Human Aging Reflects Continuous Transcriptional Remodeling of the Donor Myocardium

Donor age in heart transplantation is constantly adapting. In this study we examine the molecular basis of cardiac aging and its relevance to donor heart assessment by analyzing transcriptomic data from left ventricular tissue of brain-dead donor hearts not used for transplantation. Donors were stratified into young, middle-aged, and older adult groups to characterize age-associated transcriptional variation. The findings identified a continuous gradient of age-associated gene expression without evidence of discrete molecular state transitions, and these changes were associated with coordinated remodeling of extracellular matrix, metabolic, immune, and neurohumoral pathways. Notably, 18% of the top 50 age-associated transcripts were comprised of non-coding RNAs. Older donor hearts exhibited overlapping molecular signatures with middle-aged hearts rather than with a distinct transcriptomic profile. These findings support a continuum model of myocardial aging in donor hearts and confirm that older donor hearts should be evaluated beyond age, within a broader clinical and functional context.