012.6.2.210]
26. Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP. Risk factors for NSAID-associated upper GI clinical events in a longterm prospective study of 34 701 arthritis patients. Aliment Pharmacol Ther 2010; 32: 1240-1248. [PMID: 20955443 DOI: 10.1111/j.1365-2036.2010.04465.x]
27. Laine L. Review article: gastrointestinal bleeding with low-dose aspirin - what's the risk? Aliment Pharmacol Ther 2006; 24: 897-908. [PMID: 16948802 DOI: 10.1111/ j.1365-2036.2006.03077.x]
28. Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005; 353: 2373-2383. [PMID: 16319386 DOI: 10.1056/NEJMra052717]
29. Iwamoto J, Saito Y, Honda A, Matsuzaki Y. Clinical features of gastroduodenal injury associated with long-term lowdose aspirin therapy. World J Gastroenterol 2013; 19: 1673-1682. [PMID: 23555156 DOI: 10.3748/wjg.v19.i11.1673]
30. Samoszuk MK, Walter J, Mechetner E. Improved immunohistochemical method for detecting hypoxia gradients in mouse tissues and tumors. J Histochem Cytochem 2004; 52: 837-839. [PMID: 15150293 DOI: 10.1369/jhc.4B6248.2004]
31. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998; 95: 29-39. [PMID: 9778245 DOI: 10.1016/S0092-8674(00)81780-8]
32. Goberdhan DC, Wilson C. PTEN: tumour suppressor, multifunctional growth regulator and more. Hum Mol Genet 2003; 12 Spec No 2: R239-R248. [PMID: 12928488 DOI: 10.1093/ hmg/ddg288]
33. Hlobilková A, Knillová J, Bártek J, Lukás J, Kolár Z. The mechanism of action of the tumour suppressor gene PTEN. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2003; 147: 19-25. [PMID: 15034601 DOI: 10.5507/bp.2003.003]
34. Huang J, Kontos CD. PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects. J Biol Chem 2002; 277: 10760-10766. [PMID: 11784722]
35. Tarnawski AS, Szabo I. Apoptosis-programmed cell death and its relevance to gastrointestinal epithelium: survival signal from the matrix. Gastroenterology 2001; 120: 294-299. [PMID: 11208739 DOI: 10.1053/gast.2001.21402]
36. Chiou SK, Jones MK, Tarnawski AS. Survivin - an antiapoptosis protein: its biological roles and implications for cancer and beyond. Med Sci Monit 2003; 9: PI25-PI29. [PMID: 12709681]
37. Chiou SK, Tanigawa T, Akahoshi T, Abdelkarim B, Jones MK, Tarnawski AS. Survivin: a novel target for indomethacin- induced gastric injury. Gastroenterology 2005; 128: 63-73. [PMID: 15633124 DOI: 10.1053/j.gastro.2004.10.008]
38. Liu L, Liu Y, Cui J, Liu H, Liu YB, Qiao WL, Sun H, Yan CD. Oxidative stress induces gastric submucosal arteriolar dysfunction in the elderly. World J Gastroenterol 2013; 19: 9439-9446. [PMID: 24409074 DOI: 10.3748/wjg.v19.i48.9439]
39. Gire V. [Senescence: a telomeric limit to immortality or a cellular response to physiologic stresses?]. Med Sci (Paris) 2005; 21: 491-497. [PMID: 15885198 DOI: 10.1051/medsci/ 2005215491]
40. Penfield JD, Anderson M, Lutzke L, Wang KK. The role of cellular senescence in the gastrointestinal mucosa. Gut Liver 2013; 7: 270-277. [PMID: 23710306 DOI: 10.5009/ gnl.2013.7.3.270]
41. Ahluwalia A, Jones MK, Deng X, Sandor Z, Szabo S, Tarnawski AS. An imbalance between VEGF and endostatin underlies impaired angiogenesis in gastric mucosa of aging rats. Am J Physiol Gastrointest Liver Physiol 2013; 305: G325-G332. [PMID: 23788612 DOI: 10.1152/ajpgi.00127.2013]
