Extension of Life-Span by Introduction of Telomerase into Normal
Human Cells
Science, Jan 16, (1998).
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.
could have? That's the understatement of the century! |
