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 instability^3,4 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 elongation^6–10, which may involve de novo synthesis of additional repeats by a novel DNA polymerase called telomerase^11–14. 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 sequences^1,16,17. 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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