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.
PubMed
Google Scholar
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.
PubMed
Google Scholar
Castelo-Branco C, Soveral I. The immune system and aging: a review. Gynecol Endocrinol. 2014;30(1):16–22.
CAS
PubMed
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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
Shen-Orr SS, Furman D. Variability in the immune system: of vaccine responses and immune states. Curr Opin Immunol. 2013;25(4):542–7.
CAS
PubMed
PubMed Central
Google Scholar
Eke PI, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009-2012. J Periodontol. 2015:1–18.
Baelum V, Lopez R. Periodontal disease epidemiology—learned and unlearned? Periodontol. 2013;62(1):37–58.
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
• 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.
PubMed
PubMed Central
Google Scholar
Di Benedetto A, et al. Periodontal disease: linking the primary inflammation to bone loss. Clin Dev Immunol. 2013;2013:503754.
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Ebersole JL. Humoral immune responses in gingival crevice fluid: local and systemic implications. Periodontol. 2003;31:135–66.
Google Scholar
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.
CAS
PubMed
Google Scholar
Liang S, Hosur KB, Domon H, Hajishengallis G. Periodontal inflammation and bone loss in aged mice. J Periodontal Res. 2010;45(4):574–8.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
PubMed
Google Scholar
• 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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Vallejo AN. Immunological hurdles of ageing: indispensable research of the human model. Ageing Res Rev. 2011;10(3):315–8.
PubMed
PubMed Central
Google Scholar
Gomez CR, Nomellini V, Faunce DE, Kovacs EJ. Innate immunity and aging. Exp Gerontol. 2008;43(8):718–28.
CAS
PubMed
PubMed Central
Google Scholar
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.
PubMed
Google Scholar
Miller RA. The aging immune system: primer and prospectus. Science. 1996;273(5271):70–4.
CAS
PubMed
Google Scholar
Hajishengallis G. Too old to fight? Aging and its toll on innate immunity. Mol Oral Microbiol. 2010;25(1):25–37.
CAS
PubMed
PubMed Central
Google Scholar
Kornman KS. Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging. Am J Clin Nutr. 2006;83(2):475S–83S.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
PubMed
Google Scholar
Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
Kinane DF, Mooney J, Ebersole JL. Humoral immune response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in periodontal disease. Periodontol. 1999;20:289–340.
CAS
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
Jonsson D, et al. Gingival tissue transcriptomes in experimental gingivitis. J Clin Periodontol. 2011;38(7):599–611.
PubMed
PubMed Central
Google Scholar
Kebschull M, Papapanou PN. The use of gene arrays in deciphering the pathobiology of periodontal diseases. Methods Mol Biol. 2010;666:385–93.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
Graves D. Cytokines that promote periodontal tissue destruction. J Periodontol. 2008;79(8 Suppl):1585–91.
CAS
PubMed
Google Scholar
• 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.
PubMed
Google Scholar
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
Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol. 2013;13(12):875–87.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
Tseng CW, Liu GY. Expanding roles of neutrophils in aging hosts. Curr Opin Immunol. 2014;29:43–8.
CAS
PubMed
Google Scholar
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.
Franceschi C. Cell proliferation, cell death and aging. Aging (Milano). 1989;1(1):3–15.
CAS
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
Agrawal A, Agrawal S, Gupta S. Role of dendritic cells in inflammation and loss of tolerance in the elderly. Front Immunol. 2017;8:896.
PubMed
PubMed Central
Google Scholar
Cuervo AM, Macian F. Autophagy and the immune function in aging. Curr Opin Immunol. 2014;29:97–104.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
Marwah AS, Meyer J, Weinmann JP. Mitotic rate of gingival epithelium in two age groups. J Investig Dermatol. 1956;27(4):237–47.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Oz HS, Puleo DA. Animal models for periodontal disease. J Biomed Biotechnol. 2011;2011:754857.
PubMed
PubMed Central
Google Scholar
Holt SC, et al. Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. Science. 1988;239(4835):55–7.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Sato S, Kiyono H, Fujihashi K. Mucosal immunosenescence in the gastrointestinal tract: a mini-review. Gerontology. 2015;61(4):336–42.
CAS
PubMed
Google Scholar
• 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.
