Tissular senescence and modifications of oral ecosystem in the elderly: Risk factors for mucosal pathologies

Current Aging Science

Volumn 2, Issue 2, 2009, Pages 109-120

  Bodineau, Agnès ^a,b   Folliguet, Marysette ^a,b   Séguier, Sylvie ^a,b  

^a UNIVERSITÉ PARIS DESCARTES   (France)

^b HÔPITAL LOUIS MOURIER   (France)

Author keywords

Elderly subjects; Oral mucosal pathologies; Risk factors

Indexed keywords

AGING; ALZHEIMER DISEASE; ARTICLE; ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; CANDIDIASIS; CELL STRUCTURE; DIABETES MELLITUS; HUMAN; KERATINIZATION; MOUTH CANCER; MOUTH HYGIENE; MOUTH MUCOSA; MOUTH ULCER; NONHUMAN; OROPHARYNX CANCER; PARKINSON DISEASE; PERIODONTAL DISEASE; PRIORITY JOURNAL; RISK FACTOR; SALIVARY GLAND; SALIVARY GLAND FUNCTION; SENESCENCE; THYMUS; TOOTH PLAQUE; XEROSTOMIA; AGE; CELL AGING; IMMUNOLOGY; METABOLISM; MOUTH DISEASE; MUCOSAL IMMUNITY; PATHOLOGY; REVIEW; SALIVA;

AGE FACTORS; AGING; CELL AGING; HUMANS; IMMUNITY, MUCOSAL; MOUTH DISEASES; MOUTH MUCOSA; RISK FACTORS; SALIVA; SALIVARY GLANDS;

EID: 77449092005     PISSN: 18746098     EISSN: 18746128     Source Type: Journal    
DOI: 10.2174/1874609810902020109     Document Type: Article

References (161)

1. Dalziel KL. Aspects of cutaneous ageing. Clin Exp Dermatol 1991;16: 315-23.
2. Nagler RM. Salivary glands and the aging process: mechanisticaspects, health-status and medicinal-efficacy monitoring. Biogeron-tology 2004; 5: 223-33.
3. Chakravarti B, Abraham GN. Aging and T-cell-mediatedimmunity. Mech Ageing Dev 1999; 108: 183-206.
4. Uyemura K, Castle SC, Makinodan T. The frail elderly: role ofdendritic cells in the susceptibility of infection. Mech Ageing Dev 2002; 123: 955-62.
5. Castle SC. Clinical relevance of age-related immune dysfunction.Clin Infect Dis 2000; 31: 578-85.
6. Kydd W, Daly C. The biologic and mechanical effects of stress onoral mucosa. J Prosthet Dent 1982; 47: 317-29.
7. Bottomly W. Physiology of the oral mucosa. Otolaryngol ClinNorth Am 1979; 12: 15-20.
8. Scott J, Valentine J, Hill C, Balasooriya B. A quantitativehistologic analysis of the effects of age and sex on human lingualepithelium. J Biol Buccale 1983; 11: 303-15.
9. Löe H, Karring T. The three dimensional morphology of theepithelium connective tissue interface of the gingiva as related toage and sex. Scand J Dent Res 1971; 79: 315-326.
10. Wolff A, Ship J, Tylenda C, Fox P, Baum B. Oral mucosalappearance is unchanged in healthy, different-age persons. OralSurg Oral Med Oral Pathol 1991; 71: 569-72.
11. Scahill RI, Fost C, Jenkins R, Whitwell JL, Rossor MN, Fox NC. Alongitudinal study of brain volumes changes in normal aging usingserial registered magnetic resonance imaging. Arch Neurol 2003;60(7): 989-94.
12. Sakai T, Kiyoshima T, Kobayashi I, Moroi R, Ibuki T, Nagadome M, et al. Age-dependent changes in the distribution of BrdU- andTUNEL-positive cells in the murine gingival tissue. J Periodontol 1999; 70(9): 973-81.
13. Enoki N, Kiyoshima T, Sakai T, Kobayashi I, Takahashi K, Terada Y, et al. Age-dependent changes in cell proliferation and cell deathin the periodontal tissue and the submandibular gland in mice: acomparison with other tissues and organs. J Mol Histol 2007;38(4): 321-32.
