Telomeres and telomerase in ageing and cancer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Telomeres lie at the ends of human chromosomes and contain long tandem repeats of a simple nucleotide sequence. Because DNA replication cannot proceed to the very end of chromosomes, copies of these repeats are lost at each cell division. If the telomeres shorten below a critical length, the cells will eventually die as a result of genomic instability. Aging cells usually avoid death by entering senescence before the critical telomere length is reached. Malignantly transformed, immortal cells overcome senescence but they must still avoid the final, critical shortening of telomeres to survive. In the vast majority of cases, tumor cells achieve this by activating the telomerase enzyme, a ribonucleoprotein complex which repairs the end of chromosomes and prevents telomere shortening. Normal mortal cells do not normally express telomerase, although some stem cell populations which must regenerate thought the life span of the organism, retain enzyme activity. Cellular senescence can be overcome by inducing telomerase expression in mortal cells, firmly establishing the role of telomere length in the senescence signaling pathway. In tumor cells, the evidence of a role for telomerase in immortality is still largely correlative, with 80-90% of tumors expressing telomerase activity. To establish whether telomerase activity is important in maintaining the malignant phenotype, attempts have been made to inactivate it in tumor cells, using a variety of approaches, where there is evidence that disrupting telomerase function can result in the induction of apoptosis. The background and implications of these observations is discussed.

Original languageEnglish (US)
Pages (from-to)59-64
Number of pages6
JournalAge
Volume22
Issue number2
DOIs
StatePublished - Apr 1 1999

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Telomerase
Telomere
Telomere Shortening
Cell Aging
Neoplasms
Chromosomes
Tandem Repeat Sequences
Ribonucleoproteins
Genomic Instability
Human Chromosomes
Enzymes
DNA Replication
Cell Division
Stem Cells
Apoptosis
Phenotype
Population

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Telomeres and telomerase in ageing and cancer. / Cowell, John Kenneth.

In: Age, Vol. 22, No. 2, 01.04.1999, p. 59-64.

Research output: Contribution to journalArticle

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