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本文引用的文献

1
Bmi1 regulates mitochondrial function and the DNA damage response pathway.Bmi1调节线粒体功能和DNA损伤反应途径。
Nature. 2009 May 21;459(7245):387-392. doi: 10.1038/nature08040. Epub 2009 Apr 29.
2
The ageing immune system: is it ever too old to become young again?衰老的免疫系统:是否会老到再也无法恢复活力?
Nat Rev Immunol. 2009 Jan;9(1):57-62. doi: 10.1038/nri2471.
3
Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss.在成年小鼠中删除发育必需基因ATR会导致与年龄相关的表型和干细胞丢失。
Cell Stem Cell. 2007 Jun 7;1(1):113-126. doi: 10.1016/j.stem.2007.03.002.
4
Foxo3a is essential for maintenance of the hematopoietic stem cell pool.Foxo3a对维持造血干细胞池至关重要。
Cell Stem Cell. 2007 Jun 7;1(1):101-112. doi: 10.1016/j.stem.2007.02.001.
5
Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis.衰老过程中Wnt信号增加会改变肌肉干细胞命运并增加纤维化。
Science. 2007 Aug 10;317(5839):807-10. doi: 10.1126/science.1144090.
6
Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation.衰老的造血干细胞功能衰退,并表现出表观遗传失调。
PLoS Biol. 2007 Aug;5(8):e201. doi: 10.1371/journal.pbio.0050201.
7
A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche.低水平的活性氧会选择可能存在于低氧微环境中的原始造血干细胞。
Blood. 2007 Oct 15;110(8):3056-63. doi: 10.1182/blood-2007-05-087759. Epub 2007 Jun 26.
8
Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age.随着年龄增长,DNA损伤修复缺陷会限制造血干细胞的功能。
Nature. 2007 Jun 7;447(7145):725-9. doi: 10.1038/nature05862.
9
DNA repair is limiting for haematopoietic stem cells during ageing.在衰老过程中,DNA修复对造血干细胞具有限制作用。
Nature. 2007 Jun 7;447(7145):686-90. doi: 10.1038/nature05875.
10
"Laminopathies": a wide spectrum of human diseases.“核纤层蛋白病”:一系列广泛的人类疾病。
Exp Cell Res. 2007 Jun 10;313(10):2121-33. doi: 10.1016/j.yexcr.2007.03.028. Epub 2007 Mar 30.

造血干细胞衰老的机制。

Mechanisms of hematopoietic stem cell aging.

机构信息

Baylor College of Medicine, TX 77030, USA.

出版信息

Exp Gerontol. 2010 Apr;45(4):286-90. doi: 10.1016/j.exger.2009.12.010. Epub 2009 Dec 23.

DOI:10.1016/j.exger.2009.12.010
PMID:20034552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3632712/
Abstract

New blood cells are continually produced from the hematopoietic stem cells (HSCs) that reside in the bone marrow. Throughout the life-span of the organism, this stem cell reservoir sustains life. Although HSCs can persist in vivo longer than one life-span (Harrison et al., 1978), with aging, HSC regenerative potential diminishes and skewing from lymphopoiesis toward myelopoiesis occurs. The expansion in the HSC pool with aging provides sufficient, yet abnormal, blood production. Examination of gene expression changes in aged HSCs has provided a link between aging and genomic instability. Furthermore, studies on the effects of reactive oxygen species (ROS) on HSC aging has given more insight into the reasons for HSC failure. Understanding of the interactions between niche cells and HSCs and changes in them with aging, may give us insights into the lineage skewing phenotype observed in the aged, and also other immune dysfunctions.

摘要

新的血细胞不断地从骨髓中造血干细胞(HSCs)产生。在生物的整个生命周期中,这个干细胞库维持着生命。尽管 HSCs 在体内的存活时间可以超过一个生命周期(Harrison 等人,1978),但随着年龄的增长,HSC 的再生潜能会降低,向髓系造血的偏倚发生。随着年龄的增长,HSC 池的扩张提供了足够但异常的血液生成。对衰老 HSCs 中基因表达变化的研究为衰老和基因组不稳定性之间提供了联系。此外,对活性氧(ROS)对 HSC 衰老影响的研究更深入地了解了 HSC 衰竭的原因。了解龛细胞与 HSCs 之间的相互作用及其随年龄的变化,可能使我们深入了解衰老时观察到的谱系偏倚表型,以及其他免疫功能障碍。