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Cited by 2,200Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsNuclear Structure and Function

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Telomere length predicts replicative capacity of human fibroblasts.

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Allsopp, R C, Vaziri, H, Patterson, C, Goldstein, S, Younglai, E V, Futcher, A B, Greider, C W, Harley, C B·1992·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.89.21.10114PMC PMC50288
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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.

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Research works printed but not linked: 9

  1. [5]Rohme, D. (1981) Proc. Natl. Acad. Sci. USA 78, 5009–5013.
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  5. [29]Sherwood, S. W., Rush, D., Ellsworth, J. L. & Schimke, R. T. (1989) Proc. Natl. Acad. Sci. USA 85, 9086–9090.
  6. [34]Goldstein, S. (1978) in Genetics of Aging, ed. Schneider, E. L. (Plenum, New York), pp. 171–224.
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Metadata

Authors
Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., & Harley, C. B.
Affiliations
McMaster University (CA)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1992-11
Volume
89
Issue
21
Pages
10114-10118
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.89.21.10114
PMC
PMC50288
OpenAlex
W1998663807
Cited by
2,200
References
43
Citations by year
2026: 14 · 2025: 25 · 2024: 25 · 2023: 39 · 2022: 36 · 2021: 39 · 2020: 42 · 2019: 67 · 2018: 67 · 2017: 52 · 2016: 60 · 2015: 79 · 2014: 82 · 2013: 68 · 2012: 74
FWCI
15.78
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • McMaster University
  • Medical Research Council Canada
  • National Institutes of Health (5r01ag008708-05)
  • Medical Research Council
  • National Institute on Aging (AG09383, AG08708)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
telomere length, replicative capacity, human fibroblasts, telomere shortening, telomerase, chronological age
MeSH terms
Base Sequence, Cell Division, Cells, Cultured, DNA, Fibroblasts, Humans, Male, Progeria, Reference Values, Repetitive Sequences, Nucleic Acid, Skin, Skin Physiological Phenomena, Spermatozoa, Skin Aging, Telomere

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