PubMed
Google Scholar
Fulop T, et al. On the immunological theory of aging. Interdiscip Top Gerontol. 2014;39:163–76.
PubMed
Google Scholar
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.
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5(2):133–9.
CAS
PubMed
Google Scholar
Linehan E, Fitzgerald DC. Ageing and the immune system: focus on macrophages. Eur J Microbiol Immunol (Bp). 2015;5(1):14–24.
CAS
Google Scholar
Weng NP. Aging of the immune system: how much can the adaptive immune system adapt? Immunity. 2006;24(5):495–9.
CAS
PubMed
PubMed Central
Google Scholar
Allman D, Miller JP. The aging of early B-cell precursors. Immunol Rev. 2005;205:18–29.
CAS
PubMed
Google Scholar
Swain S, Clise-Dwyer K, Haynes L. Homeostasis and the age-associated defect of CD4 T cells. Semin Immunol. 2005;17(5):370–7.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
Riley RL. Impaired B lymphopoiesis in old age: a role for inflammatory B cells? Immunol Res. 2013;57(1–3):361–9.
CAS
PubMed
PubMed Central
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
Dunn-Walters DK, Ademokun AA. B cell repertoire and ageing. Curr Opin Immunol. 2010;22(4):514–20.
CAS
PubMed
Google Scholar
Allman D, Miller JP. B cell development and receptor diversity during aging. Curr Opin Immunol. 2005;17(5):463–7.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Frasca D, Blomberg BB. Aging affects human B cell responses. J Clin Immunol. 2011;31(3):430–5.
PubMed
PubMed Central
Google Scholar
Geier JK, Schlissel MS. Pre-BCR signals and the control of Ig gene rearrangements. Semin Immunol. 2006;18(1):31–9.
CAS
PubMed
Google Scholar
Ebersole JL, Taubman MA. The protective nature of host responses in periodontal diseases. Periodontol. 1994;5:112–41.
CAS
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Vink C, Rudenko G, Seifert HS. Microbial antigenic variation mediated by homologous DNA recombination. FEMS Microbiol Rev. 2012;36(5):917–48.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
Hall LM, et al. Sequence diversity and antigenic variation at the rag locus of Porphyromonas gingivalis. Infect Immun. 2005;73(7):4253–62.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
Koomey M. Bacterial pathogenesis: a variation on variation in Lyme disease. Curr Biol. 1997;7(9):R538–40.
CAS
PubMed
Google Scholar
Valvano MA. Pathogenicity and molecular genetics of O-specific side-chain lipopolysaccharides of Escherichia coli. Can J Microbiol. 1992;38(7):711–9.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
DiRita VJ, Mekalanos JJ. Genetic regulation of bacterial virulence. Annu Rev Genet. 1989;23:455–82.
CAS
PubMed
Google Scholar
Riddle MS, Guerry P. Status of vaccine research and development for Campylobacter jejuni. Vaccine. 2016;34(26):2903–6.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Ebersole JL, Hall EE, Steffen MJ. Antigenic diversity in the periodontopathogen, Actinobacillus actinomycetemcomitans. Immunol Investig. 1996;25(3):203–14.
CAS
Google Scholar
Oliveira RR, et al. Levels of candidate periodontal pathogens in subgingival biofilm. J Dent Res. 2016;95(6):711–8.
CAS
PubMed
PubMed Central
Google Scholar
Mysak J, et al. Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res. 2014;2014:476068.
PubMed
PubMed Central
Google Scholar
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
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
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.
PubMed
PubMed Central
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Slots J. Periodontology: past, present, perspectives. Periodontol. 2013;62(1):7–19.
Google Scholar
Slots J. Periodontitis: facts, fallacies and the future. Periodontol. 2017;75(1):7–23.
Google Scholar
Wong C, Goldstein DR. Impact of aging on antigen presentation cell function of dendritic cells. Curr Opin Immunol. 2013;25(4):535–41.
CAS
PubMed
PubMed Central
Google Scholar
Makala LH, et al. Immunology. Antigen-presenting cells in the gut. J Biomed Sci. 2004;11(2):130–41.
CAS
PubMed
Google Scholar
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
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.
CAS
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
Takayanagi H. Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol. 2009;5(12):667–76.
CAS
PubMed
Google Scholar
Feng X, McDonald JM. Disorders of bone remodeling. Annu Rev Pathol. 2011;6:121–45.
