AbstractChronological age represents the main factor in donor selection criteria for organ transplantation, however aging is very heterogeneous. Defining the biological aging of individual organs may contribute to supporting this process. In this study we examined the biological age of the heart [right (RA)/left atrium (LA)] and peripheral blood leucocytes in the same subject, and compared these to assess whether blood mirrors cardiac biological aging. Biological aging was studied in 35 donors (0.4–72 years) by exploring mitotic and non-mitotic pathways, using telomere length (TL) and age-dependent methylation changes in certain CpG loci (DNAmAge). Heart non-mitotic DNAmAge was strongly younger than that of both blood (− 10 years, p < 0.0001) and chronological age (− 12 years, p < 0.0001). Instead, heart and blood mitotic age (TL) were similar, and there was no difference in DNAmAge and TL between RA and LA. DNAmAge negatively correlated with TL in heart and blood (p ≤ 0.01). Finally, blood and heart TL (p < 0.01) and DNAmAge (p < 0.0001) were correlated. Therefore, blood can be a proxy indicator of heart biological age. While future investigation on post-transplant graft performance in relation to biological aging is still needed, our study could contribute to opening up novel basic and clinical research platforms in the field of organ transplantation.