14. Levy MZ, Allsopp BA, Futcher CW, Greider CB, Harley TR.Telomere end-replication problem and cell aging. J Mol Biol 1992;225: 951-60.
15. Hayflick L, Moohead PS. The serial cultivation of human diploidcell strains. Exp Cell Res 1961; 25: 585-621.
16. Harley CB, Futcher AB, Greider CB. Telomeres shorten duringaging in human fibroblasts. Nature 1990; 345: 458-60.
17. Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC. Telomere reduction in human colorectal carcinomaand with ageing. Nature 1990; 346: 866-68.
18. Allsopp RC, Chang E, Kashefi-Aazam M, Rogaev EI, Piatyszek MA, Shay JW, et al. Telomere shortening is associated with celldivision in vitro and in vivo. Exp Cell Res 1995; 220(194): 200.
19. Vaziri H, Benchimol S. From telomere loss to p53 induction andactivation of a DNA-damage pathway at senescence: the telomereloss/DNA damage model of cell aging. Exp Gerontol 1996; 31:295-301.
20. Butler MG, Tilburt J, DeVries A, Muralidhar B, Aue G, Hedges L, et al. Comparison of chromosome telomere integrity in multipletissues from subjects at different ages. Cancer Genet Cytogenet 1998; 105: 138-44.
21. Kinouchi Y, Hiwatashi N, Chida M, Nagashima F, Takagi S, Maekawa H, et al. Telomere shortening in the colonic mucosa ofpatients with ulcerative colitis. J Gastroenterol 1998; 33: 343-48.
22. Kang MK, Swee J, Kim RH, Baluda MA, Park N. The telomericlenght and heterogeneity decrease with age in normal human oralkeratinocytes. Meh Ageing Dev 2002; 123: 585-92.
23. Grossman N, Slovik Y, Bodner L. Effect of donor age oncultivation of human oral mucosal keratinocytes. Arch GerontolGeriatr 2004; 38(2):114-22.
24. Thomas P, Harvey S, Gruner T, Fenech M. The buccal cytome andmicronucleus frequency is substancially altered in Down'ssyndrome and normal ageing compared to young healthy controls.Mutat Res 2008; 638(1-2): 37-47.
25. Junqueira VB. Aging and oxidative stress. Mol Aspects Med 2004;25: 5-16.
26. Golden TR, Hinerfeld DA, Melov S. Oxidative stress and aging:beyond correlation. Aging Cell 2002; 1: 117-23.
27. Sohal RS, Weindruch R. Oxidative stress, caloric restriction, andaging. Science 1996; 273: 59-63.
28. Kang MK, Kim RH, Shin K, Zhong W, Faull KF, Park N.Senescence-associated decline in the intranuclear accumulation ofhOGG1-a and impaired 8-oxo-dG repair activity in senescingnormal human oral keratinocytes in vivo. Exp Cell Res 2005; 310:186-95.
29. Shckorbatov Y, Shakhbazov V, Bogoslavsky A, Rudenko A. Onage-related changes of cell membrane permeability in humanbuccal epithelium cells. Mech Ageing Dev 1995; 83: 87-90.
30. Harman D. Free radical theory of aging. Mutat Res 1992; 275: 257-66.
31. Anuradha A, Sivapathasundharam B. Image analysis of normalexfoliated gingival cells. Indian J Med Res 2007; 18(2): 63-6.
32. Avery N, Bailey A. The effects of the Maillard reaction on thephysical properties and interactions of collagen. Pathol Biol 2006;54(7): 387-95.
33. Monnier V, Glomb M, Elgawish A, Sell D. The mechanism ofcollagen cross-linking in diabetes. A puzzle nearing resolution.Diabetes 1996; 45 (Suppl 3): s67-s72.
34. Gogly B, Godeau G, Gilbert S, Legrand JM, Kut C, Pellat B et al.Morphometric analysis of collagen and elastic fibers in normal skinand gingiva in relation to age. Clin Oral Invest 1997; 1: 147-52.
35. Johnson MD, Page RC, Narayanan A, Pieters HP. Effects of donorage on protein and collagen synthesis in vitro by human diploidfibroblasts. Lab Invest 1986; 55: 490-96.
