The biological age of the heart is consistently younger than chronological age

Abstract

Chronological 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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

In (A) and (B), non-parametric linear regression plots showing correlation between donor chronological age and DNAmAge of the right atrium (RA) and the left atrium (LA) (Kendall’s rank correlation coefficient tau b for RA = 0.741, for LA = 0.852). In (C) and (D), non-parametric linear regression plots showing the correlation between AgeAcc and chronological age of RA in A and LA donors in B (Kendall’s rank correlation coefficient tau b = − 0.589 and tau b = − 0.578). In (E) and (F), non-parametric linear regression plots showing the correlation between DNAmAge of the circulating blood leucocytes (indicated as “blood age”) and the chronological age of the donor in A (Kendall’s rank correlation coefficient tau b = 0.842), whereas in B no correlation is shown between chronological age and blood AgeAcc (Kendall’s rank correlation coefficient tau b = 0.011).

Figure 2

In (A) and (B), non-parametric linear regression plots showing correlation between donor telomere length (T/S) and donor DNAmAge of the right atrium (RA) and the left atrium (LA) (Kendall’s rank correlation coefficient tau b for RA = − 0.440, for LA = − 0.317). In (C), non-parametric linear regression plots showing the correlation between donor telomere length and DNAmAge of the circulating blood leucocytes (indicated as “Blood T/S” and “Blood DNAmAge”) (Kendall’s rank correlation coefficient tau b = − 0.347). Mean, Standard Error (SE) and 95% coefficient intervals (CI) are represented as green, pink and black lines, respectively.

Figure 3

In (A) and (B), non-parametric linear regression plots showing correlation between telomere length (T/S) of the Right Atrium (RA) and the Left Atrium (LA) and donor chronological age (Kendall’s rank correlation coefficient tau b for RA = − 0.446, for LA = − 0.304). In (C), non-parametric linear regression plots showing the correlation between telomere length (T/S) of the circulating blood leucocytes (indicated as “blood T/S”) and the chronological age of the donors (Kendall’s rank correlation coefficient tau b = − 0.472). Mean, Standard Error (SE) and 95% coefficient intervals (CI) are represented as green, pink and black lines, respectively.

Figure 4

In (A) and (B), non-parametric linear regression plots showing correlation between donor DNAmAge of the circulating blood leucocytes (indicated as “Blood DNAmAge”) and the DNAmAge of the Right Atrium (RA) and Left Atrium (LA) (Kendall’s rank correlation coefficient tau b for RA = 0.735, for LA = 0.852). In (C) and (D), non-parametric linear regression plots showing correlation between donor TL of the circulating blood leucocytes (indicated as “Blood T/S”) and the TL of the Right Atrium (RA) and Left Atrium (LA) (Kendall’s rank correlation coefficient tau b for RA = 0.645 and for LA = 0.438). Mean, Standard Error (SE) and 95% coefficient intervals (CI) are represented as green, pink and black lines, respectively.