Abstract
BACKGROUND: Oxidative stress plays a pivotal role in cellular aging, and dietary antioxidants may modulate this process through regulation of the aging-related Klotho gene. This cross-sectional study investigated the association between dietary total antioxidant capacity (DTAC) and Klotho gene expression in 50 healthy Iranian adults (aged 18-40 years). METHODS: Using validated food frequency questionnaires, we calculated DTAC (mmol Trolox equivalents/day) and assessed Klotho mRNA levels in peripheral blood mononuclear cells (PBMCs) via RT-PCR (ΔCt method). Linear regression models evaluated these associations, with Model 1 showing crude associations and Model 2 adjusting for age, sex, BMI, waist circumference, physical activity, and fiber intake. RESULTS: Unadjusted analysis revealed DTAC significantly predicted Klotho expression (β = -0.662, p < 0.001, R² = 0.438), with higher antioxidant intake associated with lower ΔCt values (indicating greater Klotho expression). This association remained significant after full adjustment (β = -0.599, p = 0.002, Adjusted R² = 0.381). Notably, among individual antioxidants, only zinc maintained an independent inverse relationship with ΔCt Klotho in the adjusted model (β = -0.439, p = 0.016), while other antioxidants lost significance. CONCLUSION: These findings demonstrate that higher dietary antioxidant intake, particularly zinc, is significantly associated with increased Klotho gene expression, suggesting a potential mechanism by which antioxidant-rich diets may influence aging processes. This study provides novel evidence linking DTAC to Klotho expression in humans, supporting further investigation into dietary strategies for modulating aging-related pathways.