LAUSR

Background: Behavioral lifestyle factors are promising for prevention of numerous diseases and mortality risk by contributing to overall healthy ageing. Healthy diet and regular physical activity have been associated with longer telomere length, indicating younger biological aging. More recently, algorithm-based measurements of biological aging, which integrate information across panels of molecular or clinical indicators, have proven both more technically reliable and more precise in their predictions of morbidity and mortality than telomere length. The aim of this study was to examine the association of diet, physical activity, and their interaction with biological ageing measured by PhenoAge blood chemistry algorithm. Methods: This study included adult participants (≥20 years-old) from the National Health and Nutrition Examination Survey (NHANES), 1999-2018. We evaluated adherence to a Mediterranean diet (MeDi) and level of leisure time physical activity (LTPA) using standard instruments. We measured biological aging using the PhenoAge algorithm, developed using data from NAHNES III (1988-1994) and validated as a predictor of morbidity/mortality in the NHANES data we analyzed. We defined PhenoAge advancement as the difference between biological age derived from eight blood biomarkers and chronological age, with higher score indicating being biologically older. We evaluated the associations of MeDi and LTPA with PhenoAge in adjusted linear regressions. We explored synergies between these two health behaviors and heterogeneity in their associations across strata of sex age, gender, and body mass index (BMI). Results: In total, 38,617 participants (mean age 47.1 years, 51% women) were included. Both higher adherence to MeDi and higher level of LTPA were associated with lower PhenoAge advancement, in mutually adjusted model controlled for demographic, socioeconomic and lifestyle variables (β = 0.15 SD [95% CI, -0.18; -0.11] for high vs low tertile of adherence to MeDi, and β = 0.12 SD [-0.15; -0.09] for high LTPA level vs sedentarity). The associations of diet and physical activity phenotypes with biological aging were independent and additive (p-interaction >0.05). Stratified analyses indicated consistent significant associations across strata of age, gender, and BMI, although stronger associations were observed among women and participants with normal weight than among their respective counterparts for MeDi (p-interaction = 0.001 and 0.04, respectively) and among older participants for LTPA (p-interaction <0.001). Sensitivity analysis using the Healthy Eating Index 2015 did not change the results. Conclusion: Healthy diet and regular physical activity are independently associated with lower clinically defined biological aging, regardless of age, sex, and BMI category.