Extension of Life-Span by Introduction of Telomerase into Normal Human Cells

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1998-01, Vol.279 (5349), p.349-352
Main Authors: Bodnar, Andrea G., Ouellette, Michel, Frolkis, Maria, Holt, Shawn E., Chiu, Choy-Pik, Morin, Gregg B., Harley, Calvin B., Shay, Jerry W., Lichsteiner, Serge, Wright, Woodring E.
Format: Article
Language:English
Subjects:
Ageing, cell death
Aging
Aging (Biology)
beta-Galactosidase - metabolism
Biological and medical sciences
Biomarkers
Catalysis
Cell aging
Cell Division
Cell growth
Cell Line
Cell lines
Cell physiology
Cell Transformation, Neoplastic
Cells
Cellular biology
Cellular Senescence
Cloning, Molecular
Cultured cells
Diploidy
DNA-Binding Proteins
Endothelial cells
Fibroblasts
Fibroblasts - cytology
Fundamental and applied biological sciences. Psychology
Homeostasis
Humans
Karyotyping
Medical research
Molecular and cellular biology
Phenotype
Pigment Epithelium of Eye - cytology
Prevention
Proteins
Proteins - genetics
Proteins - metabolism
RNA
RNA-Directed DNA Polymerase - genetics
RNA-Directed DNA Polymerase - metabolism
Stem cells
Stem Cells - cytology
Stem Cells - enzymology
Telomerase - genetics
Telomerase - metabolism
Telomere - metabolism
Telomere - physiology
Telomere - ultrastructure
Telomeres
Transfection
Tumor Cells, Cultured
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Summary: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 fore-skin 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 staining for β-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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.279.5349.349