Biological Age Predicts Mortality in Cardio-Kidney-Metabolic Syndrome

BIOLOGICAL age acceleration was associated with increased all-cause and cause-specific mortality among U.S. adults with cardio-kidney-metabolic (CKM) syndrome stages 0–3, with phenotypic age acceleration showing particularly strong prognostic associations. 

Biological Age Acceleration Assessed 

Researchers evaluated whether Klemera-Doubal Method Biological Age Acceleration (KDM-BAA) and Phenotypic Age Acceleration (PAA) were associated with mortality among adults with CKM syndrome stages 0–3. They also developed models to assess the potential of these measures for predicting long-term mortality. 

The analysis included 16,837 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999–2010 and 2015–2018. Mortality data were linked through 2019. Biological age was estimated using KDM-BA and Phenotypic Age algorithms, with residuals used to define biological age acceleration. 

Over a median follow-up of 11.33 years, 10.8% of the weighted population, equivalent to 9.75 million adults, died. 

Higher Mortality Risk Observed 

After full adjustment for confounding factors, positive KDM-BAA was associated with a 41% higher risk of all-cause mortality, a 74% higher risk of cardiovascular disease mortality, and a 31% higher risk of non-cardiovascular disease mortality. 

Positive PAA showed stronger associations with all-cause and non-cardiovascular disease mortality. The respective increases in risk were 103%, 79%, and 112% for all-cause, cardiovascular disease, and non-cardiovascular disease mortality. 

Both measures demonstrated consistent positive associations across multiple subgroups and sensitivity analyses. These findings indicated that accelerated biological ageing was associated with long-term mortality risk among adults at CKM syndrome stages 0–3. 

Phenotypic Age Shows Prognostic Potential 

The researchers also developed LASSO-Cox nomograms to predict mortality. The models demonstrated favourable discrimination, with training area under the curve values of 0.776 and 0.775 at 10 and 20 years, respectively. Corresponding validation values were 0.765 and 0.757, with good calibration reported. 

The findings suggested that biological age acceleration may provide prognostic information beyond conventional measures among individuals with early-stage CKM syndrome. PAA demonstrated greater prognostic value than KDM-BAA in the analysis. 

The researchers concluded that biological age acceleration independently predicted long-term mortality and suggested that monitoring biological ageing could potentially support earlier intervention and improve long-term outcomes. 

Reference 

Chen X et al. Biological age acceleration and mortality risk among U.S. adults with cardio-kidney-metabolic syndrome, stages 0-3: an NHANES cohort study. Medicine (Baltimore). 2026;105(35):e50450. 

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