Aging and replicative senescence have related effects on human stem and progenitor cells.
Aging and replicative senescence have related effects on human stem and progenitor cells.
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DOI：
10.1371/journal.pone.0005846
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发表时间：
2009-06-09
期刊：
影响因子：
3.7
通讯作者：
Ho AD
中科院分区：
文献类型：
--
作者：
Wagner W;Bork S;Horn P;Krunic D;Walenda T;Diehlmann A;Benes V;Blake J;Huber FX;Eckstein V;Boukamp P;Ho AD
再生潜力随着年龄的增长而减弱，这被归因于成体干细胞的功能损伤。培养的细胞经过一定数量的细胞分裂后开始衰老，细胞随之扩大并最终停止增殖。这种复制性衰老的观察结果已被推断为体内体细胞干细胞，可能反映了整个生物体的衰老过程。在这项研究中，我们分析了衰老对人间充质间质细胞（MSC）和人造血祖细胞（HPC）基因表达谱的影响。骨髓间充质干细胞是从21 - 92岁的供者骨髓中分离出来的。年龄诱导基因67个，年龄抑制基因60个。从27岁至73岁的献血者的脐带血或动员的外周血中分离出HPC，其中432个基因是年龄诱导基因，495个是年龄抑制基因。HPC和MSC中年龄相关差异基因表达的重叠是中度的。然而，令人惊讶的是，MSC和HPC中一些与年龄相关的基因表达变化在MSC的体外复制衰老中也有差异表达。特别是涉及基因组完整性和转录调控的基因被年龄抑制。尽管端粒酶活性和端粒长度在HPC中有所不同，尤其是老年供体，但年龄依赖性下降并不显著，这表明端粒衰竭是衰老表型的原因。这些研究表明，衰老导致人类MSC和HPC的基因表达变化，这种变化在两种不同的细胞类型之间有所不同。MSC和HPC在体外的衰老变化与MSC的复制衰老有关，这表明我们的干细胞和祖细胞在体内也经历了类似的过程。
The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo.
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影响因子：
7.8
作者：
Giangreco A;Qin M;Pintar JE;Watt FM
通讯作者：
Watt FM
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
3.6
作者：
Gazit, Roi;Weissman, Irving L.;Rossi, Derrick J.
通讯作者：
Rossi, Derrick J.
DOI：
10.1073/pnas.95.18.10614
发表时间：
1998-09-01
影响因子：
11.1
作者：
Cristofalo, VJ;Allen, RG;Beck, JC
通讯作者：
Beck, JC
影响因子：
5.2
作者：
Baxter, MA;Wynn, RF;Bellantuono, I
通讯作者：
Bellantuono, I