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Current Oral Health Reports

, Volume 5, Issue 4, pp 229–241 | Cite as

Age and Periodontal Health—Immunological View

  • Jeffrey L. EbersoleEmail author
  • D. A. DawsonIII
  • P. Emecen Huja
  • S. Pandruvada
  • A. Basu
  • L. Nguyen
  • Y. Zhang
  • O. A. Gonzalez
Epidemiology (M Laine, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Epidemiology

Abstract

Purpose of the Review

Aging clearly impacts a wide array of systems, in particular the breadth of the immune system leading to immunosenescence, altered immunoactivation, and coincident inflammaging processes. The net result of these changes leads to increased susceptibility to infections, increased neoplastic occurrences, and elevated frequency of autoimmune diseases with aging. However, as the bacteria in the oral microbiome that contribute to the chronic infection of periodontitis is acquired earlier in life, the characteristics of the innate and adaptive immune systems to regulate these members of the autochthonous microbiota across the lifespan remains ill-defined.

Recent Findings

Clear data demonstrate that both cells and molecules of the innate and adaptive immune response are adversely impacted by aging, including in the oral cavity, yielding a reasonable tenet that the increased periodontitis noted in aging populations is reflective of the age-associated immune dysregulation. Additionally, this facet of host-microbe interactions and disease needs to accommodate the population variation in disease onset and progression, which may also reflect an accumulation of environmental stressors and/or decreased protective nutrients that could function at the gene level (i.e., epigenetic) or translational level for production and secretion of immune system molecules.

Summary

Finally, the majority of studies of aging and periodontitis have emphasized the increased prevalence/severity of disease with aging, all based upon chronological age. However, evolving areas of study focusing on “biological aging” to help account for population variation in disease expression may suggest that chronic periodontitis represents a co-morbidity that contributes to “gerovulnerability” within the population.

Keywords

Aging Periodontitis Immunology Environment Nutrition 

Notes

Acknowledgements

We want to thank M.J. Steffen, J. Stevens, and Dr. S.S. Kirakodu for expert technical support in developing biologic marker data for these types of studies. We also acknowledge the substantial contribution of the clinical personnel in the Delta Dental of Kentucky Clinical Research Center including L. Johnston, D. Dawson, D. Fogle, and H. Gallivan.

Funding Information

This work was supported by USPHS grants RR020145, DE017793, GM110788, GM103538, and TR000117 from the National Institutes of Health and funding from the Center for Oral Health Research in the UK College of Dentistry, as well as the Office of Research Infrastructure Programs (ORIP) of the National Institutes of Health (NIH) through Grant Number 5P40OD012217 to the Caribbean Primate Research Center. Infrastructure support was also provided, in part, by grants from the National Center for Research Resources G12RR003051 (National Center for Research Resources) and G12MD007600 (National Institute on Minority Health and Health Disparities) from the National Institutes of Health.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

40496_2018_202_MOESM1_ESM.jpg (103 kb)
Supplemental Figure 1 Schematic of identified immunosenescence effects on cells of the innate and adaptive immune system. (JPG 103 kb)
40496_2018_202_MOESM2_ESM.jpg (68 kb)
Supplemental Figure 2 Transcriptomic profiles of gingival tissue genes associated with a range of pathways regulating the host responses to oral microbial challenge. The findings document the significant impact of aging on the biologic response features of these oral tissues, with certain pathways being elevated in aging (red) and others being decreased (blue) during aging processes. (JPG 68 kb)
40496_2018_202_MOESM3_ESM.jpg (68 kb)
Supplemental Figure 3 Schematic describing the contribution of cells and biomolecules to innate and adaptive immunity with interactions that link these host response systems to afford protection from infection and noxious challenge. (JPG 67 kb)