36. Engeland C, Bosch J, Cacioppo J, Marucha P. Mucosal woundhealing. Arch Surg 2006; 141: 1193-97.
37. Scott J. Qualitative and quantitative observations on the histologyof human labial salivary glands obtained post mortem. J BiolBuccale 1980; 8: 187-200.
38. Drummond JR, Chisholm DM. A qualitative and quantitative studyof the aging human labial salivary glands. Arch Oral Biol 1984; 29:151-55.
39. Syrjanen S. Age-related changes in structure of labial minorsalivary glands. Age Aging 1984; 13: 156-65.
40. Navazesh M, Mulligan RS, Kipnis V, Denny PA, Denny PC.Comparison of whole saliva flow rates and mucin concentrations inhealthy caucasian young and aged adults. J Dent Res 1992; 71(6):1275-78.
41. Ben-Aryeh H, Miron D, Szargel R, Gutman D. Whole-salivasecretion ates in old and young healthy subjects. J Dent Res 1984;63: 1147-48.
42. Eliasson L, Carlen A, Laine M, Bifkhed D. Minor gland and wholesaliva in postmenopausal women using a low potncy oestrogen.Arch Oral Biol 2003; 48(7): 511-17.
43. Ben-Aryeh H, Shalev A, Szargel R, Laor A, Laufer D, Gutman D.The salivary flow rate and composition of whole and parotidresting and stimulated saliva in young and old healthy subjects.Biochem Med Metab Biol 1986; 36(2): 260-65.
44. Percival RS, Challacombe SJ, March PD. Flow rates of restingwhole and stimulated parotid saliva in relation to age and gender. JDent Res 1994; 73: 1416-20.
45. Wu AJ, Atkinson J, Fox PC, Baum BJ, Ship J. Cross-sectional andlongitudinal analyses of stimulated parotid salivary constituents inhealth, different-aged subjects. J Gerodontol 1993; 48: M219-M224.
46. Tylenda C, Ship J, Fox PC, Baum BJ. Evaluation of submandibularsalivary flow rate in different age groups. J Dent Res 1998; 67:1225-28.
47. Pedersen W, Schubers M, Izutsu K, Mersai T, Truelove E. Age-dependent decreases in human submandibular gland flow rates asmeasured under resting and post-stimulation conditions. J Dent Res 1985; 64: 922-25.
48. Wu AJ, Baum BJ, Ship J. Extended stimulated parotid andsubmandibular secretion in a healthy young and old population. JGerodontol 1995; 50(A): 45-48.
49. Smith DJ, Joshipura K, Kent R, Taubman MA. Effect of age inimmunoglobulin content and volume of human labial gland saliva.J Dent Res 1992; 71: 1891-94.
50. Shern RJ, Fox PC, Li SH. Influence of age on the secretory rates ofthe human minor salivary glands and whole saliva. Arch Oral Biol 1993; 38: 755-61.
51. Ghezzi EM, Ship JA. Aging and secretory reserve capacity ofmajor salivary glands. J Dent Res 2003; 82(10): 844-48.
52. Miletic ID, Schiffman SS, Miletic VD, Sattely-Miller EA. SalivaryIgA secretion rate in young and elderly persons. Physiol Behav 1996; 60(1): 243-48.
53. Tanida T, Ueta E, Tobiume A, Hamada R, Rao F, Osaki T. Influence of aging on candidal growth and adhesion regulatoryagents in saliva. J Oral Pathol Med 2001; 30(6): 328-35.
54. Akimoto T, Kumai Y, Akama T, Hayashi E, Murakami H, Soma R et al. Effects of 12 months of exercise training on salivary secretoryIgA levels in elderly subjects. Br J SportsMed 2003; 37(1): 76-79.
55. Shugars DC, Watkins CA, Cowen HJ. Salivary concentrations ofsecretory leucocyte protease inhibitor, and antimicrobial prpotein,is decreased with advanced age. Gerontology 2001; 47(5): 246-53.
56. Denny PC, Denny PA, Klauser DK, Hong SH, Navazesh M, Tabak L A. Age-related changes in mucins from humans whole saliva. JDent Res 1991; 70: 1320-27.
57. Westermark A, Pyykko I, Magnusson M, Ishizaki H, Jantti P, VanSetten G. Basic fibroblast growth factor in human salva decreaseswith aging. Laryngoscope 2002; 112(5): 887-89.
