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Telomere length regulates ISG15 expression in human cells.

Lou Z, Wei J, Riethman H, Baur JA, Voglauer R, Shay JW, Wright WE - Aging (Albany NY) (2009)

Bottom Line: 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).In human skin specimens obtained from various aged individuals, ISG15 is up-regulated in a subset of cells in older individuals.The upregulation of ISG15 with telomere shortening may contribute to chronic inflammatory states associated with human aging.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

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.

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ISG15 is increased in human skin with aging. (A)                                            Immunofluorescence staining of ISG15 in BJ cells at different population                                            doublings. The negative sample was treated identically except no primary                                            antibody was added. Nuclei were stained with DAPI. Staining intensity                                            increases in cells with short telomeres. (B) Immunochemical staining                                            illustrating an age-dependent up-regulation of ISG15 expression in the                                            dermis of human skin tissues. 2-4 cases were examined in each group.                                            Infant, 0-1 year old; young adult, 20-24 year old; older adult, 53-68 year                                            old. No primary antibody was added to the negative control. (C)                                            Quantitation of the results of all the samples described above. 8-10 random                                            fields were counted for each sample.
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Figure 5: ISG15 is increased in human skin with aging. (A) Immunofluorescence staining of ISG15 in BJ cells at different population doublings. The negative sample was treated identically except no primary antibody was added. Nuclei were stained with DAPI. Staining intensity increases in cells with short telomeres. (B) Immunochemical staining illustrating an age-dependent up-regulation of ISG15 expression in the dermis of human skin tissues. 2-4 cases were examined in each group. Infant, 0-1 year old; young adult, 20-24 year old; older adult, 53-68 year old. No primary antibody was added to the negative control. (C) Quantitation of the results of all the samples described above. 8-10 random fields were counted for each sample.

Mentions: Significant up-regulation in ISG15 protein expression with telomere shortening was also confirmed by immunofluorescence staining (Figure 5A) in human skin fibroblasts. Intense staining was observed in the cells with short telomeres at PD78. Since telomeresshor- ten with in vivo aging [39], we also examined ISG15 expression in human skin tissues from donors of different ages (Figure 5B). The older adult group (ages 53-68) showed a significant increase in the number of ISG15-positive cells in the dermis (Figure 5C), indicating that up-regulation of ISG15 can occur in vivo.


Telomere length regulates ISG15 expression in human cells.

Lou Z, Wei J, Riethman H, Baur JA, Voglauer R, Shay JW, Wright WE - Aging (Albany NY) (2009)

ISG15 is increased in human skin with aging. (A)                                            Immunofluorescence staining of ISG15 in BJ cells at different population                                            doublings. The negative sample was treated identically except no primary                                            antibody was added. Nuclei were stained with DAPI. Staining intensity                                            increases in cells with short telomeres. (B) Immunochemical staining                                            illustrating an age-dependent up-regulation of ISG15 expression in the                                            dermis of human skin tissues. 2-4 cases were examined in each group.                                            Infant, 0-1 year old; young adult, 20-24 year old; older adult, 53-68 year                                            old. No primary antibody was added to the negative control. (C)                                            Quantitation of the results of all the samples described above. 8-10 random                                            fields were counted for each sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806043&req=5

Figure 5: ISG15 is increased in human skin with aging. (A) Immunofluorescence staining of ISG15 in BJ cells at different population doublings. The negative sample was treated identically except no primary antibody was added. Nuclei were stained with DAPI. Staining intensity increases in cells with short telomeres. (B) Immunochemical staining illustrating an age-dependent up-regulation of ISG15 expression in the dermis of human skin tissues. 2-4 cases were examined in each group. Infant, 0-1 year old; young adult, 20-24 year old; older adult, 53-68 year old. No primary antibody was added to the negative control. (C) Quantitation of the results of all the samples described above. 8-10 random fields were counted for each sample.
Mentions: Significant up-regulation in ISG15 protein expression with telomere shortening was also confirmed by immunofluorescence staining (Figure 5A) in human skin fibroblasts. Intense staining was observed in the cells with short telomeres at PD78. Since telomeresshor- ten with in vivo aging [39], we also examined ISG15 expression in human skin tissues from donors of different ages (Figure 5B). The older adult group (ages 53-68) showed a significant increase in the number of ISG15-positive cells in the dermis (Figure 5C), indicating that up-regulation of ISG15 can occur in vivo.

Bottom Line: 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).In human skin specimens obtained from various aged individuals, ISG15 is up-regulated in a subset of cells in older individuals.The upregulation of ISG15 with telomere shortening may contribute to chronic inflammatory states associated with human aging.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

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.

Show MeSH
Related in: MedlinePlus