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    O’Connor JE, Herrera G, Martínez-Romero A, de Oyanguren FS, Díaz L, Gomes A, et al. Systems biology and immune aging. Immunol Lett. 2014;162(1 Pt B):334–45.PubMedGoogle Scholar
  2. 2.
    Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4–9.PubMedGoogle Scholar
  3. 3.
    Castelo-Branco C, Soveral I. The immune system and aging: a review. Gynecol Endocrinol. 2014;30(1):16–22.PubMedGoogle Scholar
  4. 4.
    Taverna G, et al. Senescent remodeling of the innate and adaptive immune system in the elderly men with prostate cancer. Curr Gerontol Geriatr Res. 2014;2014:478126.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Mabbott NA, Kobayashi A, Sehgal A, Bradford BM, Pattison M, Donaldson DS. Aging and the mucosal immune system in the intestine. Biogerontology. 2015;16(2):133–45.PubMedGoogle Scholar
  6. 6.
    Ebersole JL, Graves CL, Gonzalez OA, Dawson D III, Morford LA, Huja PE, et al. Aging, inflammation, immunity and periodontal disease. Periodontol. 2016;72(1):54–75.Google Scholar
  7. 7.
    Shen-Orr SS, Furman D. Variability in the immune system: of vaccine responses and immune states. Curr Opin Immunol. 2013;25(4):542–7.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Eke PI, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009-2012. J Periodontol. 2015:1–18.Google Scholar
  9. 9.
    Baelum V, Lopez R. Periodontal disease epidemiology—learned and unlearned? Periodontol. 2013;62(1):37–58.Google Scholar
  10. 10.
    Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ. Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res. 2012;91(10):914–20.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Eke PI, Zhang X, Lu H, Wei L, Thornton-Evans G, Greenlund KJ, et al. Predicting periodontitis at state and local levels in the United States. J Dent Res. 2016;95(5):515–22.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Saraiva L, Rebeis ES, Martins ES, Sekiguchi RT, Ando-Suguimoto ES, Mafra CES, et al. IgG sera levels against a subset of periodontopathogens and severity of disease in aggressive periodontitis patients: a cross-sectional study of selected pocket sites. J Clin Periodontol. 2014;41(10):943–51.PubMedGoogle Scholar
  13. 13.
    Hwang AM, Stoupel J, Celenti R, Demmer RT, Papapanou PN. Serum antibody responses to periodontal microbiota in chronic and aggressive periodontitis: a postulate revisited. J Periodontol. 2014;85(4):592–600.PubMedGoogle Scholar
  14. 14.
    • Ebersole JL, Dawson DR III, Morford LA, Peyyala R, Miller CS, Gonzaléz OA. Periodontal disease immunology: ‘double indemnity’ in protecting the host. Periodontol 2000. 2013;62(1):163–202 This article provides an overview of the breadth of armamentarium of responses that are generated in the oral cavity that define the host-microbe interactions to maintain health or succumb to disease. PubMedPubMedCentralGoogle Scholar
  15. 15.
    Di Benedetto A, et al. Periodontal disease: linking the primary inflammation to bone loss. Clin Dev Immunol. 2013;2013:503754.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Garlet GP, Cardoso CR, Mariano FS, Claudino M, de Assis GF, Campanelli AP, et al. Regulatory T cells attenuate experimental periodontitis progression in mice. J Clin Periodontol. 2010;37(7):591–600.PubMedGoogle Scholar
  17. 17.
    Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010;89(12):1349–63.PubMedGoogle Scholar
  18. 18.
    Rams TE, Listgarten MA, Slots J. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis subgingival presence, species-specific serum immunoglobulin G antibody levels, and periodontitis disease recurrence. J Periodontal Res. 2006;41(3):228–34.PubMedGoogle Scholar
  19. 19.
    Pussinen PJ, Nyyssönen K, Alfthan G, Salonen R, Laukkanen JA, Salonen JT. Serum antibody levels to Actinobacillus actinomycetemcomitans predict the risk for coronary heart disease. Arterioscler Thromb Vasc Biol. 2005;25(4):833–8.PubMedGoogle Scholar
  20. 20.
    Ebersole JL. Humoral immune responses in gingival crevice fluid: local and systemic implications. Periodontol. 2003;31:135–66.Google Scholar
  21. 21.
    Salminen A, Gursoy UK, Paju S, Hyvärinen K, Mäntylä P, Buhlin K, et al. Salivary biomarkers of bacterial burden, inflammatory response, and tissue destruction in periodontitis. J Clin Periodontol. 2014;41(5):442–50.PubMedGoogle Scholar
  22. 22.
    Liang S, Hosur KB, Domon H, Hajishengallis G. Periodontal inflammation and bone loss in aged mice. J Periodontal Res. 2010;45(4):574–8.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Bullon P, Battino M, Varela-Lopez A, Perez-Lopez P, Granados-Principal S, Ramirez-Tortosa MC, et al. Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alveolar bone resorption by mitochondrial-related mechanisms. PLoS One. 2013;8(9):e74234.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Arai K, Tanaka S, Yamamoto-Sawamura T, Sone K, Miyaishi O, Sumi Y. Aging changes in the periodontal bone of F344/N rat. Arch Gerontol Geriatr. 2005;40(3):225–9.PubMedGoogle Scholar
  25. 25.
