Accelerated in vivo epidermal telomere loss in Werner syndrome
Accelerated in vivo epidermal telomere loss in Werner syndrome
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DOI：
10.18632/aging.100315
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发表时间：
2011-04-01
期刊：
影响因子：
5.2
通讯作者：
Takubo, Kaiyo
中科院分区：
文献类型：
--
作者：
Ishikawa, Naoshi;Nakamura, Ken-Ichi;Takubo, Kaiyo
Werner综合征（WS）是一种典型的早衰综合征，其引起的细胞端粒加速丢失的研究已积累了大量的资料。然而，在WS患者体内端粒缩短方面还没有明确的数据。在本研究中，我们测量了末端限制性片段（TRF）长度的10个皮肤样本收集四肢的8个WS患者年龄在30岁至61岁之间，已手术截肢，因为皮肤溃疡，并估计每年的端粒损失。年轻WS患者（30多岁）的TRF长度值在正常范围内，而老年WS患者的TRF长度相对于非WS对照组明显较短。回归分析表明，WS组TRF长度显著短于对照组（P < 0.001）。此外，我们发现，TRF长度在肌肉相邻的检查表皮也显着短于对照组（p = 0.047）。这些数据首次表明，在体内端粒损失加速全身器官的WS患者，这表明异常端粒侵蚀是早期发病的年龄相关的症状和肉瘤和癌的易感性在WS的主要原因之一。
Many data pertaining to the accelerated telomere loss in cultured cells derived from Werner syndrome (WS), a representative premature aging syndrome, have been accumulated. However, there have been no definitive data on in vivo telomere shortening in WS patients. In the present study, we measured terminal restriction fragment (TRF) lengths of 10 skin samples collected from extremities of 8 WS patients aged between 30 and 61 years that had been surgically amputated because of skin ulceration, and estimated the annual telomere loss. Whereas the values of TRF length in younger WS patients (in their thirties) were within the normal range, those in older WS patients were markedly shorter relative to non-WS controls. Regression analyses indicated that the TRF length in WS was significantly shorter than that in controls (p < 0.001). Furthermore, we found that TRF lengths in muscle adjacent to the examined epidermis were also significantly shorter than those of controls (p = 0.047). These data demonstrate for the first time that in vivo telomere loss is accelerated in systemic organs of WS patients, suggesting that abnormal telomere erosion is one of the major causes of early onset of age-related symptoms and a predisposition to sarcoma and carcinoma in WS.