PhenoAge and PhenoAgeAccel do not outperform chronological age in predicting physical performance decline or...

Chronological age inadequately captures interindividual variability in aging-related functional decline. Biological age metrics such as PhenoAge and PhenoAgeAccel, based on clinical biomarkers, have shown associations with frailty and mortality in clinical populations, but their utility in predicting physical performance decline in community-dwelling older adults remains uncertain.

We used data from 979 participants aged ≥65 years in the InCHIANTI (Invecchiare in Chianti) study, with complete baseline biomarker and physical performance data. Associations of standardized (z-scores) chronological age, phenotypic age (PhenoAge), and Phenotypic Age Acceleration (PhenoAgeAccel) with longitudinal changes in physical function (rescaled SPPB [rSPPB], continuous rescaled Short Physical Performance Battery) and 10-year all-cause mortality were analyzed using linear mixed and Cox models, respectively. A secondary analysis in 504 participants with normal baseline physical performance (Short Physical Performance Battery [SPPB] ≥ 10) assessed the predictive value of each rescaled metric for the onset of compromised function (SPPB ≤ 9) at 6 years. Model performance was evaluated using Akaike information criterion (AIC) and area under the receiver operating characteristic curve (AUC).

All 3 metrics showed statistically significant positive associations with physical function decline and mortality. Chronological age showed the strongest associations with rSPPB decline (β = -0.41, AIC = 3793) and mortality (hazard ratio [HR] = 2.78). PhenoAge (β = -0. 32, AIC = 4338, HR = 2.57) and PhenoAgeAccel (β = -0.14, AIC = 4642, HR = 1.71) showed weaker effects. Chronological age also outperformed PhenoAge and PhenoAgeAccel in predicting SPPB decline (AUC = 0.71 vs 0.69 and 0.55, respectively).

While PhenoAge and PhenoAgeAccel are associated with adverse functional outcomes, they do not outperform chronological age in a general older population.