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Letters to Nature
Nature 345, 458 - 460 (31 May 1990); doi:10.1038/345458a0

Telomeres shorten during ageing of human fibroblasts

Calvin B. Harley*, A. Bruce Futcher & Carol W. Greider

*Department of Biochemistry, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

THE terminus of a DNA helix has been called its Achilles' heel1. Thus to prevent possible incomplete replication2 and instability3,4 of the termini of linear DNA, eukaryotic chromosomes end in characteristic repetitive DNA sequences within specialized structures called telomeres5. In immortal cells, loss of telomeric DNA due to degradation or incomplete replication is apparently balanced by telomere elongation6–10, which may involve de novo synthesis of additional repeats by a novel DNA polymerase called telomerase11–14. Such a polymerase has been recently detected in HeLa cells15. It has been proposed that the finite doubling capacity of normal mammalian cells is due to a loss of telomeric DNA and eventual deletion of essential sequences1,16,17. In yeast, the est1 mutation causes gradual loss of telomeric DNA and eventual cell death mimicking senescence in higher eukaryotic cells17. Here, we show that the amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo. It is not known whether this loss of DNA has a causal role in senescence.

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