CAS
PubMed
PubMed Central
Google Scholar
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–42.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
PubMed Central
Google Scholar
Pandruvada S, Ebersole JL, Huja SS. Inhibition of osteoclastogenesis by opsonized Porphyromonas gingivalis. FASEB BioAdvances. 2018.
Benjamin RM. Oral health: the silent epidemic. Public Health Rep. 2010;125(2):158–9.
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809–20.
PubMed
Google Scholar
Meyle J, Chapple I. Molecular aspects of the pathogenesis of periodontitis. Periodontol. 2015;69(1):7–17.
Google Scholar
Vaiserman A. Early-life exposure to endocrine disrupting chemicals and later-life health outcomes: an epigenetic bridge? Aging Dis. 2014;5(6):419–29.
PubMed
PubMed Central
Google Scholar
Saraiva MC, et al. Lead exposure and periodontitis in US adults. J Periodontal Res. 2007;42(1):45–52.
CAS
PubMed
Google Scholar
Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014;35(1):3–11.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Gammone MA, Riccioni G, D’Orazio N. Carotenoids: potential allies of cardiovascular health? Food Nutr Res. 2015;59:26762.
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol. 2006;72:1439–52.
CAS
PubMed
Google Scholar
Chapple IL. Potential mechanisms underpinning the nutritional modulation of periodontal inflammation. J Am Dent Assoc. 2009;140(2):178–84.
PubMed
Google Scholar
Najeeb S, Zafar M, Khurshid Z, Zohaib S, Almas K. The role of nutrition in periodontal health: an update. Nutrients. 2016;8(9).
PubMed Central
Google Scholar
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.
CAS
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Papapanou PN, Susin C. Periodontitis epidemiology: is periodontitis under-recognized, over-diagnosed, or both? Periodontol. 2017;75(1):45–51.
Google Scholar
Hajishengallis G. Aging and its impact on innate immunity and inflammation: implications for periodontitis. J Oral Biosci. 2014;56(1):30–7.
CAS
PubMed
PubMed Central
Google Scholar
Kim S, Jazwinski SM. Quantitative measures of healthy aging and biological age. Healthy Aging Res. 2015;4.
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.
PubMed
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
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.
PubMed
PubMed Central
Google Scholar
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.
PubMed
Google Scholar
• 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.
CAS
PubMed
PubMed Central
Google Scholar
Gurau F, et al. Anti-senescence compounds: a potential nutraceutical approach to healthy aging. Ageing Res Rev. 2018;46:14–31.
CAS
PubMed
Google Scholar
Schmitt R. Senotherapy: growing old and staying young? Pflugers Arch. 2017;469(9):1051–9.
CAS
PubMed
Google Scholar
Saraswat K, Rizvi SI. Novel strategies for anti-aging drug discovery. Expert Opin Drug Discov. 2017;12(9):955–66.
CAS
PubMed
Google Scholar
Moskalev A, Chernyagina E, Kudryavtseva A, Shaposhnikov M. Geroprotectors: a unified concept and screening approaches. Aging Dis. 2017;8(3):354–63.
PubMed
PubMed Central
Google Scholar
Bulterijs S. Metformin as a geroprotector. Rejuvenation Res. 2011;14(5):469–82.
CAS
PubMed
Google Scholar
Vaiserman AM. Epigenetic engineering and its possible role in anti-aging intervention. Rejuvenation Res. 2008;11(1):39–42.
CAS
PubMed
Google Scholar
Linden GJ, Lyons A, Scannapieco FA. Periodontal systemic associations: review of the evidence. J Periodontol. 2013;84(4 Suppl):S8–S19.
PubMed
Google Scholar
Byerley LO, et al. Development of a serum profile for healthy aging. Age (Dordr). 2010;32(4):497–507.
CAS
Google Scholar
Jazwinski SM, Kim S. Metabolic and genetic markers of biological age. Front Genet. 2017;8:64.
PubMed
PubMed Central
Google Scholar
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.
CAS
Google Scholar
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
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.
PubMed
Google Scholar
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.
CAS
PubMed
Google Scholar
Kim S, Jazwinski SM. The gut microbiota and healthy aging: a mini-review. Gerontology. 2018:1–8.
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.
PubMed
Google Scholar