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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 and Wright, WE (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349-52

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.

Links

PubMed

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; Proteins/metabolism; RNA; RNA-Directed DNA Polymerase/genetics; RNA-Directed DNA Polymerase/metabolism; Stem Cells/cytology; Stem Cells/enzymology; Telomerase/genetics; Telomerase/metabolism; Telomere/metabolism; Telomere/physiology; Telomere/ultrastructure; Transfection; Tumor Cells, Cultured; beta-Galactosidase/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TERT

involved_in

GO:0090399: replicative senescence

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TERT

involved_in

GO:0007004: telomere maintenance via telomerase

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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