Transient expression of human telomerase extends the life span of normal human fibroblasts

Susanne Steinert, Jerry W. Shay, Woodring E. Wright

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

We utilized the Cre/lox recombination system to transiently express the catalytic subunit of telomerase (hTERT) in normal diploid foreskin fibroblasts (BJ cells). A retroviral construct containing an hTERT cDNA, flanked by loxP-sites was introduced into near senescent BJ cells (population doubling 85). At population doubling (PD) 92, which exceeds the typical life span of these cells, we excised the gene via Cre-mediated recombination. All clones lost telomerase activity and showed telomere shortening over an additional 50 PDs. Interestingly, the average telomere length in these cells became shorter than in untreated BJ cells at senescence. This may be due to hTERT preferentially elongating the shortest telomeres, leading to greater length uniformity. In summary, transient telomerase expression and only a very small average telomere elongation by hTERT resulted in a 50% increase in life span of human fibroblasts. This suggests a potentially safe use of hTERT in tissue engineering. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)1095-1098
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume273
Issue number3
DOIs
StatePublished - Jul 14 2000

Fingerprint

Telomerase
Fibroblasts
Telomere
Genetic Recombination
Telomere Shortening
Foreskin
Tissue engineering
Elongation
Cell Aging
Tissue Engineering
Complementary DNA
Genes
Diploidy
Population
Clone Cells

Keywords

  • Cre/lox-recombination
  • Telomerase
  • Telomeres

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Transient expression of human telomerase extends the life span of normal human fibroblasts. / Steinert, Susanne; Shay, Jerry W.; Wright, Woodring E.

In: Biochemical and Biophysical Research Communications, Vol. 273, No. 3, 14.07.2000, p. 1095-1098.

Research output: Contribution to journalArticle

@article{2d8f5e2bb24045e68ff6f3195af3440d,
title = "Transient expression of human telomerase extends the life span of normal human fibroblasts",
abstract = "We utilized the Cre/lox recombination system to transiently express the catalytic subunit of telomerase (hTERT) in normal diploid foreskin fibroblasts (BJ cells). A retroviral construct containing an hTERT cDNA, flanked by loxP-sites was introduced into near senescent BJ cells (population doubling 85). At population doubling (PD) 92, which exceeds the typical life span of these cells, we excised the gene via Cre-mediated recombination. All clones lost telomerase activity and showed telomere shortening over an additional 50 PDs. Interestingly, the average telomere length in these cells became shorter than in untreated BJ cells at senescence. This may be due to hTERT preferentially elongating the shortest telomeres, leading to greater length uniformity. In summary, transient telomerase expression and only a very small average telomere elongation by hTERT resulted in a 50{\%} increase in life span of human fibroblasts. This suggests a potentially safe use of hTERT in tissue engineering. (C) 2000 Academic Press.",
keywords = "Cre/lox-recombination, Telomerase, Telomeres",
author = "Susanne Steinert and Shay, {Jerry W.} and Wright, {Woodring E.}",
year = "2000",
month = "7",
day = "14",
doi = "10.1006/bbrc.2000.3080",
language = "English (US)",
volume = "273",
pages = "1095--1098",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Transient expression of human telomerase extends the life span of normal human fibroblasts

AU - Steinert, Susanne

AU - Shay, Jerry W.

AU - Wright, Woodring E.

PY - 2000/7/14

Y1 - 2000/7/14

N2 - We utilized the Cre/lox recombination system to transiently express the catalytic subunit of telomerase (hTERT) in normal diploid foreskin fibroblasts (BJ cells). A retroviral construct containing an hTERT cDNA, flanked by loxP-sites was introduced into near senescent BJ cells (population doubling 85). At population doubling (PD) 92, which exceeds the typical life span of these cells, we excised the gene via Cre-mediated recombination. All clones lost telomerase activity and showed telomere shortening over an additional 50 PDs. Interestingly, the average telomere length in these cells became shorter than in untreated BJ cells at senescence. This may be due to hTERT preferentially elongating the shortest telomeres, leading to greater length uniformity. In summary, transient telomerase expression and only a very small average telomere elongation by hTERT resulted in a 50% increase in life span of human fibroblasts. This suggests a potentially safe use of hTERT in tissue engineering. (C) 2000 Academic Press.

AB - We utilized the Cre/lox recombination system to transiently express the catalytic subunit of telomerase (hTERT) in normal diploid foreskin fibroblasts (BJ cells). A retroviral construct containing an hTERT cDNA, flanked by loxP-sites was introduced into near senescent BJ cells (population doubling 85). At population doubling (PD) 92, which exceeds the typical life span of these cells, we excised the gene via Cre-mediated recombination. All clones lost telomerase activity and showed telomere shortening over an additional 50 PDs. Interestingly, the average telomere length in these cells became shorter than in untreated BJ cells at senescence. This may be due to hTERT preferentially elongating the shortest telomeres, leading to greater length uniformity. In summary, transient telomerase expression and only a very small average telomere elongation by hTERT resulted in a 50% increase in life span of human fibroblasts. This suggests a potentially safe use of hTERT in tissue engineering. (C) 2000 Academic Press.

KW - Cre/lox-recombination

KW - Telomerase

KW - Telomeres

UR - http://www.scopus.com/inward/record.url?scp=0034647836&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034647836&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2000.3080

DO - 10.1006/bbrc.2000.3080

M3 - Article

C2 - 10891377

AN - SCOPUS:0034647836

VL - 273

SP - 1095

EP - 1098

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -