Telomere length predicts replicative capacity of human fibroblasts.

• R C Allsopp

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

• H Vaziri

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

• C Patterson

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

• S Goldstein

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

• E V Younglai

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

• A B Futcher

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

• C W Greider

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

• C B Harley

  Department of Biochemistry, McMaster University, Hamilton, ON, Canada.

抄録

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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 89 (21), 10114-10118, 1992-11

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1361699994811947136
• NII論文ID: 80006774203
• DOI: 10.1073/pnas.89.21.10114
• ISSN: 10916490
• ISSN: 00278424
• ISSN: http://id.crossref.org/issn/00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.89.21.10114
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