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

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.

The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients

“…Patients receiving both chemotherapy and radiation exhibited a significant increase in GEAA (F(1,34) = 13.6, p = 8.0 × 10 −4 ), and non-significant increases in EEAA (F(1,34) = 0.66, p = 0.42) and PEAA (F(1,34) = 0.87, p = 0.36). There was a notable decrease (of borderline significance) from pre-to post-treatment in IEAA in the group receiving both chemotherapy and radiotherapy (F = 3.68, p = 0.064), and this finding is consistent with a recent report of decreased DNAm age with G-CSF administration 35 .…”

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches

“…The increase in HSC number in the elderly is due to the expansion of functionally attenuated HSCs [ 23 ]. Several potential mechanisms were proposed to explain how cell divisions attenuate HSC activity, including the induction of replicative stress, DNA damage, epigenetic landscape changes, metabolic stress and shorting telomere length [ 94 – 96 ].…”

Acute Myeloid Leukemia: Aging and Epigenetics

“…Moreover, large-scale methylome analysis has shown that DNA methylation patterns can reliably predict chronological age [68,89,90]. Interestingly, donor HSCs transplanted into recipient patients of different age have been shown to maintain their chronological DNA methylation age, which suggests that DNA methylation age is an intrinsic property of the cell and is not affected by the environment [91]. Further, multiple studies reported the presence of various types of epigenetic alterations as well as changes in the expression of epigenetic regulators in aged hematopoietic cells [63,64,66,67,69].…”