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.

Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity

“…After the onset of hyperglycemia, bacterial community composition in the diabetic and normoglycemic were significantly different (P<0.05). It is known that changes occur in normoglycemic mice over time (Wu et al, 2016). However, diabetes has a distinct effect as shown by the comparison of normoglycemic and diabetic groups that were age matched.…”

“…Bacteria were eluted and suspended in 1 ml sterile PBS. Colony forming units (CFU) were measured as previously described using a standard curve (Hajishengallis et al, 2011; Jiao et al, 2013; McIntosh and Hajishengallis, 2012; Wu et al, 2016). A standard bacterial reference sample was made consisting of a 1:1 mixture of Pg (ATCC 33277) and Fn (ATCC 25586) serially diluted 1:4 from 10 9 to 10 6 CFU.…”

Osteocytes play an important role in experimental periodontitis in healthy and diabetic mice through expression of RANKL

“…Paraffin‐embedded sections were stained with haematoxylin and eosin (H&E), and histomorphometric analysis was performed using Nikon NIS‐elements image analysis software (Nikon, Tokyo, Japan) at 200× magnification following the same approach described for micro‐CT. Osteoclasts were counted as multinucleated tartrate‐resistant acid phosphatase (TRAP)‐positive cells lining the coronal 0.35 mm of alveolar bone adjacent to the second molar as we have previously described (Wu et al., ). We focused on the bone adjacent to the second molar because of the “distal drift” of teeth noted in the mouse (Gilmore & Glickman, ).…”

“…RANKL is critical cytokine in this process although its key cellular source in periodontitis is unknown. the second molar as we have previously described (Wu et al, 2016).…”

Age and Periodontal Health—Immunological View

“…Only in the presence of persistent periodontal inflammation do pathological changes in clinical parameters of soft and hard tissue lead to loss of function occur [36–39], which are reported in a significant proportion of the aged population [34, 40]. Beyond the identification of elevated inflammatory mediators in periodontal lesions, substantial evidence has been obtained regarding the role of innate immune responses in chronic periodontitis [41].…”