BMI Mediates the Association between Macronutrient Subtypes and Phenotypic Age Acceleration

<b>Background:</b> There is growing evidence that diet and aging are associated; however, few studies have examined the relationship between macronutrient subtypes and phenotypic age acceleration, and the extent to which BMI (body mass index) mediates this association is unclear. <b>Methods:</b> This study included 6911 individuals who were 20 years or older and had participated in the National Health and Nutrition Examination Survey. Daily macronutrient intakes were calculated and classified by the quartile of their subtypes. PhenoAgeAccel was calculated as an aging index using nine chemistry biomarkers. Multivariable linear regression and isocaloric substitution effects were used to evaluate the association of macronutrients with PhenoAgeAccel. Mediation analyses were used to examine the mediation role of BMI in the association. <b>Results:</b> After adjusting for the potential covariates, the consumption of high-quality carbohydrates (β = -1.01, 95% CI: -1.91, -0.12), total protein (β = -2.00, 95% CI: -3.16, -0.84), and plant protein (β = -1.65, 95% CI: -2.52, -0.78) was negatively correlated with PhenoAgeAccel; the consumption of SFAs (β = 1.77, 95% CI: 0.72, 2.81) was positively correlated with PhenoAgeAccel. For every serving of low-quality carbohydrates/animal protein and other calories replaced by one serving of high-quality carbohydrates/plant protein, PhenoAgeAccel would be reduced by about 25 percent. The ratio between BMI-mediated high-quality carbohydrates and PhenoAgeAccel accounted for 19.76% of the total effect, while the ratio between BMI-mediated total fat and PhenoAgeAccel accounted for 30.78% of the total effect. <b>Conclusions:</b> Different macronutrient consumption subtypes are related to PhenoAgeAccel, which is partially mediated by BMI, depending on the quality of macronutrients. Replacing low-quality macronutrients with high-quality macronutrients might slow aging.