58. Almstahl A, Wikstorm M. Electrolytes in stimulated whole salivain individuals with hyposalivation of different origins. Arch OralBiol 2003; 48(5): 337-44.
59. Hirokawa K, Utsuyama M, Kasai M, Kurashima C, Ishijima S, Zeng YX. Understanding the mechanism of the age-change ofthymic function to promote T cell differentiation. Immunol Lett 1994; 40: 269-77.
60. Globerson A. Thymocyte progenitors in aging. Immunol Lett 1994;40: 219-24.
61. Utsuyama M, Hirokawa K, Kurashima C, Fukayama M, Inamatsu T, Suzuki K, et al. Differential age-change in the numbers ofCD4+CD45RA+ and CD4+CD29+ T cell subsets in humanperipheral blood. Mech Ageing Dev 1992; 63: 57-68.
62. Jackola D, Ruger JK, Miller RA. Age-associated changes in humanT cell phenotype and function. Aging 1994; 6: 25-34.
63. Kurashima C, Utsuyama M, Kasai M, Ishijima SA, Konno A, Hirokawa K. The role of thymus in the aging of Th cellsubpopulations and age-associated alteration of cytokineproduction by these cells. Int Immunol 1995; 7: 97-104.
64. Song L, Kim Y, Chopra RK, Proust J, Nagel J, Nordin A, et al. Age-related effects in T cell activation and proliferation. ExpGerontol 1993; 28(4-5): 313-21.
65. Thoman ML, Weigle WO. Lymphokines and aging: interleukin-2production and activity in aged animals. J Immunol 1981; 127:2102-06.
66. Thoman ML, Weigle WO. Partial restoration of ConA-inducedproliferation, IL-receptor expression, and IL-2 synthesis in agedmurine lymphocytes by phorbol myristate acetate and ionomycin.Cell Immunol 1988; 114(1): 1-11.
67. Nagel J, Chopra RK, Chrest FJ, McCoy MT, Schneider EL, Holbrook NJ, et al. Decreased proliferation, interleukin 2 synthesis,and interleukin 2 receptor expression are accompagnied bydecreased mRNA expression in phytohemagglutinin-stimulatedcells from elderly donors. J Clin Invest 1988; 81: 1096-1102.
68. Fong TC, Makinodan T. In situ hybridization analysis of the age-associated decline in IL-2 mRNA expressing murine T cells. CellImmunol 1989; 118: 199-207.
69. Jackola D, Hallgren H. Diminished cell-cell binding bylymphocytes from healthy, elderly humans. Evidence of alteredactivation of LFA-1 function with age. J Gerontol A Biol Sci MedSci 1995; 50(6): B368-B77.
70. Gupta S, Su H, Bi R, Agrawal S, Gollapudi S. Life and death oflymphocytes: a role in immunesenescence. Immun Ageing 2005; 2:12.
71. Goronzy JJ, Weyand CM. T-cell senescence and contraction of T-cell repertoire diversity - catalysts of autoimmunity and chronicinflammation. Arthritis Res Ther 2003; 5: 225-34.
72. Moosig F, Csernok E, Wang G, Gross WL. Costimulatorymolecules in Wegener's granulomatosis (WG): lack of expressionof CD28 and preferential up-regulation of its ligands B7-1 (CD80)and B7-2 (CD86) on T cells. Clin Exp Immunol 1998; 114: 113-18.
73. Markovic-Plese S, Cortese I, Wandinger KP, McFarland HF,Martin R. CD4+CD28- costimulation-independent T cells inmultiple sclerosis. J Clin Invest 2001; 108: 1185-94.
74. Schmidt D, Martens PB, Weyand CM, Goronzy JJ. The repertoireof CD4+CD28- T cells in reuhmatoid arthritis. Mol Med 1996; 2:608-18.
75. Liuzzo G, Kopecky SL, Frye RL, O'Fallon WM, Maseri A, Goronzy JJ, et al. Perturbation of the T-cell repertoire in patientswith unstable angina. Circulation 1999; 100: 2135-39.