    Lam RS, O’Brien-Simpson NM, Hamilton JA, Lenzo JC, Holden JA, Brammar GC, et al. GM-CSF and uPA are required for Porphyromonas gingivalis-induced alveolar bone loss in a mouse periodontitis model. Immunol Cell Biol. 2015;93(8):705–15.PubMedGoogle Scholar
  26. 26.
    Kim PD, Xia-Juan X, Crump KE, Abe T, Hajishengallis G, Sahingur SE. Toll-like receptor 9-mediated inflammation triggers alveolar bone loss in experimental murine periodontitis. Infect Immun. 2015;83(7):2992–3002.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Araujo-Pires AC, Vieira AE, Francisconi CF, Biguetti CC, Glowacki A, Yoshizawa S, et al. IL-4/CCL22/CCR4 axis controls regulatory T-cell migration that suppresses inflammatory bone loss in murine experimental periodontitis. J Bone Miner Res. 2015;30(3):412–22.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Jiao Y, Darzi Y, Tawaratsumida K, Marchesan JT, Hasegawa M, Moon H, et al. Induction of bone loss by pathobiont-mediated Nod1 signaling in the oral cavity. Cell Host Microbe. 2013;13(5):595–601.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Graves DT, Kang J, Andriankaja O, Wada K, Rossa C Jr. Animal models to study host-bacteria interactions involved in periodontitis. Front Oral Biol. 2012;15:117–32.PubMedGoogle Scholar
  30. 30.
    • Franceschi C, Bonafè M, Valensin S, Olivieri F, de Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54 This overview provides a developing perspective of the relationship of chronic low level inflammation (inflammaging) and the observation of concomittant loss of immune response capabilities (immunoscenescence) with aging. PubMedGoogle Scholar
  31. 31.
    Baggio G, et al. Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors. FASEB J. 1998;12(6):433–7.PubMedGoogle Scholar
  32. 32.
    Mari D, Mannucci PM, Coppola R, Bottasso B, Bauer KA, Rosenberg RD. Hypercoagulability in centenarians: the paradox of successful aging. Blood. 1995;85(11):3144–9.PubMedGoogle Scholar
  33. 33.
    Vallejo AN. Immunological hurdles of ageing: indispensable research of the human model. Ageing Res Rev. 2011;10(3):315–8.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Gomez CR, Nomellini V, Faunce DE, Kovacs EJ. Innate immunity and aging. Exp Gerontol. 2008;43(8):718–28.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Huttner EA, Machado DC, de Oliveira RB, Antunes AGF, Hebling E. Effects of human aging on periodontal tissues. Spec Care Dentist. 2009;29(4):149–55.PubMedGoogle Scholar
  36. 36.
    Miller RA. The aging immune system: primer and prospectus. Science. 1996;273(5271):70–4.PubMedGoogle Scholar
  37. 37.
    Hajishengallis G. Too old to fight? Aging and its toll on innate immunity. Mol Oral Microbiol. 2010;25(1):25–37.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Kornman KS. Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging. Am J Clin Nutr. 2006;83(2):475S–83S.PubMedGoogle Scholar
  39. 39.
    Agrawal A, Agrawal S, Cao JN, Su H, Osann K, Gupta S. Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol. 2007;178(11):6912–22.PubMedGoogle Scholar
  40. 40.
    Wu Y, Dong G, Xiao W, Xiao E, Miao F, Syverson A, et al. Effect of aging on periodontal inflammation, microbial colonization, and disease susceptibility. J Dent Res. 2016;95(4):460–6.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Tortorella C, Simone O, Piazzolla G, Stella I, Cappiello V, Antonaci S. Role of phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways in granulocyte macrophage-colony-stimulating factor failure to delay Fas-induced neutrophil apoptosis in elderly humans. J Gerontol A Biol Sci Med Sci. 2006;61(11):1111–8.PubMedGoogle Scholar
  42. 42.
    Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Ebersole JL, Cappelli D, Holt SC. Periodontal diseases: to protect or not to protect is the question? Acta Odontol Scand. 2001;59(3):161–6.PubMedGoogle Scholar
  44. 44.
    Kinane DF, Mooney J, Ebersole JL. Humoral immune response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in periodontal disease. Periodontol. 1999;20:289–340.Google Scholar
  45. 45.
    Kebschull M, Demmer RT, Grün B, Guarnieri P, Pavlidis P, Papapanou PN. Gingival tissue transcriptomes identify distinct periodontitis phenotypes. J Dent Res. 2014;93(5):459–68.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Kebschull M, Guarnieri P, Demmer RT, Boulesteix AL, Pavlidis P, Papapanou PN. Molecular differences between chronic and aggressive periodontitis. J Dent Res. 2013;92(12):1081–8.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Jonsson D, et al. Gingival tissue transcriptomes in experimental gingivitis. J Clin Periodontol. 2011;38(7):599–611.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Kebschull M, Papapanou PN. The use of gene arrays in deciphering the pathobiology of periodontal diseases. Methods Mol Biol. 2010;666:385–93.PubMedGoogle Scholar
  49. 49.
    Demmer RT, Behle JH, Wolf DL, Handfield M, Kebschull M, Celenti R, et al. Transcriptomes in healthy and diseased gingival tissues. J Periodontol. 2008;79(11):2112–24.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Ji S, Choi Y. Innate immune response to oral bacteria and the immune evasive characteristics of periodontal pathogens. J Periodontal Implant Sci. 2013;43(1):3–11.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Graves D. Cytokines that promote periodontal tissue destruction. J Periodontol. 2008;79(8 Suppl):1585–91.PubMedGoogle Scholar
