Abstract
The age of tissues and cells can be accurately estimated by DNA methylation analysis. The multitissue DNA methylation (DNAm) age predictor combines the DNAm levels of 353 CpG dinucleotides to arrive at an age estimate referred to as DNAm age. Recent studies based on short‐term observations showed that the DNAm age of reconstituted blood following allogeneic hematopoietic stem cell transplantation (HSCT) reflects the age of the donor. However, it is not known whether the DNAm age of donor blood remains independent of the recipient's age over the long term. Importantly, long‐term studies including child recipients have the potential to clearly reveal whether DNAm age is cell‐intrinsic or whether it is modulated by extracellular cues in vivo. Here, we address this question by analyzing blood methylation data from HSCT donor and recipient pairs who greatly differed in chronological age (age differences between 1 and 49 years). We found that the DNAm age of the reconstituted blood was not influenced by the recipient's age, even 17 years after HSCT, in individuals without relapse of their hematologic disorder. However, the DNAm age of recipients with relapse of leukemia was unstable. These data are consistent with our previous findings concerning the abnormal DNAm age of cancer cells, and it can potentially be exploited to monitor the health of HSCT recipients. Our data demonstrate that transplanted human hematopoietic stem cells have an intrinsic DNAm age that is unaffected by the environment in a recipient of a different age.
Highlights
We found that the DNA methylation (DNAm) age of the reconstituted blood was not influenced by the recipient's age, even 17 years after hematopoietic stem cell transplantation (HSCT), in individuals without relapse of their hematologic disorder
Et al, 2016; Stölzel et al, 2017; Weidner et al, 2015). It is Several publications describe DNA methylation (DNAm)‐based not yet known if the DNAm age of the donor cells is affected by biomarkers of aging which can be used to estimate the age of a tisthe recipient's age after prolonged exposure to the recipient's signalsue
The present study shows that the DNAm age of donor blood is not relapse samples (n = 12) and the donor age was 10 years, which was influenced by the environment of the recipient's body, whether younger or older, and that the DNAm age continues to increase after transfer to the recipient's body as if the donor cells were still in the donor's body
Summary
University Hosptial, Norway; Raagholtstiftelsen, Norway from HSCT donor and recipient pairs who greatly differed in chronological age (age differences between 1 and 49 years). The DNAm age of recipients with relapse of leukemia was unstable. These data are consistent with our previous findings concerning the abnormal DNAm age of cancer cells, and it can. Our data demonstrate that transplanted human hematopoietic stem cells have an intrinsic DNAm age that is unaffected by the environment in a recipient of a different age. KEYWORDS aging, DNA methylation, epigenetic clock, glanulocyte-colony stimulating- factor (G-CSF), hematopietic stem cell transfer (HSCT)
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