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

Werner's syndrome (WS) is an autosomal recessive disorder displaying many f eatures consistent with accelerated ageing. Fibroblasts from WS patients sh ow a distinct mutator phenotype (characterised by the production of large c hromosomal deletions) and a profound reduction in proliferative capacity. T he disorder results from a mutation in a novel ReqQ helicase. Recently, we demonstrated that the proliferative defect was corrected by the ectopic exp ression of telomerase. From these data, Eve propose that mutations in the w rn gene lead to deletions at or near the telomere which reduce the cells re plicative life-span. This hypothesis predicts that cell types which retain the ability to upregulate telomerase as part of their response to a prolife rative stimulus would fail to show any significant effect of wrn gene mutat ions upon life-span. Human T lymphocytes represent a well-characterised exa mple of such a cell type. To test the hypothesis, WS T lymphocytes were cul tured until they reached replicative senescence. These cultures displayed l ife-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. (C) 2000 Publishe d by Elsevier Science Ireland Ltd.