Associations of urinary phthalate metabolites with DNA methylation algorithms of aging among U.S. adults: 1999-2002 NHANES data

Urinary phthalate (PAE) metabolites are prevalent environmental pollutants linked to various health risks. Although several promising DNA methylation (DNAm) algorithms have emerged as strong predictors of biological age and adverse health outcomes in older adults, the specific relationship between exposure to these chemical contaminants and DNAm algorithms remains largely unexplored. This study aimed to evaluate this association of urinary PAE metabolites with five widely used DNAm-based aging signatures in a representative sample of U.S. adults. Data from the National Health and Nutrition Examination Survey 1999-2002 were analyzed, focusing on urine samples from 831 participants for seven PAE metabolites. Methylation data were generated using the EPIC array (Illumina, San Diego, CA, USA), and five DNAm-based aging signatures, the HannumAgeacc, SkinBloodAgeacc, PhenoAgeacc, GrimAgeMortacc, and GrimAge2Mortacc, were estimated and employed in linear models to investigate their relationships with urinary PAE metabolite concentrations. Significant associations (P-values: 0.0001-0.0393) were observed between MBzP and all five DNAm aging algorithms, with multivariable adjusted β values ranging from 0.22 (95%CI: 0.07-0.38) for GrimAgeMortacc to 0.68 (95%CI: 0.18-1.18) for PhenoAgeacc. In males, significant associations between MBzP and PhenoAgeacc, GrimAgeMortacc, and GrimAge2Mortacc were noted (P-values: 0.0027-0.0205). Among participants aged 50-64, MBzP exhibited significant associations with all five DNAm aging algorithms (P-values: 0.0012-0.0155), with multivariable adjusted β values ranging from 0.30 (95%CI: 0.10-0.51) for GrimAgeMortacc to 0.93 (95%CI: 0.34-1.52) for PhenoAgeacc. These findings suggest that MBzP may accelerate biological aging in older populations, particularly in males aged 50-64.