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

Andrea G. Bodnar, Michel Ouellette, Maria Frolkis, Shawn E. Holt, Choy Pik Chiu, Gregg B. Morin, Calvin B. Harley, Jerry W. Shay, Serge Lichtsteiner, Woodring E. Wright

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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 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.

Original languageEnglish (US)
Pages (from-to)349-352
Number of pages4
JournalScience
Volume279
Issue number5349
DOIs
StatePublished - Jan 16 1998

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Cite this

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. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science, 279(5349), 349-352. https://doi.org/10.1126/science.279.5349.349