Weng N P, Hodes R J
National Institute on Aging and National Cancer Institute, Bethesda, Maryland 20892, USA.
J Clin Immunol. 2000 Jul;20(4):257-67. doi: 10.1023/a:1017223602293.
The molecular regulation of telomere length has been well elucidated by a series of elegant studies over the past decade. More recently, experimental evidence has accrued that addresses the challenging question of if and how telomere length regulation may contribute to normal human aging or to human disease. Recent studies in mice have provided a mammalian precedent indicating that telomerase deficiency can lead to in vivo dysfunction, most probably as a consequence of progressive telomere shortening. In humans, the evidence that telomere shortening might lead to in vivo dysfunction is far less direct, although the recent description of telomerase deficiency and telomere shortening associated with the DKC syndrome is suggestive of such a link. Methodologies exist and continue to be developed that are increasingly capable of manipulating telomerase activity and telomere length in human cells. It remains to be determined whether scientifically rigorous and (equally important) medically ethical approaches will emerge to directly assess the ability of telomere length modulation to correct functional disorders of human cellular function ex vivo or more challenging still, in vivo.
在过去十年中，一系列出色的研究已经充分阐明了端粒长度的分子调控机制。最近，越来越多的实验证据开始探讨一个具有挑战性的问题，即端粒长度调控是否以及如何导致正常人类衰老或引发人类疾病。最近对小鼠的研究提供了一个哺乳动物的实例，表明端粒酶缺乏可导致体内功能障碍，这很可能是端粒逐渐缩短的结果。在人类中，虽然最近对与DKC综合征相关的端粒酶缺乏和端粒缩短的描述暗示了这种联系，但端粒缩短可能导致体内功能障碍的证据远没有那么直接。目前已经存在并不断发展出一些方法，这些方法越来越能够在人类细胞中操纵端粒酶活性和端粒长度。科学严谨且（同样重要的）医学伦理方法能否出现，以直接评估调节端粒长度在体外纠正人类细胞功能障碍的能力，或者更具挑战性的是在体内的能力，仍有待确定。
