Extension of life-span by introduction of telomerase into normal human cells
Extension of life-span by introduction of telomerase into normal human cells
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DOI：
10.1126/science.279.5349.349
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发表时间：
1998-01-16
期刊：
影响因子：
56.9
通讯作者：
Wright, WE
中科院分区：
文献类型：
--
作者：
Bodnar, AG;Ouellette, M;Wright, WE
正常人类细胞经历有限次数的细胞分裂，并最终进入一种称为复制性衰老的非分裂状态。为了验证这一假设，我们用编码人端粒酶催化亚单位的载体转染了两种端粒酶阴性的正常人细胞类型，视网膜色素上皮细胞和包皮成纤维细胞。与表现出端粒缩短和衰老的端粒酶阴性对照克隆相反，表达端粒酶的克隆具有延长的端粒，剧烈分裂，并且显示出对β-半乳糖苷酶（衰老的生物标志物）的染色减少。值得注意的是，表达端粒酶的克隆具有正常的核型并且已经超过其正常寿命至少20倍。从而建立了端粒缩短和体外细胞衰老之间的因果关系。保持正常人类细胞处于表型年轻状态的能力可能在研究和医学方面具有重要应用。
Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence, To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced staining for beta-galactosidase, a biomarker for senescence, Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.