Telomere length regulates ISG15 expression in human cells.

Zhenjun Lou, Jun Wei, Harold Riethman, Joseph A. Baur, Regina Voglauer, Jerry W. Shay, Woodring E. Wright

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)608-621
Number of pages14
JournalAging
Volume1
Issue number7
StatePublished - Jul 2009

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Telomere
Telomere Shortening
DNA Damage
Up-Regulation
Genes
Interferon Type I
Cell Aging
Interferons
RNA
Skin
Proteins

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

Lou, Z., Wei, J., Riethman, H., Baur, J. A., Voglauer, R., Shay, J. W., & Wright, W. E. (2009). Telomere length regulates ISG15 expression in human cells. Aging, 1(7), 608-621.

Telomere length regulates ISG15 expression in human cells. / Lou, Zhenjun; Wei, Jun; Riethman, Harold; Baur, Joseph A.; Voglauer, Regina; Shay, Jerry W.; Wright, Woodring E.

In: Aging, Vol. 1, No. 7, 07.2009, p. 608-621.

Research output: Contribution to journalArticle

Lou, Z, Wei, J, Riethman, H, Baur, JA, Voglauer, R, Shay, JW & Wright, WE 2009, 'Telomere length regulates ISG15 expression in human cells.', Aging, vol. 1, no. 7, pp. 608-621.
Lou Z, Wei J, Riethman H, Baur JA, Voglauer R, Shay JW et al. Telomere length regulates ISG15 expression in human cells. Aging. 2009 Jul;1(7):608-621.
Lou, Zhenjun ; Wei, Jun ; Riethman, Harold ; Baur, Joseph A. ; Voglauer, Regina ; Shay, Jerry W. ; Wright, Woodring E. / Telomere length regulates ISG15 expression in human cells. In: Aging. 2009 ; Vol. 1, No. 7. pp. 608-621.
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