  52. 52.
    • Lamster IB, Asadourian L, del Carmen T, Friedman PK. The aging mouth: differentiating normal aging from disease. Periodontol 2000. 2016;72(1):96–107 This report emphasizes the array of physiologic changes that occur with aging, emphasizing the characteristics of a healthy versus unhealthy aging mouth. PubMedGoogle Scholar
  53. 53.
    Lamster IB. Geriatric periodontology: how the need to care for the aging population can influence the future of the dental profession. Periodontol. 2016;72(1):7–12.Google Scholar
  54. 54.
    Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol. 2013;13(12):875–87.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Wenisch C, Patruta S, Daxböck F, Krause R, Hörl W. Effect of age on human neutrophil function. J Leukoc Biol. 2000;67(1):40–5.PubMedGoogle Scholar
  56. 56.
    Niwa Y, Kasama T, Miyachi Y, Kanoh T. Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies. Life Sci. 1989;44(22):1655–64.PubMedGoogle Scholar
  57. 57.
    Eskan MA, Jotwani R, Abe T, Chmelar J, Lim JH, Liang S, et al. The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat Immunol. 2012;13(5):465–73.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Butcher SK, Chahal H, Nayak L, Sinclair A, Henriquez NV, Sapey E, et al. Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol. 2001;70(6):881–6.PubMedGoogle Scholar
  59. 59.
    Fulop T, Larbi A, Douziech N, Fortin C, Guérard KP, Lesur O, et al. Signal transduction and functional changes in neutrophils with aging. Aging Cell. 2004;3(4):217–26.PubMedGoogle Scholar
  60. 60.
    Tseng CW, Kyme PA, Arruda A, Ramanujan VK, Tawackoli W, Liu GY. Innate immune dysfunctions in aged mice facilitate the systemic dissemination of methicillin-resistant S. aureus. PLoS One. 2012;7(7):e41454.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Tomay F, Wells K, Duong L, Tsu JW, Dye DE, Radley-Crabb HG, et al. Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T- and B-cell zones. Immunol Cell Biol. 2018;96:831–40.PubMedGoogle Scholar
  62. 62.
    Tseng CW, Liu GY. Expanding roles of neutrophils in aging hosts. Curr Opin Immunol. 2014;29:43–8.PubMedGoogle Scholar
  63. 63.
    Borenstein A, Fine N, Hassanpour S, Sun C, Oveisi M, Tenenbaum HC, et al. Morphological characterization of para- and proinflammatory neutrophil phenotypes using transmission electron microscopy. J Periodontal Res. 2018.Google Scholar
  64. 64.
    Franceschi C. Cell proliferation, cell death and aging. Aging (Milano). 1989;1(1):3–15.Google Scholar
  65. 65.
    Zhao J, Zhao J, Legge K, Perlman S. Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice. J Clin Invest. 2011;121(12):4921–30.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL, et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell. 2012;11(5):867–75.PubMedGoogle Scholar
  67. 67.
    Aprahamian T, Takemura Y, Goukassian D, Walsh K. Ageing is associated with diminished apoptotic cell clearance in vivo. Clin Exp Immunol. 2008;152(3):448–55.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Gardner JK, Cornwall SMJ, Musk AW, Alvarez J, Mamotte CDS, Jackaman C, et al. Elderly dendritic cells respond to LPS/IFN-gamma and CD40L stimulation despite incomplete maturation. PLoS One. 2018;13(4):e0195313.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Gardner JK, Mamotte CDS, Jackaman C, Nelson DJ. Modulation of dendritic cell and T cell cross-talk during aging: the potential role of checkpoint inhibitory molecules. Ageing Res Rev. 2017;38:40–51.PubMedGoogle Scholar
  70. 70.
    Agrawal A, Agrawal S, Gupta S. Role of dendritic cells in inflammation and loss of tolerance in the elderly. Front Immunol. 2017;8:896.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Cuervo AM, Macian F. Autophagy and the immune function in aging. Curr Opin Immunol. 2014;29:97–104.PubMedGoogle Scholar
  72. 72.
    Jing Y, Shaheen E, Drake RR, Chen N, Gravenstein S, Deng Y. Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum Immunol. 2009;70(10):777–84.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol. 2010;184(5):2518–27.PubMedGoogle Scholar
  74. 74.
    Sridharan A, Esposo M, Kaushal K, Tay J, Osann K, Agrawal S, et al. Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity. Age (Dordr). 2011;33(3):363–76.Google Scholar
  75. 75.
    Qian F, Wang X, Zhang L, Lin A, Zhao H, Fikrig E, et al. Impaired interferon signaling in dendritic cells from older donors infected in vitro with West Nile virus. J Infect Dis. 2011;203(10):1415–24.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Hazeldine J, Hampson P, Lord JM. Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell. 2012;11(5):751–9.PubMedGoogle Scholar
  77. 77.
    Dunston CR, Griffiths HR. The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens. Clin Exp Immunol. 2010;161(3):407–16.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Stahl SS, Tonna EA, Weiss R. The effects of aging on the proliferative activity of rat periodontal structures. J Gerontol. 1969;24(4):447–50.PubMedGoogle Scholar
