Association between metabolic heterogeneity of obesity and biological aging among adults: a population-based study

BACKGROUND Obesity is a major global health issue with significant metabolic heterogeneity. While it is associated with accelerated biological aging, the relationship between distinct metabolic obesity phenotypes and biological age (BA) remains unclear. In this study, we evaluated the interaction between metabolic health status and adiposity in relation to biological aging. METHODS We analyzed data from 8,986 adults participating in NHANES 1999-2018. Participants were categorized into four BMI-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHOO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obesity (MUOO). BA was estimated using phenotypic age (PhenoAge), and age acceleration was calculated. Weighted multivariable regression, subgroup, interaction, and sensitivity analyses were conducted. RESULTS Our study included 8,986 participants (38.5% male) with a mean chronological age of 48.15 ± 17.18 years and a PhenoAge of 47.65 ± 18.82 years. MHOO individuals showed 1.91 years greater PhenoAge acceleration than MHNW (β = 1.91; P < 0.001), while MUNW showed 1.21 years (β = 1.21; P = 0.006). The largest effect was observed in MUOO individuals, with 3.70 years accelerated aging (β = 3.70; P < 0.001). Subgroup analyses showed the MHOO association was more pronounced in younger adults, while the MUNW effect was stronger in older individuals. Females consistently showed larger effect sizes than males. CONCLUSION Compared to the MHNW group, the MUOO, MUNW, and MHOO phenotypes all demonstrated accelerated biological aging, with the most pronounced effect observed in the MUOO group. These findings underscore the importance of evaluating both metabolic health and excess adiposity in mitigating aging-related risks.