Publication Date:
1998-02-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bodnar, A G -- Ouellette, M -- Frolkis, M -- Holt, S E -- Chiu, C P -- Morin, G B -- Harley, C B -- Shay, J W -- Lichtsteiner, S -- Wright, W E -- AG05747/AG/NIA NIH HHS/ -- AG07992/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geron Corporation, Menlo Park, CA 94025, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9454332" target="_blank"〉PubMed〈/a〉
Keywords:
Biomarkers
;
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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