Hallmarks of telomeres in ageing research

Jerry W. Shay, W. E. Wright

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Telomeres are repetitive DNA sequences at the ends of linear chromosomes. Telomerase, a cellular reverse transcriptase, helps maintain telomere length in human stem cells, reproductive cells and cancer cells by adding TTAGGG repeats onto the telomeres. However, most normal human cells do not express telomerase and thus each time a cell divides some telomeric sequences are lost. When telomeres in a subset of cells become short (unprotected), cells enter an irreversible growth arrest state called replicative senescence. Cells in senescence produce a different constellation of proteins compared to normal quiescent cells. This may lead to a change in the homeostatic environment in a tissue-specific manner. In most instances cells become senescent before they can become cancerous; thus, the initial growth arrest induced by short telomeres may be thought of as a potent anti-cancer protection mechanism. When cells can be adequately cultured until they reach telomere-based replicative senescence, introduction of the telomerase catalytic protein component (hTERT) into telomerase-silent cells is sufficient to restore telomerase activity and extend cellular lifespan. Cells with introduced telomerase are not cancer cells, since they have not accumulated the other changes needed to become cancerous. This indicates that telomerase-induced telomere length manipulations may have utility for tissue engineering and for dissecting the molecular mechanisms underlying genetic diseases, including cancer.

Original languageEnglish (US)
Pages (from-to)114-123
Number of pages10
JournalJournal of Pathology
Volume211
Issue number2
DOIs
StatePublished - Jan 2007

Fingerprint

Telomere
Telomerase
Research
Cell Aging
Neoplasms
Inborn Genetic Diseases
Nucleic Acid Repetitive Sequences
RNA-Directed DNA Polymerase
Tissue Engineering
Growth
Proteins
Stem Cells
Chromosomes

Keywords

  • Ageing
  • Cancer
  • Telomerase
  • Telomeres

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Hallmarks of telomeres in ageing research. / Shay, Jerry W.; Wright, W. E.

In: Journal of Pathology, Vol. 211, No. 2, 01.2007, p. 114-123.

Research output: Contribution to journalArticle

Shay, Jerry W. ; Wright, W. E. / Hallmarks of telomeres in ageing research. In: Journal of Pathology. 2007 ; Vol. 211, No. 2. pp. 114-123.
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