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

AG Bodnar, M Ouellette, M Frolkis, SE Holt, CP Chiu… - science, 1998 - science.org
AG Bodnar, M Ouellette, M Frolkis, SE Holt, CP Chiu, GB Morin, CB Harley, JW Shay
science, 1998science.org
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 …
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 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.
AAAS