Institute of Molecular Medicine and Max-Planck-Research Department for Stem Cell Aging, Ulm, Germany.
Ann N Y Acad Sci. 2012 Aug;1266:28-39. doi: 10.1111/j.1749-6632.2012.06547.x.
The analysis of model systems has broadened our understanding of telomere-related aging processes. Telomerase-deficient mouse models have demonstrated that telomere dysfunction impairs tissue renewal capacity and shortens lifespan. Telomere shortening limits cell proliferation by activating checkpoints that induce replicative senescence or apoptosis. These checkpoints protect against an accumulation of genomically instable cells and cancer initiation. However, the induction of these checkpoints can also limit organ homeostasis, regeneration, and survival during aging and in the context of diseases. The decline in tissue regeneration in response to telomere shortening has been related to impairments in stem cell function. Telomere dysfunction impairs stem cell function by activation of cell-intrinsic checkpoints and by the induction of alterations in the micro- and macro-environment of stem cells. In this review, we discuss the current knowledge about the impact of telomere shortening on disease stages induced by replicative cell aging as indicated by studies on telomerase model systems.
对模型系统的分析拓宽了我们对端粒相关衰老过程的理解。端粒酶缺陷型小鼠模型表明，端粒功能障碍会损害组织更新能力并缩短寿命。端粒缩短通过激活检查点来限制细胞增殖，从而诱导复制性衰老或细胞凋亡。这些检查点可防止基因组不稳定细胞的积累和癌症的发生。然而，这些检查点的诱导也可能限制衰老和疾病背景下器官的动态平衡、再生和存活。端粒缩短导致组织再生能力下降与干细胞功能障碍有关。端粒功能障碍通过细胞内在检查点的激活以及干细胞微环境和宏环境的改变来损害干细胞功能。在这篇综述中，我们讨论了关于端粒缩短对端粒酶模型系统研究中指示的由复制性细胞衰老引起的疾病阶段的影响的现有知识。
