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Telomeres and telomerase in aging, regeneration and cancer.

Authors
  • Djojosubroto, Meta Wulandari
  • Choi, Yoon Sik
  • Lee, Han-Woong
  • Rudolph, Karl Lenhard
Type
Published Article
Journal
Molecules and cells
Publication Date
Apr 30, 2003
Volume
15
Issue
2
Pages
164–175
Identifiers
PMID: 12803478
Source
Medline
License
Unknown

Abstract

The finding that telomere shortening limits the replicative lifespan of primary human cells has fueled speculations that telomere shortening plays a role during aging and regeneration of tissues in vivo. Support for this hypothesis comes from studies showing telomere shortening in a variety of human tissues as a consequence of aging and chronic disease. Studies in telomerase-deficient mice have given first experimental support that telomere shortening limits the replicative potential of organs and tissues in vivo and have identified telomerase as a promising target to treat regenerative disorders induced by telomere shortening. A potential downside of such an approach could be the development of malignant tumors, which has been linked to reactivation of telomerase in human cancers. In telomerase-deficient mice, telomere shortening showed a dual role in tumorigenesis, enhancing the initiation of tumors by induction of chromosomal instability but inhibiting tumor progression by induction of DNA-damage responses. The success in using telomerase activation for the treatment of regenerative disorders could depend on which of the mechanisms of telomere shortening is dominantly effecting carcinogenesis.

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