Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes
Authors: Ori Fridlich, Ayelet Peretz, Ilana Fox-Fisher, Sheina Pyanzin, Ziv Dadon, Eilon Shcolnik, Ronen Sadeh, Gavriel Fialkoff, Israa Sharkia, Joshua Moss, Ludovica Arpinati, Shachar Nice, Christopher D. Nogiec, Samuel Terkper Ahuno, Rui Li, Eddie Taborda, Sonia Dunkelbarger, Zvi G. Fridlender, Paz Polak, Tommy Kaplan, Nir Friedman, Benjamin Glaser, Ruth Shemer, Naama Constantini, Yuval Dor
Published: 2026

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(Cell Reports Medicine 4, 101074; June 20, 2023)

In the original version of this article, an error was introduced by the authors during the assembly of Figure 1C. The pie chart representing the cfDNA tissue origins for Runner 1 at rest was inadvertently duplicated from the data for Runner 2 at rest. This was strictly a figure assembly error—the underlying numerical values and data described were correct. In the corrected Figure 1, panel 1C has been updated to include the correct pie chart for Runner 1 at rest. This correction does not affect data analysis, results, or conclusions of the study.

We also identified a minor textual error in the legend to Figure 1D. The correct legend is as follows:

Figure 1cfDNA is elevated after physical exercise and originates from neutrophils(A) cfDNA levels increase time dependently after running. Exercise test, 12 min of incremental treadmill running until exhaustion (n = 17); 40-min run, designed to reach the heart rate measured at anaerobic threshold (n = 12); half marathon (n = 15), run time 1:40–2:20 h; full marathon (n = 14), run time 3:31–6:15 h. Dots represent individuals. Vertical lines represent mean. ∗∗∗∗p < 0.0001, two-tailed Mann-Whitney test. Green numbers represent cfDNA fold change from baseline.(B) cfDNA levels decline rapidly at the end of physical effort. Bars represent mean.(C) Deconvolution of the plasma methylome, obtained using Illumina EPIC arrays. Two individuals donated blood at rest and after a 40-min run. Two other individuals donated blood after a marathon. Deconvolution was performed using a reference atlas containing 25 tissue methylomes, as described (Moss et al.8).(D) Targeted methylation analysis of cfDNA using markers for selected tissues.(E) The relative contribution of neutrophils to the total cfDNA pool in different exercise protocols, measured by targeted methylated analysis. Each dot is one individual. Vertical lines represent mean. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ns, non-significant. Rest vs. exercise test and exercise test vs. run 40 min: two-tailed Wilcoxon matched-pairs signed rank test. Run 40 min vs. half marathon and half marathon vs. marathon: two-tailed Mann-Whitney test.(F) cfDNA from specific tissues after exercise, in GE per milliliter of plasma. Concentration was derived by multiplying the concentration of cfDNA in each sample by the fraction contributed by each cell type as shown in (D). Numbers in brackets represent fold change from baseline. Bars represent mean (of data from 12 individuals) and standard deviation.

cfDNA is elevated after physical exercise and originates from neutrophils

(A) cfDNA levels increase time dependently after running. Exercise test, 12 min of incremental treadmill running until exhaustion (n = 17); 40-min run, designed to reach the heart rate measured at anaerobic threshold (n = 12); half marathon (n = 15), run time 1:40–2:20 h; full marathon (n = 14), run time 3:31–6:15 h. Dots represent individuals. Vertical lines represent mean. ∗∗∗∗p < 0.0001, two-tailed Mann-Whitney test. Green numbers represent cfDNA fold change from baseline.

(B) cfDNA levels decline rapidly at the end of physical effort. Bars represent mean.

(C) Deconvolution of the plasma methylome, obtained using Illumina EPIC arrays. Two individuals donated blood at rest and after a 40-min run. Two other individuals donated blood after a marathon. Deconvolution was performed using a reference atlas containing 25 tissue methylomes, as described (Moss et al.8).

(D) Targeted methylation analysis of cfDNA using markers for selected tissues.

(E) The relative contribution of neutrophils to the total cfDNA pool in different exercise protocols, measured by targeted methylated analysis. Each dot is one individual. Vertical lines represent mean. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ns, non-significant. Rest vs. exercise test and exercise test vs. run 40 min: two-tailed Wilcoxon matched-pairs signed rank test. Run 40 min vs. half marathon and half marathon vs. marathon: two-tailed Mann-Whitney test.

(F) cfDNA from specific tissues after exercise, in GE per milliliter of plasma. Concentration was derived by multiplying the concentration of cfDNA in each sample by the fraction contributed by each cell type as shown in (D). Numbers in brackets represent fold change from baseline. Bars represent mean (of data from 12 individuals) and standard deviation.