Introduction:
Individuals with obesity are thought to be protected against some chronic disease as long as they do not incur metabolic health (MH) conditions. A new epigenetic biomarker of accelerated biological aging and health span, PhenoAge, was developed using DNA methylation (DNAm) markers. We hypothesized that obesity would be associated with higher PhenoAge than normal weight and overweight individuals only in the presence of MH conditions.
Methods:
DNAm was measured in leukocyte DNA for 2,454 African American participants (mean age=56.4 years) and used to calculate PhenoAge. BMI status was categorized as normal weight, overweight, and obese and MH was categorized by 0, 1, or at least 2 of the following: coronary heart disease, stroke, hypertension, type-2 diabetes, and hyperlipidemia. Linear regression tested the cross-sectional association of PhenoAge with BMI and MH, adjusting for sociodemographic variables, smoking, and technical variables. Stratified analyses by MH status were conducted to illustrate the statistical effects of BMI status in adults with and without MH conditions.
Results:
Participants with obesity had approximately 8 months higher PhenoAge compared to normal weight (β=0.68, 95% CI=0.21, 1.14, p=4.1E-3), and those with one (β=0.55, 95% CI=0.15, 0.94, p=6.4E-3) or at least 2 (β=0.81, 95% CI=0.38, 1.25, p=2E-4) MH conditions also had higher PhenoAge compared to those with 0 conditions. Figure 1 shows increments in PhenoAge with increments in number of MH conditions regardless of BMI. PhenoAge was significantly higher for obese compared to overweight for 0 and 1 MH conditions, but not compared to normal weight.
Conclusions:
In African American adults, both obesity status and presence of MH conditions were associated with a higher PhenoAge, suggesting metabolically healthy obesity is not entirely benign. Further phenotyping of the “metabolic health” obese condition is warranted to understand its relevance for healthspan.