42. Ahluwalia A, Jones MK, Tarnawski AS. Key role of endothelial importin-α in VEGF expression and gastric angiogenesis: novel insight into aging gastropathy. Am J Physiol Gastrointest Liver Physiol 2014; 306: G338-G345. [PMID: 24356884 DOI: 10.1152/ajpgi.00382.2013]
43. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M. Suppression of aging in mice by the hormone Klotho. Science 2005; 309: 1829-1833. [PMID: 16123266 DOI: 10.1126/science.1112766]
44. Xiao NM, Zhang YM, Zheng Q, Gu J. Klotho is a serum factor related to human aging. Chin Med J (Engl) 2004; 117: 742-747. [PMID: 15161545]
45. Izbeki F, Asuzu DT, Lorincz A, Bardsley MR, Popko LN, Choi KM, Young DL, Hayashi Y, Linden DR, Kuro-o M, Farrugia G, Ordog T. Loss of Kitlow progenitors, reduced stem cell factor and high oxidative stress underlie gastric dysfunction in progeric mice. J Physiol 2010; 588: 3101-3117. [PMID: 20581042 DOI: 10.1113/jphysiol.2010.191023]
46. Tarnawski AS, Ahluwalia A, Gandhi V, Deng X, Xiong X. Hydrotalcite Protects Aging Gastric Mucosa Against NSAIDAnd Ethanol-Induced Injury by Preserving Endothelial and Progenitor Cells. Underlying Molecular Mechanisms Include Activation of Survivin and VEGF. Gastroenterology 2010; 138 Suppl 1: S-721. [DOI: 10.1016/S0016-5085(10)63316-1]
47. Akbulut KG, Akbulut H, Akgun N, Gonul B. Melatonin decreases apoptosis in gastric mucosa during aging. Aging Clin Exp Res 2012; 24: 15-20. [PMID: 21406955]
48. Akbulut KG, Gonul B, Akbulut H. The role of melatonin on gastric mucosal cell proliferation and telomerase activity in ageing. J Pineal Res 2009; 47: 308-312. [PMID: 19796046 DOI: 10.1111/j.1600-079X.2009.00715.x]
49. Greenwald DA. Aging, the gastrointestinal tract, and risk of acid-related disease. Am J Med 2004; 117 Suppl 5A: 8S-13S. [PMID: 15478847]
50. Tarnawski AS, Caves TC. Aspirin in the XXI century: its major clinical impact, novel mechanisms of action, and new safer formulations. Gastroenterology 2004; 127: 341-343. [PMID: 15236206 DOI: 10.1053/j.gastro.2004.05.037]
51. Wallace JL. Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy. World J Gastroenterol 2013; 19: 1861-1876. [PMID: 23569332 DOI: 10.3748/wjg.v19.i12.1861]
52. Ricci V, Romano M, Boquet P. Molecular cross-talk between Helicobacter pylori and human gastric mucosa. World J Gastroenterol 2011; 17: 1383-1399. [PMID: 21472096 DOI: 10.3748/ wjg.v17.i11.1383]
53. Davidovic M, Svorcan P, Milanovic P, Antovic A, Milosevic D. Specifics of Helicobacter pylori infection/NSAID effects in the elderly. Rom J Gastroenterol 2005; 14: 253-258. [PMID: 16200236]
54. Pilotto A, Malfertheiner P. Review article: an approach to Helicobacter pylori infection in the elderly. Aliment Pharmacol Ther 2002; 16: 683-691. [PMID: 11929385]
55. Pilotto A, Salles N. Helicobacter pylori infection in geriatrics. Helicobacter 2002; 7 Suppl 1: 56-62. [PMID: 12197911]
56. Taira K, Watanabe T, Tanigawa T, Shiba M, Tominaga K, Fujiwara Y, Oshitani N, Higuchi K, Arakawa T. Roles of cyclooxygenase-2 and prostaglandin E receptors in gastric mucosal defense in Helicobacter pylori-infected mice. Inflammopharmacology 2007; 15: 132-138. [PMID: 19847955]
