Prall Wolf C, Czibere Akos, Jäger Marcus, Spentzos Dimitrios, Libermann Towia A, Gattermann Norbert, Haas Rainer, Aivado Manuel
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University of Duesseldorf, 40225 Duesseldorf, Germany.
Mech Ageing Dev. 2007 Sep;128(9):503-10. doi: 10.1016/j.mad.2007.06.008. Epub 2007 Jul 4.
Despite the known longevity of human hematopoietic stem and progenitor cells (HSC), numerous functional impairments of these cells can be observed in an age-dependent manner. However, the molecular alterations associated with aging of HSC are largely unknown. Therefore, we scrutinized gene expression patterns of HSC from newborn, young and old healthy donors. CD34+ HSC were isolated via immuno-magnetic separation and evaluated by FACS analysis. We performed cDNA macroarray analyses on a first set of CD34+ samples (n=13). We found the genes encoding KU-antigen 70 kD (KU70), microsomal glutathione S-transferase 1 (MGST1) and BCL2-interacting killer (BIK) to possess age-related mRNA expression levels. KU70 is a DNA repair gene and part of the DNA-dependent protein kinase (DNA-PK) complex. Its expression was negatively correlated with donor age showing highest expression levels in newborn, 2.6-fold lower levels in young and 6.3-fold lower levels in old donors. The transcription levels of MGST1, a gene protecting against oxidative stress, progressively increased with age. Expression was lowest in newborn, 2.6-fold higher in young and 4.3-fold higher in old donors. BIK is a proapoptotic gene and its expression was positively correlated with donor age: lowest in newborn, 1.8-fold higher in young and 4.1-fold higher in old donors. These findings were confirmed with an independent, second set of CD34+ samples (n=16) by means of quantitative real-time RT-PCR. Elucidation of age-dependent molecular alterations in healthy HSC facilitate a better understanding of functional impairments in hematopoiesis and may become valuable for anti-aging drug development and the emerging field of regenerative medicine.
尽管已知人类造血干细胞和祖细胞（HSC）具有较长寿命，但这些细胞的许多功能损伤会以年龄依赖性方式出现。然而，与HSC衰老相关的分子改变在很大程度上尚不清楚。因此，我们仔细研究了来自新生儿、年轻和老年健康供体的HSC的基因表达模式。通过免疫磁珠分离法分离出CD34 + HSC，并通过流式细胞术分析进行评估。我们对第一组CD34 +样本（n = 13）进行了cDNA宏阵列分析。我们发现编码KU抗原70 kD（KU70）、微粒体谷胱甘肽S -转移酶1（MGST1）和BCL2相互作用杀手（BIK）的基因具有与年龄相关的mRNA表达水平。KU70是一种DNA修复基因，是DNA依赖性蛋白激酶（DNA - PK）复合物的一部分。其表达与供体年龄呈负相关，在新生儿中表达水平最高，在年轻人中低2.6倍，在老年人中低6.3倍。MGST1是一个抗氧化应激基因，其转录水平随年龄增长而逐渐增加。在新生儿中表达最低，在年轻人中高2.6倍，在老年人中高4.3倍。BIK是一种促凋亡基因，其表达与供体年龄呈正相关：在新生儿中最低，在年轻人中高1.8倍，在老年人中高4.1倍。这些发现通过定量实时RT - PCR在另一组独立的CD34 +样本（n = 16）中得到证实。阐明健康HSC中与年龄相关的分子改变有助于更好地理解造血功能损伤，并且可能对抗衰老药物开发和新兴的再生医学领域具有重要价值。
