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Research Paper|Volume 3, Issue 4|pp 417—429

Accelerated in vivo epidermal telomere loss in Werner syndrome

Naoshi Ishikawa1, Ken-Ichi Nakamura1, Naotaka Izumiyama-Shimomura1, Junko Aida1, Akio Ishii1, Makoto Goto2, Yuichi Ishikawa3, Reimi Asaka3, Masaaki Matsuura4, Atsushi Hatamochi5, Mie Kuroiwa6, Kaiyo Takubo1
  • 1Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan
  • 2Department Medical Technology, Faculty of Medical Engineering, Toin University of Yokohama, Yokohama 225-8503, Japan
  • 3Division of Pathology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
  • 4Bioinformatics Group, Genome Center, The Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
  • 5Department of Dermatology, Dokkyo University School of Medicine, Tochigi 321-0293, Japan
  • 6Department of Pathophysiology, Yokohama College of Pharmacy, Yokohama 245-0066, Japan
Received: April 3, 2011Accepted: April 23, 2011Published: April 25, 2011

Copyright: © 2011 Ishikawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.