76. Liuzzo G, Goronzy JJ, Yang H, Kopecky SL, Holmes DR, Frye RL, et al. Monoclonal T-cell proliferation and plaque instability inacute coronary syndromes. Circulation 2000; 101: 2883-88.
77. Spaulding C, Guo W, Effros R. Resistance to apoptosis in humanCD8+ T cells that reach replicative senescence after multiplerounds of antigen-specific proliferation. Exp Gerontol 1999; 34(5):633-44.
78. Caruso C, Candore G, Cigna D, DiLorenzo G, Sireci G, Dieli F.Cytokine production pathway in the elderly. Immunol Res 1996;15: 84-90.
79. Boren E, Gershwin E. Inflammaging: autoimmunity and theimmune-risk phenotype. Autoimmun Rev 2004; 3: 401-06.
80. Ghia P, Melchers F, Rolink AG. Age-dependent changes in Blymphocyte development in man and mouse. Exp Gerontol 2000;35: 159-65.
81. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E. Inflamm-aging. An evolutionary perspective onimmunosenescence. Ann NY Acad Sci 2000; 908: 244-54.
82. Lesourd BM, Mazari L, Ferry M. The role of nutrition in immunityin the aged. Nutr Rev 1998; 56: S113-S125.
83. Plowden J, Renshaw-Hoelscher M, Engleman C, Katz J, Sambhara S. Innate immunity in aging: impact on macrophage function.Aging Cell 2004; 3(4): 161-67.
84. Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J, Sambhara S. Cutting edge: impaired toll-like receptor expressionand function in aging. J Immunol 2002; 169: 4697-4701.
85. Fietta A, Merlini C, De Bernardi PM, Gandola L, Piccioni PD, Grassi C. Non specific immunity in aged healthy subjects and inpatients with chronic bronchitis. Aging 1993; 5: 357-61.
86. Ashcroft GS, Horan MA, Ferguson MW. Aging alters theinflammatory and endothelial cell adhesion molecule profilesduring human cutaneous wound healing. Lab Invest 1998; 78: 47-58.
87. Ershler WB, Sun WH, Binkley N, Gravenstein S, Volk MJ, Kamoske G, et al. Interleukin-6 and aging: blood levels andmononuclear cell production increase with advancing age and invitro production is modifiable by dietary restriction. LymphokineCytokine Res 1993; 12: 225-30.
88. Clark JA, Peterson TC. Cytokine production and aging:overproduction of IL-8 in elderly males in response tolipopolysaccharide. Mech Ageing Dev 1994; 77: 127-39.
89. OMahony L, Holland J, Jackson J, Feighery C, Hennessy TP, Mealy K. Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production. Clin ExpImmunol 1998; 113: 213-19.
90. Gon Y, Hashimoto S, Hayashi S, Koura T, Matsumoto K, Horie T. Lower serum concentrations of cytokines in elderly patients withpneumonia and the impaired production of cytokines by peripheralblood monocytes in the elderly. Clin Exp Immunol 1996; 106: 120-26.
91. Beharka AA, Meydani M, Wu D, Leka LS, Meydani A, Meydani SN. Interleukin-6 production does not increase with age. J Gerontol 2001; 56: B81-B88.
92. Ahluwalia N, Mastro AM, Ball R, Miles MP, Rajendra R, Handte G. Cytokine production by stimulated mononuclear cells did notchange with aging in apparently healthy, well-nourished women. Mech Ageing Dev 2001; 122: 1269-79.
93. Steinman RM, Inaba K, Turley S, Pierre P, Mellman I. Antigencapture, processing, and presentation by dendritic cells: recent cellbiological studies. Hum Immunol 1999; 60: 562-67.
94. Xu X, Beckman I, Dimopoulos K, Ahern M, Bradley J. Age-relatedchanges in the expression of T cell activation antigens followingphytohaemagglutinin stimulation. Exp Clin Immunogenet 1992; 9:203-11.
95. Steger MM, Maczek C, Grubeck-Loebenstein B. Morphologicallyand functionally intact dendritic cells can be derived from theperipheral blood of aged individuals. Clin Exp Immunol 1996; 105:544-50.
96. Steger MM, Maczek C, Grubeck-Loebenstein B. Peripheral blooddendritic cells reinduce proliferation in in vitro aged T cellpopulations. Mech Ageing Dev 1997; 93: 125-30.
