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Aging Cell. 2019 Feb 2:e12897. doi: 10.1111/acel.12897. [Epub ahead of print]

Epigenetic age is a cell-intrinsic property in transplanted human hematopoietic cells.

Author information

1
Department of Microbiology, Oslo University Hospital, Oslo, Norway.
2
Division of Hematology/Oncology, Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
3
Stem Cell Transplant Program, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio.
4
Department of Pathology, Case Western Reserve University, Cleveland, Ohio.
5
Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway.
6
Department of Hematology, Oslo University Hospital, Oslo, Norway.
7
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
8
Department of Cardiology, Oslo University Hospital, Oslo, Norway.
9
National Institute of Aging (NIA), National Institute of Health, Bethesda, Maryland.
10
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
11
Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California.
12
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.

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.

KEYWORDS:

DNA methylation; aging; epigenetic clock; glanulocyte-colony stimulating- factor (G-CSF); hematopietic stem cell transfer (HSCT)

PMID:
30712319
DOI:
10.1111/acel.12897
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