57. Navabi N, Johansson ME, Raghavan S, Lindén SK. Helicobacter pylori infection impairs the mucin production rate and turnover in the murine gastric mucosa. Infect Immun 2013; 81: 829-837. [PMID: 23275091 DOI: 10.1128/IAI.01000-12]
58. Goggin PM, Marrero JM, Spychal RT, Jackson PA, Corbishley CM, Northfield TC. Surface hydrophobicity of gastric mucosa in Helicobacter pylori infection: effect of clearance and eradication. Gastroenterology 1992; 103: 1486-1490. [PMID: 1426866]
59. Marcus EA, Vagin O, Tokhtaeva E, Sachs G, Scott DR. Helicobacter pylori impedes acid-induced tightening of gastric epithelial junctions. Am J Physiol Gastrointest Liver Physiol 2013; 305: G731-G739. [PMID: 23989011 DOI: 10.1152/ajpgi. 00209.2013]
60. Wu J, Xu S, Zhu Y. Helicobacter pylori CagA: a critical destroyer of the gastric epithelial barrier. Dig Dis Sci 2013; 58: 1830-1837. [PMID: 23423500 DOI: 10.1007/s10620-013-2589-x]
61. Fiorentino M, Ding H, Blanchard TG, Czinn SJ, Sztein MB, Fasano A. Helicobacter pylori-induced disruption of monolayer permeability and proinflammatory cytokine secretion in polarized human gastric epithelial cells. Infect Immun 2013; 81: 876-883. [PMID: 23297384 DOI: 10.1128/IAI.01406-12]
62. Valenzuela M, Bravo D, Canales J, Sanhueza C, Díaz N, Almarza O, Toledo H, Quest AF. Helicobacter pylori-induced loss of survivin and gastric cell viability is attributable to secreted bacterial gamma-glutamyl transpeptidase activity. J Infect Dis 2013; 208: 1131-1141. [PMID: 23847060 DOI: 10.1093/infdis/jit286]
63. Ji R, Zuo XL, Yu T, Gu XM, Li Z, Zhou CJ, Li YQ. Mucosal barrier defects in gastric intestinal metaplasia: in vivo evaluation by confocal endomicroscopy. Gastrointest Endosc 2012; 75: 980-987. [PMID: 22325805 DOI: 10.1016/j.gie.2011.12.016]
64. Ahmed A, Stanley AJ. Acute upper gastrointestinal bleeding in the elderly: aetiology, diagnosis and treatment. Drugs Aging 2012; 29: 933-940. [PMID: 23192436 DOI: 10.1007/ s40266-012-0020-5]
65. Tang CL, Ye F, Liu W, Pan XL, Qian J, Zhang GX. Eradication of Helicobacter pylori infection reduces the incidence of peptic ulcer disease in patients using nonsteroidal anti-inflammatory drugs: a meta-analysis. Helicobacter 2012; 17: 286-296. [PMID: 22759329 DOI: 10.1111/j.1523-5378.2012.00942.x]
66. Iijima K, Ara N, Abe Y, Koike T, Iwabuchi T, Shinkai H, Uno K, Endo H, Asano N, Shimosegawa T. Biphasic effects of H. pylori infection on low-dose aspirin-induced gastropathy depending on the gastric acid secretion level. J Gastroenterol 2012; 47: 1290-1297. [PMID: 22549566 DOI: 10.1007/ s00535-012-0598-8]
67. Fukuzawa M, Kawai T, Watanabe M, Tomiyama H, Yamash-ina A, Moriyasu F. Correlation between Helicobacter pylori infection and low-dose aspirin use on damage of the upper gastrointestinal tract. J Gastroenterol Hepatol 2012; 27 Suppl 3: 76-81. [PMID: 22486876 DOI: 10.1111/j.1440-1746.2012.07077. x]
68. Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 2013; 155: 1624-1638. [PMID: 24360282 DOI: 10.1016/j.cell.2013.11.037]
69. Ahluwalia A, Narula J, Jones MK, Deng X, Tarnawski AS. Impaired angiogenesis in aging myocardial microvascular endothelial cells is associated with reduced importin alpha and decreased nuclear transport of HIF1 alpha: mechanistic implications. J Physiol Pharmacol 2010; 61: 133-139. [PMID: 20436213]