由于DNA损伤修复的缺陷,随着年龄的增长,造血干细胞的功能受到限制
Derrick J Rossi1, David Bryder, Jun Seita
1Department of Pathology, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|June 8, 2007
概括
衰老会损害干细胞的功能,导致组织平衡下降. 干细胞中累积的DNA损伤有助于这种与年龄相关的功能衰竭和减少组织修复能力.
科学领域:
- 老年学是指老年学的学科.
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 组织平衡维护随着年龄的增长而下降.
- 干细胞功能和储备对于组织修复至关重要.
- 累积的DNA损伤是与年龄相关的干细胞衰退的一个拟议机制.
研究的目的:
- 研究基因组维护途径在依赖年龄的干细胞衰退中的作用.
- 为了确定DNA损伤的积累是否有助于干细胞衰老.
- 评估DNA修复中的遗传缺陷对造血干细胞功能的影响.
主要方法:
- 检查了核酸切除修复,端粒维护和非同源端结合缺陷的老年小鼠的造血干细胞储量和功能.
- 在压力下评估干细胞的功能能力,包括重构潜力,自我更新和亡.
- 在野生型和转基因老化的干细胞中测量了内源性DNA损伤积累.
主要成果:
- 基因组维护途径的缺陷并没有随着年龄的增长而耗尽干细胞储备.
- 干细胞的功能能力在压力下严重受损,显示复制和增殖潜力降低.
- 在老化的干细胞中观察到自我更新的减少,亡的增加和功能疲.
- 在野生类型干细胞中发现了内源性DNA损伤随着年龄的增加而积累的证据.
结论:
- 累积DNA损伤是一种促进干细胞衰老的生理机制.
- 与年龄相关的干细胞功能障碍,由DNA损伤驱动,损害组织平衡和修复.
- 了解这些机制对于解决与年龄相关的组织衰退和改善再生能力至关重要.
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