Abstract
Werner syndrome (WS) is a rare disorder inherited in an autosomal recessive manner and characterized by accelerated ageing1. WS fibroblasts display an accelerated rate of senescence in vitro2, which has been linked to this progeroid phenotype. The senescence of normal human fibroblasts is triggered by telomere shortening3,4,5, whereas the premature senescence of WS fibroblasts has been assumed6,7 to reflect the accumulation of DNA damage. Here we show that forced expression of telomerase in WS confers extended cellular lifespan and probable immortality.
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Kipling, D. & Faragher, R.G.A. J. Clin. Path. Mol. Path. 50, 234–241 (1997).
Faragher, R.G.A. et al. Proc. Natl Acad. Sci. USA 90, 12030 –12034 (1993).
Bodnar, A.G. et al. Science 279, 349–352 (1998).
Vaziri, H. & Benchimol, S. Curr. Biol. 8, 279–282 (1998).
Counter, C.M. et al. Proc. Natl Acad. Sci. USA 95, 14723 –14728 (1998).
Kirkwood, T. Time of Our Lives (Weidenfeld and Nicolson, London, 1999).
Beckman, K.B. & Ames, B.N. Physiol. Rev. 78, 547–581 (1998).
Moser, M.J., Oshima, J. & Monnat, R.J. Hum. Mut. 13, 271– 279 (1999).
Gebhart, E. et al. Hum. Genet. 80, 135– 139 (1988).
Fukuchi, K.-I., Martin, G.M. & Monnat, R.J. Proc. Natl Acad. Sci. USA 86, 5893–5897 (1989).
Nakamura, T.M. et al. Science 277, 955–959 (1997).
Morgenstern, J.P. & Land, H. Nucleic Acids Res. 18, 3587–3596 ( 1990).
Bond, J.A. et al. Mol. Cell. Biol. 19, 3103– 3114 (1999).
Bennett, S.E. et al. Mol. Biol. Aging 44, 214– 224 (1999).
Jones, C.J. et al. Exp. Cell Res. 240, 333– 339 (1998).
Acknowledgements
We thank C. Harley for providing pGRN121 and J. Smith for providing the HCA2 cell strain. This work was supported by the Cancer Research Campaign and the Biotechnology and Biological Sciences Research Council's Science of Ageing Initiative. D.K. is a Fellow of the Lister Institute of Preventive Medicine.
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Wyllie, F., Jones, C., Skinner, J. et al. Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts . Nat Genet 24, 16–17 (2000). https://doi.org/10.1038/71630
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DOI: https://doi.org/10.1038/71630
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