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Premature ageing following allogeneic hematopoietic stem cell transplantation
Bone Marrow Transplantation ( IF 4.5 ) Pub Date : 2020-02-24 , DOI: 10.1038/s41409-020-0839-z
Orit Uziel 1, 2 , Meir Lahav 1, 2, 3 , Liat Shargian 2, 3 , Einat Beery 1 , Oren Pasvolsky 2, 3 , Uri Rozovski 1, 2, 3 , Pia Raanani 1, 2, 3 , Moshe Yeshurun 2, 3
Affiliation  

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.



中文翻译:

异基因造血干细胞移植后过早衰老

造血细胞移植 (HCT) 的幸存者已显示出加速衰老的临床和生物学特征。大多数研究使用虚弱测量、临床评估合并症和过早衰老的一些生物学评估。然而,这些测试不太适合个体患者的年龄确定。最近,DNA甲基化已成为一种测量细胞年龄的新方法。在本研究中,我们通过包括手柄和 6 分钟步行测试在内的虚弱测试以及包括 DNA 甲基化、端粒长度和 p16INK 4A表达在内的生物学测试,评估了 26 名同种异体 HCT 幸存者的衰老情况。和血清 IL-6 水平。在血液和口腔上皮细胞中都评估了 DNA 甲基化。移植幸存者的生理储备明显减少,这反映在 6 分钟步行测试中。增加的 IL-6 血清水平和 p16 ink4A与加速衰老相关。总体而言,供体血细胞的测量年龄显着高于其各自供体中的这些血细胞,这反映在 DNA 甲基化和口腔上皮甲基化状态。这些临床和生物学观察表明同种异体 HCT 与加速衰老有关。

更新日期:2020-02-24
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