Werner's syndrome T lymphocytes display a normal in vitro life-span

S.Elizabeth James, Richard Faragher, J.F. Burke, S. Shall, L.V. Mayne

Research output: Contribution to journalArticle

Abstract

Werner’s syndrome (WS) is an autosomal recessive disorder displaying many features consistent with accelerated ageing. Fibroblasts from WS patients show a distinct mutator phenotype (characterised by the production of large chromosomal deletions) and a profound reduction in proliferative capacity. The disorder results from a mutation in a novel ReqQ helicase. Recently, we demonstrated that the proliferative defect was corrected by the ectopic expression of telomerase. From these data, we propose that mutations in the wrn gene lead to deletions at or near the telomere which reduce the cells replicative life-span. This hypothesis predicts that cell types which retain the ability to upregulate telomerase as part of their response to a proliferative stimulus would fail to show any significant effect of wrn gene mutations upon life-span. Human T lymphocytes represent a well-characterised example of such a cell type. To test the hypothesis, WS T lymphocytes were cultured until they reached replicative senescence. These cultures displayed life-spans which did not differ significantly from those of normal controls. These findings are consistent with the hypothesis that the effects of wrn mutations on replicative life-span are telomere-mediated.
Original languageEnglish
Pages (from-to)139-149
Number of pages11
JournalMechanisms of Ageing and Development
Volume121
Issue number1-3
DOIs
Publication statusPublished - 20 Dec 2000

Keywords

  • Werner's syndrome
  • T lymphocytes
  • ReqQ helicase

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