  79. 79.
    Marwah AS, Meyer J, Weinmann JP. Mitotic rate of gingival epithelium in two age groups. J Investig Dermatol. 1956;27(4):237–47.PubMedGoogle Scholar
  80. 80.
    Ogura N, Matsuda U, Tanaka F, Shibata Y, Takiguchi H, Abiko Y. In vitro senescence enhances IL-6 production in human gingival fibroblasts induced by lipopolysaccharide from Campylobacter rectus. Mech Ageing Dev. 1996;87(1):47–59.PubMedGoogle Scholar
  81. 81.
    Takiguchi H, Yamaguchi M, Okamura H, Abiko Y. Contribution of IL-1 beta to the enhancement of Campylobacter rectus lipopolysaccharide-stimulated PGE2 production in old gingival fibroblasts in vitro. Mech Ageing Dev. 1997;98(1):75–90.PubMedGoogle Scholar
  82. 82.
    Oz HS, Puleo DA. Animal models for periodontal disease. J Biomed Biotechnol. 2011;2011:754857.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Holt SC, et al. Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. Science. 1988;239(4835):55–7.PubMedGoogle Scholar
  84. 84.
    Schou S, Holmstrup P, Kornman KS. Non-human primates used in studies of periodontal disease pathogenesis: a review of the literature. J Periodontol. 1993;64(6):497–508.PubMedGoogle Scholar
  85. 85.
    Roth GS, Mattison JA, Ottinger MA, Chachich ME, Lane MA, Ingram DK. Aging in rhesus monkeys: relevance to human health interventions. Science. 2004;305(5689):1423–6.PubMedGoogle Scholar
  86. 86.
    Sato S, Kiyono H, Fujihashi K. Mucosal immunosenescence in the gastrointestinal tract: a mini-review. Gerontology. 2015;61(4):336–42.PubMedGoogle Scholar
  87. 87.
    • Muller L, Pawelec G. As we age: does slippage of quality control in the immune system lead to collateral damage? Ageing Res Rev. 2015;23(Pt A):116–23 This article emphasizes progressive changes in immune response capabilities that contribute to variation in the level and quality of immune responses that occur with aging. PubMedGoogle Scholar
  88. 88.
    Fulop T, et al. On the immunological theory of aging. Interdiscip Top Gerontol. 2014;39:163–76.PubMedGoogle Scholar
  89. 89.
    Boraschi D, Aguado MT, Dutel C, Goronzy J, Louis J, Grubeck-Loebenstein B, et al. The gracefully aging immune system. Sci Transl Med. 2013;5(185):185ps8.PubMedGoogle Scholar
  90. 90.
    Kirkwood TB, Franceschi C. Is aging as complex as it would appear? New perspectives in aging research. Ann N Y Acad Sci. 1992;663:412–7.PubMedGoogle Scholar
  91. 91.
    Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5(2):133–9.PubMedGoogle Scholar
  92. 92.
    Linehan E, Fitzgerald DC. Ageing and the immune system: focus on macrophages. Eur J Microbiol Immunol (Bp). 2015;5(1):14–24.Google Scholar
  93. 93.
    Weng NP. Aging of the immune system: how much can the adaptive immune system adapt? Immunity. 2006;24(5):495–9.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Allman D, Miller JP. The aging of early B-cell precursors. Immunol Rev. 2005;205:18–29.PubMedGoogle Scholar
  95. 95.
    Swain S, Clise-Dwyer K, Haynes L. Homeostasis and the age-associated defect of CD4 T cells. Semin Immunol. 2005;17(5):370–7.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Frasca D, Diaz A, Romero M, Landin AM, Blomberg BB. Age effects on B cells and humoral immunity in humans. Ageing Res Rev. 2011;10(3):330–5.PubMedGoogle Scholar
  97. 97.
    Riley RL. Impaired B lymphopoiesis in old age: a role for inflammatory B cells? Immunol Res. 2013;57(1–3):361–9.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Frasca D, Blomberg BB. Aging impairs murine B cell differentiation and function in primary and secondary lymphoid tissues. Aging Dis. 2011;2(5):361–73.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Dunn-Walters DK, Ademokun AA. B cell repertoire and ageing. Curr Opin Immunol. 2010;22(4):514–20.PubMedGoogle Scholar
  100. 100.
    Allman D, Miller JP. B cell development and receptor diversity during aging. Curr Opin Immunol. 2005;17(5):463–7.PubMedGoogle Scholar
  101. 101.
    Frasca D, Riley RL, Blomberg BB. Humoral immune response and B-cell functions including immunoglobulin class switch are downregulated in aged mice and humans. Semin Immunol. 2005;17(5):378–84.PubMedGoogle Scholar
  102. 102.
    Frasca D, Blomberg BB. Aging affects human B cell responses. J Clin Immunol. 2011;31(3):430–5.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Geier JK, Schlissel MS. Pre-BCR signals and the control of Ig gene rearrangements. Semin Immunol. 2006;18(1):31–9.PubMedGoogle Scholar
  104. 104.
    Ebersole JL, Taubman MA. The protective nature of host responses in periodontal diseases. Periodontol. 1994;5:112–41.Google Scholar
  105. 105.
    Reinhardt RA, McDonald TL, Bolton RW, DuBois LM, Kaldahl WB. IgG subclasses in gingival crevicular fluid from active versus stable periodontal sites. J Periodontol. 1989;60(1):44–50.PubMedGoogle Scholar
  106. 106.
    Ebersole JL, al-Sabbagh M, Gonzalez OA, Dawson DR III. Aging effects on humoral immune responses in chronic periodontitis. J Clin Periodontol. 2018;45:680–92.PubMedGoogle Scholar
  107. 107.
