Oxidative Stress Factors Mediate the Association Between Life’s Essential 8 and Accelerated Phenotypic Aging: NHANES 2005–2018

Abstract Cardiovascular health (CVH) is a well-known predictor of morbidity and mortality, while phenotypic age (PhenoAge) is a promising biomarker of aging. This study aimed to explore the association between Life’s Essential 8 (LE8), a novel CVH measure, and PhenoAge acceleration (PhenoAgeAccel), as well as the potential mediating role of oxidative stress biomarkers in this relationship. A total of 23 896 individuals were included in the National Health and Nutrition Examination Survey database (2005–2018). Life’s Essential 8 scores were categorized into low, moderate, and high groups. PhenoAge, measured through clinical laboratory blood chemistries, served as a marker of biological aging. Weighted linear regression analyses were performed to assess the association between LE8 scores and PhenoAgeAceel. In the multivariable linear regression, LE8 scores were significantly and inversely associated with PhenoAgeAccel, showing a decreased risk in the moderate CVH group (β −2.98; 95% CI −3.29, −2.66) and high CVH group (β −4.72; 95% CI −5.08, −4.35) compared to the low CVH group. When treated as a continuous variable, each 10-point increase in LE8 scores corresponded to a 1.14-year decrease in PhenoAge (β −1.14; 95% CI −1.21, −1.06). Among the 8 individual components in LE8, 7 exhibited a significant negative correlation with PhenoAgeAccel, except for blood lipids. Additionally, mediation analysis revealed that oxidative stress biomarkers, including γ-glutamyltransferase, bilirubin, and uric acid, collectively mediated 17.1% of the associations between LE8 scores and PhenoAgeAccel (p < .001). Higher LE8 scores, representing ideal CVH, are significantly related to a deceleration in PhenoAge, and oxidative stress biomarkers may play a mediating role in this relationship.