Telomere length predicts replicative capacity of human fibroblasts

Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., Harley, C. B. (November 1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A, 89 (21). pp. 10114-8. ISSN 0027-8424 (Print)0027-8424 (Linking)

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Abstract

When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. Analysis of cells from 31 donors (aged 0-93 yr) indicated relatively weak correlations between proliferative ability and donor age (m = -0.2 doubling per yr; r = -0.42; P = 0.02) and between telomeric DNA and donor age (m = -15 base pairs per yr; r = -0.43; P = 0.02). However, there was a striking correlation, valid over the entire age range of the donors, between replicative capacity and initial telomere length (m = 10 doublings per kilobase pair; r = 0.76; P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue.

Item Type:	Paper
Uncontrolled Keywords:	Base Sequence *Cell Division Cells, Cultured DNA/genetics/isolation & purification Fibroblasts/cytology/physiology Humans Male Progeria/pathology/physiopathology Reference Values Repetitive Sequences, Nucleic Acid Skin/cytology Skin Aging/*physiology Skin Physiological Phenomena Spermatozoa/*physiology Telomere/*physiology/ultrastructure
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > telomeres
CSHL Authors:	Futcher, Bruce Greider, Carol
Communities:	CSHL labs > Futcher lab CSHL labs > Greider lab
Depositing User:	Matt Covey
Date:	1 November 1992
Date Deposited:	22 Sep 2015 15:06
Last Modified:	09 Nov 2017 20:07
PMCID:	PMC50288
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/31851

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