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

Science. 1998 Jan 16;279(5349):349-52. doi: 10.1126/science.279.5349.349.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers
  • Catalysis
  • Cell Division*
  • Cell Line
  • Cell Transformation, Neoplastic
  • Cellular Senescence*
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Fibroblasts / cytology
  • Homeostasis
  • Humans
  • Karyotyping
  • Phenotype
  • Pigment Epithelium of Eye / cytology
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA*
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / metabolism
  • Stem Cells / cytology
  • Stem Cells / enzymology
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / metabolism
  • Telomere / physiology*
  • Telomere / ultrastructure
  • Transfection
  • Tumor Cells, Cultured
  • beta-Galactosidase / metabolism


  • Biomarkers
  • DNA-Binding Proteins
  • Proteins
  • telomerase RNA
  • RNA
  • RNA-Directed DNA Polymerase
  • Telomerase
  • beta-Galactosidase