Unveiling the mediating role of oxidative stress in the association between endocrine-disrupting chemicals and phenotypic age acceleration: a cross-sectional study

• Linear regression, BKMR and QGC were employed to investigate the association between EDCs and the process of aging. • Phthalates, phenols, and pesticide mixtures exhibited a negative correlation with phenotypic aging acceleration. • MECCP and BP3 were identified as the primary chemicals. • Oxidative stress may potentially mediate the relationship between EDCs and aging. Aging presents a significant global public health challenge, raising concerns about environmental factors. However, evidence linking multiple endocrine-disrupting chemicals (EDCs) to aging and their mechanisms is limited. This study explored the link between ten phthalates, four phenols, and two pesticides and biological senescence, along with oxidative stress's regulatory role. This cross-sectional study analyzed data from the National Health and Nutrition Examination Surveys (2005-2016) with 2668 participants and sixteen chemicals. It used multiple linear regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC) to explore the relationships between EDCs and phenotypic aging, as well as the mediating effects of oxidative stress. Multiple linear regression indicated that MCNP, MECPP, MEHHP, and MEOHP were linked to decreased phenotypic age acceleration (PAA). BKMR analysis showed that phthalates significantly impacted both the total population and men, with group PIP values of 0.6335 and 0.8546, respectively. QGC results confirmed negative confounding effects (Estimation [95 % CI]: -0.79 [-1.31, -0.27] for the total population; -0.89 [-1.65, -0.13] for men). Both models identified MECCP and BP3 as key contributors. Mediation analyses revealed that bilirubin and iron mediated the relationship between the chemical mixture and PAA, with proportions of -24.86 % and -21.06 %, respectively.Our findings suggest that exposure to EDCs, both individually and in combination, is linked to slowed aging, particularly with MECCP and BP3. Additional laboratory and multicenter studies are needed to validate these results.