97. Rich EA, Mincek MA, Armitage KB, Duffy EG, Owen DC, Fayen JK, et al. Accessory function and properties of monocytes fromhealthy elderly humans for T lymphocyte responses to mitogen andantigen. Gerontology 1993; 39: 93-108.
98. Castle SC, Uyemura K, Crawford W, Wong W, Makinodan T. Antigen presenting cell function is enhanced in healthy elderly. Mech Ageing Dev 1999; 107: 137-45.
99. Donnini A, Argentati K, Mancini R, Smorlesi A, Bartozzi B, Bernardini G, et al. Phenotype, antigen-presenting capacity, andmigration of antigen-presenting cells in young and old age. ExpGerontol 2002; 37: 1097-1112.
100. Wick G, Grubeck-Loebenstein B. The aging immune system:primary and secondary alterations of immune reactivity in theelderly. Exp Gerontol 1997; 32: 401-13.
101. Gilchrst BA, Murphy GF, Soter NA. Effect of chronologic agingand ultraviolet irradiation on Langerhans cells in human epidermis.J Invest Dermatol 1982; 79: 85-88.
102. Thiers BH, Maize JC, Spicer SS, Cantor AB. The effect of agingand chronic sun exposure on human Langerhans cell populations. JInvest Dermatol 1984; 82: 223-26.
103. Grewe M. Chronological ageing and photoageing of dendritic cells.Clin Exp Dermatol 2001; 26: 608-12.
104. Zavala W, Cavicchia JC, Sacerdote F. Age variations in numberand structure of human gingival Langerhans cells. Biocell 1997;21(3): 205-10.
105. Castle SC, Uyemura K, Crawford W, Wong W, Klauster-meyer WM, Makinodan T. Age-related impaired proliferation ofperipheral blood mononuclear cells is associated with an increasein both IL-10 and IL-12. Exp Gerontol 1999; 34: 243-52.
106. Fagiola U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, et al. Increased cytokine production in mononuclear cellsof healthy elderly people. Eur J Immunol 1993; 23: 2375-78.
107. Cohen HJ, Pieper CF, Harris T, Rao KM, Currie MS. Theassociation of plasma IL-6 levels with functional disability incommunity-dwelling elderly. J Gerontol 1997; 52: M201-M08.
108. Mealey BL, Moritz AJ. Hormonal influences: effects of diabetesmellitus and endogenous female sex steroid hormones on theperiodontium. Periodontol 2000 2003; 32: 59-81.
109. Willershauschen-Zonchen B, Lemmen C, Hamm G. Influence ofhigh glucose concentrations on glycosaminoglycan and collagensynthesis in cultured human gingival fibroblasts. J Clin Periodontol 1991; 18: 190-95.
110. Seppala B, Seppala M, Ainamo J. Morphometric analysis ofcellular and vascular changes in gingival connective tissue in long-term insulin-dependent diabetes. J Periodontol 1997; 68: 1237-45.
111. Oliver RC, Tervonen T, Flynn DG, Keenan KM. Enzyme activityin crevicular fluid in relation to metabolic control of diabetes andother periodontal risk factors. J Periodontol 1993; 64: 358-62.
112. Offenbacher S. World Workshop in Clinical Periodontics.Periodontal diseases: pathogenesis. Ann Periodontol 1996; 1: 821-78.
113. Salvi GE, Collins JG, Yalda B, Arnold RR, Lang NP, Offenbacher S. Monocytic TNF-alpha secretion patterns in IDdiabetes mellituspatients with periodontal diseases. J Clin Periodontol 1997; 24: 8-16.
114. Salvi GE, Yalda B, Collins JG, Jones BH, Smith FW, Arnold RR. et al. Inflammatory mediator response as a potential risk marker forperiodontal diseases in insulin-dependent diabetes mellitus patients.J Periodontol 1997; 68: 127-35.
115. Lesourd BM, Meaume S. Cell mediated immunity changes inageing, relative importance of cell subpopulation switches and ofnutritional factors. Immunol Lett 1994; 40: 235-42.
116. Mazari L, Lesourd BM. Nutritional influences on immune responsein healthy aged persons. Mech Ageing Dev 1998; 140(1): 25-40.
