Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Epigenetic aging upon allogeneic transplantation: the hematopoietic niche does not affect age-associated DNA methylation

Leukemia volume 29, pages 985–988 (2015)Cite this article

Subjects

Aging is associated with highly reproducible DNA methylation (DNAm) changes at specific sites in the genome. These age-associated DNAm changes represent a biomarker to estimate the chronological age in blood samples.1 It has been proposed that the microenvironment, the so called ‘stem cell niche’, has major impact on declining stem cell function in the elderly individuals.2 Therefore, we anticipated that after allogeneic hematopoietic stem cell transplantation (HSCT)—particularly from a young donor to an elderly patient—the estimated epigenetic age adapts to the chronological age of the patient owing to impact of the hematopoietic microenvironment. In contrast, the results of this study demonstrate that predictions based on age-associated DNAm clearly correlate with donor age. Therefore the underlying process seems to reflect a phenomenon cell intrinsic to the transplanted hematopoietic cells.

Aging of the niche seems to contribute to loss of regenerative function upon aging. Transplantation of hematopoietic stem cells (HSCs) from young mice to old mice revealed reduced homing and engraftment.3 Aged animals transplanted with an identical pool of transduced HSCs displayed reduced clonality as compared with young animals.4 Furthermore, an aged microenvironment-enhanced myeloid skewing—a phenomenon usually observed in old mice.5 Heterochronic parabiosis models that are based on surgical connection of the circulatory systems of young and old mice, indicated that aged progenitor cells can be rejuvenated by exposure to a young systemic environment.6 Thus, aging of the hematopoietic system appears to be not only a cell-intrinsic phenomenon, but also involves extracellular signals from the microenvironment.2 These findings are of clinical relevance for HSCT because they indicate that long-term performance of the graft may depend on recipient age rather than on donor age.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Weidner CI, Lin Q, Koch CM, Eisele L, Beier F, Ziegler P et al. Aging of blood can be tracked by DNA methylation changes at just three CpG sites. Genome Biol 2014; 15: R24.

    Article  PubMed Central  Google Scholar 

  2. Geiger H, de Haan G, Florian MC . The ageing haematopoietic stem cell compartment. Nat Rev Immunol 2013; 13: 376–389.

    Article  CAS  Google Scholar 

  3. Liang Y, Van ZG, Szilvassy SJ . Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 2005; 106: 1479–1487.

    Article  CAS  PubMed Central  Google Scholar 

  4. Vas V, Senger K, Dorr K, Niebel A, Geiger H . Aging of the microenvironment influences clonality in hematopoiesis. PLoS One 2012; 7: e42080.

    Article  CAS  PubMed Central  Google Scholar 

  5. Ergen AV, Boles NC, Goodell MA . Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood 2012; 119: 2500–2509.

    Article  CAS  PubMed Central  Google Scholar 

  6. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA . Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 2005; 433: 760–764.

    Article  CAS  Google Scholar 

  7. Weidner CI, Wagner W . The epigenetic tracks of aging. Biol Chem 2014; 395: 1307–1314.

    Article  CAS  Google Scholar 

  8. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 2013; 49: 359–367.

    Article  CAS  Google Scholar 

  9. Horvath S . DNA methylation age of human tissues and cell types. Genome Biol 2013; 14: R115.

    Article  PubMed Central  Google Scholar 

  10. Bork S, Pfister S, Witt H, Horn P, Korn B, Ho AD et al. DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells. Aging Cell 2010; 9: 54–63.

    Article  CAS  PubMed Central  Google Scholar 

  11. Bocklandt S, Lin W, Sehl ME, Sanchez FJ, Sinsheimer JS, Horvath S et al. Epigenetic predictor of age. PLoS One 2011; 6: e14821.

    Article  CAS  PubMed Central  Google Scholar 

  12. Cawthon RM . Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 2009; 37: e21.

    Article  PubMed Central  Google Scholar 

  13. Brummendorf TH, Balabanov S . Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia 2006; 20: 1706–1716.

    Article  CAS  Google Scholar 

  14. Rufer N, Brummendorf TH, Chapuis B, Helg C, Lansdorp PM, Roosnek E . Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood 2001; 97: 575–577.

    Article  CAS  Google Scholar 

  15. Kröger N, Zabelina T, de Wreede L, Berger J, Alchalby H, van Biezen A et al. Allogeneic stem cell transplantation for older advanced MDS patients: improved survival with young unrelated donor in comparison with HLA-identical siblings. Leukemia 2013; 27: 604–609.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Renate Schulz for excellent technical assistance. This work was supported by the German Research Foundation (WA/1706/2-1) and the Interdisciplinary Center for Clinical Research within the Faculty of Medicine at the RWTH Aachen University (IZKF grants O1-1, O1-5 and O1-6).

Author information

Authors and Affiliations

  1. Department of Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen, Germany

    C I Weidner & W Wagner

  2. Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical School, Aachen, Germany

    P Ziegler & T H Brümmendorf

  3. Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany

    M Hahn, A D Ho & P Dreger

Authors
  1. C I Weidner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Ziegler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T H Brümmendorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A D Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Dreger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W Wagner.

Ethics declarations

Competing interests

RWTH Aachen has applied for a patent application for the Epigenetic-Aging-Signature. WW is involved in the company Cygenia GmbH that can provide service for the Epigenetic-Aging-Signature. The remaining authors declare no conflict of interest.

Additional information

Supplementary Table 1 accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Weidner, C., Ziegler, P., Hahn, M. et al. Epigenetic aging upon allogeneic transplantation: the hematopoietic niche does not affect age-associated DNA methylation. Leukemia 29, 985–988 (2015). https://doi.org/10.1038/leu.2014.323

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2014.323

This article is cited by

Search

Advanced search

Quick links