Association Between Iron Availability and Accelerated Biological Aging in Non-Anemic Women of Reproductive Age: A Nationally Representative Cross-Sectional Study.

Abstract

Iron is essential for mitochondrial function, yet iron insufficiency without anemia in reproductive-aged women is often overlooked. Traditional markers like ferritin are influenced by inflammation, which may complicate the assessment of iron status and its association with biological aging. We analyzed 5,686 non-anemic reproductive-aged women (20-49 years) from NHANES cycles 2003-2010 and 2015-2023. We examined the association between the soluble transferrin receptor-to-log(ferritin) index (sTfR index), an indirect marker of iron status, and biological aging, measured by Phenotypic Age Acceleration (PhenoAgeAccel). Analyses included weighted multivariable regression, restricted cubic spline (RCS) modeling, and sensitivity analysis (CRP ≤ 5 mg/L). Each 1-unit increase in sTfR index was associated with a 1.94-year increase in PhenoAgeAccel (95% CI: 1.56-2.32). The association remained robust after excluding participants with elevated inflammation (β = 1.79; 95% CI: 1.41-2.17). Separately, ferritin RCS analysis showed that compared with the median (47 μg/L), women at the WHO threshold (15 μg/L) exhibited 1.93 additional years of biological aging (95% CI: 1.58-2.29). Notably, women with higher sTfR index values (median ferritin 29 μg/L) showed PhenoAgeAccel values, despite a substantial proportion having ferritin levels above commonly used deficiency thresholds. The magnitude of this association varied across levels of bilirubin and socioeconomic status. Higher sTfR index values, even in the absence of anemia, were associated with accelerated biological aging in reproductive-aged women. The sTfR index may provide additional information regarding iron status beyond conventional markers.