title: Effect of Aging on Periodontal Inflammation, Microbial Colonization, and Disease Susceptibility.
abstract: Periodontitis is a chronic inflammatory disease induced by a biofilm that forms on the tooth surface. Increased periodontal disease is associated with aging. We investigated the effect of aging on challenge by oral pathogens, examining the host response, colonization, and osteoclast numbers in aged versus young mice. We also compared the results with mice with lineage-specific deletion of the transcription factor FOXO1, which reduces dendritic cell (DC) function. Periodontitis was induced by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in young (4 to 5 mo) and aged (14 to 15 mo) mice. Aged mice as well as mice with reduced DC function had decreased numbers of DCs in lymph nodes, indicative of a diminished host response. In vitro studies suggest that reduced DC numbers in lymph nodes of aged mice may involve the effect of advanced glycation end products on DC migration. Surprisingly, aged mice but not mice with genetically altered DC function had greater production of antibody to P. gingivalis, greater IL-12 expression, and more plasma cells in lymph nodes following oral inoculation as compared with young mice. The greater adaptive immune response in aged versus young mice was linked to enhanced levels of P. gingivalis and reduced bacterial diversity. Thus, reduced bacterial diversity in aged mice may contribute to increased P. gingivalis colonization following inoculation and increased periodontal disease susceptibility, reflected by higher TNF levels and osteoclast numbers in the periodontium of aged versus young mice.
authors.affiliation: State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: E
authors.initials: E
authors.lastname: Xiao
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA Shanxi Province People's Hospital, Taiyuan, China.
authors.forename: F
authors.initials: F
authors.lastname: Miao
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Syverson
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Missaghian
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Vafa
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara-UNESP, Araraquara, Brazil.
authors.forename: A A
authors.initials: AA
authors.lastname: Cabrera-Ortega
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara-UNESP, Araraquara, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Rossa
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA dtgraves@dental.upenn.edu.
authors.forename: D T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D056704:Adaptive Immunity; D000375:Aging / Q000276:immunology*; D000818:Animals; D002465:Cell Movement; D003713:Dendritic Cells / Q000378:metabolism; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D016967:Fusobacterium nucleatum / Q000276:immunology; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12
keywords: DNA-seq; bacteria; dendritic cell; lymphocyte; osteoclast; periodontitis