Frailty and the biology of accelerated ageing

This commentary refers to ‘Frailty and long-term outcomes in younger patients with acute myocardial infarction’, by H. Mohiaddin et al., https://doi.org/10.1093/eurheartj/ehaf876 and the discussion piece ‘Beyond the label of ‘young frailty’: toward phenotype-driven precision management’, by L. Yao and H. Li, https://doi.org/10.1093/eurheartj/ehag192. We thank Yao et al. for their correspondence regarding our study.1 While we agree that mechanism-based ‘precision management’ is the ultimate goal, we fundamentally disagree with the premise that the label of ‘young frailty’ represents a ‘clinical dead end’. On the contrary, it is the vital clinical starting point. Yao et al. correctly highlight that drivers of physiological depletion vary by population—predominantly cardiometabolic in acute myocardial infarction, inflammatory in HIV, or senescent in cancer survivors. This heterogeneity validates the frailty framework rather than diminishing it. The clinical utility of frailty lies precisely in its ability to capture the cumulative impact of these diverse aetiological routes on physiological reserve. In our study, the ‘cardiometabolic phenotype’ identified in young patients was not merely a list of comorbidities, but a quantifiable burden of deficits that resulted in severe frailty and was strongly associated with mortality beyond expectations based on chronological age.2