Telomere length predicts replicative capacity of human fibroblasts

Richard C. Allsopp, Homayoun Vaziri, Christopher Patterson, Samuel Goldstein, Edward V. Younglai, A. Bruce Futcher, Carol W Greider, Calvin B. Harley

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)10114-10118
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number21
Publication statusPublished - 1992
Externally publishedYes

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Keywords

  • Aging
  • Cellular senescence
  • Progeria
  • Sperm

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., ... Harley, C. B. (1992). Telomere length predicts replicative capacity of human fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 89(21), 10114-10118.