The age illusion: why ASA physical status requires biological recalibration

The nationwide cohort study by Kilhamn et al. 1, provides robust contemporary evidence on the relationship between ASA physical status, age and mortality. Analysing 460,046 procedures, the authors showed that ASA physical status remains a powerful predictor of 30-day mortality, with an adjusted OR of 13.7 for elective ASA physical status 3 vs. 1. Whilst the study validates the enduring value of the long-standing ASA physical status system, it also highlights a critical demographic tension. The median ages of 66 and 68 y in the elective and acute cohorts, respectively, conceal substantial biological heterogeneity that chronological age fails to capture. As discussed in recent perspectives on the age illusion in medicine, chronological age is often an imperfect proxy for biological ageing 2. As the authors suggest, continuous evaluation of risk assessment tools is essential as populations age. We contend that a logical next step for ASA physical status is the integration of the brain age gap, a validated neuroimaging metric that quantifies the discrepancy between predicted brain age and chronological age 3. In a large-scale study across 34 countries, brain age gap was shown to be a sensitive indicator of accelerated brain ageing, influenced by cumulative physical and social exposures, and associated with up to 9.1-fold increased risk of adverse outcomes, often exceeding the impact of clinical diagnoses alone 3. In our clinical practice, we frequently encounter fit 80-year-olds with preserved physiological reserve and frail 60-year-olds with accelerated systemic decline. The marked increase in mortality risk between ASA physical status 3 vs. 4 (OR 13.7 vs. 62.2 in elective surgery) reported by Kilhamn et al. suggests that, within these high-risk strata, a substantial burden of biological vulnerability remains unrecognised and brain age gap may help quantify it. We propose that the ASA physical status should transition from a subjective clinical snapshot to a molecularly and neurologically grounded portrait. By leveraging validated biomarkers such as epigenetic clocks or brain age gap derived from structural and functional magnetic resonance imaging, anaesthetists may be able to recalibrate peri-operative risk more precisely. A patient with accelerated brain ageing, defined as brain age gap significantly exceeding zero, may represent a distinct phenotype that may require tailored neuroprotective and cardioprotective strategies, especially under the stress of anaesthesia and surgery. It also remains an open question whether anaesthesia and surgery accelerate brain ageing, thereby altering the biological trajectory of a patient permanently 4. Incorporating brain age gap into nationwide registers would allow us to move from empirical art to precision science. Anaesthetists should not merely be guardians of vital signs but interpreters of biological reality. We thank Kilhamn et al. for their important data, which provide an ideal baseline for this necessary recalibration.