Comparative Analysis of Gene Expression Patterns for Oral Epithelium-Related Functions with Aging.

Abstract

Epithelial cells and functions of the epithelium are critical to the health of the oral cavity. We used a nonhuman primate model to profile the transcriptome of gingival tissues in health across the lifespan and hypothesized that in older animals, epithelial-related transcriptome patterns would reflect epithelial cells that are aggressively responsive to the surrounding environment and less able to modulate and resolve the noxious challenge from the bacteria. Rhesus monkeys (n=34) with a healthy periodontium were distributed into four groups: ≤3years (young), 3-7years (adolescent), 12-16years (adult), and 18-23years (aged), and a buccal gingival sample from the premolar/molar region of each animal was obtained. RNA was subjected to a microarray analysis (GeneChip® Rhesus Macaque Genome Array, Affymetrix), and 336 genes examined that are linked to epithelium and epithelial cell functions categorized into 9 broad functional groups: extracellular matrix and cell structure; extracellular matrix remodeling enzymes; cell adhesion molecules, cytoskeleton regulation; inflammatory response; growth factors; kinases/cell signaling; cell surface receptors; junction associated molecules; autophagy/apoptosis; antimicrobial peptides; and transcription factors. Total of 255 genes displayed a normalized signal >100, and differences across the age groups were observed primarily in extracellular matrix and cell structure, cell adhesion molecules, and cell surface receptor gene categories with elevations in the aged tissues. Keratins 2, 5, 6B, 13, 16, 17 were all significantly increased in healthy-aged tissues versus adults, and keratins 1 and 2 were significantly decreased in young animals. Approximately 15 integrins are highly expressed in the gingival tissues across the age groups with only ITGA8, ITGAM (CD11b), and ITGB2 significantly increased in the aged tissues. Little impact of aging on desmosomal/hemidesmosomal genes was noted. These results suggest that healthy gingival aging has a relatively limited impact on the broader functions of the epithelium and epithelial cells, with some effects on genes for extracellular matrix and cell adhesion molecules (e.g., integrins). Thus, while there is a substantial impact of aging on immune system targets even in healthy gingiva, it appears that the epithelial barrier remains reasonably molecularly intact in this model system.