Extending Cellular Life-Span with Telomerase

Recent news stories have announced the results of a research article from the 16 January issue of Science. To facilitate evaluation and understanding of the research results, Science is providing online the full text of this article along with a related research commentary by de Lange.

--Research Article

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

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 b-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.

Download full text of this research article in Adobe Acrobat 3.0 PDF format.

See Help with Printing for information or to download the latest version of Adobe Acrobat.

--Science's Compass Research

Telomeres and Senescence: Ending the Debate

Titia de Lange

DNA, the genetic material, is arranged in chromosomes, linear structures in the nucleus capped with a long series of repeated sequences called telomeres. As de Lange describes in her Perspective, in 1986 the telomere theory of senescence was put forward, in which progressive loss of bits of the telomere with each cell division serves as a sort of clock, with the cell reaching the end of its life as it runs out of telomere. The corollary--that tumor cells can maintain their telomeres at a "young" length and so escape death--suggested an attractive site for cancer therapeutics. But the theory had come under fire since its introduction and had fallen out of favor with much of the scientific community. Now in a paper in the 16 January, 1998 issue of Science, the telomeric theory of aging is dramatically resuscitated.Bodnar et al. transfect adult differentiated human cells with a critical subunit of telomerase and rescue them from senescent death.

[Full Text]