Abstract

Background and Objectives: Iron is essential but potentially toxic; both deficiency and overload may affect aging. Population-level evidence linking iron exposure to biological aging is limited, and aging-based optimal iron ranges are undefined. We examined associations of total, dietary, and supplemental iron intake and serum iron with three biological age (BA) measures and derived optimal ranges. Methods and Study Design: We analyzed 13,284 U.S. adults (≥20 years) from NHANES 2007–2010 and 2015–2018. BA deviations (PA, GoldBA, LightBA) were derived from clinical biomarkers. Weighted linear and restricted cubic spline (RCS) models assessed associations; optimal ranges were exposure intervals with significantly beneficial associations. Models adjusted for demographics, lifestyle, comorbidities, and diet quality. Subgroup analyses examined sex, age, menopause, and chronic disease. Results: Dietary iron was associated with younger BA (PA β = -0.07; GoldBA β = -0.09 per 2-fold increase), whereas supplemental iron accelerated aging above 18 mg/day (GoldBA β = 0.35 for >18 mg/day). Serum iron showed the strongest benefit (GoldBA β = -0.25 per 2-fold increase), with a U/J-shaped optimal range of 15.2-18.8 µmol/L. Optimal ranges were also identified for total iron (15.7 - 37.3 mg/day) and dietary iron (≥13.6 mg/day). The optimal serum iron range varied by subgroup (wider in postmenopausal women and those with chronic diseases; interaction p < 0.05). Conclusions: The iron-aging relationship is source-dependent: dietary iron is protective, supplemental iron >18 mg/day is detrimental, and serum iron 15.2–18.8 µmol/L is optimal. Optimal ranges should be stratified by population.

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