Circulating miR-483-5p predicts long term all-cause mortality in hospitalized older adults

Accurately predicting long-term mortality in older adults remains challenging, as chronological age and conventional clinical indices incompletely capture biological vulnerability. Circulating microRNAs (miRNAs) have emerged as potential biomarkers of aging-related pathophysiology, but their long-term prognostic value remains poorly defined. In this prospective observational study nested within the Report-AGE cohort, we evaluated whether selected circulating miRNAs predict 10-year all-cause mortality in hospitalized adults aged ≥65 years. Baseline circulating levels of miR-483-5p, miR-320b, miR-21-5p, and miR-146a-5p were measured in 648 participants and categorized into tertiles. During follow-up, 525 deaths occurred. Among the four miRNAs examined, higher circulating levels of miR-483-5p were associated with increased mortality. In fully adjusted Cox models accounting for demographic characteristics, comorbidity burden, polypharmacy, renal function, hematological indices, inflammatory parameters, albumin, and calcium, participants in the highest miR-483-5p tertile had significantly higher mortality risk than those in the lowest tertile. This association remained robust after exclusion of individuals with chronic kidney disease. In exploratory analyses, miR-483-5p and miR-320b showed stronger associations with Phenotypic Age acceleration than with chronological age. Addition of miR-483-5p modestly improved mortality discrimination at early and intermediate follow-up. These findings suggest that circulating miR-483-5p is associated with mortality and may reflect biological vulnerability in late life. • Circulating miR-483-5p predicts 10-year all-cause mortality in hospitalized older adults • miR-483-5p is independently associated with mortality beyond clinical and laboratory risk factors • The prognostic value of miR-483-5p is robust after exclusion of chronic kidney disease • miR-483-5p improves early and intermediate mortality risk discrimination