Extension of life-span by introduction of telomerase into normal human cells.

Authors: Bodnar AG; Ouellette M; Frolkis M; Holt SE; Chiu CP; Morin GB; Harley CB; Shay JW; Lichtsteiner S; Wright WE

Abstract: Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced straining for beta-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.

Keywords: Biological Markers; Catalysis; *Cell Aging; *Cell Division; Cell Line; Cell Transformation, Neoplastic; Cloning, Molecular; DNA-Binding Proteins; Fibroblasts/cytology; Homeostasis; Humans; Karyotyping; Phenotype; Pigment Epithelium of Eye/cytology; Proteins/genetics/*metabolism; *RNA; RNA-Directed DNA Polymerase/genetics/metabolism; Stem Cells/cytology/enzymology; Telomerase/genetics/*metabolism; Telomere/metabolism/*physiology/ultrastructure; Transfection; Tumor Cells, Cultured; beta-Galactosidase/metabolism
Journal: Science (New York, N.Y.)
Volume: 279
Issue: 5349
Pages: 349-52
Date: Feb. 7, 1998
PMID: 9454332
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Citation:

Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE (1998) Extension of life-span by introduction of telomerase into normal human cells. Science (New York, N.Y.) 279: 349-52.



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