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

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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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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: Allsopp, R C
Goldstein, S
Greider, C W
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: green
www.ncbi.nlm.nih.gov
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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Telomere length predicts replicative capacity of human fibroblasts.

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