Age as a Modulator of Salivary TIMP-1 and IL-6 in Periodontal Health and Disease

Periodontal diseases are common chronic inflammatory conditions, and saliva provides a practical window into local immune activity. Among salivary biomarkers, IL-6 and TIMP-1 are promising for capturing inflammation and tissue remodeling, yet their age-related behavior across health, gingivitis, and periodontitis remains insufficiently defined. The objective was to investigate the modulatory effect of age on the salivary levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) and interleukin-6 (IL-6) in individuals with varying periodontal conditions, specifically periodontal health, gingivitis, and periodontitis (Stages 1–3). This cross-sectional study was conducted on 107 systemically healthy, non-smoking participants, categorized according to the 2017 World Workshop criteria as periodontal health, gingivitis, or periodontitis (Stages 1-3). Unstimulated whole saliva was collected and analyzed using ELISA. Statistical tests included ANOVA, Tukey HSD, Spearman correlation, and multiple linear regression adjusted for sex and BMI.  Both salivary TIMP-1 and IL-6 levels significantly increased with age (TIMP-1: β = +24.31 ng/mL/year, 95% CI [12.8–35.8], R² = 0.123; IL-6: β = +1.75 pg/mL/year, 95% CI [0.9–2.6], R² = 0.169; p < 0.001). Periodontitis groups exhibited 2.4–2.5× higher TIMP-1 and 1.5–2.3× higher IL-6 than healthy controls (p < 0.001). IL-6 also differentiated gingivitis from health (p = 0.026), while TIMP-1 surged notably in Stage 1 periodontitis (p < 0.001). A strong positive correlation was observed between TIMP-1 and IL-6 (ρ = 0.649, p < 0.001). Aging independently modulates periodontal biomarker profiles, with IL-6 responding earlier in inflammation and TIMP-1 rising in advanced disease, supporting inflammaging and compensatory repair.