Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Am J Hum Genet. 2009 Dec;85(6):823-32. doi: 10.1016/j.ajhg.2009.10.028.
Telomerase function is critical for telomere maintenance. Mutations in telomerase components lead to telomere shortening and progressive bone marrow failure in the premature aging syndrome dyskeratosis congenita. Short telomeres are also acquired with aging, yet the role that they play in mediating age-related disease is not fully known. We generated wild-type mice that have short telomeres. In these mice, we identified hematopoietic and immune defects that resembled those present in dyskeratosis congenita patients. When mice with short telomeres were interbred, telomere length was only incrementally restored, and even several generations later, wild-type mice with short telomeres still displayed degenerative defects. Our findings implicate telomere length as a unique heritable trait that, when short, is sufficient to mediate the degenerative defects of aging, even when telomerase is wild-type.
端粒酶的功能对于端粒的维持至关重要。端粒酶成分的突变导致端粒缩短，并导致早老综合征先天性角化不良的骨髓衰竭。端粒缩短也随着年龄的增长而获得，但它们在介导与年龄相关的疾病中的作用尚不完全清楚。我们生成了端粒较短的野生型小鼠。在这些小鼠中，我们鉴定出了类似于先天性角化不良患者中存在的造血和免疫缺陷。当端粒较短的小鼠进行杂交时，端粒长度仅逐渐恢复，即使几代之后，端粒较短的野生型小鼠仍然表现出退行性缺陷。我们的研究结果表明，端粒长度是一种独特的可遗传特征，当端粒较短时，即使端粒酶为野生型，端粒长度也足以介导衰老的退行性缺陷。