117. Mysliwska J, Bryl E, Foerster J, Mysliwski A. Increase ofinterleukin 6 and decrease of interleukin 2 production during theaging process are influenced by the health status. Mech AgeingDev 1998; 100: 313-28.
118. Lesourd BM. Nutrition and immunity in the elderly: modificationof immune responses with nutritional treatments. Am J Clin Nutr 1997; 66: 478S-484S.
119. Vissink A, Spijkervet FK, Van Nieuw Amreongen A. Aging andsaliva: a review of the literature. Spec Care Dentist 1996; 16: 95-103.
120. Pajukoski H, Meurman JH, Halonen P, Sulkava R. Prevalence ofsubjective dry mouth and burning mouth in hospitalized elderlypatients and outpatients in relation to saliva, medication andsystemic diseases. Oral Surg Oral Med Oral Pathol 2001; 92(6):641-49.
121. Ship J, Pillemer SR, Baum BJ. Xerostomia and the geriatric patient.J Am Geriatr Soc 2002; 50: 535-43.
122. Sreebny LM, Banoczy J, Baum JL. Saliva: its role in health anddisease. Int Dental J 1992; 42: 291-304.
123. Nicol R, Sweeney MP, McHugh S, Bagg J. Effectiveness of healthcare worker training on the oral health of elderly residents ofnursing homes. Community Dent Oral Epidemiol 2002; 33: 115-24.
124. Dormenval V, Budtz-Jorgensen E, Mojon P, Bruyère A, Rapin CH. Associations between malnutrition, poor general health and oraldryness in hospitalized elderly patients. Age Ageing 1998; 27: 123-28.
125. Navazesh M, Brightman VJ, Pogoda JM. Relationship of medicalstatus, medications and salivary flow rate in adults of differentages. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996; 81:172-76.
126. Streckfus CF, Baur U, Brown LJ, Bacal C, Metter J, Nick T. Effects of estrogen status and aging on salivary flow rates inhealthy caucasian women. Gerontology 1998; 44: 32-39.
127. Rhodus NL, Brown J. The association of xerostomia andinadequate intake in older adults. J Am Diet Assoc 1990; 90(12):1688-692.
128. Ghezzi EM, Ship JA. Systemic diseases and their treatments in theelderly: impact on oral health. J Public Health Dent 2000; 60: 289-96.
129. Ship JA, DeCarli C, Friedland RP, Baum BJ. Diminishedsubmandibular salivary flow in dementia of the Alzheimer type. JGerontol 1990; 45(2): M61-M66.
130. Sreebny LM, Yu A, Green A, Valdini A. Xerostomia in diabetesmellitus. Diabetes Care 1992; 15: 900-04.
131. Collin HL, Niskanen L, Uusitupa M, Toyry J, Collin P, Koivisto AM, et al. Oral symptoms and signs in elderly patients with Type 2diabetes mellitus. A focus on diabetic neuropathy. Oral Surg OralMed Oral Pathol Oral Radiol Endod 2000; 90: 299-305.
132. Meurman JH, Collin HL, Niskanen L, Toyry J, Alakuijala P, Keinanen S, et al. Saliva in non-insulin-dependent diabetic patientsand control subjects. The role of the autonomic nervous system.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 86: 69-76.
133. Avlund K, Holm-Pedersen P, Schroll M. Functional ability and oralhealth among older people: A longitudinal study from age 75 to 80.J Am Geriatr Soc 2001; 49: 954-962.
134. Berkey DB, Call RL, Gordon SK, Berkey KG. Barriers influencingdental care in longterm care facilities. Gerodontics 1998; 4: 315-19.
135. Frenkel HF. Behind the screens: care staff observations on deliveryof oral health care in nursing homes. J Gerodontol 1999; 16: 76-80.
136. Munro CL, Grap MJ, Jablonski R, Boyle A. Oral healthmeasurement in nursing research: State of the science. Biol ResNurs 2006; 8(1): 35-42.
137. Scannapieco FA, Stewart EM, Mylotte JM. Colonization of dentalplaque by respiratory pathogens in medical intensive care patients.Crit Care Med 1992; 20: 740-45.
138. Mylotte JM, Ksiazek S, Bentley DW. Rational approach to theantibiotic treatment of pneumonia in the elderly. Drugs Aging 1994; 4: 21-33.
