Telomere erosion varies during in vitro aging of normal human fibroblasts from young and adult donors.
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 approximately 7 kb at senescence (after approximately 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.
Figueroa
R
R
Division of Carcinogenesis and Differentiation, German Cancer Research Center, Heidelberg.
Lindenmaier
H
H
Hergenhahn
M
M
Nielsen
K V
KV
Boukamp
P
P
D000328:Adult; D000375:Aging; D015139:Blotting, Southern; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere / Q000648:ultrastructure*; D035341:Telomeric Repeat Binding Protein 2; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D035341:Telomeric Repeat Binding Protein 2