    Johnson V, Johnson BD, Sims TJ, Whitney CW, Moncla BJ, Engel LD, et al. Effects of treatment on antibody titer to Porphyromonas gingivalis in gingival crevicular fluid of patients with rapidly progressive periodontitis. J Periodontol. 1993;64(6):559–65.PubMedGoogle Scholar
  108. 108.
    Vink C, Rudenko G, Seifert HS. Microbial antigenic variation mediated by homologous DNA recombination. FEMS Microbiol Rev. 2012;36(5):917–48.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Vinogradov E, King JD, Pathak AK, Harvill ET, Preston A. Antigenic variation among Bordetella: Bordetella bronchiseptica strain MO149 expresses a novel o chain that is poorly immunogenic. J Biol Chem. 2010;285(35):26869–77.PubMedPubMedCentralGoogle Scholar
  110. 110.
    Hall LM, et al. Sequence diversity and antigenic variation at the rag locus of Porphyromonas gingivalis. Infect Immun. 2005;73(7):4253–62.PubMedPubMedCentralGoogle Scholar
  111. 111.
    Grogono-Thomas R, Blaser MJ, Ahmadi M, Newell DG. Role of S-layer protein antigenic diversity in the immune responses of sheep experimentally challenged with Campylobacter fetus subsp. fetus. Infect Immun. 2003;71(1):147–54.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Sims TJ, Ali RW, Brockman ES, Skaug N, Page RC. Antigenic variation in Porphyromonas gingivalis ribotypes recognized by serum immunoglobulin G of adult periodontitis patients. Oral Microbiol Immunol. 1999;14(2):73–85.PubMedGoogle Scholar
  113. 113.
    Koomey M. Bacterial pathogenesis: a variation on variation in Lyme disease. Curr Biol. 1997;7(9):R538–40.PubMedGoogle Scholar
  114. 114.
    Valvano MA. Pathogenicity and molecular genetics of O-specific side-chain lipopolysaccharides of Escherichia coli. Can J Microbiol. 1992;38(7):711–9.PubMedGoogle Scholar
  115. 115.
    Roggen EL, de Breucker S, van Dyck E, Piot P. Antigenic diversity in Haemophilus ducreyi as shown by western blot (immunoblot) analysis. Infect Immun. 1992;60(2):590–5.PubMedPubMedCentralGoogle Scholar
  116. 116.
    DiRita VJ, Mekalanos JJ. Genetic regulation of bacterial virulence. Annu Rev Genet. 1989;23:455–82.PubMedGoogle Scholar
  117. 117.
    Riddle MS, Guerry P. Status of vaccine research and development for Campylobacter jejuni. Vaccine. 2016;34(26):2903–6.PubMedGoogle Scholar
  118. 118.
    Bai X, Borrow R. Genetic shifts of Neisseria meningitidis serogroup B antigens and the quest for a broadly cross-protective vaccine. Expert Rev Vaccines. 2010;9(10):1203–17.PubMedGoogle Scholar
  119. 119.
    Ebersole JL, Hall EE, Steffen MJ. Antigenic diversity in the periodontopathogen, Actinobacillus actinomycetemcomitans. Immunol Investig. 1996;25(3):203–14.Google Scholar
  120. 120.
    Oliveira RR, et al. Levels of candidate periodontal pathogens in subgingival biofilm. J Dent Res. 2016;95(6):711–8.PubMedPubMedCentralGoogle Scholar
  121. 121.
    Mysak J, et al. Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res. 2014;2014:476068.PubMedPubMedCentralGoogle Scholar
  122. 122.
    Cugini C, Klepac-Ceraj V, Rackaityte E, Riggs JE, Davey ME. Porphyromonas gingivalis: keeping the pathos out of the biont. J Oral Microbiol. 2013;5.Google Scholar
  123. 123.
    Holt SC, Ebersole JL. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the “red complex”, a prototype polybacterial pathogenic consortium in periodontitis. Periodontol. 2005;38:72–122.Google Scholar
  124. 124.
    Chen T, Siddiqui H, Olsen I. In silico comparison of 19 Porphyromonas gingivalis strains in genomics, phylogenetics, phylogenomics and functional genomics. Front Cell Infect Microbiol. 2017;7:28.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Demmer RT, Squillaro A, Papapanou PN, Rosenbaum M, Friedewald WT, Jacobs DR, et al. Periodontal infection, systemic inflammation, and insulin resistance: results from the continuous National Health and Nutrition Examination Survey (NHANES) 1999-2004. Diabetes Care. 2012;35(11):2235–42.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Dye BA, Nowjack-Raymer R, Barker LK, Nunn JH, Steele JG, Tan S, et al. Overview and quality assurance for the oral health component of the National Health and Nutrition Examination Survey (NHANES), 2003-04. J Public Health Dent. 2008;68(4):218–26.PubMedGoogle Scholar
  127. 127.
    Dye BA, Barker LK, Selwitz RH, Lewis BG, Wu T, Fryar CD, et al. Overview and quality assurance for the National Health and Nutrition Examination Survey (NHANES) oral health component, 1999-2002. Community Dent Oral Epidemiol. 2007;35(2):140–51.PubMedGoogle Scholar
  128. 128.
    Slots J. Periodontology: past, present, perspectives. Periodontol. 2013;62(1):7–19.Google Scholar
  129. 129.
    Slots J. Periodontitis: facts, fallacies and the future. Periodontol. 2017;75(1):7–23.Google Scholar
  130. 130.
    Wong C, Goldstein DR. Impact of aging on antigen presentation cell function of dendritic cells. Curr Opin Immunol. 2013;25(4):535–41.PubMedPubMedCentralGoogle Scholar
  131. 131.
    Makala LH, et al. Immunology. Antigen-presenting cells in the gut. J Biomed Sci. 2004;11(2):130–41.PubMedGoogle Scholar
  132. 132.
    Cutler CW, Teng YT. Oral mucosal dendritic cells and periodontitis: many sides of the same coin with new twists. Periodontol. 2007;45:35–50.Google Scholar
