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肿瘤抑制因子剂量在衰老过程中调节干细胞动态变化。

Tumor suppressor dosage regulates stem cell dynamics during aging.

作者信息

Gatza Catherine, Moore Lynette, Dumble Melissa, Donehower Lawrence A

机构信息

Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

出版信息

Cell Cycle. 2007 Jan 1;6(1):52-5. doi: 10.4161/cc.6.1.3667. Epub 2007 Jan 4.

Abstract

The ability of tissues to maintain homeostasis is dependent in part on the function of adult tissue stem cells, which have the capability to self-renew and differentiate into multiple lineages. It has been hypothesized that the ability of stem cells to maintain tissue homeostasis declines functionally with age and that this decline may account for many of the biological phenotypes associated with aging. Recently, tumor suppressors such as p53 have been implicated in both aging and the regulation of stem cell dynamics. Our recent findings suggest that p53 may impact hematopoietic stem cell (HSC) dynamics during mammalian aging. Utilizing mouse models of varying levels of p53 dosage, we have shown that alteration of p53 activity affects stem cell number, proliferation, and functionality with age. Several other recent studies have implicated other tumor suppressors in potential age-related regulation of HSC dynamics as well. These data support a model in which aging is caused in part by a decline in tissue stem cell regenerative function, regulated in part by tumor suppressors.

摘要

组织维持内环境稳定的能力部分取决于成体组织干细胞的功能,这些干细胞具有自我更新和分化为多种谱系的能力。据推测,干细胞维持组织内环境稳定的能力会随着年龄的增长而在功能上下降,这种下降可能是许多与衰老相关的生物学表型的原因。最近,诸如p53等肿瘤抑制因子已被证明与衰老以及干细胞动态调节有关。我们最近的研究结果表明,p53可能会影响哺乳动物衰老过程中的造血干细胞(HSC)动态。利用不同p53剂量水平的小鼠模型,我们已经表明p53活性的改变会随着年龄的增长影响干细胞数量、增殖和功能。最近的其他几项研究也表明,其他肿瘤抑制因子也参与了HSC动态的潜在年龄相关调节。这些数据支持了一种模型,即衰老部分是由组织干细胞再生功能的下降引起的,而这种下降部分是由肿瘤抑制因子调节的。

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