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Divisions of Carcinogenesis and Differentiation [R. F., H. L., P. B.] and Genetic Alterations in Carcinogenesis [M. H.], German Cancer Research Center, D-69120 Heidelberg, Germany, and DAKO A/S, DK-2600 Glostrup, Denmark [K. V. N.]
The life span of normal fibroblasts in vitro (Hayflick
limit) depends on donor age, and telomere shortening has been proposed
as a potential mechanism. By quantitative fluorescence in
situ hybridization and Southern blot analysis, we show
progressive telomere loss to about 5 kb mean telomere restriction
fragment length in fibroblasts from two adult donors within 40
population doublings, whereas in fibroblasts from two infant donors,
telomere erosion is reduced, leaving a mean telomere restriction
fragment length of
7 kb at senescence (after
60 population
doublings). Aging of fibroblasts from both infant and adult donors was
not accompanied by chromosomal abnormalities but was correlated with
increased telomere repeat-binding factor 2 expression at both the
protein and transcriptional level.
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