Accelerated biological aging predicts poor outcomes in frail ICU patients

Chronological age often fails to reflect biological vulnerability in critical illness. In this prospective multinational prevalence study, we assessed whether accelerated biological aging, measured by the Levine PhenoAge model, improves prognostication among frail adults (clinical frailty scale ≥4) admitted to eight ICUs across six countries. Accelerated aging (PhenoAgeAccel) was defined as PhenoAge exceeding chronological age after regression adjustment. Among 784 ICU bed-days, 327 bed-days (41.7%) were occupied by frail patients, of whom 208 (63.6%) showed PhenoAgeAccel. Biological age outperformed chronological age for predicting 30-day mortality (AUROC 0.66 vs. 0.54). PhenoAgeAccel was associated with longer ICU stay, higher 30-day mortality (30% vs. 11%; relative risk [RR] 2.70), and greater risk of death or ICU readmission (RR 2.48), remaining significant after adjustment for frailty. Accelerated biological aging is common in frail ICU patients and may improve short-term risk stratification beyond chronological age alone.