  133. 133.
    Gonzalez OA, Novak MJ, Kirakodu S, Stromberg A, Nagarajan R, Huang CB, et al. Differential gene expression profiles reflecting macrophage polarization in aging and periodontitis gingival tissues. Immunol Investig. 2015;44(7):643–64.Google Scholar
  134. 134.
    Ebersole JL, Kirakodu S, Novak MJ, Stromberg AJ, Shen S, Orraca L, et al. Cytokine gene expression profiles during initiation, progression and resolution of periodontitis. J Clin Periodontol. 2014;41:853–61.PubMedPubMedCentralGoogle Scholar
  135. 135.
    Takayanagi H. Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol. 2009;5(12):667–76.PubMedGoogle Scholar
  136. 136.
    Feng X, McDonald JM. Disorders of bone remodeling. Annu Rev Pathol. 2011;6:121–45.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–42.PubMedGoogle Scholar
  138. 138.
    Pandruvada SN, Gonzalez OA, Kirakodu S, Gudhimella S, Stromberg AJ, Ebersole JL, et al. Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates. J Clin Periodontol. 2016;43(5):408–17.PubMedPubMedCentralGoogle Scholar
  139. 139.
    Pandruvada S, Ebersole JL, Huja SS. Inhibition of osteoclastogenesis by opsonized Porphyromonas gingivalis. FASEB BioAdvances. 2018.Google Scholar
  140. 140.
    Benjamin RM. Oral health: the silent epidemic. Public Health Rep. 2010;125(2):158–9.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Grossi SG, Zambon JJ, Ho AW, Koch G, Dunford RG, Machtei EE, et al. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol. 1994;65(3):260–7.PubMedGoogle Scholar
  142. 142.
    Roberts FA, Darveau RP. Microbial protection and virulence in periodontal tissue as a function of polymicrobial communities: symbiosis and dysbiosis. Periodontol. 2015;69(1):18–27.Google Scholar
  143. 143.
    Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809–20.PubMedGoogle Scholar
  144. 144.
    Meyle J, Chapple I. Molecular aspects of the pathogenesis of periodontitis. Periodontol. 2015;69(1):7–17.Google Scholar
  145. 145.
    Vaiserman A. Early-life exposure to endocrine disrupting chemicals and later-life health outcomes: an epigenetic bridge? Aging Dis. 2014;5(6):419–29.PubMedPubMedCentralGoogle Scholar
  146. 146.
    Saraiva MC, et al. Lead exposure and periodontitis in US adults. J Periodontal Res. 2007;42(1):45–52.PubMedGoogle Scholar
  147. 147.
    Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014;35(1):3–11.PubMedGoogle Scholar
  148. 148.
    Larsson L, Thorbert-Mros S, Rymo L, Berglundh T. Influence of epigenetic modifications of the interleukin-10 promoter on IL10 gene expression. Eur J Oral Sci. 2012;120(1):14–20.PubMedGoogle Scholar
  149. 149.
    Schulz S, Immel UD, Just L, Schaller HG, Gläser C, Reichert S. Epigenetic characteristics in inflammatory candidate genes in aggressive periodontitis. Hum Immunol. 2016;77(1):71–5.PubMedGoogle Scholar
  150. 150.
    Abreu OJ, Tatakis DN, Elias-Boneta AR, López del Valle L, Hernandez R, Pousa MS, et al. Low vitamin D status strongly associated with periodontitis in Puerto Rican adults. BMC Oral Health. 2016;16(1):89.PubMedPubMedCentralGoogle Scholar
  151. 151.
    Antonoglou GN, Knuuttila M, Niemelä O, Raunio T, Karttunen R, Vainio O, et al. Low serum level of 1,25(OH)2 D is associated with chronic periodontitis. J Periodontal Res. 2015;50(2):274–80.PubMedGoogle Scholar
  152. 152.
    Jimenez M, Giovannucci E, Krall Kaye E, Joshipura KJ, Dietrich T. Predicted vitamin D status and incidence of tooth loss and periodontitis. Public Health Nutr. 2014;17(4):844–52.PubMedGoogle Scholar
  153. 153.
    Pattison DJ, Symmons DPM, Lunt M, Welch A, Bingham SA, Day NE, et al. Dietary beta-cryptoxanthin and inflammatory polyarthritis: results from a population-based prospective study. Am J Clin Nutr. 2005;82(2):451–5.PubMedGoogle Scholar
  154. 154.
    Gammone MA, Riccioni G, D’Orazio N. Carotenoids: potential allies of cardiovascular health? Food Nutr Res. 2015;59:26762.PubMedGoogle Scholar
  155. 155.
    Daraghmeh AH, Bertoia ML, al-Qadi MO, Abdulbaki AM, Roberts MB, Eaton CB. Evidence for the vitamin D hypothesis: the NHANES III extended mortality follow-up. Atherosclerosis. 2016;255:96–101.PubMedGoogle Scholar
  156. 156.
    Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol. 2006;72:1439–52.PubMedGoogle Scholar
  157. 157.
    Chapple IL. Potential mechanisms underpinning the nutritional modulation of periodontal inflammation. J Am Dent Assoc. 2009;140(2):178–84.PubMedGoogle Scholar
  158. 158.
    Najeeb S, Zafar M, Khurshid Z, Zohaib S, Almas K. The role of nutrition in periodontal health: an update. Nutrients. 2016;8(9).PubMedCentralGoogle Scholar
  159. 159.
    Kondo K, Ishikado A, Morino K, Nishio Y, Ugi S, Kajiwara S, et al. A high-fiber, low-fat diet improves periodontal disease markers in high-risk subjects: a pilot study. Nutr Res. 2014;34(6):491–8.PubMedGoogle Scholar
  160. 160.
    Linden GJ, McClean KM, Woodside JV, Patterson CC, Evans A, Young IS, et al. Antioxidants and periodontitis in 60-70-year-old men. J Clin Periodontol. 2009;36(10):843–9.PubMedGoogle Scholar
  161. 161.