139. Jobbins J, Bagg J, Parsons K, Finlay I, Addy M, Newcombe RG.Oral carriage of yeasts, coli-forms and staphylococci in patientswith advanced malignant disease. J Oral Pathol Med 1992; 21: 305-08.
140. Gibson G, Barrett E. The role of salivary function on oropharyn-geal colonization. Spec Care Dentist 1992; 12: 153-56.
141. Millns B, Gosney MA, Martin MV, McNally L, Doherty U, Field EA. The oral flora of stroke patients. J Dent Res 1997; 76: 1071.
142. Ohman SC, Osterberg T, Dahlen G, Landahl S. The prevalence ofstaphylococcus aureus, enterobacteriaceae species and candidaspecies and their relation to oral mucosal lesions in a group of 79-year-olds in Göteborg. Acta Odontol Scand 1995; 53: 49-54.
143. Österberg T, Ohman A, Heyden G. The condition of the oralmucosa at age 70: a population study. Gerodontology 1985; 4: 71-5.
144. Hand J, Whitehill J. The prevalence of oral mucosal lesions in anelderly population. J Am Dent Assoc 1986; 112: 73-6.
145. Lockhart S, Joly S, Vargas K, Swails-Wenger J, Enger L, Soll D. Natural defenses against Candida colonization breakdown in theoral cavities of the elderly. J Dent Res 1999; 78: 857-68.
146. Qi Q, Hu T, Zhou XD. Frequency, species and molecularcharacterization of oral candida in hosts of different age in China.Oral Pathol Med 2005; 34: 352-56.
147. LI L, Redding S, Dongari-Bagtzoglou A. Candida glabrata, anemerging oral opportunistic pathogen. J Dent Res 2007; 86(3): 204-15.
148. Wilkieson C, Samaranayake L, MacFarlane T, Lamey P,MacKenzie D. Oral candidosis in the elderly in long term hospitalcare. Oral Pathol Med 1991; 20: 13-16.
149. Friedlander AH. The physiology, medical management and oralimplications of menopause. J Am Dent Assoc 2002; 133: 73-81.
150. Fransson C, Mooney J, Kinane DF, Berglundh T. Differences in theinflammatory response in young and old human subjects during thecourse of experimental gingivitis. J Clin Periodontol 1999; 26: 453-60.
151. Bodineau A, Coulomb B, Folliguet M, Igondjo-Tchen S, Godeau G, Brousse N, et al. Do Langerhans cells behave similarly inelderly and younger patients with chronic periodontitis? Arch OralBiol 2007; 52: 189-94.
152. Bodineau A, Coulomb B, Tedesco AC, Seguier S. Increase ofgingival matured dendritic cells number in elderly patients withchronic periodontitis. Arch Oral Biol 2009; 54(1): 12-16.
153. Abiko Y, Shimizu N, Yamaguchi M, Suzuki H, Takiguchi H. Effect of aging on functional changes of periodontal tissue cells.Ann Periodontol 1998; 3(1): 350-69.
154. Okamura H, Yamaguchi M, Abiko Y. Enhancement of lipopoly-saccharide-stimulated PGE2 and IL-1b production in gingivalfibroblast cells from old rats. Exp Gerontol 1999; 34: 379-92.
155. Mochizuki K, Yamaguchi M, Abiko Y. Enhancement of LPS-stimulated plasmonigen activator production in aged gingivalfibroblasts. J Periodontal Res 1999; 34(5): 251-60.
156. Berglundh T, Donati M. Aspects of the adaptative host response inperiodontitis. J Clin Periodontol 2005; 32(Suppl 6): 87-107.
157. Berglundh T, Donati M, Zitzmann N. B cells in periodontitis -friends or enemies? Periodontol 2000; 45: 51-66.
158. Yancik R. Population aging and cancer: a cross-national concern.Cancer J 2005; 11(6): 437-41.
159. Jemal A, Siegel R, Ward E. Cancer statistics, 2006. Cancer J Clin 2006; 56: 106-130.
160. Wynford-Thomas D. Cellular senescence and cancer. J Pathol 1999; 187: 100-111.
161. Coates P. Markers of senescence? J Pathol 2002; 196: 371-73.