Abstract
Survivors of hematopoietic cell transplantation (HCT) have been shown to exhibit both clinical and biological features of accelerated ageing. Most studies used frailty measures, comorbidities for clinical assessment and several biological assessment of premature ageing. However, these tests are less suitable for age determination of individual patients. Recently, DNA methylation has emerged as a novel test to measure cellular age. In the present study, we assessed ageing in a cohort of 26 survivors of allogeneic HCT by frailty tests comprising the handgrip and 6 min walk tests and by biological tests including DNA methylation, telomere length and expression of p16INK4A and serum levels of IL-6. DNA methylation was evaluated both in blood and buccal epithelial cells. Physiological reserve was markedly reduced in transplant survivors, reflected by 6 min walk test. Increased IL-6 serum levels and p16ink4A correlated with accelerated ageing. Overall, the measured age of donor blood cells was significantly higher than these blood cells residing in their respective donors, as reflected by DNA methylation and by buccal epithelium methylation status. These clinical and biological observations suggest that allogeneic HCT is associated with accelerated ageing.
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Change history
08 April 2020
A Correction to this paper has been published: https://doi.org/10.1038/s41409-020-0900-y
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OU wrote the paper. ML designed the study and contributed to the paper. LS contributed to patient recruitment and to data analysis. EB performed the laboratory tests. OP contributed to patient recruitment and to data analysis. UR contributed to data analysis. PR contributed to data analysis. MY designed, coordinated the study and contributed to the paper.
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Uziel, O., Lahav, M., Shargian, L. et al. Premature ageing following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 1438–1446 (2020). https://doi.org/10.1038/s41409-020-0839-z
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DOI: https://doi.org/10.1038/s41409-020-0839-z