干细胞
归巢(生物学)
造血
生物
细胞生物学
再生(生物学)
老化
癌症研究
骨髓
干细胞衰老理论
造血干细胞
免疫学
干细胞因子
遗传学
生态学
作者
Viktor Janzen,Randolf Forkert,Heather E. Fleming,Yoriko Saito,Michael T. Waring,David Dombkowski,Tao Cheng,Ronald A. DePinho,Norman E. Sharpless,David T. Scadden
出处
期刊:Nature
[Springer Nature]
日期:2006-09-01
卷期号:443 (7110): 421-426
被引量:1040
摘要
Stem-cell ageing is thought to contribute to altered tissue maintenance and repair. Older humans experience increased bone marrow failure and poorer haematologic tolerance of cytotoxic injury. Haematopoietic stem cells (HSCs) in older mice have decreased per-cell repopulating activity, self-renewal and homing abilities, myeloid skewing of differentiation, and increased apoptosis with stress. Here we report that the cyclin-dependent kinase inhibitor p16INK4a, the level of which was previously noted to increase in other cell types with age, accumulates and modulates specific age-associated HSC functions. Notably, in the absence of p16INK4a, HSC repopulating defects and apoptosis were mitigated, improving the stress tolerance of cells and the survival of animals in successive transplants, a stem-cell-autonomous tissue regeneration model. Inhibition of p16INK4a may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue.
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