Ju Zhenyu, Lenhard Rudolph K
Institute of Molecular Medicine and Max-Planck-Research Group on Stem Aging, Ulm University, Ulm, Germany.
Biochimie. 2008 Jan;90(1):24-32. doi: 10.1016/j.biochi.2007.09.006. Epub 2007 Sep 22.
Ageing is characterized by a decline in organ maintenance and repair. Adult stem cells contribute to tissue repair and organ maintenance. Thus it is conceivable that ageing is partly due to a decline of stem cell function. At molecular level, ageing is associated with an accumulation of damage affecting DNA, proteins, membranes, and organelles, as well as the formation of insoluble protein aggregates. Telomere shortening represents a cell intrinsic mechanism, which contributes to the accumulation of DNA damage during cellular ageing. Telomere dysfunction in response to critical telomere shortening induces DNA damage checkpoints that lead to cell cycle arrest and/or cell death. Checkpoint responses induced by telomere dysfunction have mostly been studied in somatic cells but there are emerging data on cell intrinsic checkpoints that impair the maintenance and function of adult stem cell in response to telomere dysfunction. Moreover, telomere dysfunction induces alterations in the stem cell environment that limit the function of adult stem cells. In this review we summarize our current knowledge on the role of telomere dysfunction in adult stem cell ageing.
衰老的特征是器官维持和修复能力下降。成体干细胞有助于组织修复和器官维持。因此可以想象，衰老部分是由于干细胞功能下降所致。在分子水平上，衰老与影响DNA、蛋白质、膜和细胞器的损伤积累以及不溶性蛋白质聚集体的形成有关。端粒缩短是一种细胞内在机制，它导致细胞衰老过程中DNA损伤的积累。端粒功能障碍对关键端粒缩短的反应会诱导DNA损伤检查点，导致细胞周期停滞和/或细胞死亡。端粒功能障碍诱导的检查点反应大多在体细胞中进行了研究，但也有新的数据表明，细胞内在检查点会损害成体干细胞在端粒功能障碍时的维持和功能。此外，端粒功能障碍会导致干细胞环境的改变，从而限制成体干细胞的功能。在这篇综述中，我们总结了目前关于端粒功能障碍在成体干细胞衰老中的作用的知识。
