Circulating Immune Mediators and Habitual Exercise Practice Among Older Adults: Beyond the Statistical Significance, Towards Clinical Significance

Physical exercise is considered an effective and relatively safe practice to reduce or control levels of pro-inflammatory mediators during aging. However, findings are often interpreted primarily through statistical significance, while the magnitude and potential clinical relevance of observed effects receive less attention. Therefore, the primary objective of this cross-sectional study was to investigate whether regular physical exercise was associated with differences in circulating levels of systemic inflammatory mediators (high-sensitivity C-reactive protein [hsCRP], TNF-α, IL-6, IL-8, IL-10, and IL-12) among community-dwelling older adults, emphasizing the magnitude and potential clinical relevance of these differences rather than an interpretation based exclusively on statistical significance. The results suggest that exercisers exhibited hsCRP levels 0.68 mg/L lower than those observed among non-exercisers (95% CI: −0.98 to −0.34 mg/L; p = 0.001). Although serum IL-6 levels did not differ statistically between groups (p = 0.072), the interval estimates remained compatible with potentially relevant reductions among exercisers. The estimated between-group difference indicated that exercisers presented median IL-6 concentrations 4.34 pg/mL lower than non-exercisers (95% CI: −9.41 to 0.24 pg/mL). No meaningful differences were observed for TNF-α, IL-8, IL-10, or IL-12. Taken together, these findings suggest that regular physical exercise is associated with a more favorable inflammatory profile in older adults, particularly through lower hsCRP concentrations. The findings for IL-6 remain inconclusive but support the need for future studies with more precise estimates of the magnitude and potential clinical relevance of this association.