Joint association of objective and subjective aging with premature mortality

Objective and subjective aging indicators reflect diverse biological and psychosocial processes, yet their combined association with premature mortality remains underexplored. This study aimed to investigate the association between a multidomain framework of aging indicators and premature mortality, addressing gaps in understanding cumulative effects. We included 369,741 UK Biobank participants initially free of cardiovascular disease (CVD) and cancer, followed until December 31, 2022. Four indicators, hearing loss, tooth loss, falls and subjective aging, were counted, and their joint associations with all-cause and cause-specific premature mortality were analyzed using the Cox proportional hazard models. During a median follow-up of 13.74 years, we documented 22,934 premature mortality. Participants with all indicators had an 81% (95%CI: 59-107%), 96% (47-160%), 55% (26-91%), and 114% (73-165%) higher risk of all-cause, CVD, cancer, and other-cause premature mortality, respectively, compared to those without indicators. The associations were particularly elevated among younger participants, those with unhealthy lifestyles, and those of lower socioeconomic status (P for interactions <0.05). Additive interaction with frailty contributed an additional 16.08% (7.91-24.25%) risk of premature mortality. Findings were replicated in the Health and Retirement Study, supporting the robustness of the multidomain aging framework. This study highlights the potential of integrating objective and subjective aging indicators to refine risk assessments and inform interventions targeting aging-related diseases.