Sex and Age Effects on Healthy Gingival Transcriptomic Patterns

Many chronic inflammatory diseases demonstrate demographic associations such as sex, age, and race-ethnicity. Periodontitis has been found to be increased with age and in males. This study used nonhuman primates representing a human-like model for periodontitis and examined the gingival transcriptome stratified on sex and age. Thirty-six Macaca mulatta in 4 age groups-young (<3 y), adolescent (3-7 y), adult (12-15 y), and aged (>17 y)-with a healthy periodontium were used to characterize gene expression in healthy gingival tissues. Gene expression was compared to clinical measures of bleeding on probing (BOP) and probing pocket depth (PPD). The results demonstrated sex differences in number of up- and downregulated genes that increased with age. Female animals generally showed elevated expression of genes related to host immunoinflammatory responses, and males showed increased expression of tissue structural genes. Gene expression correlations with BOP and/or PPD showed minimal overlap between the sexes, while male animals demonstrated substantial overlap in genes that correlated with both BOP and PPD clinical features. A cluster analysis of genes significantly different between sexes showed a clear sex and age discrimination in the young and adolescent animals. In the older groups, the genes clustered predominately by sex, irrespective of age group. A pathway analysis identified that significant gene expression patterns were quite similar in adolescent and adult animals, while the young and aged samples were quite distinct. The results confirmed substantial sex related variations in gingival tissue biology that were affected by age and observed even in adolescent animals. This suggests that "programming" of the gingival tissues related to sex can occur rather early in life and presage variations in future risk for periodontitis.