Biological age acceleration and extrahepatic multimorbidity in U.S. adults with metabolic dysfunction-associated...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystem condition in which extrahepatic comorbidities are major determinants of outcomes. Biological age (BA) acceleration captures an individual's pace of ageing relative to their chronological age. We examined the association between BA acceleration and extrahepatic multimorbidity in a nationally representative sample of U.S. adults with MASLD.

We conducted a cross-sectional analysis of 1,559 adults with MASLD from the NHANES 2017-March 2020 cycle. MASLD was defined by controlled attenuation parameter (CAP) ≥ 248 dB/m and the presence of at least one cardiometabolic criterion. Three BA acceleration measures were examined: KDM Acceleration, PhenoAge Acceleration, and Homeostatic Dysregulation (HD). Multimorbidity was defined using 17 extrahepatic chronic conditions and operationalized as: binary, ordinal, and a count of conditions. Survey-weighted regression models adjusted for confounders.

In adjusted models, a 1-SD increase in each BA measure was associated with a higher multimorbidity burden. PhenoAge Acceleration showed the strongest and most consistent associations: binary multimorbidity (OR = 1.31, 95% CI: 1.07-1.62, p = 0.013), ordinal outcome (OR = 1.40, 95% CI: 1.16-1.68, p < 0.001), and condition count (IRR = 1.20, 95% CI: 1.11-1.29, p < 0.001). KDM Acceleration and HD showed smaller but statistically significant associations with the ordinal and count outcomes.

Among adults with MASLD, higher BA acceleration, especially PhenoAge Acceleration, is associated with a greater burden of extrahepatic multimorbidity. These findings position MASLD as a systemic disorder linked to accelerated physiological decline. BA measures may serve as valuable tools for identifying patients at high risk for comorbid disease accumulation.