Age and Inflammation: Insights on "Age Three Ways" from Midlife in the United States Study

Introduction: Chronological age is a particularly well-known indicator of variability in systemic inflammation. Other pertinent aspects of age (or "age proxies") - subjective or epigenetic age - may offer nuanced information about age and inflammation associations. Using the Midlife in the United States Study, we explored how chronological, subjective, and epigenetic age were associated with inflammation. Further, we tested whether chronological age remained a unique predictor of inflammation after accounting for the variance of subjective and epigenetic age. Using an intersectionality framework, we also tested whether associations differed by race and gender. Method: 1,307 (85.39% White, 52.99% men) participants reported on their chronological and subjective age and provided blood from which epigenetic DNA and inflammatory biomarkers (IL-6, IL-8, fibrinogen, TNF-alpha, and E-selectin) were determined. Results: Linear regressions showed that being chronologically older was related to higher levels of inflammation. Being biologically older (higher epigenetic age or pace of aging) was also related to higher levels of all but IL-8. Subjective age was related to inflammatory biomarkers but only for people who identified their racial identity as White. Gender differences emerged, primarily with biological and chronological age. With all age indicators in one model, chronological age remained a unique indicator of inflammation in the sample, as similar to or a better predictor than biological age. Conclusion: The current study provides a better scientific understanding of the relative association of chronological age versus subjective and epigenetic age on inflammation with evidence suggesting that chronological age provides novel information above and beyond other proxies of age.