    Papapanou PN, Susin C. Periodontitis epidemiology: is periodontitis under-recognized, over-diagnosed, or both? Periodontol. 2017;75(1):45–51.Google Scholar
  162. 162.
    Hajishengallis G. Aging and its impact on innate immunity and inflammation: implications for periodontitis. J Oral Biosci. 2014;56(1):30–7.PubMedPubMedCentralGoogle Scholar
  163. 163.
    Kim S, Jazwinski SM. Quantitative measures of healthy aging and biological age. Healthy Aging Res. 2015;4.Google Scholar
  164. 164.
    Belsky DW, Moffitt TE, Cohen AA, Corcoran DL, Levine ME, Prinz JA, et al. Eleven telomere, epigenetic clock, and biomarker-composite quantifications of biological aging: do they measure the same thing? Am J Epidemiol. 2018;187(6):1220–30.PubMedGoogle Scholar
  165. 165.
    Maffei VJ, Kim S, Blanchard E IV, Luo M, Jazwinski SM, Taylor CM, et al. Biological aging and the human gut microbiota. J Gerontol A Biol Sci Med Sci. 2017;72(11):1474–82.PubMedPubMedCentralGoogle Scholar
  166. 166.
    Hastings WJ, Shalev I, Belsky DW. Translating measures of biological aging to test effectiveness of geroprotective interventions: what can we learn from research on telomeres? Front Genet. 2017;8:164.PubMedPubMedCentralGoogle Scholar
  167. 167.
    Belsky DW, et al. Change in the rate of biological aging in response to caloric restriction: CALERIE biobank analysis. J Gerontol A Biol Sci Med Sci. 2017;73(1):4–10.PubMedGoogle Scholar
  168. 168.
    • Belsky DW, Caspi A, Houts R, Cohen HJ, Corcoran DL, Danese A, et al. Quantification of biological aging in young adults. Proc Natl Acad Sci U S A. 2015;112(30):E4104–10 This report summarizes findings from the population in the Dunedin Study birth cohort related to an array of measures that would better predict aging outcomes via modeling biological rather than chronological age. PubMedPubMedCentralGoogle Scholar
  169. 169.
    Gurau F, et al. Anti-senescence compounds: a potential nutraceutical approach to healthy aging. Ageing Res Rev. 2018;46:14–31.PubMedGoogle Scholar
  170. 170.
    Schmitt R. Senotherapy: growing old and staying young? Pflugers Arch. 2017;469(9):1051–9.PubMedGoogle Scholar
  171. 171.
    Saraswat K, Rizvi SI. Novel strategies for anti-aging drug discovery. Expert Opin Drug Discov. 2017;12(9):955–66.PubMedGoogle Scholar
  172. 172.
    Moskalev A, Chernyagina E, Kudryavtseva A, Shaposhnikov M. Geroprotectors: a unified concept and screening approaches. Aging Dis. 2017;8(3):354–63.PubMedPubMedCentralGoogle Scholar
  173. 173.
    Bulterijs S. Metformin as a geroprotector. Rejuvenation Res. 2011;14(5):469–82.PubMedGoogle Scholar
  174. 174.
    Vaiserman AM. Epigenetic engineering and its possible role in anti-aging intervention. Rejuvenation Res. 2008;11(1):39–42.PubMedGoogle Scholar
  175. 175.
    Linden GJ, Lyons A, Scannapieco FA. Periodontal systemic associations: review of the evidence. J Periodontol. 2013;84(4 Suppl):S8–S19.PubMedGoogle Scholar
  176. 176.
    Byerley LO, et al. Development of a serum profile for healthy aging. Age (Dordr). 2010;32(4):497–507.Google Scholar
  177. 177.
    Jazwinski SM, Kim S. Metabolic and genetic markers of biological age. Front Genet. 2017;8:64.PubMedPubMedCentralGoogle Scholar
  178. 178.
    Chen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai PC, et al. DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging (Albany NY). 2016;8(9):1844–65.Google Scholar
  179. 179.
    Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573–91.Google Scholar
  180. 180.
    Levine ME, Crimmins EM. Is 60 the new 50? Examining changes in biological age over the past two decades. Demography. 2018;55(2):387–402.PubMedGoogle Scholar
  181. 181.
    Kim S, Bi X, Czarny-Ratajczak M, Dai J, Welsh DA, Myers L, et al. Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity. Biogerontology. 2012;13(2):119–31.PubMedGoogle Scholar
  182. 182.
    Kim S, Jazwinski SM. The gut microbiota and healthy aging: a mini-review. Gerontology. 2018:1–8.Google Scholar
  183. 183.
    Levine ME. Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age? J Gerontol A Biol Sci Med Sci. 2013;68(6):667–74.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Jeffrey L. Ebersole
    • 1
    Email author
  • D. A. DawsonIII
    • 2
  • P. Emecen Huja
    • 3
  • S. Pandruvada
    • 4
  • A. Basu
    • 5
  • L. Nguyen
    • 1
  • Y. Zhang
    • 6
  • O. A. Gonzalez
    • 1
    • 7
  1. 1.Department of Biomedical Sciences, School of Dental MedicineUniversity of Nevada Las VegasLas VegasUSA
  2. 2.Division of Periodontology, College of DentistryUniversity of KentuckyLexingtonUSA
  3. 3.Department of Periodontics, JBE College of Dental MedicineMedical University of South CarolinaCharlestonUSA
  4. 4.Department of Oral Health Sciences, JBE College of Dental MedicineMedical University of South CarolinaCharlestonUSA
  5. 5.Department of Kinesiology and Nutrition, School of Allied Health SciencesUniversity of Nevada Las VegasLas VegasUSA
  6. 6.Southern Nevada Health DistrictLas VegasUSA
  7. 7.Center for Oral Health Research, College of DentistryUniversity of KentuckyLexingtonUSA

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