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Priority Research Paper|Volume 1, Issue 7|pp 608—621

Telomere length regulates ISG15 expression in human cells

Zhenjun Lou1, Jun Wei2, Harold Riethman2, Joseph A. Baur1,3, Regina Voglauer4, Jerry W. Shay1, Woodring E. Wright1
  • 1Department of Cell Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
  • 2Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA
  • 3Current address: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
  • 4Department of Biotechnology, Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, A-1190 Vienna, Austria
Received: June 15, 2009Accepted: July 16, 2009Published: July 17, 2009
https://doi.org/10.18632/aging.100066

Copyright: © 2009 Lou 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

Endogenous genes regulated by telomere length have not previously been identified in human cells. Here we show that telomere length regulates the expression of interferon stimulated gene 15 (ISG15, 1p36.33). ISG15 expression (RNA and protein) increases in human cells with short telomeres, and decreases following the elongation of telomeres by human telomerase reverse transcriptase (hTERT). The short-telomere-dependent up-regulation of ISG15 is not mediated by replicative senescence/DNA damage signaling or type I interferons. In human skin specimens obtained from various aged individuals, ISG15 is up-regulated in a subset of cells in older individuals. Our results demonstrate that endogenous human genes can be regulated by the length of telomeres prior to the onset of DNA damage signals, and suggest the possibility that cell turnover/telomere shortening may provide a mechanism for adjusting cellular physiology. The upregulation of ISG15 with telomere shortening may contribute to chronic inflammatory states associated with human aging.