Telomeres shorten during ageing of human fibroblasts

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.